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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Making maternity and neonatal care personalised in the COVID-19 pandemic: results from the Babies Born Better Survey in the UK and the Netherlands</strong> -
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Background: The COVID-19 pandemic had a severe impact on women’s birth experiences. To date, there are no studies that use both quantitative and qualitative data to compare women’s birth experiences before and during the pandemic, across more than one country. Aim: To examine women’s birth experiences during the COVID-19 pandemic and to compare the experiences of women who gave birth in the United Kingdom (UK) or the Netherlands (NL) either before or during the pandemic. Method: This study is based on analyses of quantitative and qualitative data from the online Babies Born Better survey. Responses recorded by women giving birth in the UK and the NL between June and December 2020 have been used, encompassing women who gave birth between 2017 and 2020. Quantitative data were analysed descriptively, and chi-squared tests were performed to compare women who gave birth pre- versus during pandemic and separately by country. Qualitative data was analysed by inductive thematic analysis. Findings: Respondents in both the UK and the NL who gave birth during the pandemic were as likely, or, if they had a self-reported above average standard of life, more likely to rate their labour and birth experience positively when compared to women who gave birth pre-pandemic. This was despite the fact that those labouring in the pandemic reported less support and choice. Two potential explanatory themes emerged from the qualitative data: respondents had lower expectations during the pandemic, and they appreciated that care providers tried hard to personalise care. Conclusion: Our study implies that many women labouring during the COVID-19 pandemic experienced restrictions, but their experience was mitigated by staff actions. However, personalised care should not be maintained by the good will of care providers, but should be a priority in maternity care policy to benefit all service users equitably.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.11.22273702v1" target="_blank">Making maternity and neonatal care personalised in the COVID-19 pandemic: results from the Babies Born Better Survey in the UK and the Netherlands</a>
</div></li>
<li><strong>Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease</strong> -
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DNA methylation commonly occurs at cytosine-phosphate-guanine sites (CpGs) that can serve as biomarkers for many diseases. We analyzed whole genome sequencing data to identify DNA methylation quantitative trait loci (mQTLs) in 4,126 Framingham Heart Study participants. Our mQTL mapping identified 94,362,817 cis-mQTLvariant-CpG pairs (for 210,156 unique autosomal CpGs) at P&lt;1e-7 and 33,572,145 trans-mQTL variant-CpG pairs (for 213,606 unique autosomal CpGs) at P&lt;1e-14. Using cis-mQTL variants for 1,258 CpGs associated with seven cardiovascular disease risk factors, we found 104 unique CpGs that colocalized with at least one cardiovascular disease trait. For example, cg11554650 (PPP1R18) colocalized with type 2 diabetes, driven by a single nucleotide polymorphism (rs2516396). We performed Mendelian randomization (MR) analysis and demonstrated 58 putatively causal relations of CVD risk factor-associated CpGs to one or more risk factors (e.g., cg05337441 [APOB] with LDL; MR P=1.2e-99, and 17 causal associations with coronary artery disease (e.g. cg08129017 [SREBF1] with coronary artery disease; MR P=5e-13). We also showed that three CpGs, e.g., cg14893161 (PM20D1), are putatively causally associated with COVID-19 severity. To assist in future analyses of the role of DNA methylation in disease pathogenesis, we have created a browsable and downloadable resource of mQTLs through the NCBI Molecular QTL Browser.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.13.22273848v1" target="_blank">Elucidating the genetic architecture of DNA methylation to identify promising molecular mechanisms of disease</a>
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<li><strong>High prevalence of burnout syndrome among medical and nonmedical residents during the COVID-19 pandemic</strong> -
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Background: Since the beginning of the COVID-19 pandemic, health professionals have been working under extreme conditions, increasing the risk of physical and mental illness. We evaluated the prevalence of burnout and its associated factors among postgraduate student residents in health professions during the global health crisis. Methods : Healthcare residents were recruited from all across Brazil between July and September 2020 through digital forms containing instruments for assessing burnout (Oldenburg Burnout Inventory (OLBI)), resilience (brief resilient coping scale (BRCS)) and anxiety, stress and depression (depression, anxiety and stress scale (DASS-21) and Patient Health Questionnaire (PHQ-9)). Additionally, the relationships between burnout and chronic diseases, autonomy and educational adequacy in the residency programme, personal protective equipment (PPE), workload and care for patients with COVID-19 were evaluated. The chi-square test , Student’s t test, Pearson’s correlation test and logistic regression were performed. Results : A total of 1,313 participants were included: mean (standard deviation) age, 27.8 (4.4) years; female gender, 78.1%; white race, 59.3%; and physicians, 51.3%. The overall prevalence of burnout was 33.4%. The odds (odds ratio [95% confidence interval]) of burnout were higher in the presence of pre-existing diseases (1.76 [ 1.26–2 .47]) and weekly work &gt; 60 h (1.36 [1.03–1.79]) and were lower in the presence of high resilience (0.84 [0.81–0.88]), autonomy (0.87 [0.81–0.93]), and educational structure (0.77 [0.73–0.82]), adequate availability of PPE (0.72 [0.63–0.83]) and non-white race (0.63 [0.47–0.83]). Burnout was correlated with anxiety (r = 0.47; p &lt; 0.05), stress (r: 0.58; p &lt; 0.05) and depression (r: 0.65; p &lt; 0.05). Conclusions : We observed a high prevalence of burnout among residents during the COVID-19 pandemic. Individual characteristics and conditions related to the work environment were associated with a higher or lower occurrence of the syndrome.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.12.22273783v1" target="_blank">High prevalence of burnout syndrome among medical and nonmedical residents during the COVID-19 pandemic</a>
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<li><strong>COVID-19 and Curcumin: Using VOSviewer software to explore scientific landscape, A bibliometric analysis</strong> -
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Background: Curcumin is derived from Turmeric which is a spice with an old history in the oriental world. For this reason, it was a subject for continuous research over years and some studies reported preliminary positive results in arthritis and metabolic syndrome. When COVID-19 declared as a global pandemic, debates exploded again regarding its effects in mitigating deleterious effects of the viral infection. However, being a traditional remedy flooded readers with thousands of publications, some of these was scientifically rigid and others were fraudulent. We aim to use VOSviewer software to visualize scientific landscape in this topic, to highlight the trends and identify main supporting bodies. Methods: We searched Web of Science (WOS) core collection database for publications between December 2019 and April 2022. Data collected include: year of publication, keywords, type of the document, author names, affiliations, abstracts and number of citations. VOSviewer 1.6.18 was used to analyze co-citation, co-occurrence, and publication trends. Analysis considered one weight attribute which is total link strength attributes. Results: A total of 205 publications (N=205) were included in the analysis. Most studies were original research articles (50.7%). Mean citation count of the top 10 cited articles was 37.9 (range 22 and 111). Country of corresponding author of these 10 studies was India in 5 (50%), Iran in 3 (30%). Organizational analysis revealed 5 Iranian universities as being the main research bodies with total link strengths (TLS) of 100. Co-occurrence of keywords identified viral inhibition, oxidative stress, molecular docking, NF-kB pathway as the most frequent mentioned keywords. Trend analysis showed negative trend with less publications covering this topic, chronologically. Conclusion: Curcumin resided within the oriental tradition for years, it is no surprise that main supporting bodies were oriental. VOSviewer provides an easy, user-friendly options to handle bibliographic data.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.10.22273674v1" target="_blank">COVID-19 and Curcumin: Using VOSviewer software to explore scientific landscape, A bibliometric analysis</a>
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<li><strong>Profile of Brazilian inpatients with COVID-19 vaccine breakthrough infection and risk factors for unfavorable outcome</strong> -
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Objective. To characterize the epidemiological and clinical profile of individuals more likely to become infected by SARS-CoV-2 after the fully vaccination schedule in order to profile priority groups to receive a booster dose in situations of vaccine doses shortage as well as for maintenance of personal protective care. Methods. Data from hospitalized COVID-19 patients who had been fully vaccinated and had a SARS-CoV-2 infection positive diagnosis were collected from the SIVEP-Gripe database (Influenza Epidemiological Surveillance Information System) from January 18, 2021 to September 15, 2021. Demographic data, clinical symptoms/signs and preexisting medical conditions (comorbidities) were analyzed. The primary outcome was in-hospital death. Results. The majority of hospitalized patients with vaccine breakthrough infection were elderly ≥60 years old, male, with critical or severe COVID-19. The fatality rate was extremely high (50.27%) and more pronounced in elderly groups. The most prevalent symptoms were cough, dyspnoea, respiratory distress, and low blood oxygen saturation. The most frequent comorbidities were heart disease and diabetes. High fatality rates were observed among patients admitted to the intensive care units (72.88%) and those who required invasive mechanical ventilation (87.82%). The main risk factors for an unfavorable outcome were older age, respiratory compromise, inactivated virus vaccine immunization, and preexisting medical conditions. Conclusions. We characterize the profile of hospitalized Brazilian patients with COVID-19 vaccine breakthrough infection and the risk factors for an unfavorable outcome. These data have made it possible to identify priority groups to receive a booster dose, in addition to not neglecting personal protection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.12.22273589v1" target="_blank">Profile of Brazilian inpatients with COVID-19 vaccine breakthrough infection and risk factors for unfavorable outcome</a>
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<li><strong>Dynamics of anti-Spike IgG antibody titer after the third BNT162b2 COVID-19 vaccination in the Japanese health care workers</strong> -
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Introduction: Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity is insufficient. This study aimed to evaluate anti-spike immunoglobulin G (IgG) titers in the health care workers after the third BNT162b2 vaccination. Methods: Dynamics of anti-spike IgG titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations between anti-spike IgG titer, baseline characteristics, and adverse reactions were also evaluated. Results: The geometric mean titer of anti-spike IgG one month after the third vaccination was 17400 AU/ml, which increased to approximately 30 times immediately before the third vaccination and approximately twice that one month after the second vaccination. In addition, participants with anti-spike IgG titers less than 10000 AU/ml after the second vaccination tended to have higher increases in ant-spike IgG titers before and after the third vaccination. The decline rate of anti-spike IgG was significantly slower after the third vaccination as 35.7% than that after the second vaccination as 59.1%. The anti-spike IgG titer was significantly negatively associated with age (r = -0.31). Participants who had a headache at the vaccination showed significantly higher anti-spike IgG titer than those without a headache. Conclusions: The anti-spike IgG induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the anti-spike IgG with a slower decline rate.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.10.22273678v1" target="_blank">Dynamics of anti-Spike IgG antibody titer after the third BNT162b2 COVID-19 vaccination in the Japanese health care workers</a>
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<li><strong>A meta-epidemiological assessment of transparency indicators of infectious disease models</strong> -
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Mathematical models have become very influential, especially during the COVID-19 pandemic. Data and code sharing are indispensable for reproducing them, protocol registration may be useful sometimes, and declarations of conflicts of interest (COIs) and of funding are quintessential for transparency. Here, we evaluated these features in publications of infectious disease-related models and assessed whether there were differences before and during the COVID-19 pandemic and for COVID-19 models versus models for other diseases. We analysed all PubMed Central open access publications of infectious disease models published in 2019 and 2021 using previously validated text mining algorithms of transparency indicators. We evaluated 1338 articles: 216 from 2019 and 1122 from 2021 (of which 818 were on COVID-19); almost a six- fold increase in publications within the field. 511 (39.2%) were compartmental models, 337 (25.2%) were time series, 279 (20.9%) were spatiotemporal, 186 (13.9%) were agent-based and 25 (1.9%) contained multiple model types. 288 (21.5%) articles shared code, 332 (24.8%) shared data, 6 (0.4%) were registered, and 1197 (89.5%) and 1109 (82.9%) contained COI and funding statements, respectively. There was no major changes in transparency indicators between 2019 and 2021. COVID-19 articles were less likely to have funding statements and more likely to share code. Manual assessment of 10% of the articles that were identified by the text mining algorithms as fulfilling transparency indicators showed that 24/29 (82.8%) actually shared code, 29/33 (87.9%) actually shared data; and all had COI and funding statements, but 95.8% disclosed no conflict and 11.7% reported no funding. On manual assessment, 5/6 articles identified as registered had indeed been registered. Transparency in infectious disease modelling is relatively low, especially for data and code sharing. This is concerning, considering the nature of this research and the heightened influence it has acquired.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.11.22273744v1" target="_blank">A meta-epidemiological assessment of transparency indicators of infectious disease models</a>
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<li><strong>COVID-19 relevant genetic variants confirmed in an admixed population</strong> -
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The dissection of factors that contribute to COVID-19 infection and severity has overwhelmed the scientific community for almost 2 years. Current reports highlight the role of in disease incidence, progression, and severity. Here, we aimed to confirm the presence of previously reported genetic variants in an admixed population. Allele frequencies were assessed and compared between the general population (N=3079) for which at least 30% have not been infected with SARS-CoV2 as per July 2021 versus COVID-19 patients (N=106). Genotyping data from the Illumina GSA array was used to impute genetic variation for 14 COVID-relevant genes, using the 1000G phase 3 as reference based on the human genome assembly hg19, following current standard protocols and recommendations for genetic imputation. Bioinformatic and statistical analyses were performed using MACH v1.0, R, and PLINK. A total of 7953 variants were imputed on, ABO, CCR2, CCR9, CXCR6, DPP9, FYCO1, IL10RB/IFNAR2, LZTFL1, OAS1, OAS2, OAS3, SLC6A20, TYK2, and XCR1. Statistically significant allele differences were reported for 10 and 7 previously identified and confirmed variants, ABO rs657152, DPP9 rs2109069, LZTFL1 rs11385942, OAS1 rs10774671, OAS1 rs2660, OAS2 rs1293767, and OAS3 rs1859330 p&lt;0.03. In addition, we identified 842 variants in these COVID-related genes with significant allele frequency differences between COVID patients and the general population (p-value &lt;E-2 to E-179). Our observations confirm the presence of genetic differences in COVID-19 patients in an admixed population and prompts for the investigation of the statistical relevance of additional variants on these and other genes that could identify local and geographical patterns of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273925v1" target="_blank">COVID-19 relevant genetic variants confirmed in an admixed population</a>
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<li><strong>Seroprevalence, correlates and kinetics of SARS-CoV-2 Nucleocapsid IgG antibody in healthcare workers at a tertiary hospital: a prevaccine census study</strong> -
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Background: Healthcare workers are perceived to be a high-risk group for acquiring SAR-CoV-2 infection, and more so in countries where COVID-19 vaccination uptake is low. Serosurveillance may best determine the true extent of SARS- CoV-2 infection since most infected HCWs may be asymptomatic or present with only mild symptoms. Over time, determining the true extent of SARS-CoV-2 infection could inform hospital management and staff whether the preventive measures instituted are effective and valuable in developing targeted solutions. Methods: This was a census survey study conducted at the Aga Khan University Hospital, Nairobi, between November 2020 and February 2021 before the implementation of the COVID-19 vaccination. The SARS-CoV-2 nucleocapsid IgG test was performed using a chemiluminescent assay. Results: One thousand six hundred thirty-one (1631) staff enrolled, totalling 60% of the workforce. The overall crude seroprevalence was 18.4% and the adjusted (for assay sensitivity of 86%) was 21.4% (95% CI; 19.2-23.7). The HCW groups with higher prevalence included pharmacy (25.6%), outreach (24%), hospital- based nursing (22.2%) and catering staff (22.6%). Independent predictors of a positive IgG result included prior COVID-19 like symptoms, odds ratio (OR) 1.9 [95% confidence interval (CI) 1.3-2.9, p=0.002]; a prior positive SARS-CoV-2 PCR result OR 11.7 (CI: 7.5-18.1, p&lt;0.001) and working in a designated clinical COVID-19 location (high risk), OR 1.8 (CI: 1.04-3.11, p=0.033). Age, sex or comorbidities were not associated with seropositivity. The odds of testing positive for IgG after a positive PCR test were lowest if the antibody test was performed more than 2 months later OR 0.7 (CI: 0.48-0.95, p= 0.025). Conclusions: The prevalence of anti- SARS-CoV-2 nucleocapsid IgG among HCWs was lower than in the general population. Staff working in clinical areas were not at increased risk when compared to staff working in non-clinical areas.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.13.22273817v1" target="_blank">Seroprevalence, correlates and kinetics of SARS-CoV-2 Nucleocapsid IgG antibody in healthcare workers at a tertiary hospital: a prevaccine census study</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Can We Really Trust the Findings of the COVID-19 Research? Quality Assessment of Randomized Controlled Trials Published on COVID-19</strong> -
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Objective: To evaluate the quality of randomized controlled trials (RCTs) published on Coronavirus Disease-19 (COVID-19) and to investigate the reasons behind compromising the quality, if found. Methods: A systematic literature search was performed in PubMed, Google Scholar, and Cochrane CENTRAL to identify the Randomized Controlled Trails published on Coronavirus Disease-19 between 1st Dec 2019 to 31st Aug 2021. Research articles met with study criteria were included in the study. Assessment of quality of randomized controlled trials was done using modified Jadad scale. Results: 21,259 records of randomized controlled trials were identified through database searching, out of which 90 randomized controlled trials were included in the study and, 34 (37.8%) were of high-quality, 46 (51.1%) were of moderate quality, and 10 (11.1 %) were of low-quality studies. There were 40 (44.4%), 38 (42.2%), and 12 (13.3%) randomized controlled trials published in the early, middle, and late terms with Jadad score 5.12, 5.34, and 5.68 respectively (P=0.52). When comparing the blinding status, appropriate blinding, and methods to evaluate adverse events in randomized controlled trials with modified Jadad score, a significant difference was observed (P&lt;0.001). A significant moderate positive correlation was found between the impact factor of the journal and the modified Jadad scale score (R2= 0.48, P&lt;0.001). Conclusion: Findings from our study indicate that accelerated publication of Coronavirus Disease-19 researches along with the fast-track review process has resulted in lowering study quality scores. With the emergence of stronger evidence, Coronavirus Disease-19 clinical studies with lower methodological quality should be revisited. Keywords: COVID-19, Randomized Controlled Trials, Jadad scale, Quality Assessment
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273881v1" target="_blank">Can We Really Trust the Findings of the COVID-19 Research? Quality Assessment of Randomized Controlled Trials Published on COVID-19</a>
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<li><strong>The effect of antidepressants on severity of COVID-19 in hospitalized patients: A systematic review and meta- analysis</strong> -
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Introduction:  Clinical depression and the subsequent low immunity is a comorbidity that can act as a risk factor for severity of COVID-19 cases. Antidepressants such as SSRI and SNRI are associated with immune-modulatory effects, which dismiss inflammatory response and reduce lung tissue damage. The current systematic review and meta- analysis aims to evaluate the effect of antidepressant drugs on prognosis and severity of COVID-19 in hospitalized patients.   Methods: A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to January 16, 2022. The following keywords were used: “COVID-19”, “SARS-CoV-2”, “2019-nCoV”, “SSRI”, “SNRI”, “TCA”, “MAOI”, and “Antidepressant”. The pooled risk ratio (RR) with 95% CI was assessed using a fixed or random-effect model. We considered P &lt; 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta- Analysis software, Version 2.0 (Biostat, Englewood, NJ).   Results: Twelve studies were included in our systematic review. Three of them were experimental with 1751, and nine of them were observational with 290,950 participants. Seven out of twelve articles revealed the effect of antidepressants on reducing severity of COVID-19. SSRI medications, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine and also among the SNRI drugs Venlafaxine are also reasonably associated with reduced risk of intubation or death. There were four studies showing no significant effect and one study showing the negative effect of antidepressants on prognosis of covid-19. The meta-analysis on clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.745; 95% CI: 0.580-0.956)   Conclusions: Most of the evidence supports that the use of antidepressant medications, mainly Fluvoxamine may decrease the severity and improve the outcome in hospitalizes patients with sars-cov-2. Some studies showed contradictory findings regarding the effects of antidepressants on severity of COVID-19. Further experimental studies should be conducted to clarify the effects of antidepressants on severity of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.11.22273709v1" target="_blank">The effect of antidepressants on severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021</strong> -
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Background. Monitoring the emergence and spread of SARS-CoV-2 variants is an important public health objective. Travel restrictions, aimed to prevent viral spread, have major economic consequences and unclear effectiveness despite considerable research. We investigated the introduction and establishment of the Gamma variant in New York City (NYC) in</p></div></li>
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<ol start="2021" type="1">
<li>Methods. We performed phylogeographic analysis on 15,967 Gamma sequences available on GISAID and sampled between March 10th through May 1st, 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. Findings. We identified 16 phylogenetically-distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes). Most of the NYC clusters were introduced from Florida and Illinois; only one was introduced from outside the United States (US). By the time the first Gamma case was reported by genomic surveillance in NYC on March 10th, the majority (57%) of circulating Gamma lineages had already been established in the city for at least two weeks. Interpretation. Despite the expansion of SARS-CoV-2 genomic surveillance in NYC, there was a substantial gap between Gamma variant introduction and establishment in January/February 2021, and its identification by genomic surveillance in March 2021. Although travel from Brazil to the US was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273909v1" target="_blank">Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021</a>
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<li><strong>Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States</strong> -
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ABSTRACT Importance: Understanding the severity of post-vaccination COVID-19 breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. Objective: Estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, setting, and participants: The Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration consists of four US longitudinal cohorts from integrated health systems and academic centers. Adults (≥18 years old), in-care, fully vaccinated by June 30, 2021 with HIV, and matched PWoH (on date fully vaccinated, age group, race/ethnicity, and sex) were the source population. Those who experienced a post-vaccination SARS-CoV-2 breakthrough infection were eligible. Severe COVID-19 breakthrough illness was defined as hospitalization due to COVID-19. Discrete time proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals ([,]) of severe breakthrough illness by HIV status adjusting for demographics, COVID-19 vaccine type, and clinical factors. The proportion of patients requiring mechanical ventilation or died was compared by HIV status. Exposure: HIV infection Outcome: Severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Results: Among 1,241 PWH and 2,408 PWoH with breakthrough infections, the cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs. 6.7%, respectively, risk difference=-0.67% [-2.58%, 1.23%]). The risk of severe breakthrough illness was 59% higher in PWH with CD4 counts &lt;350 cells/mm3 compared with PWoH (aHR=1.59 [0.99, 2.46]). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 count increased the risk of severe breakthrough illness, while previous COVID-19 reduced the risk. Among all patients, 10% were mechanically ventilated and 8% died, with no difference by HIV status. Conclusions and Relevance: The risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. However, PWH with moderate and severe immune suppression had a higher risk of severe breakthrough infection. Recommendations for additional vaccine doses and risk-reduction strategies for PWH with moderate immune suppression may be warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273913v1" target="_blank">Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States</a>
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<li><strong>Linking Genotype to Phenotype: Further Exploration of Mutations in SARS-CoV-2 Associated with Mild or Severe Outcomes</strong> -
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We previously interrogated the relationship between SARS-CoV-2 genetic mutations and associated patient outcomes using publicly available data downloaded from GISAID in October 2020 [1]. Using high-level patient data included in some GISAID submissions, we were able to aggregate patient status values and differentiate between severe and mild COVID-19 outcomes. In our previous publication, we utilized a logistic regression model with an L1 penalty (Lasso regularization) and found several statistically significant associations between genetic mutations and COVID-19 severity. In this work, we explore the applicability of our October 2020 findings to a more current phase of the COVID-19 pandemic. Here we first test our previous models on newer GISAID data downloaded in October 2021 to evaluate the classification ability of each model on expanded datasets. The October 2021 dataset (n=53,787 samples) is approximately 15 times larger than our October 2020 dataset (n=3,637 samples). We show limitations in using a supervised learning approach and a need for expansion of the feature sets based on progression of the COVID-19 pandemic, such as vaccination status. We then re-train on the newer GISAID data and compare the performance of our two logistic regression models. Based on accuracy and Area Under the Curve (AUC) metrics, we find that the AUC of the re-trained October 2021 model is modestly decreased as compared to the October 2020 model. These results are consistent with the increased emergence of multiple mutations, each with a potentially smaller impact on COVID-19 patient outcomes. Bioinformatics scripts used in this study are available at https://github.com/JPEO-CBRND/opendata-variant-analysis. As described in Voss et al. 2021, machine learning scripts are available at https://github.com/Digital- Biobank/covid_variant_severity.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.15.22273922v1" target="_blank">Linking Genotype to Phenotype: Further Exploration of Mutations in SARS-CoV-2 Associated with Mild or Severe Outcomes</a>
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<li><strong>COVID-19 in the Mexican Social Security Institute (IMSS) population. Prevalent symptoms</strong> -
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Background. The disease caused by the new coronavirus SARS-CoV-2, COVID-19, which appeared in early 2020 in Mexico, was the second leading cause of mortality in the country that year and has generated an increasing demand for medical care. By January 2022, 4.13 million cases and 300 thousand direct deaths have been documented. Objective: To describe the main symptoms of people with a positive test for SARS-CoV-2 treated at the Mexican Institute of Social Security (IMSS) by sex, age group, and IMSS delegation. Methods. 4.5 million epidemiological reports were registered in the IMSS epidemiological surveillance system between February 2020 and November 2021. They were analyzed, reporting for those with either a positive PCR or rapid test, the prevalence of symptoms by sex, groups of age, and IMSS delegation. Results. Among the population treated at the IMSS, six symptoms are observed as the most prevalent in general, as well as by sex, age groups, and delegation of care: headache, fever, cough, myalgia, odynophagia, and arthralgias. Conclusions. A better understanding of the clinical picture with which confirmed cases of COVID-19 present contributes to reporting timely diagnoses, considering the particularities by sex, age, and place of residence.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.12.22273734v1" target="_blank">COVID-19 in the Mexican Social Security Institute (IMSS) population. Prevalent symptoms</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Randomized Controlled Clinical Trial to Evaluate The Efficacy and Safety of Healthtone as Prophylaxis for COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Dietary Supplement: Rhea® Health Tone<br/><b>Sponsor</b>:   Indonesia University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Functional Capacity in Patients Post Mild COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Device: Cardiopulmonary exercise test (CPET)<br/><b>Sponsor</b>:   Rambam Health Care Campus<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Circuit Training Program in Post COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: Circuit Training Exercise Program;   Other: Aerobic Training Exercise Program<br/><b>Sponsor</b>:   Riphah International University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Home-based Rehabilitation Program After COVID-19 Infection</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Add-on telerehabilitation and home-based rehabilitation;   Behavioral: Home-based rehabilitation alone<br/><b>Sponsor</b>:  <br/>
National Taiwan University Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy, Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: SARS-CoV-2 protein subunit recombinant vaccine;   Biological: placebo<br/><b>Sponsors</b>:   PT Bio Farma;   Faculty of Medicine, Universitas Indonesia, Jakarta;   Faculty of Medicine, Diponegoro University, Semarang;   Faculty of Medicine, Universitas Andalas, Padang;   Faculty of Medicine, Universitas Hassanudin, Makassar<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Effectiveness and Safety of SCTV01E (a Recombinant Protein COVID-19 Vaccine) in Population Aged ≥12 Years</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: SCTV01E;   Biological: CoronaVac;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: other approved COVID-19 vaccines<br/><b>Sponsor</b>:   Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E (Two Recombinant Protein COVID-19 Vaccines) in Population Aged ≥12 Years</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: mRNA vaccine manufactured by Pfizer or Moderna;   Biological: Sinopharm inactivated COVID-19 vaccine<br/><b>Sponsor</b>:   Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines</strong> - <b>Conditions</b>:   COVID-19;   SARS-CoV-2 Infection<br/><b>Interventions</b>:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: mRNA-1273<br/><b>Sponsor</b>:   Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years</strong> - <b>Conditions</b>:   SARS-CoV-2 Infection;   COVID-19<br/><b>Interventions</b>:   Biological: SCTV01E;   Biological: Comirnaty<br/><b>Sponsor</b>:   Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Enoxaparin and Hydroxychloroquine in COVID-19</strong> - <b>Condition</b>:   COVID-19 Pandemic<br/><b>Intervention</b>:   Drug: Enoxaparin, Hydroxychloroquine<br/><b>Sponsor</b>:   Beni-Suef University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years.</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: 1 Nebulized inhalation for booster groups;   Biological: 2 Nebulized inhalation for booster groups;   Biological: 3 Nebulized inhalation for booster groups;   Biological: 4 Nebulized inhalation for booster groups;   Biological: 5 Intramuscular injection for booster groups;   Biological: 6 Intramuscular injection for booster groups;   Biological: 7 Intramuscular injection for booster groups;   Biological: 8 Intramuscular injection for booster groups;   Biological: 9 Intramuscular injection for booster groups;   Biological: 10 Intramuscular injection for booster groups;   Biological: 11 Nebulized inhalation for booster groups;   Biological: 12 Nebulized inhalation for booster groups;   Biological: 13 Nebulized inhalation for booster groups;   Biological: 14 Nebulized inhalation for booster groups;   Biological: 15 Intramuscular injection for booster groups;   Biological: 16 Intramuscular injection for booster groups;   Biological: 17 Intramuscular injection for booster groups;   Biological: 18 Intramuscular injection for booster groups;   Biological: 19 Intramuscular injection for booster groups;   Biological: 20 Intramuscular injection for booster groups;   Biological: 21 Nebulized inhalation for primary groups;   Biological: 22 Nebulized inhalation for primary groups;   Biological: 23 Nebulized inhalation for primary groups;   Biological: 24 Nebulized inhalation for primary groups<br/><b>Sponsor</b>:  <br/>
Seventh Medical Center of PLA General Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Evaluation of Rapid RNA Test for Covid-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Diagnostic Test: rapid RT-LAMP test to detect SARS-COV-2 RNA<br/><b>Sponsors</b>:   University of Southampton;   West Hertfordshire Hospitals NHS Trust;   University of Oxford<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-inferiority Trial on Treatments in Early COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Sotrovimab;   Drug: Tixagevimab Cilgavimab;   Drug: Nirmatrelvir Ritonavir<br/><b>Sponsors</b>:   Azienda Ospedaliera Universitaria Integrata Verona;   Agenzia Italiana del Farmaco;   Azienda Sanitaria-Universitaria Integrata di Udine<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neutralizing Power of Anti-SARS-CoV-2 (Anti-COVID-19) Serum Antibodies</strong> - <b>Conditions</b>:   COVID-19;   SARS CoV 2 Infection<br/><b>Intervention</b>:  <br/>
Other: Collection of biological samples<br/><b>Sponsor</b>:   Centre Hospitalier Régional d’Orléans<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of Recombinant Two-Component COVID-19 Vaccine (CHO Cell)(ReCOV)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsor</b>:   Jiangsu Rec- Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Regulatory T Cells in Immunopathogenesis and Severity of COVID-19: A Systematic Review</strong> - CONCLUSION: Regulatory T cells can be one of the determinants of disease severity and prognosis in patients with COVID-19 by inhibiting rampant inflammation and preventing cytokine storms.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 3CLpro whole human proteome cleavage prediction and enrichment/depletion analysis</strong> - A novel coronavirus (SARS-CoV-2) has devastated the globe as a pandemic that has killed millions of people. Widespread vaccination is still uncertain, so many scientific efforts have been directed toward discovering antiviral treatments. Many drugs are being investigated to inhibit the coronavirus main protease, 3CLpro, from cleaving its viral polyprotein, but few publications have addressed this protease’s interactions with the host proteome or their probable contribution to virulence. Too few…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The association of intensity and duration of non-pharmacological interventions and implementation of vaccination with COVID-19 infection, death, and excess mortality: Natural experiment in 22 European countries</strong> - CONCLUSIONS: Our study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Aloe-derived natural products as prospective lead scaffolds for SARS-CoV-2 main protease (M<sup>pro</sup>) inhibitors</strong> - In the past two years, the COVID-19 pandemic has caused over 5 million deaths and 250 million infections worldwide. Despite successful vaccination efforts and emergency approval of small molecule therapies, a diverse range of antivirals is still needed to combat the inevitable resistance that will arise from new SARS-CoV-2 variants. The main protease of SARS-CoV-2 (M^(pro)) is an attractive drug target due to the clinical success of protease inhibitors against other viruses, such as HIV and HCV….</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS-CoV-2 nucleocapsid phosphoprotein- induced interleukin (IL)-6 in the lung</strong> - Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger excessive interleukin (IL)-6 signalling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID-19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS-CoV-2 increased IL-6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease <em>in vitro</em></strong> - SARS-CoV-2 main protease is a possible target for protection against viral infection. This study examined the inhibitory effect of food phytochemicals on the main protease of SARS-CoV-2 by determining a cleaved product after chromatographic separation. First, 37 phytochemicals, including glycosides and metabolites, were screened at 20 µM; epigallocatechin gallate, myricetin, theaflavin, herbacetin, piceatannol, myricitrin, and isothiocyanates inhibited the enzyme in varying degrees. The IC(50)…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mitoxantrone dihydrochloride, an FDA approved drug, binds with SARS-CoV-2 NSP1 C-terminal</strong> - One of the major virulence factors of SARS-CoV-2, NSP1, is a vital drug target due to its role in host immune evasion through multiple pathways. NSP1 protein is associated with inhibiting host mRNA translation by binding to the small subunit of ribosome through its C-terminal region. Previously, we have shown the structural dynamics of the NSP1 C-terminal region (NSP1-CTR) in different physiological environments. So, it would be very interesting to investigate the druggable compounds that could…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Insights into the binding and covalent inhibition mechanism of PF-07321332 to SARS-CoV-2 M<sup>pro</sup></strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the COVID-19 pandemic, resulting in several million deaths being reported. Numerous investigations have been carried out to discover a compound that can inhibit the biological activity of the SARS-CoV-2 main protease, which is an enzyme related to the viral replication. Among these, PF-07321332 (Nirmatrelvir) is currently under clinical trials for COVID-19 therapy. Therefore, in this work, atomistic and electronic…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach</strong> - The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to disrupt the RBD-hACE2 complex using molecular screening and simulation approaches</strong> - A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Titanium dioxide and fluoropolymer-based coating for smart fabrics with antimicrobial and water-repellent properties</strong> - In the coronavirus disease 2019 pandemic, protective clothing is required for medical staff at risk of infection. This study proposes functional smart fabrics with antimicrobial and water-repellent properties, using titanium dioxide (TiO(2)) and fluoropolymer-based precursors as coating materials. Experimental results indicated a uniform distribution of TiO(2) particles with an average size below 200 nm throughout the fabric. A zone of inhibition test revealed that the fabric inhibited bacterial…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of (2<em>R</em>,3<em>R</em>)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets; a systematic molecular modelling approach</strong> - Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS- CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive. We aimed to…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Flavonoids of <em>Salvadora persica</em> L. (meswak) and its liposomal formulation as a potential inhibitor of SARS- CoV-2</strong> - Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The inhibition of Mpro, the primary protease of COVID-19, by <em>Poria cocos</em> and its active compounds: a network pharmacology and molecular docking study</strong> - Poria cocos is a traditional Chinese medicine (TCM) that can clear dampness, promote diuresis, and strengthen the spleen and stomach. Poria cocos has been detected in many TCM compounds that are used for COVID-19 intervention. However, the active ingredients and mechanisms associated with the effect of Poria cocos on COVID-19 remain unclear. In this paper, the active ingredients of Poria cocos, along with their potential targets related to COVID-19, were screened using TCMSP, GeneCards, and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study</strong> - The global breakout of COVID-19 and raised death toll has prompted scientists to develop novel drugs capable of inhibiting SARS-CoV-2. Conducting studies on repurposing some FDA-approved glucocorticoids can be a promising prospective for finding a treatment for COVID-19. In addition, the use of anti-inflammatory drugs, such as glucocorticoids, is a pivotal step in the treatment of critical cases of COVID-19, as they can provoke an inflammatory cytokine storm, damaging lungs. In this study, 22…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SYSTEM FOR MONITORING COVID-19 PATIENTS USING A VIRTUAL TELEPRESENCE ROBOT</strong> - Attached Separately - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN356991740">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MASCARA FACIAL PARA LA INHALACION DE SUBSTANCIAS NEBULIZADAS, CON SISTEMA DE ASPIRACION INCORPORADO</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=ES355538276">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19</strong> - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN353347401">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种吡咯烷酮中间体的合成方法</strong> - 本发明涉及药物中间体合成技术领域，尤其是一种吡咯烷酮中间体的合成方法，包括以下步骤：化合物1溶液和有机锂试剂溶液泵入连续反应器，反应生成锂氢交换中间体，再泵入卤代乙腈与中间态发生反应生成化合物2；化合物2用固定床反应装置内进行氢化反应，后处理得到化合物3；将化合物3的溶液和氨水溶液泵入连续反应器生成酰胺化合物4；化合物4和脱水剂使用恒流泵泵入连续化反应器，生成化合物5或其氨基上有保护基的中间体；应用串联连续反应技术，将传统釜式数步反应改进为连续化工艺，解决了传统釜式反应的放大效应问题，降低了含金属试剂以及高压氢化等危险反应的安全风险进而避免了超低温反应釜和高压氢化釜等设备，提高了生产效率。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN357081864">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体</strong> - 本发明属于细胞工程与免疫学领域，具体涉及一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体。本发明筛选获得一株能高效稳定分泌表达新冠病毒S1蛋白单克隆抗体的杂交瘤细胞系以及其分泌的新冠病毒S1蛋白单克隆抗体；利用普通细胞培养皿培养本发明的重组杂交瘤细胞系，产量可达10mg/L，且纯度能达90%以上；本发明的单抗具有高中和活性，单抗浓度为0.00103μg/mL时即可抑制50％以上新冠假病毒活性，是目前所报告的新冠单抗中和活性最佳的。本发明提供的杂交瘤细胞系或单克隆抗体在新冠病毒的血清学检测、制备新冠病毒感染的试剂或药物及制备新冠病毒抗原或抗体检测的试剂中具有重要的应用价值。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN357081918">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>基于SARS-CoV-2的S蛋白的疫苗及其用途</strong> - 本公开提供了基于SARS‑CoV‑2的S蛋白的疫苗及其用途，并具体涉及重组SARS‑CoV‑2刺突蛋白(S蛋白)及编码其的mRNA和DNA。本公开还涉及包含编码重组S蛋白的DNA序列的重组质粒。本公开的重组质粒经转录得到mRNA，其包含SEQ ID NO.12所示的序列。本公开进一步涉及包含前述mRNA的mRNA‑载体颗粒例如脂质纳米颗粒(LNP)和组合物例如疫苗组合物。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073372">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CBD Covid 19 Protection</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU353359094">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种双价可电离脂质化合物、组合物及其应用</strong> - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073405">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种双价可电离脂质化合物、组合物及其应用</strong> - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073406">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>新冠肺炎CT图像分割方法及终端设备</strong> - 本发明公开了一种新冠肺炎CT图像分割方法及终端设备，方法包括获取待分割新冠肺炎CT图像；将该图像输入至训练好的分割模型中，得到新冠肺炎病灶区域的图像；其中分割模型包括依次连接的多个下采样模块和下采样模块对应的上采样模块；每个采样模块均包括依次连接的第一提取单元和第二提取单元；上述两个提取单元的卷积模块均为结构重参数化卷积模块。本发明的结构重参数化卷积模块为训练时使用多分支结构，加强模型表达能力，推理时使用单路结构，加快推理速度，快速得出诊断结果。同时，为从不同尺度特征图中学习分层表示，加强模型对图像边缘信息提取，并使梯度更快回流，上采样每一侧输出都连接混合损失函数，实现图像的像素级分割。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073393">link</a></p></li>
</ul>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Grim Journey of the Accused Brooklyn Subway Shooter</strong> - Frank James, the man charged with carrying out the Sunset Park attack, appears to have inhabited a world of conspiracy theories, grievance, and mental illness. - <a href="https://www.newyorker.com/news/news-desk/the-grim-journey-of-the-accused-brooklyn-subway-shooter">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Siege of Chernihiv</strong> - For more than a month, the Russian military pummelled residents with bombing raids and missile fire, turning a locked-in Ukrainian city into an urban death trap. - <a href="https://www.newyorker.com/news/dispatch/the-siege-of-chernihiv">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Case for an Immediate Energy Embargo on Russia</strong> - An aide to Ukrainian President Volodomyr Zelensky argues that halting the purchase of oil and gas is the surest way to stop Vladimir Putin’s military machine. - <a href="https://www.newyorker.com/news/our-columnists/the-case-for-an-immediate-energy-embargo-on-russia">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Danyel Smith Tells the History of Black Women in Pop Music</strong> - The author discusses Whitney Houston, Gladys Knight, racism in magazines, and why she’s so hopeful for the future of music and writing. - <a href="https://www.newyorker.com/culture/the-new-yorker-interview/danyel-smith-tells-the-history-of-black-women-in-%20pop">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sunday Reading: Looking Ahead to Earth Day</strong> - From the archive: a series of pieces from some of our finest writers on the environment. - <a href="https://www.newyorker.com/books/double-take/sunday-reading-looking-ahead-to-earth-day">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How to fight the affordable housing and climate crises at once</strong> -
<figure>
<img alt="Volunteers repairing house in Pennsylvania" src="https://cdn.vox-
cdn.com/thumbor/bRTnROCIEMJO_cSZ7ZN1-VbOozc=/72x0:4363x3218/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70759113/1330600207.0.jpg"/>
<figcaption>
Members of a church fix up a house in Amity Township, Pennsylvania. Homes in a state of disrepair are not eligible for federal weatherization money, contributing to higher energy bills. | Ben Hasty/MediaNews Group/Reading Eagle via Getty Images
</figcaption></figure></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
It’s all about the energy bills.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cpWDbj">
Alicia Cruz was homeless before she and her four daughters moved into a newly vacant apartment in Lancaster City, Pennsylvania, about three years ago. As she stood in the kitchen and watched dirty water clog up the sink, the landlord promised he’d have it fixed before they moved in.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9x1aO0">
But it was just the beginning. The ceiling of her apartment was cracked; the heating was inadequate, so she and her daughters are usually freezing; due to water damage, they regularly deal with roaches. She’s tried to leave but couldn’t find suitable alternatives she could afford.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="8AqE7p">
“If I knew then what I know now, I probably would have ran out the door and stayed homeless a little longer,” Cruz testified to Pennsylvania state lawmakers in December, later adding: “To this day, the landlord won’t fix this place, but he wants to collect my rent money. It’s just really sad.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eMk6bc">
The nation’s affordable housing crisis has gotten some semblance of attention — with journalists writing stories on the <a href="https://www.cbsnews.com/news/rents-post-pandemic-
hikes/">rising cost of rent</a>, the <a href="https://www.npr.org/2022/03/29/1089174630/housing-shortage-new-home-
construction-supply-chain">scarce supply of new housing</a>, the <a href="https://www.washingtonpost.com/business/2021/08/28/supreme-court-eviction-housing/">looming threat of eviction</a> — but<strong> </strong>one aspect of the crisis has gone consistently overlooked. On top of the severe housing shortage that currently exists, nearly <a href="https://www.greenandhealthyhomes.org/home-and-health/home-health-hazards/">6 million homes</a> nationwide have moderate to serious home health hazards. They require repairs that, if left ignored, will make them uninhabitable, and eventually they’ll disappear from the market altogether.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C05CPM">
The National Low Income Housing Coalition, a research and advocacy group, <a href="https://nlihc.org/resource/nlihc-
releases-2021-edition-gap-finding-extremely-low-income-renters-face-
shortage-7#:~:text=NLIHC%20released%20its%20annual%20report,income%20renter%20households%20in%202019.">estimates</a> a shortage of 7 million affordable housing units for low-income renters, but those figures don’t account for all the existing affordable units that stand at risk of demolition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WKgbYq">
Issues like lead paint, leaky roofs, and knob-and-tube wiring don’t just leave tenants and homeowners in substandard, unsafe housing.<strong> </strong>They also leave families — mostly poor families — shut out from energy efficiency programs the federal government already funds to upgrade homes. Due to inflexible program restrictions, homes with outstanding repairs aren’t eligible for existing weatherization subsidies, despite those families arguably needing them the most. Addressing this problem could help solve both the affordable housing and the climate crisis at once.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RyOkZO">
Low-income households in particular have a lot to gain from the federal <a href="https://www.energy.gov/eere/wap/weatherization-assistance-
program">Weatherization Assistance Program</a> (WAP), which provides funds to repair or replace heating and cooling systems, treat windows, or make any of the other upgrades that can not only reduce home energy use but also substantially reduce utility bills. But as it stands now, it’s people living in homes with no mold, asbestos, or structural issues who can access those WAP funds. Low-income homeowners and renters must first find the resources to fix their units, with some repairs running as high as $50,000.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rdhYBt">
The sheer number of homes barred from weatherization due to outstanding health and safety issues is immense. In Connecticut, for example, between 2017 and 2019, <a href="https://e4thefuture.org/wp-content/uploads/2021/01/Weatherization-Barriers-White-Paper-1-6-21.pdf">nearly 25 percent</a> of income-eligible homes were barred from weatherization upgrades. Steve Luxton, who heads a nonprofit focused on helping Philadelphians weatherize their homes, told me 55 to 65 percent of those in his city who apply for WAP assistance are denied because of structural issues. And nationally, according to a <a href="https://e4thefuture.org/wp-content/uploads/2022/04/E4-EFG_Weatherization-Barriers-Toolkit-4-7-2022.pdf">recently published E4TheFuture analysis</a>,<strong> </strong>10 to 30 percent of income-eligible clients are deferred from weatherization upgrades each year for health and safety problems, with those deferrals on the rise.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RjTRow">
Not being able to weatherize homes doesn’t just present cost burdens for low-income households, it also has a direct impact on the climate crisis. The energy required to cool, heat, and provide electricity to residential buildings accounts for <a href="https://constructionphysics.substack.com/p/looking-at-energy-use-in-us-
residential?s=r">20 percent</a> of annual energy use in the US, with older homes emitting more carbon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QJLzzc">
Included in the $1 trillion infrastructure bill Congress passed in November was a $3.5 billion investment in the federal weatherization program, with the stated goal to increase energy efficiency, increase health and safety, and reduce annual energy costs for low-income households. A 2015 Department of Energy evaluation of WAP found the energy efficiency upgrades it subsidized led to households saving <a href="https://www.energy.gov/eere/articles/energy-
department-announces-results-national-evaluation-weatherization-assistance">an average of $283 per year</a> on their bills.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="OyFUYW">
The Biden administration estimates the new infusion of funds from the infrastructure bill will allow the government to help 450,000 households weatherize over a decade. But low-income homeowners and tenants will remain shut out from the new money if they aren’t able to make the repairs they need.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jp1N3l">
“There will always be a tension, saying, ‘Okay, should I spend a thousand dollars to fix that roof when I could weatherize someone else’s house now?” said Charlie Harak, senior attorney for energy and utilities issues at the National Consumer Law Center. “But I’d go so far as to say that often the houses most in need of weatherization get walked away from.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JLPXwj">
It’s certainly not easy to come up with money for those repairs. If you’re a low-income homeowner, you would likely struggle to get an affordable home improvement loan from a bank. You may have less than optimal credit, and depending on where your house is located, the house itself may have low equity. If you’re a renter, your landlord probably feels little pressure to make your unit energy efficient, given that it’s tenants, not the property owners, who typically shoulder the electricity and gas bills.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C0iwz9">
According to US census data, low-income households <a href="https://www.aceee.org/research-report/u2006">spent an average of 8.1 percent</a> of their income on energy costs, compared to 2.3 percent for wealthier households. It’s not uncommon for poor families to pull back on other expenses, like medicine, groceries, or child care to cover their energy bills.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="96ylOv">
Jeff Genzer, who has served as counsel for the National Association of State Energy Officials since 1986, told me the intersection of housing and energy issues is one of the most difficult problems he’s worked on in his career. Steve Cowell, executive director of E4TheFuture and a longtime energy efficiency advocate, said the problem originates from treating health and safety issues as a footnote.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="85cfQt">
“The whole energy efficiency world that developed over the last 30 years was focused on pieces of the puzzle, and primarily the costs and benefits of energy on an economic dollar basis,” he said. “The health, safety, and conditions of a home has just been seen in the background, a side deal.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="E8rHwk">
Experts like Cowell have been trying to urge attention on the so-called “non-energy impacts” of weatherization, such as reduced asthma, reduced missed days of work, and fewer home fires. One <a href="https://ma-
eeac.org/wp-content/uploads/Low-Income-Single-Family-Health-and-Safety-Related-Non-Energy-Impacts-Study.pdf">evaluation published in 2016</a> assessed that each weatherized Massachusetts housing unit yielded an estimated $1,381 in combined savings to the individual household and society, with some of those savings coming from literally preventing deaths.
</p>
<h3 id="jtSaPP">
The climate crisis has made this harder to ignore
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ydKKUA">
When the energy efficiency movement got its start in the 1970s following the oil crisis, talk of reducing carbon emissions was simply not a salient consideration for policymakers and practitioners, and wouldn’t become one for years.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bEGeB1">
But as the stakes of the climate crisis have grown clearer, the last 10 years have marked a sea change for the energy efficiency movement. While in prior decades policymakers could ignore home upgrades when they deemed weatherization not “cost- effective,” today they have to wrestle with the fact that the low-income renters living in subsidized apartments <a href="https://multifamily.fanniemae.com/media/6266/display">are using even more energy</a> than other households, typically because their units are older and built with less efficient tech.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YbpiAa">
One study <a href="https://www.aceee.org/fact-sheet/halfway-there">published in 2019</a> by the American Council for an Energy- Efficient Economy (ACEEE) found that making energy upgrades — including to residential buildings —<strong> </strong>could cut greenhouse gas emissions in half by 2050. Upgrades to homes and buildings could save 30 percent on average for most buildings, ACEEE wrote, while installing sensors, automated controls, and other smart software could reduce energy use by another 15 percent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="waym12">
The carbon emissions produced by old, decrepit housing are not the only environmental threat. A warming planet also threatens to put more homes into disrepair or wipe them out from the existing housing stock altogether, exacerbating our housing shortage. For example, if a fire or natural disaster doesn’t completely destroy a unit, the owner has to decide whether to then repair or demolish it. Affordable rental units are <a href="https://s3.amazonaws.com/media.hudson.org/files/publications/AffordableRentHousing2017.pdf">more likely to be demolished than rebuilt</a>, given the tight profit margins they operate on.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o0cUOz">
Upgrading home energy systems won’t make those homes more capable of withstanding the effects of climate change. As Carlos Martín, the director of the Remodeling Futures Program at the Harvard Joint Center for Housing Studies, told me, energy efficiency upgrades are climate mitigation<em> </em>steps; they would help reduce future emissions to make the crisis less severe. But addressing home repairs, like fixing broken roofs, floors, and windows — those investments would strengthen existing housing stock to better withstand more frequent storms, flooding, and heat.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hW8mDC">
The growing affordable housing crisis has brought increased pressure to this situation. Depreciation is <a href="https://preservationdatabase.org/reports/picture-of-preservation/">one of the top three threats</a> to preserving existing affordable housing. It’s a hard issue to mobilize around though, because, like global warming, it’s a crisis we’re hurtling toward but haven’t yet reached. Weatherizing affordable homes could <a href="https://www.rand.org/pubs/research_reports/RR1444.html">help avoid that fate</a>; lowering maintenance costs can improve a property’s cash flow, which can then be used to reinvest in other capital needs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="fbdvGw">
More than a quarter of American households in 2020 <a href="https://www.eia.gov/consumption/residential/">reported difficulty</a> paying their energy bills. Harak, from the National Consumer Law Center, noted that failure to pay utility bills is considered a breach of the lease in most subsidized housing, leaving the renter highly vulnerable to eviction.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="K5NG6a">
“It’s a significant issue from an aspect of equity,” said Andrew Aurand, vice president for research at the National Low Income Housing Coalition. “If these people are priced out, where would they actually go?”
</p>
<h3 id="saMM0X">
A first-of-its-kind legislative fix
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="S8eyoZ">
In Pennsylvania, lawmakers are exploring a legislative solution to this problem, through a first-of-its-kind bill in the nation. Introduced in March by Democratic state Sen. Nikil Saval, <a href="https://www.legis.state.pa.us/cfdocs/billinfo/billinfo.cfm?syear=2021&amp;sind=0&amp;body=S&amp;type=B&amp;bn=1135">the Whole-Home Repairs Act</a> would provide eligible residents with grants up to $50,000 to make needed home repairs, and small landlords could apply for the same amount in forgivable loans. The bill would also aim to ramp up investments in workforce development, to address the growing shortage of qualified workers able to address the repairs.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="J5cT0P">
By finally fixing up the homes, tenants like Alicia Cruz would not only be able to live in safer and healthier environments, they’d also be finally positioned to access weatherization dollars. More than 280,000 occupied homes across Pennsylvania are estimated to have moderate to severe physical issues, ranging from exposed wiring to failed plumbing and leaky windows. Environmental justice activists note that making the housing repairs would also help those being targeted with offers by property developers, and help more seniors age in their own homes, a strong preference for many elderly families who live on fixed incomes.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="7lxBPz">
Genzer, of the National Association of State Energy Officials, told me he thinks Saval’s proposal is an “excellent bill” but that the $50,000 price tag for repairs “tells you a lot” about how difficult this problem can be politically.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rGP4sx">
Still, it’s not a long shot. Though Saval is a left-wing Philly Democrat, his bill has captured support from <a href="https://whyy.org/articles/gop-legislators-are-backing-philly-dems-housing-bill-why-blight-is-a-statewide-
issue/">some heavyweight Republican legislators</a> in Harrisburg, including Republican Sen. Pat Browne, chair of the state appropriations committee. Another is Sen. Dave Argall, chair of the state government committee, who has worked on blight issues for more than a decade.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Va1ncj">
“I represent a lot of struggling old mining communities where most of the coal mining stopped in the 1940s and 1950s,” Argall told me. “What I liked about Sen. Saval’s bill is if we help fix up the housing before they completely go to rot, that’s better for the people living in the homes, better for the next-door neighbor, and better for the taxpayer if they don’t have to fund millions and millions in demolition costs.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tskigJ">
Argall said he thinks the bill has “a very good chance” of passage in this year’s budget cycle, though the precise dollar amount is still being negotiated. Saval is pointing to the state’s $6 billion budget surplus and unspent Covid-19 relief dollars as strong sources to seed the new program.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UqDmqV">
Saval campaigned on affordable housing issues, but his office said data <a href="https://ohiorivervalleyinstitute.org/wp-
content/uploads/2021/07/dfp-pa-survey-toplines-pt2.pdf">released last spring</a> by the progressive polling firm Data for Progress was particularly instrumental in shaping some of their thinking around the politics. A survey of likely voters across Pennsylvania found 87 percent of respondents supported weatherizing homes to make them more energy efficient, including 83 percent of Republicans and 90 percent of independents.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="edb5aE">
While the home repairs bill would not itself go toward making energy efficiency upgrades, it would position more homes to be able to access the WAP funds. “We’re trying to make that federal money work more effectively,” Saval told me.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jihEfA">
On the federal level, the Department of Energy has been slow to take this problem seriously, though advocates say conversations are starting to happen. The pandemic also elevated the conversation around staying home, indoor air quality, and respiratory illness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xMZo44">
“There’s some new efforts to think through this,” said Cowell, of E4TheFuture. “But they still struggle to decide if weatherization should go beyond just the straight economic savings.” The federal agency still doesn’t require states to report the number of homes deferred from the weatherization program for repairs, and not all states track those “weatherization walkaways” consistently.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JhT2Ng">
Some states can dedicate a portion of their <a href="https://www.acf.hhs.gov/ocs/low-income-home-energy-assistance-program-liheap">Low Income Home Energy Assistance Program </a>(LIHEAP) funds for weatherization, a pot of money that tends to have a bit more flexibility than WAP funds in how it can be spent. Still, spending patterns for LIHEAP vary dramatically across states, and most of the money still goes for its primary purpose — helping poor families defray the cost of their energy bills. In 2015, <a href="https://liheappm.acf.hhs.gov/reports_to_congress">less than 10 percent</a> of total federal LIHEAP funds were used on weatherization.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BZiInN">
In Congress, weatherization has bipartisan support, but there’s been less momentum to address the home repair issues that prevent energy upgrades. Still, Democratic Rep. Dwight Evans, who represents Pennsylvania’s Third Congressional District, including parts of Philadelphia, told me he thinks Saval’s Whole-Home Repairs Act could become a national model. After all, Pennsylvania is showing how blight issues can bring collaboration across the aisle. And a Data for Progress <a href="https://www.dataforprogress.org/blog/2022/1/18/voters-say-its-time-for-congress-to-take-action-on-climate-
change">poll from January</a> found investing in energy efficiency for buildings to be one of the most popular climate policies nationally, especially given high energy prices.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rmgFwX">
“I think this program has great potential — it can be a vital part of the federal, state, and local investment that we need,” Evans said. “I’ve supported and voted for increased federal investments in affordable housing, and this would fit well with that.”
</p>
<ul>
<li><strong>How China’s Zero Covid policy is failing Shanghai</strong> -
<figure>
<img alt="Daily Life In Shanghai During COVID-19 Lockdown" src="https://cdn.vox-cdn.com/thumbor/zV-
eRPdZG5vkGXRch9n-3h-SR5A=/166x0:2834x2001/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/70758028/1391221888.0.jpg"/>
<figcaption>
A man with a mask is seen through a window at his home in a residential area on April 13, 2022 in Shanghai, China. Some 25 million people in Shanghai are in the second week of a strict lockdown, after a surge in Omicron cases. | Getty Images
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Rare dissent flares in China’s financial hub as residents struggle to access food and medicine
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="upTh5s">
Shanghai, China’s bustling cosmopolis of 26 million, has been under lockdown since late March under the nation’s strict “dynamic Zero Covid” protocols a system so poorly managed that residents are frequently unable to access basic necessities like food, medications, and medical care, prompting fairly widespread, spontaneous protests both online and in real life.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tI5vyy">
While the government has touted the Zero Covid strategy, the government’s system of containment using intensive testing and tracing, combined with partial or complete lockdowns when a case is detected, as keeping case counts and deaths low over the past two years, the reports coming out of Shanghai suggest that the local government was unprepared for an outbreak in the country’s economic center and cast doubt on the feasibility of Zero Covid at this point in the pandemic. That’s translated into serious struggles for residents, including hours-long ambulance wait times, dwindling savings, and inadequate or rotten food supplies, among others. Although the central government is reportedly stepping up efforts to get supplies to the city, the overall policy is driving many residents to criticize the government’s policy — and Shanghai’s implementation of it — despite serious potential risks to their safety and freedom by doing so.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="JAo6vz">
“Even the authoritarian governments, they still have to take this mass reaction into account, or else will lose the cooperation from the society. We’re going to expect that [the central government] is going to improve the policy implementation, even though the policy itself is not going to change,” Yanzhong Huang, a senior fellow for global health at the Council on Foreign Relations, told Vox on Friday.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LLXVDc">
The Shanghai outbreak is thus far China’s most serious since the beginning of the pandemic; a staggering 200,000 cases have been reported since the outbreak started in March, though that’s likely under-reported, according to <a href="https://www.nytimes.com/2022/04/13/business/china-covid-zero-
shanghai.html">the New York Times</a>. What started as a patchwork of temporary lockdowns to limit the spread of disease quickly turned into an interminable, city-wide shutdown with people only allowed out to take PCR tests, as a <a href="https://nymag.com/intelligencer/2022/04/locked-down-in-shanghai.html">New York Magazine</a> piece explained earlier this week. Shanghai’s lockdown, two years into the pandemic, is rivaled only by those in Wuhan in 2020 and Xi’an at the end of last year in terms of strictness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pqAqU4">
Shanghai residents’<strong> </strong>outrage — which they’ve expressed by singing and chanting from their balconies and co-opting anti-American hashtags used by government officials to criticize the US — is borne from the fact that the government isn’t providing the stability it promises in exchange for personal freedoms, according to Rui Zhong, program associate at the Wilson Center’s Kissinger Institute on China and the United States. “I think what makes people angry in Shanghai, and what made people angry in Xi’an is, Covid has been a problem for years,” she told Vox. “I think they’ve been really stunned at the degree to which their local officials haven’t necessarily prepared, including non-supply-chain issues,” like hospital admissions.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="g5vaFW">
Still, the government is asking citizens to sacrifice, without yet having the capacity to ensure access to food and medical care. On Thursday, people in the city’s Pudong district <a href="https://www.nbcnews.com/news/world/shanghai-videos-residents-clash-police-china-covid-protest-
rcna24520">protested</a> their building being taken over by the local government for the purposes of quarantining those who had tested positive. Footage of the incident circulated around Chinese social media before being censored, showing health authorities wrangling protesters to the ground and taking them to a white van, while others shouted, “Bring them back!” The video also<strong> </strong>captured residents saying, “The police are hitting people,” as they tried to block authorities from taking control of their building, <a href="https://www.nbcnews.com/news/world/shanghai-videos-
residents-clash-police-china-covid-protest-rcna24520">according to NBC</a>.
</p>
<h3 id="1NkY6g">
There’s been a fundamental breakdown of the Zero Covid policy
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yfcF4y">
Shanghai’s local government enjoys a degree of relative autonomy<strong> </strong>in the context of President Xi Jinping’s China; it’s technically <a href="https://www.britannica.com/place/Shanghai/Administration-and-society">directly under the control of the central government</a>, as a province-level city, but enjoys special status as the country’s financial hub and a showpiece for the rest of the world. Until March, the local government had handled the pandemic well, with no major outbreaks. But the rapid onset of the Omicron variant and the corresponding draconian government measures are pushing some citizens to the brink.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DWpr9z">
“I have no more money … What am I to do? I don’t care anymore,” one man shouts to his whole building in a viral video on Weibo, China’s answer to Twitter. “Just let the Communist Party take me.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Z6ewWj">
Zhong told Vox she had heard similar stories of desperation coming from Shanghai. “I was listening to a recording of an elderly man who was asking about his heart medication to a local cadre, a local CCP official,” she said. “He was basically saying, ‘We have hundreds of these types of cases per day, and I understand, but I can’t do anything.’ A lot of the immediate pressure goes on at the most local levels — a lot of emotional conversations, like ‘I am starving,’ or ‘I just got food but the food is all rotten,’ or ‘I need medication.’ So these are all very, very basic material needs. So people are very emotional that they can’t purchase them, and they don’t have a timetable for when they get these necessities again.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PpZN5G">
Wednesday’s New York Magazine dispatch from Shanghai describes neighborhoods and residential complexes bound together via WeChat (essentially, as Zhong said, “an operating system” which serves as a messaging platform, payment system, and more, and is ubiquitous in China) with volunteers stepping up where the government has failed — organizing large wholesale grocery orders for their buildings, helping administer Covid-19 tests, and organizing medical care for those in need. Shanghai’s Covid-19 response system has relied on volunteer efforts throughout the pandemic, to support data collection, contact tracing, and elder care; that worked in the days before Omicron, the incredibly virulent strain of the disease, began ripping through densely populated areas. That, combined with <a href="https://www.bloomberg.com/news/articles/2022-03-20/hk-s-immunized-who-died-of-covid-mainly-
got-sinovac-ming-pao">less-efficacious vaccines</a> and <a href="https://www.straitstimes.com/singapore/fear-of-
complications-or-side-effects-main-reason-some-seniors-spurn-covid-19-vaccine">lower overall vaccination rates</a> due to the government’s Covid-19 policy, particularly <a href="https://www.economist.com/china/2022/04/02/why-so-many-
elderly-chinese-are-unvaccinated">among the elderly</a>, to protect against the virus, was too much for the Zero Covid system to bear.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Riiumu">
“Many Shanghai people blame the local government officials for mishandling the crisis, the coordination problems, lack of contingency planning, these issues. Which might be true,” Huang said. “But it is interesting how, within a month, Shanghai degenerated from a poster child of the pandemic control to a pariah of the Covid response.”
</p>
<figure class="e-image">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><img alt="CHINA-HEALTH-VIRUS" src="https://cdn.vox-
cdn.com/thumbor/VhnWbGIVCPnxABBdLIRw0sY01Y4=/800x0/filters:no_upscale()/cdn.vox-
cdn.com/uploads/chorus_asset/file/23394737/1240017025.jpg"/> <cite>Hector Retamal/AFP via Getty Images</cite></p>
<figcaption>
Health workers wearing personal protective equipment (PPE) cross a checkpoint during a Covid-19 coronavirus lockdown in the Jing’an district of Shanghai on April 16, 2022.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lKAAJO">
Although the local bureaucrats have borne the brunt of people’s frustration, both Zhong and Huang told Vox, they might not necessarily be the ones to blame for the current crisis. “I think in Shanghai, if you measure state capacity in terms of the fiscal capacity, in terms of also the quality of the bureaucratic officials, the capabilities of the local government officials, I think it’s still relatively high,” Huang said. “I think the fundamental issue remains the Zero Covid strategy itself.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dBWzuK">
It’s easy, and to an extent, even logical, to blame supply chain strain — a global problem throughout the pandemic — for lack of access to food and medicine, but it doesn’t work the same way when the problem is getting an ambulance to come to address an emergency, or getting access to a hospital bed. “The problem is not lack of capacity, but the single-minded pursuit of Zero Covid,” Huang told Vox.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oVHc7q">
“I think what makes some of the outcry in Shanghai distinctive is, the grievances are not new,” according to Zhong. Previous lockdowns in Wuhan and Xi’an produced some of the same effects, albeit at a smaller scale, she told Vox. “You had these gaps in care, services for people, so, making sure everybody gets their prescription medication, making sure that food supply lines are ok, making sure that people who need to go to a hospital for non-Covid emergencies have options. Some of these problems go back as far as Wuhan in 2020.”
</p>
<h3 id="OGNfSL">
Protests are getting attention — but will they make a difference?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bVnOO7">
Both Zhong and Huang told Vox that the protests against the Shanghai lockdown — both in person and online — are spontaneous, rather than an organized effort. “In terms of protests, anything that’s really organized, centralized, or has some kind of clear leader or group, those are really, really difficult to organize in China because anybody that seems to be a protest leader, basically paints a target in terms of law enforcement,” Zhong said. “It’s sort of tacitly known in mainland China that something, even to the degree of 2014 or 2019 Hong Kong protests are really difficult to materialize because of the quick law enforcement responses.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="LZLOqx">
As authorities’ response to Thursday’s protest shows, law enforcement and government reaction to dissent is indeed swift; whether it’s shuffling screaming protesters into white vans, banning hashtags, or censoring videos, the Chinese government has little appetite for dissent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RTg4Ch">
“When people take to social media, it’s not the first resort people want, because social media is so easily identifiable and people don’t want their accounts shuttered,” Zhong noted. However, there are online efforts to use the government’s own online tools against them, she told Vox: “People are doing really unorthodox things, like using hashtags that state government typically uses to say how bad America is — except to complain about Shanghai.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="auCrbh">
Social media also serves as an important form of record keeping, which is important in a state known for repressive censorship. The online so-called “lockdown diary” has been part of the Chinese public’s response to Covid-19 and the government’s containment policy since the very beginning, Zhong said. It’s a form of record-keeping for people, to say, ‘This is what happened. This is what happened to my mother, my grandmother.’ Or, ‘This official was pushed so hard and pressured so hard that they took their own life,’” she said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="W8iCsA">
As to whether this outburst of desperation and dissatisfaction could portend further, more sustained protests, Zhong is circumspect; it’s far too early to tell what effect the Shanghai protests will have on the city’s future, the Zero Covid policy, or the nation. But it does open a window for criticism of the policy, as Huang noted.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4BfX81">
“There’s already more than 44 cities that have been under full or partial lockdowns, and many more cities have started mass PCR testing that impose limits on people’s movements. It’s fair to say that a large percentage of the population has been affected by this policy,” he said. And that criticism does, at least push the government to improve delivery of core goods and services, if only to ensure stability and quiet dissent, Huang said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="A2IcrN">
But ultimately, though experts within and outside the government — as well as China’s own citizens — are saying that the Zero Covid policy no longer works in a radically different pandemic landscape, adjustments and concessions from the government won’t alter the core policy. It’s too tied to the “superiority of the Chinese model,” as Huang said. “It’s certainly a strong incentive to continue that success, because the failure would mean that you essentially give up halfway through, and all this legacy will be gone. But in the meantime, I think it is less about legacy, the policy, and more about not allowing the perceived failure undermine personal leadership, or regime legitimacy.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EJWcjh">
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qTg3hO">
</p></li>
<li><strong>How to handle a lopsided friendship</strong> -
<figure>
<img alt="Illustration of two unhappy people sitting back-to-back with a gray scribble above their heads" src="https://cdn.vox-cdn.com/thumbor/NoYS1XMfMymW-BVP9YoGp1DrfSA=/174x0:1999x1369/1310x983/cdn.vox-
cdn.com/uploads/chorus_image/image/70756513/GettyImages_1326242828.0.jpeg"/>
<figcaption>
Getty Images/iStockphoto
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
If you think a pal is way less (or way more) invested than you are, here’s what to do.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MSmeDd">
Kristen’s 12-year relationship with her best friend Heather was put to the test during the pandemic. (Both women’s names have been changed at Kristen’s request to protect their privacy.) Their experiences during the past few years couldn’t have felt more different: Kristen, a single, 35-year-old behavioral researcher in San Francisco, was unbearably lonely during the lockdown. Her best friend, Heather, also 35, married and living in Los Angeles, gave birth to her first child. Kristen expected Heather’s priorities to shift as she adjusted to being a new mom, but Kristen wasn’t prepared for how upsetting it would feel to be shuffled to an outer ring of her best friend’s life precisely when she needed Heather most.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rr1inW">
They tried to keep in touch, agreeing to hop on a phone call every other Sunday at 8 am. But Heather was a no-show week after week. “She just would get really busy and overwhelmed and kind of just forget about me,” Kristen says. With every phone date Heather blew off, Kristen’s resentment grew. “It just got so painful that I was like, ‘This is not working,’” she says.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="9mmiqb">
As we juggle the demands of this ongoing pandemic, friendships have shifted in all sorts of unexpected ways. Many people now seem to have less stamina for socializing, says <a href="https://www.katvellos.com/">Kat Vellos</a>, author of <a href="https://weshouldgettogether.com/books"><em>We Should Get Together</em></a>, a book about cultivating friendships in adulthood. Vellos believes folks became used to having smaller social circles, and some realized they prefer keeping it that way. As a result, these people might be more choosy about the friendships they <em>do</em> invest time in. That’s mostly a good thing, but it can be painful for the people who are hurt that they are no longer a priority.
</p></li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nhQFHH">
A lopsided friendship happens when one friend is more active in maintaining contact and the other friend is more passive about keeping the connection going. It’s understandable to be sad or upset if you’re the one constantly reaching out, sending thoughtful messages and asking if you can schedule brunch or happy hour together. According to a <a href="https://www.pnas.org/content/pnas/108/15/6270.full.pdf">2010 study published in <em>Proceedings of the National Academy of Sciences</em></a>, social rejection can feel as distressing as physical pain.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y01BOg">
“We live longer if we feel connected and supported,” says <a href="https://www.kasleykillam.com/">Kasley Killam</a>, a Harvard- trained social scientist who specializes in connection and loneliness, and founder of the nonprofit <a href="https://www.socialhealthlabs.com/">Social Health Labs</a>. “So when someone expresses that they’re perhaps not as interested in being friends with us or they need a break or whatever, that can trigger this innate fear inside of us that we’re going to be alone or that we’re not of value.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0spCi9">
Psychologist <a href="https://www.ascensionbehavioralhealth.com/meetdrabrams">Ayanna Abrams</a> says having a lopsided friendship doesn’t automatically mean that your friendship is unhealthy or toxic. It’s only a problem if someone is feeling negative emotions about the pattern. To help figure out whether you’re in a lopsided friendship and how to deal if you are, Vox spoke with four friendship and connection experts.
</p>
<h3 id="gqPvQp">
Resist the urge to make assumptions
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YiVBZ8">
It’s easy to jump to conclusions and assume that if we don’t hear from someone as often as we’d like to, Killam says, “that means they don’t like us, or they don’t value our friendship.” More likely: The other person is just busy — it’s not that deep.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="bY1uzI">
It’s seductive to tell yourself stories when a close friend has gone quiet. “Once that seed is in our minds, it is hard to let go,” says <a href="https://www.daniellebayardjackson.com/">Danielle Bayard Jackson</a>, a friendship coach and host of the <a href="https://podcasts.apple.com/us/podcast/friend-forward/id1500460079"><em>Friend Forward</em></a> podcast. Concocting a narrative about why your friend isn’t reciprocating is a common reason, she says, for a lot of friendships ending prematurely. People think to themselves, for example, “Oh, I guess she’s not as invested in this friendship as I thought. I guess her new boyfriend’s more important.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Ug2mtO">
“All of that stuff is a self-generated story,” Jackson says. You might find yourself behaving in response to a story you made up out of thin air.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="UFBxOt">
The solution? Challenge these beliefs, which are likely way off-base. Are these negative thoughts based in reality, or is this your insecurity speaking? When clients express these worries to Abrams, she asks the person to imagine what their friend would say about the friendship. Next, imagine the demands and commitments the friend is juggling. This exercise usually helps bring the temperature down so the client can see that their friend is likely busy and isn’t intentionally blowing them off.
</p>
<h3 id="ypOgtO">
Invite, don’t accuse
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tJbcyo">
People often wait to alert their friend to an issue until it’s boiled over from annoyance to full-on anger. The best time to address the issue “is when you begin feeling that distance or imbalance in the relationship,” Abrams says. She recommends pinpointing what you want more or less of and then verbalizing it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="k3hf15">
You might be tempted to blurt out, “Hey, I haven’t heard from you in a while. What gives?” But that could put your friend on the defense. Instead, “let them know you’re reaching out to them out of a desire for their company, and not accusing them of what they’re failing to do,” she says, “which doesn’t really feel good to anyone and is not a good motivator to get them to act.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="f1Lnca">
Jackson suggests proposing plans using what she calls the movie trailer method: You should preview the experience so the other person has a taste of what’s to come. Instead of saying, “Hey, let’s get together sometime,” with them replying, “Absolutely,” and then crickets for two months, maybe say, “Hey, do you wanna get together Saturday around 7 for an hour or two? We can try this new wine bar in town. Let’s get dressed up and sip something bubbly.” In doing this, you’re giving a visual of being there, like a scene from the movie that will be your Saturday night hang.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Kl39Tu">
Designing the plans that way makes it easier for people to commit. “And if they can’t, a friend who is equally interested will negotiate with you and say, ‘Dang, I can’t do Saturday, but let’s try Tuesday,’” Jackson adds.
</p>
<h3 id="ho7k30">
Be flexible
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mNHyj6">
Your friend may be feeling like this is more of a logistics problem, and isn’t aware that you’re open to changing your established routine. So the next time you reach out, you could say something like:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="jTau1u">
Would you want to try something different the next time we meet? Maybe we can grab tea instead of cocktails?
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ZW7Lss">
Instead of meeting up for brunch, maybe we could grab coffee or go for a walk in the park?
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="eMAdlP">
Maybe we can go on a double date so we can include our significant others?
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6Ve9A0">
Your friend also might prefer to change the mode and frequency of communication. Maybe texting is better for them instead of taking phone calls. Or they might want to talk on the phone once a week instead of exchanging DMs on a social platform they’re no longer using. Ask!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SKc1l9">
At this point, if you’ve tried a few different strategies and you’re hearing radio silence, Vellos says you should assume the universe is telling you to put your attention elsewhere. “That could be another person, another friendship, another hobby, whatever,” she says. Redirect your energy so you’re not wasting your time and getting your hopes up for something that’s unlikely to happen.
</p>
<h3 id="v6H9Ko">
If you’re the one who can’t prioritize your friendships, be upfront about it
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Klx4Q2">
Lots of people may find themselves on the opposite side of the spectrum: They’re the ones who are too snowed under to invest in their friendships. In this case, it is your responsibility, as a friend, to let the other person know about what they can expect from you for the foreseeable future. It saves a lot of heartache for everyone if you tell them the truth about what is going on with you, Abrams says. Know that you don’t have to be in a stressful or busy place to explain you need space; you can set boundaries around your time and energy even if you technically could hang out with this person more often.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mjRF7l">
When Jackson was pregnant, she messaged her friends and let them know her availability was shifting but she’ll be back soon. She communicated, “I’m thinking of you. I want to get together. I can’t for the next few months, but man, I cannot wait to see you soon and catch up then.” Her friends not only appreciated the heads-up, but were reassured that she valued their bond.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pUwWm1">
If you need to let a friend know you won’t be as available in the future, Abrams suggests saying something like:
</p>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ut4kal">
I know we tend to talk on the phone for hours, but I probably have an hour max on Sundays before I have to prepare for the week.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o1QPRF">
It’s been really hard for me to talk on the phone lately, so texting is the best way to reach me these next few weeks.
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="sP0xDG">
Hey, I know we usually talk every week. In this season of work, I’m swamped. I’ll drop you a line when things calm down.
</li>
</ul>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6pQ6nP">
The important thing is to be open, honest, and focused when you do connect. Aim for quality over quantity here — so when you do engage with your friends, they’ll feel valued and secure, knowing the friendship is meaningful to you too.
</p>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2022 | Dinesh Karthik has presented very strong case for India comeback: Kohli</strong> - Karthik, who has been playing the role of a finisher for RCB, has had the highest strike rate among the leading run- getters in the tournament scoring 197 runs in six innings at 209.57</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2022: PBKS vs SRH | Malik, Bhuvneshwar star as Hyderabad restricts Punjab</strong> - Punjab will be without their skipper Mayank Agarwal, who has injured his toe while training on Saturday</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IPL 2022: RR vs KKR | Kolkata seeks to bounce back against Rajasthan after back-to-back losses</strong> - With three wins and three losses, KKR are at the mid-table while the Royals have won three matches and lost two games till now.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bundesliga: Haaland scores 2 as Dortmund routs Wolfsburg 6-1</strong> - Striker Erling Haaland scored twice as Borussia Dortmund routed Wolfsburg 6-1 to maintain its slim chances of winning the Bundesliga</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Premier League: Ronaldo’s hat-trick saves Man Utd again; Spurs, Arsenal lose</strong> - Manchester United eye Premier League’s last remaining Champions League spot as Tottenham, Arsenal lose</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Andhra Pradesh: Farmers seek Governor’s permission for mercy killing</strong> - ‘300 ryots have lost livelihood after their lands were notified as reserve zone six years ago’</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Data | Silent survivors: 80% wives in Tamil Nadu say husbands are justified in beating them</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Uneasy calm, heavy police presence in Jahangirpuri a day after violence</strong> - The Delhi Police has arrested 14 people over the violence</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-BJP CMs likely to meet in Mumbai to discuss political situation: Sanjay Raut</strong> - Sanjay Raut alleged that recent attacks on Ram Navami and Hanuman Jayanti processions were “politically sponsored” to polarise voters</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Army top brass to review border situation, assess impact of war in Ukraine</strong> - Defence Minister Rajnath Singh is expected to interact with the senior Army commanders and address the conference on April 21.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Russian warship: Moskva crew ‘shown for first time since sinking’</strong> - Russia’s defence ministry releases a video purportedly showing the crew of the Moskva in Sevastopol.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Trucks stuck at Poland-Belarus border as EU sanctions deadline passes</strong> - An 80km queue formed on the Polish border ahead of a deadline for Russian trucks to leave the EU.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: No quick return to normal for scarred Bucha</strong> - Everything has changed in this town since the Russians came, and horrific memories will not easily be erased.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chernihiv is silent, after having been under constant attack from Russian forces</strong> - The Ukrainian city of Chernihiv was under constant attack until suddenly Russian forces withdrew.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Climate change: ‘We’re making wine in Norway’</strong> - Vineyards are moving further north, but new winemakers say they struggle to be taken seriously.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>How plants turned predator</strong> - Carnivorous plants fascinate as much now as when their gruesome diet was first discovered. - <a href="https://arstechnica.com/?p=1848433">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NASA to roll back its mega rocket after failing to complete countdown test</strong> - NASA has options for what to do next, but all will involve schedule delays. - <a href="https://arstechnica.com/?p=1848724">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The weekend’s best deals: Google Chromecast, Apple AirPods, and more</strong> - Dealmaster also has Intel and AMD CPUs, Tile trackers, and tons of video games. - <a href="https://arstechnica.com/?p=1848366">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Steph Curry stars in new Nope teaser airing during NBA playoff games</strong> - We still don’t know much about the plot, but it’s a savvy marketing move - <a href="https://arstechnica.com/?p=1848606">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The rise of brand-new, second-hand electric vehicles</strong> - Global chip shortage has triggered a surge in demand for prized, pricey used EVs. - <a href="https://arstechnica.com/?p=1848383">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
<ul>
<li><strong>An old, blind Marine wanders into an all-girl biker bar by mistake.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
He finds his way to a bar stool and orders a shot of Jack Daniels.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After sitting there for a while, he yells to the bartender, ‘Hey, you wanna hear a blonde joke?’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The bar immediately falls absolutely silent.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
In a very deep, husky voice, the woman next to him says,
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
’Before you tell that joke I think it is only fair, given that you are blind, that you should know five things:
</p>
<ol>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The bartender is a blonde girl with a baseball bat.
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The bouncer is a blonde girl.
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
I’m a 6-foot tall, 175-pound blonde woman with a black belt in karate.
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The woman sitting next to me is blonde and a professional weight lifter.
</p>
</li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The lady to your right is blonde and a professional wrestler.
</p>
</li>
</ol>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Now, think about it seriously, do you still wanna tell that blonde joke?’
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The blind Marine thinks for a second, shakes his head and mutters, ‘No…not if I’m gonna have to explain it five times.’
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/MarionScott"> /u/MarionScott </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/u5bd9x/an_old_blind_marine_wanders_into_an_allgirl_biker/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/u5bd9x/an_old_blind_marine_wanders_into_an_allgirl_biker/">[comments]</a></span></p></li>
<li><strong>“My vagina is like the local gym,” said my wife.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“What?” I asked. “Hot and sweaty?”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
“No,” she replied. “Only a few members use it regularly.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/incredibleinkpen"> /u/incredibleinkpen </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/u55z9h/my_vagina_is_like_the_local_gym_said_my_wife/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/u55z9h/my_vagina_is_like_the_local_gym_said_my_wife/">[comments]</a></span></p></li>
<li><strong>My L‌‌esbian n‌‌eighbours E‌‌va a‌‌nd J‌‌ulia a‌‌sked m‌‌e t‌‌o h‌‌elp t‌‌hem c‌‌onceive a‌‌ c‌‌hild r‌‌recently.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
They s‌‌aid t‌‌hey w‌‌ouldn’t m‌‌ind i‌‌f w‌‌e d‌‌id i‌‌t t‌‌he o‌‌ld f‌‌ashioned w‌‌ay a‌‌s t‌‌hey w‌‌eren’t m‌‌an h‌‌aters!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
For s‌‌ix m‌‌onths n‌‌ow w‌‌e’ve b‌‌een t‌‌rying b‌‌ut I‌‌ j‌‌ust d‌‌on’t h‌‌ave t‌‌he h‌‌eart t‌‌o t‌‌ell t‌‌hem I‌‌ h‌‌ad a‌‌ v‌‌asectomy l‌‌ast y‌‌ear.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/YZXFILE"> /u/YZXFILE </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/u5lapz/my_lesbian_neighbours_eva_and_julia_asked_me_to/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/u5lapz/my_lesbian_neighbours_eva_and_julia_asked_me_to/">[comments]</a></span></p></li>
<li><strong>A guy goes to the doctor because his wife can’t orgasm.</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The doctor explains his wife is probably over heating and needs to find a way to cool her down.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The guy goes to his best friend and asks him to waft a towel over him and his wife while they have sex to keep them cool.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The friend agrees and the next day he shows up and wafts the towel while they bone down, but hours go buy and the guy has climaxed several times but his wife not even once.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The man gets frustrated and tells his friend to pork her while he wafts the towel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
After just minutes the wife begins moaning and screaming as she’s wracked over and over again by waves and waves of orgasms’.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
When she finally stops, the man looks to his friend and smugly tells him “See, now that’s how you waft a fucking towel.”
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/JesterEric"> /u/JesterEric </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/u502u3/a_guy_goes_to_the_doctor_because_his_wife_cant/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/u502u3/a_guy_goes_to_the_doctor_because_his_wife_cant/">[comments]</a></span></p></li>
<li><strong>If Chewie is short for Chewbacca, and Ben Kenobi is short for Obi-Wan Kenobi. What is Luke short for?</strong> - <!-- SC_OFF -->
<div class="md">
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
A stormtrooper.
</p>
</div>
<!-- SC_ON -->
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Grasshoppa01"> /u/Grasshoppa01 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/u52d11/if_chewie_is_short_for_chewbacca_and_ben_kenobi/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/u52d11/if_chewie_is_short_for_chewbacca_and_ben_kenobi/">[comments]</a></span></p></li>
</ul>
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