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<title>13 June, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Assessment of the relationship between Google Trend search data on clinical symptoms and cases reported during the first wave of the COVID-19 outbreak in India.</strong> -
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Infodemiology and infoveillance approaches have been extensively used in recent years to support traditional epidemiology and disease surveillance. Hence, the present study aimed to explore the association between Google Trends (GTs) search of clinical symptoms and cases reported during the first wave of COVID-19. The GT data from January 30, 2020, to September 30, 2020, and daily COVID-19 cases in India and a few selected states were collected from the Ministry of Health and Family Welfare, Government of India. Correlation analysis was performed between the GT index values and the number of confirmed cases. Followed by, the COVID-19 cases were predicted using Bayesian regression and classical linear regression models. A strong association was observed between the search index of clinical symptoms and reported COVID-19 cases (cold: R=0.41, headache: R=0.46, fever: R=0.66, loss of taste: R=0.78, loss of smell R=0.86) across India. Similarly, lagged correlations were also observed (loss of smell, loss of taste, loss of taste and loss of smell, fever and headache show 3, 9, 1, 9, and 13 days lag periods respectively). Besides this, the Bayesian regression model was outperformed (MAE: 0.331164, RMSE: 0.411087) for predicting the COVID-19 cases in India and regionally than the frequentist linear regression (MAE: 0.33134, RMSE: 0.411316). The study helps health authorities better prepare and planning of health care facility timely to avoid adverse impacts.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291183v1" target="_blank">Assessment of the relationship between Google Trend search data on clinical symptoms and cases reported during the first wave of the COVID-19 outbreak in India.</a>
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<li><strong>Neurodivergence as a risk factor for Post-Covid-19 Syndrome</strong> -
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Neurodivergent (ND) individuals (e.g., Autistic people) are more likely to experience health problems that are characterised by central sensitisation9. Recent research suggests that a so-called Long-COVID syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Using a standardised assessment tool, we examined whether traits associated with Autism would predict long-term COVID-19 symptoms in 267 Healthcare Workers (HCW).. Higher autistic traits predicted COVID-19 symptoms that lasting more than 12 weeks regardless of formal autism diagnosis. A personality measure also showed that negative affect was associated with experiencing COVID-19 symptoms for 4-12 weeks, though the direction of causality in this case is uncertain. Limitations of the present study are 1) the retrospective nature of COVID-19 symptom reporting; 2) likely self-selection bias given the high number of HCWs who reported long-term COVID-19 symptoms; and 3) the gender-bias towards females in our sample.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291154v1" target="_blank">Neurodivergence as a risk factor for Post-Covid-19 Syndrome</a>
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<li><strong>Comparison of incidence and prognosis of myocardial injury in patients with COVID-19-related respiratory failure and other pulmonary infections: a contemporary cohort study</strong> -
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Background: Myocardial injury (MI) is frequent in critically ill patients with COVID-19, but its pathogenesis remains unclear. We hypothesized that MI is not solely due to viral infection by SARS-CoV-2, but rather due to the common pathophysiological mechanisms associated with severe pulmonary infections and respiratory failure. Methods: Contemporary and comparative cohort study designed to compare the incidence of MI in patients with acute respiratory failure caused by COVID-19 to that of patients with other pulmonary infections. In addition, we aim to investigate whether MI is a distinct risk factor for in-hospital mortality in patients with COVID-19-related respiratory failure compared to those with non-COVID-19 infections. Results: The study included 1444 patients with COVID-19 [55.5% men; age 58 (46;68) years] and 182 patients with other pulmonary infections [46.9% men; age 62 (44;73) years]. The incidence of MI at ICU admission was lower in COVID-19 patients (36.4%) compared to non-COVID-19 patients (56%), and this difference persisted after adjusting for age, sex, coronary artery disease, heart failure, SOFA score, lactate, and C-reactive protein [RR 0.84 (95% CI, 0.71-0.99)]. MI at ICU admission was associated with a 59% increase in mortality [RR 1.59 (1.36-1.86); P<0.001], and there was no significant difference in the mortality between patients with COVID-19 and those with other pulmonary infections (P=0.271). Conclusion: Myocardial injury is less frequent in patients with critical COVID-19 pneumonia and respiratory failure compared to those with other types of pneumonia. The occurrence of MI is a significant risk factor for in-hospital mortality, regardless of the etiology of the pulmonary infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23291222v1" target="_blank">Comparison of incidence and prognosis of myocardial injury in patients with COVID-19-related respiratory failure and other pulmonary infections: a contemporary cohort study</a>
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<li><strong>Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease</strong> -
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One in ten SARS-CoV-2 infections result in prolonged symptoms termed “long COVID”, yet disease phenotypes and mechanisms are poorly understood. We studied the blood proteome of 719 adults, grouped by long COVID symptoms. Elevated markers of monocytic inflammation and complement activation were associated with increased likelihood of all symptoms. Elevated IL1R2, MATN2 and COLEC12 associated with cardiorespiratory symptoms, fatigue, and anxiety/depression, while elevated MATN2 and DPP10 associated with gastrointestinal (GI) symptoms, and elevated C1QA was associated with cognitive impairment (the proteome of those with cognitive impairment and GI symptoms being most distinct). Markers of neuroinflammation distinguished cognitive impairment whilst elevated SCG3, indicative of brain-gut axis disturbance, distinguished those with GI symptoms. Women had a higher incidence of long COVID and higher inflammatory markers. Symptoms did not associate with respiratory inflammation or persistent virus in sputum. Thus, persistent inflammation is evident in long COVID, distinct profiles being associated with specific symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.07.23291077v1" target="_blank">Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease</a>
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<li><strong>Start Smart, Then Focus: Antimicrobial Stewardship Practice at One NHS Foundation Trust in England Before and During the COVID-19 Pandemic</strong> -
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Background Antimicrobial Resistance (AMR), a major global public health threat causing 1.2 million deaths, calls for immediate action. Antimicrobial stewardship (AMS) promotes judicious antibiotic use, but the COVID-19 pandemic increased AMR by 15%. Our study evaluated AMS implementation and inappropriate antibiotic prescribing before-the-pandemic (PD) and during-the-pandemic (DP). Methods This retrospective study examined medical records of adult patients (age 25 and above) admitted to an NHS Foundation Trust in England for respiratory tract infections (RTIs) or pneumonia in 2019 and 2020. Our objective was to evaluate antibiotic prescribing practices BP and DP in 2019 and 2020. Primary outcomes included evaluating the prevalence of inappropriate antibiotic prescribing and assessing the implementation of AMS using Public Health England9s 9Start Smart, Then Focus9 (SSTF) toolkit. Reliable data extraction was ensured by two independent reviewers using a validated data extraction tool. Results A total of 640 patient records (320 from 2019 and 320 from 2020) were analysed. The mean age of enrolled adults was 74.3 years in 2019 and 76.2 years in 2020. COVID pneumonia showed a significantly higher odds ratio (OR) of 20.24 (95% CI 5.82 to 128.19, p-value<0.001). Inappropriate antibiotic prescribing, as per local guidelines, increased from 36% in 2019 to 64% in 2020 for the second course of antibiotics DP. Differences were observed in AMS interventions, with an OR of 3.36 (95% CI 1.30-9.25, p=0.015) for 9Continue Antibiotics9 and an OR of 2.77 (95% CI 1.37-5.70, p=0.005) for 9De-escalation9. Conclusion The COVID-19 pandemic significantly impacted antibiotic prescribing, increasing inappropriate use and posing risks of antimicrobial resistance. Factors influencing prescribing practices must be considered, and proactive measures, including updating the SSTF toolkit and developing an AMS roadmap, are needed to address the challenges of AMR in the context of evolving infectious diseases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23291146v1" target="_blank">Start Smart, Then Focus: Antimicrobial Stewardship Practice at One NHS Foundation Trust in England Before and During the COVID-19 Pandemic</a>
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<li><strong>SARS-CoV-2 Nonstructural Proteins 3 and 4 tune the Unfolded Protein Response</strong> -
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Coronaviruses (CoV), including SARS-CoV-2, modulate host proteostasis through activation of stress-responsive signaling pathways such as the Unfolded Protein Response (UPR), which remedies misfolded protein accumulation by attenuating translation and increasing protein folding capacity. While CoV nonstructural proteins (nsps) are essential for infection, little is known about the role of nsps in modulating the UPR. We characterized the impact of SARS-CoV-2 nsp4, a key driver of replication, on the UPR using quantitative proteomics to sensitively detect pathway-wide upregulation of effector proteins. We find nsp4 preferentially activates the ATF6 and PERK branches of the UPR. Previously, we found an N-terminal truncation of nsp3 (nsp3.1) can suppress pharmacological ATF6 activation. To determine how nsp3.1 and nsp4 tune the UPR, their co-expression demonstrated that nsp3.1 suppresses nsp4-mediated PERK, but not ATF6 activation. Re-analysis of SARS-CoV-2 infection proteomics data revealed time-dependent activation of PERK targets early in infection, which subsequently fades. This temporal regulation suggests a role for nsp3 and nsp4 in tuning the PERK pathway to attenuate host translation beneficial for viral replication while avoiding later apoptotic signaling caused by chronic activation. This work furthers our understanding of CoV-host proteostasis interactions and highlights the power of proteomic methods for systems-level analysis of the UPR.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.22.537917v2" target="_blank">SARS-CoV-2 Nonstructural Proteins 3 and 4 tune the Unfolded Protein Response</a>
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<li><strong>Low Dose Naltrexone use for the management of post acute sequelae of COVID 19</strong> -
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Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long COVID, is globally estimated to have affected up to 40-50% of individuals who were infected with SARS-CoV-2. The causes of PASC are being investigated, and there are no established therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increased systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. In this study we performed retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with improved clinical symptoms (fatigue, brain fog, post exertional malaise/PEM, unrefreshing sleep, sleep pattern, and headache), fewer number of symptoms, and better functional status. This observational finding warrants further testing in rigorous, randomized, placebo-controlled clinical trials.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291102v1" target="_blank">Low Dose Naltrexone use for the management of post acute sequelae of COVID 19</a>
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<li><strong>Global seasonal activities of respiratory syncytial virus before the COVID-19 pandemic: a systematic review</strong> -
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Background: Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We aimed to review the patterns of RSV activity globally before the COVID-19 pandemic and to explore factors potentially associated with RSV seasonality. Methods: We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. Information on the timing of the start, peak, and end of an RSV season, study location, study period, and details in study methods were extracted. RSV seasonal patterns were examined by geographic location, calendar month, analytic method and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. Results: RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Variations were identified in types of data, data collection and analytical methods across the studies. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Durations of RSV seasons were relatively longer in subtropical and tropical regions than from temperate regions. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. Conclusions: The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection. Heterogeneity in study methods highlighted the importance of developing and applying standardized approaches in RSV surveillance and data reporting.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.12.23291266v1" target="_blank">Global seasonal activities of respiratory syncytial virus before the COVID-19 pandemic: a systematic review</a>
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<li><strong>Lifespan of COVID-19 living guideline recommendations: a survival analysis</strong> -
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Background NICE has maintained a portfolio of COVID-19 living guidelines since March 2020. Recommendations within these living guidelines are subject to continuous surveillance and updates in response to triggers. However, the lifespan of individual living guideline recommendations and features that may impact on whether a recommendation becomes out of date sooner, is unknown. Objectives This study aimed to describe the length of time NICE COVID-19 living guideline recommendations have remained valid. Methods All guidelines within the NICE COVID-19 portfolio were included to determine the lifespan of living guideline recommendations. Data were collected on all recommendations that had been developed, undergone surveillance or updated between 1 March 2020 and 31 August 2022. Information on initial publication date, decision to update, and update publication date was extracted. Updates were labelled as major changes in evidence synthesis or minor changes without a substantial change in evidence base. Any recommendation that had not been updated or withdrawn was censored. Survival analysis (Kaplan-Meier Curve) was carried out to determine the lifespan of recommendations. Results Overall, 26 COVID-19 living guidelines and 1182 recommendations were included in the analysis. Living recommendations had median survival time of 739 days (IQR: 332, 781). Based on recommendation type, intervention recommendations had a shorter survival time (354 days, IQR 312, 775) compared to diagnosis (368 days, IQR: 328, 795), patient experience (733 days, IQR: 345, 795) and service delivery (739 days, IQR: 643, 781). Within intervention type, pharmacological recommendations had shortest survival time versus non-pharmacological recommendations [335 days (IQR: 161, 775) vs 775 days (IQR: 354, 775)]. Updates were published an average of 29.12 days following a surveillance decision. Conclusion Within living guidelines, some recommendations need to be updated sooner than others. This study outlines the value of a flexible responsive approach to surveillance within the living mode according to pace of change and expectation of update triggers.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291123v1" target="_blank">Lifespan of COVID-19 living guideline recommendations: a survival analysis</a>
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<li><strong>SARS-CoV-2 Spread Under the Controlled-Distancing Model of Rio Grande do Sul, Brazil</strong> -
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In early 2020, the government of Rio Grande do Sul established a public-health assessment-response framework to halt the spread of SARS-CoV-2, called 9controlled-distancing model9 (CDM). This framework subdivided the state in 21 regions where it evaluated a composite index of disease transmission and health-service capacity. Updated on a weekly basis, the index placed regions on a color-coded scale of flags, which guided adoption of non-pharmaceutical interventions. We aim to evaluate the extent to which the CDM accurately assessed transmission and the effectiveness of its responses throughout 2020. We estimated the weekly effective reproduction number (<i>R<sub>t</sub></i>) of SARS-CoV-2, for each region, using a renewal-equation-based statistical model of notified COVID-19 deaths. Using <i>R<sub>t</sub></i> estimates, we explored whether flag colors assigned by the CDM either reflected or affected SARS-CoV-2 dissemination. Flag assignments did reflect variations in <i>R<sub>t</sub></i>, to a limited extent, but we found no evidence that they affected <i>R<sub>t</sub></i> in the short term. Medium-term effects were apparent in only four regions after eight or more weeks of red-flag assignment. Analysis of Google movement metrics showed no evidence that people moved differently under different flags. The dissociation between flag colors and the propagation of SARS-CoV-2 does not support the claim that non-pharmaceutical interventions are ineffective. Our results show, however, that decisions made under the CDM framework were ineffective both for influencing the movement of people and for halting the spread of the virus.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23291044v1" target="_blank">SARS-CoV-2 Spread Under the Controlled-Distancing Model of Rio Grande do Sul, Brazil</a>
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<li><strong>Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals or no treatment in Scotland</strong> -
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Introduction: Severe acute respiratory syndrome coronavirus 2 is constantly evolving. The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe the real-world use of, and clinical outcomes associated with, early COVID-19 treatments among non-hospitalised patients with COVID-19 at highest risk of developing severe disease in Scotland. Methods: Retrospective cohort study of non-hospitalised patients diagnosed with COVID-19 from 1 December 2021 to 25 October 2022, using administrative health data managed by Public Health Scotland and National Records of Scotland. Patients included in the study were aged ≥18 years, met at least one of the National Health Service highest-risk conditions criteria for early COVID-19 treatment, and had received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of either COVID-19-positive diagnosis or early COVID-19 treatment during the study period. Baseline patient characteristics and acute clinical outcomes in the 28 days following the index date were reported. To protect patient confidentiality, values of ≤5 were suppressed. Results: A total of 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709 eligible highest-risk untreated). Patients aged ≥75 years accounted for 6.9% (n=34/492) of the sotrovimab-treated group, 21.0% (n=58/276) of those treated with nirmatrelvir/ritonavir, 16.9% (n=12/71) of those treated with molnupiravir and 13.2% (n=225/1709) of untreated patients. Advanced renal disease was reported for 6.7% (n=33/492) of sotrovimab-treated and 4.7% (n=81/1709) of untreated patients, and five or fewer patients in the nirmatrelvir/ritonavir and molnupiravir cohorts. A high proportion of treated patients did not have a highest-risk condition reported in the database (71.7% for sotrovimab [n=353/492], 85.1% for nirmatrelvir/ritonavir [n=235/276], 85.9% for molnupiravir [n=61/71]). Five or fewer patients in each treated cohort experienced COVID-19-related hospitalisations during the 28-day acute period. For untreated patients, the percentage of COVID-19-related hospitalisations was 3.0% (n=48/1622). All-cause hospitalisations were experienced by 5.3% (n=25/476) of sotrovimab-treated patients, 6.9% (n=12/175) of nirmatrelvir/ritonavir-treated patients and 13.3% (n=216/1622) of untreated patients. Five or fewer patients in the molnupiravir cohort experienced all-cause hospitalisation. There were no deaths within 28 days of index for patients in the treated cohorts. Mortality was 4.3% (n=70/1622) in untreated patients (18.6% [n=13/70] had COVID-19 as the primary cause). In our analyses of outcomes for sotrovimab-treated and untreated patients during BA.1, BA.2 and BA.5 predominance, COVID-19-related hospitalisation rates were consistent, with n≤5 for sotrovimab-treated patients in each period. Conclusions: Our findings indicate that sotrovimab was often used amongst patients who were aged <75 years old and had advanced renal disease. Among patients who received early COVID-19 treatment, proportions of all-cause hospitalisation and death within 28 days of treatment were low.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23291195v1" target="_blank">Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals or no treatment in Scotland</a>
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<li><strong>SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia</strong> -
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Objectives SARS-CoV-2 transmission in Sub-Saharan Africa has probably been underestimated. Population-based seroprevalence studies are needed to determine the extent of transmission in the continent. Methods Blood samples from a cohort of Gambian pregnant women were tested for SARS-CoV-2 total IgM/IgG before (Pre-pandemic1: October-December 2019 and Pre-pandemic2: February-June 2020) and during the pandemic (Post-wave1: October-December 2020, Post-wave2: May-June 2021; and Post-wave3: October-December 2021). Samples positive for total SARS-CoV-2 IgM/IgG were tested for protein-specific antibodies. Results SARS-CoV-2 total IgM/IgG seroprevalence was 0.9% 95%CI (0.2, 4.9) in Pre-pandemic1; 4.1% (1.4, 11.4) in Pre-pandemic2; 31.1% (25.2, 37.7) in Post-wave1; 62.5% (55.8, 68.8) in Post-wave2 and 90.0% (85.1, 93.5) in Post-wave3. S-protein IgG and NCP-protein IgG seroprevalence also increased at each Post-wave period. Although S-protein IgG and NCP-protein IgG seroprevalence was similar at Post-wave1, S-protein IgG seroprevalence was higher at Post-wave2 and Post-wave3, [prevalence difference (PD) 13.5 (0.1, 26.8) and prevalence ratio (PR) 1.5 (1.0, 2.3) in Post-wave2; and 22.9 (9.2, 36.6) and 1.4 (1.1, 1.8) in Post-wave3 respectively, p<0.001]. Conclusion SARS-CoV-2 transmission in The Gambia during the first three COVID-19 waves was high, differing significantly from official numbers of COVID-19 cases reported. Our findings are important for policy makers in managing the near-endemic COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23291201v1" target="_blank">SARS-CoV-2 seroprevalence in pregnant women during the first three COVID-19 waves in The Gambia</a>
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<li><strong>User adherence and perceptions of a Volunteer-Led Telemonitoring and Teleorientation Service for COVID-19 community management in Peru: The COVIDA project</strong> -
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Background: During the pandemic in Peru, the COVIDA project proposed an innovative way to provide telemonitoring and teleorientation to COVID-19 pandemics led by health student volunteers. However, it has not been described how this interaction is perceived from the user9s perspective. The aim of this study is to describe the adherence and perceptions of users about COVIDA. Methods: A mixed-method study was conducted to evaluate the adherence and perceptions of COVIDA users. This telehealth intervention implemented in Peru from August to December 2020 involved daily phone-calls by volunteer students to monitor registered users for 14 days or until a warning sign was identified. The volunteers also provided teleorientation to address the users9 needs and concerns. Quantitative analysis described the characteristics of users and assessed the factors related to adherence to the service. Qualitative analysis trough semi-structured interviews evaluated the user9s perceptions about the service. Results: Of the 778 users enrolled in COVIDA, 397 (54.7%) were female and had a mean age of 41 years (SD: 15.3). During the monitoring, 380 users (44.4%) developed symptoms, and 471 (55.5%) showed warning signs for COVID-19. The overall median of adherence was 93% (p25:36%, p75:100%). Among those users who did not develop warning symptoms, a high level of adherence (>66%) was seen predominantly in users that developed symptoms and those with a positive COVID-19 test (p<0.05). Users referred that the information provided by volunteers was clear and valuable and, their accompaniment provided them with emotional support. Communications via phone calls were developed fluently without interruptions. Conclusions: COVIDA represented an affordable, well-accepted, and perceived alternative model for telemonitoring, teleorientation and emotional support from student volunteers to users with diseases such as COVID-19 in a context of overwhelmed demand for healthcare services.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291037v1" target="_blank">User adherence and perceptions of a Volunteer-Led Telemonitoring and Teleorientation Service for COVID-19 community management in Peru: The COVIDA project</a>
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<li><strong>Poor immunogenicity upon SARS-CoV-2 mRNA vaccinations in autoimmune SLE patients is associated with pronounced EF-mediated responses and anti-BAFF/Belimumab treatment.</strong> -
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Novel mRNA vaccines have resulted in a reduced number of SARS-CoV-2 infections and hospitalizations. Yet, there is a paucity of studies regarding their effectiveness on immunocompromised autoimmune subjects. In this study, we enrolled subjects naive to SARS- CoV-2 infections from two cohorts of healthy donors (HD, n=56) and systemic lupus erythematosus (SLE, n=69). Serological assessments of their circulating antibodies revealed a significant reduction of potency and breadth of neutralization in the SLE group, only partially rescued by a 3rd booster dose. Immunological memory responses in the SLE cohort were characterized by a reduced magnitude of spike-reactive B and T cell responses that were strongly associated with poor seroconversion. Vaccinated SLE subjects were defined by a distinct expansion and persistence of a DN2 spike-reactive memory B cell pool and a contraction of spike-specific memory cTfh cells, contrasting with the sustained germinal center (GC)-driven activity mediated by mRNA vaccination in the healthy population. Among the SLE-associated factors that dampened the vaccine responses, treatment with the monoclonal antibody anti-BAFF/Belimumab (a lupus FDA- approved B cell targeting agent) profoundly affected the vaccine responsiveness by restricting the de novo B cell responses and promoting stronger extra-follicular (EF)-mediated responses that were associated with poor immunogenicity and impaired immunological memory. In summary, this study interrogates antigen-specific responses and characterized the immune cell landscape associated with mRNA vaccination in SLE. The identification of factors associated with reduced vaccine efficacy illustrates the impact of SLE B cell biology on mRNA vaccine responses and provides guidance for the management of boosters and recall vaccinations in SLE patients according to their disease endotype and modality of treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.08.23291159v1" target="_blank">Poor immunogenicity upon SARS-CoV-2 mRNA vaccinations in autoimmune SLE patients is associated with pronounced EF-mediated responses and anti-BAFF/Belimumab treatment.</a>
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<li><strong>Naked-eye Detection of LAMP-Produced Nucleic Acids in Saliva using Chitosan-capped AuNPs in a Single-Tube Assay</strong> -
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Loop-mediated isothermal amplification (LAMP) is a low-technology molecular assay highly adaptable to point-of-care (POC) applications. However, achieving sensitive naked-eye detection of the amplified target in a crude sample is challenging. Herein, we report a simple, yet highly efficient and sensitive methodology for the colorimetric visualization of a single target copy in saliva, using chitosan-capped gold nanoparticles (Chit-AuNPs) synthesized via a green-chemistry approach. The presence or absence of free Chit in the Chit-AuNPs solution was shown to affect LAMP colorimetric detection oppositely: the observed stabilization in the negative samples and aggregation in the positive samples in the presence of free Chit was reversed in the case of neat Chit-AuNPs. The mechanism of the two assays was investigated and attributed to electrostatic and depletion effects exerted between the Chit-AuNPs, free Chit and the solution components. The developed contamination-free, one-tube assay successfully amplified and detected down to 1-5 cfu of Salmonella and 10 copies of SARS-CoV-2 per reaction (25 uL) in the presence of 20% saliva, making the method suitable for POC applications. Compared to the commonly used pH sensitive dyes, Chit-AuNPs are shown to have an enhanced sensitivity toward the naked-eye colorimetric observation owing to the direct detection of DNA amplicons. Thus, this is a simple, highly sensitive, fast and versatile naked-eye detection methodology that could be coupled to any LAMP or RT-LAMP assay, avoiding the need of using complicated sample pretreatments and/or AuNPs long and laborious functionalization processes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.09.23291198v1" target="_blank">Naked-eye Detection of LAMP-Produced Nucleic Acids in Saliva using Chitosan-capped AuNPs in a Single-Tube Assay</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Extracorporeal photopheresis<br/><b>Sponsor</b>: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation; Biological: Bivalent COVID-19 mRNA Vaccine; Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation<br/><b>Sponsors</b>: Zhongnan Hospital; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences</strong> - <b>Conditions</b>: COVID-19; COVID-19 Pandemic<br/><b>Interventions</b>: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety Study of COVID19 Vaccine on the Market</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant new coronavirus vaccine (CHO cell)<br/><b>Sponsors</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Other: Placebo; Drug: Montelukast<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluvoxamine; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Diagnostic Test: SARS CoV-2 antigen tests<br/><b>Sponsors</b>: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19</strong> - <b>Conditions</b>: SARS-CoV Infection; COVID-19<br/><b>Interventions</b>: Drug: Mitoquinone/mitoquinol mesylate; Other: Placebo<br/><b>Sponsor</b>: University of Texas Southwestern Medical Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pycnogenol® in Post-COVID-19 Condition</strong> - <b>Conditions</b>: Post COVID-19 Condition; Long COVID<br/><b>Interventions</b>: Drug: Pycnogenol®; Drug: Placebo<br/><b>Sponsor</b>: University of Zurich<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis; COVID-19 Pneumonia<br/><b>Intervention</b>: Drug: Bailing capsule<br/><b>Sponsor</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating Emetine for Viral Outbreaks (EVOLVE)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Emetine Hydrochloride; Drug: Placebo<br/><b>Sponsors</b>: Johns Hopkins University; Nepal Health Research Council; Bharatpur Hospital Chitwan; Stony Brook University; Rutgers University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)<br/><b>Sponsor</b>: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.<br/><b>Completed</b></p></li>
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<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 Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: PF-07817883<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody responses to mRNA versus non-mRNA COVID vaccines among the Mongolian population</strong> - CONCLUSIONS: The BNT162b2 vaccine showed the highest level of antibody against SARS-CoV-2, followed by the BBIBP-CorV, Gam-COVID-Vac, and ChAdOx1 n-CoV-19 vaccines. The level of antibodies was increased in people infected with SARS-CoV-2 after vaccination, as compared to uninfected but vaccinated individuals.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibiting C5 in patients with severe COVID-19-the incorrect target? - Authors’ reply</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibiting C5 in patients with severe COVID-19-the incorrect target?</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacological properties and derivatives of saikosaponins-a review of recent studies</strong> - CONCLUSIONS: An increasing amount of data have indicated diverse SS pharmacological properties, indicating crucial clues for future studies and the production of novel saikosaponin-based anti-inflammatory, efficacious anticancer, and anti-novel-coronavirus agents with improved efficacy and reduced toxicity.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Applications of advances in mRNA-based platforms as therapeutics and diagnostics in reproductive technologies</strong> - The recent COVID-19 pandemic led to many drastic changes in not only society, law, economics, but also in science and medicine, marking for the first time when drug regulatory authorities cleared for use mRNA-based vaccines in the fight against this outbreak. However, while indeed representing a novel application of such technology in the context of vaccination medicine, introducing RNA into cells to produce resultant molecules (proteins, antibodies, etc.) is not a novel principle. It has been…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Biotransformation and brain distribution of the anti-COVID-19 drug molnupiravir and herb-drug pharmacokinetic interactions between the herbal extract Scutellaria formula-NRICM101</strong> - The aim of this study was to explore the effects of herbal drug pharmacokinetic interactions on the biotransformation of molnupiravir and its metabolite β-D-N4-hydroxycytidine (NHC) in the blood and brain. To investigate the biotransformation mechanism, a carboxylesterase inhibitor, bis(4-nitrophenyl)phosphate (BNPP), was administered. Not only molnupiravir but also the herbal medicine Scutellaria formula-NRICM101 is potentially affected by coadministration with molnupiravir. However, the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium</strong> - Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Binding properties of selective inhibitors of P323L mutated RdRp of SARS-CoV-2: a combined molecular screening, docking and dynamics simulation study</strong> - Since 2019 the SARS-CoV-2 and its variants caused COVID-19, such incidents brought the world in pandemic situation. This happened due to furious mutations in SARS-CoV-2, in which some variants had high transmissibility and infective, this led the virus emerged as virulent and worsened the COVID-19 situation. Among the variants, P323L is one of the important mutants of RdRp in SARS-CoV-2. To inhibit the erroneous function of this mutated RdRp, we have screened 943 molecules against the P323L…</p></li>
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<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 Flavonoids from <em>Scutellaria barbata</em> D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships</strong> - Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Docking-Based Evidence for the Potential of ImmunoDefender: A Novel Formulated Essential Oil Blend Incorporating Synergistic Antiviral Bioactive Compounds as Promising Mpro Inhibitors against SARS-CoV-2</strong> - Essential oils (Eos) have demonstrated antiviral activity, but their toxicity can hinder their use as therapeutic agents. Recently, some essential oil components have been used within safe levels of acceptable daily intake limits without causing toxicity. The “ImmunoDefender,” a novel antiviral compound made from a well-known mixture of essential oils, is considered highly effective in treating SARS-CoV-2 infections. The components and doses were chosen based on existing information about their…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Luteolin Isolated from <em>Juncus acutus</em> L., a Potential Remedy for Human Coronavirus 229E</strong> - The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH(2)Cl(2)) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: <em>A Mini Review</em></strong> - Inflammation has been described for two millennia, but cellular aspects and the paradigm involving different mediators have been identified in the recent century. Two main groups of molecules, the prostaglandins (PG) and the cytokines, have been discovered and play a major role in inflammatory processes. The activation of prostaglandins PGE2, PGD2 and PGI2 results in prominent symptoms during cardiovascular and rheumatoid diseases. The balance between pro- and anti-inflammatory compounds is…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Free Light Chains <em>κ</em> and <em>λ</em> as New Biomarkers of Selected Diseases</strong> - Diagnostic and prognostic markers are necessary to help in patient diagnosis and the prediction of future clinical events or disease progression. As promising biomarkers of selected diseases, the free light chains (FLCs) κ and λ were considered. Measurements of FLCs are currently used in routine diagnostics of, for example, multiple myeloma, and the usefulness of FLCs as biomarkers of monoclonal gammopathies is well understood. Therefore, this review focuses on the studies concerning FLCs as new…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Eupatin, a Flavonoid, Inhibits Coronavirus 3CL Protease and Replication</strong> - The coronavirus disease 2019 (COVID-19) pandemic has caused more than six million deaths worldwide since 2019. Although vaccines are available, novel variants of coronavirus are expected to appear continuously, and there is a need for a more effective remedy for coronavirus disease. In this report, we isolated eupatin from Inula japonica flowers and showed that it inhibits the coronavirus 3 chymotrypsin-like (3CL) protease as well as viral replication. We showed that eupatin treatment inhibits…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of low-intensity pulsed ultrasound for the treatment of viral pneumonia: study protocol for a randomized controlled trial</strong> - BACKGROUND: Viral pneumonia has always been a problem faced by clinicians because of its insidious onset, strong infectivity, and lack of effective drugs. Patients with advanced age or underlying diseases may experience more severe symptoms and are prone to severe ventilation dysfunction. Reducing pulmonary inflammation and improving clinical symptoms is the focus of current treatment. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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