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184 lines
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<title>13 February, 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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<ul>
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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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Use of machine learning for triage and transfer of ICU patients in the Covid-19 pandemic period: Scope Review</strong> -
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Objective: To map, summarize and analyze the available studies on the use of artificial intelligence, for both triage and transfer of patients in intensive care units in situations of bed shortage crisis so that health teams and organizations make decisions based on updated technological tools of triage and transfer. Methods: Scope review made in the databases Pubmed, Embase, Web of Science, CINAHL, Cochrane, LILACS, Scielo, IEEE, ACM and the novel Rayyan Covid database were searched. Supplementary studies were searched in the references of the identified primary studies. The time restriction is from 2020, and there was no language restriction. All articles aiming at the use of machine learning within the field of artificial intelligence in healthcare were included, as well as studies using data analysis for triage and reallocation of elective patients to ICU vacancies within the specific context of crises, pandemics, and Covid-19 outbreak. Studies involving readmission of patients were excluded. Results: The results excluded specific triage such as oncological patients, emergency room, telemedicine and non structured data. Conclusion: Machine learning can help ICU triage, bed management and patient transfer with the use of artificial intelligence in situations of crisis and outbreaks. Descriptors: Artificial Intelligence. Machine learning. Intensive Care Units. Triage. Patient Transfer. COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.08.23285446v1" target="_blank">Use of machine learning for triage and transfer of ICU patients in the Covid-19 pandemic period: Scope Review</a>
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</div></li>
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<li><strong>Impact of COVID-19 Outbreak on Healthcare Workers in a Tertiary Healthcare Center in India - A cross sectional study</strong> -
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Numerous speculations have continually emerged, trying to explore the association between COVID-19 infection and a varied range of demographic and clinical factors. Frontline healthcare workers have been at the forefront of this illness exposure. However, there is a paucity of large cohort-based association studies, performed among Indian health care professionals, exploring their potential risk and predisposing factors. This study aims to systematically utilize the demographic and clinical data of over 3000 healthcare workers from a tertiary hospital in India to gain significant insights on the associations between disease prevalence, severity, and post-infection symptoms.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.11.23285507v1" target="_blank">Impact of COVID-19 Outbreak on Healthcare Workers in a Tertiary Healthcare Center in India - A cross sectional study</a>
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</div></li>
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<li><strong>Relative effectiveness of BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines and homologous boosting in preventing COVID-19 in adults in the US</strong> -
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Background: Few head-to-head comparisons have been performed on the real-world effectiveness of COVID-19 booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 versus BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against medically-attended, outpatient, and hospitalized COVID-19. Methods: A dataset linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients ≥18 years vaccinated with a primary series between February and October 2021 (Part 1) and a homologous mRNA booster between October 2021 and January 2022 (Part 2). Adjusted hazard ratios (HR) were derived from 1:1 matching adjusted across potential covariates. rVE was (1-HRadjusted) x 100. Additional analysis was performed across regions and age groups. Results: Following adjustment, Part 1 rVE for mRNA-1273 versus BNT162b2 was 23% (95% CI: 22%-25%), 23% (22%-25%), and 19% (14%-24%) whilst the rVE for mRNA-1273 versus Ad26.COV2.S was 50% (48%-51%), 50% (48%-52%), and 57% (53%-61%) against any medically-attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 versus BNT162b2 was 14% (10%-18%), 13% (8%-17%), and 19% (1%-34%) against any medically-attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically-attended COVID-19 was higher in adults ≥65 years (35%; 24%-47%) than those 18-64 years (13%; 9%-17%) after the booster. Conclusions: In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following primary series during a Delta-dominant period, and than BNT162b2 as a booster during an Omicron-dominant period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.10.23285603v1" target="_blank">Relative effectiveness of BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines and homologous boosting in preventing COVID-19 in adults in the US</a>
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<li><strong>Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England</strong> -
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As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.1 (95% credible interval (CrI) 6.8-9.3). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of protection in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.8%, 95% CrI 2.3-3.2), followed by Delta (2.0%, 95% CrI 1.5-2.4), Wildtype (1.2%, 95% CrI 1.0-1.3), and Omicron (0.6%, 95% CrI 0.4-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.10.23285516v1" target="_blank">Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England</a>
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<li><strong>Summaries, Analysis and Simulations of Recent COVID-19 Epidemic in Mainland China During December 31 2021-December 6 2022</strong> -
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Background: The recent COVID-19 epidemic in mainland China is an important issue for studying the prevention and disease control measures and the spread of the COVID-19 epidemic. Following our previous study for the mainland China epidemic during December 6 2021 to 30 April 2021, this paper studies and compares the the mainland China epidemic during December 6 2021 to December 6, 2022. Methods: Using differential equations and real word data (both domestic and foreign input infected individuals) modelings and simulates COVID-19 epidemic in mainland China during May 1 2021 to December 6 2022, estimates the transmission rates, the recovery rates, and the blocking rates to the symptomatic and the asymptomatic infections. Results: The simulation results were in good agreement with the real word data. (1) The average input transmission rate of the foreign input symptomatic infection individuals was much lower than the average transmission rate of the symptomatic infection causing by the mainland symptomatic individuals. (2) The average input transmission rate of the foreign input asymptomatic infection individuals was was much lower than the average transmission rate of the asymptomatic infection causing by the mainland symptomatic individuals (3) The average recovery rates of the foreign input COVID-19 symptomatic and asymptomatic infected individuals were much higher than the average recovery rates of the mainland COVID-19 symptomatic and asymptomatic infected ndividuals, respectively. For the mainland epidemic simulations: (1) If kept the transmission rates, the recovery rates, the death rate and the blocking rates on day 181 (June 30, 2022), the numbers of the current symptomatic and asymptomatic individuals would reduce to about one on day 277 (October 4, 2022). (2) If kept the transmission rates, the recovery rates, the death rate and the blocking rates on day 340 (December 6, 2022) until day 377 (January 16, 2023), the numbers of the current symptomatic and the asymptomatic infected individuals would increase to 38896 and 230924, respectively, the cumulative death individuals would increase from 599 to 615, respectively. (3) If kept the transmission rates, the recovery rates on day 340, but decreased the blocking rates to 30% and select the death rate to equal to the average death rate during days 104-150, then the simulation showed that on day 377, the numbers of current symptomatic and the asymptomatic infected individuals would increase to about 33 723 8057 and 501 626 885, espectively, and the cumulative death individuals would reach about 1 012 543. For the foreign input epidemic simulations: (1) If kept the transmission rates, the recovery rates, and the blocking rates day 242 (August 30, 2022), until day 340, the numbers of the current symptomatic and the asymptomatic infected individuals would decrease to 13 and 430, respectively. (2) If kept the transmission rates, the recovery rates, the death rate and the blocking rates on day 340 until day 377 (January 16,2023), the numbers of the current symptomatic and the asymptomatic infected individuals would decrease and increase to 185 and 1935,respectively. (3) Recommendations on COVID-19 epidemic base on WHO9s technic guidelines and HBV Infection in Chimpanzees are provided. Conclusions: (1) For the mainland individuals9 epidemic, keeping the blocking rates of over 86% and 93% to the symptomatic and asymptomatic infections , and the recovery rates of over 0.119 and 0.112 to the symptomatic and asymptomatic individuals may make the numbers of the current symptomatic and asymptomatic infected individuals to decrease to very low levels in three months. (2) For the foreign input individuals9 epidemic, keeping the transmission rates of under 0.07 to the symptomatic and asymptomatic infections , and the recovery rates of over 0.125 and 0.099 to the symptomatic and asymptomatic individuals may make the numbers of the current symptomatic and asymptomatic infected individuals to decrease to very low levels in four months. (3) After December 6, 2022, decreasing the blocking
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.07.23285380v1" target="_blank">Summaries, Analysis and Simulations of Recent COVID-19 Epidemic in Mainland China During December 31 2021-December 6 2022</a>
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<li><strong>GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</strong> -
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<div>
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Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targets in vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils’ yield, purity, functionality, and maturity through the deletion of the transcription factor GATA1. GATA1 knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils, GATA1 KO iNeutrophils generate NETs in response to the physiologic stimulant lipid polysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, we demonstrate that GATA1 KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.08.526339v1" target="_blank">GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</a>
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<li><strong>Long COVID in Elderly Patients: An Epidemiologic Exploration Using a Medicare Cohort</strong> -
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Background: Incidence of long COVID in the elderly is difficult to estimate and can be under-reported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call “long Flu”. In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients. Methods and Findings: This is a cohort study of Medicare (the U.S. federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza and residual symptoms. Long COVID was identified by a) the designated long COVID-19 code B94.8 (code-based definition), or b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from one to 3 months post infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in four outcome measures: a) hospitalization (any cause), b) hospitalization (for long COVID symptom), c) emergency department (ED) visit (for long COVID symptom), and d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) vs. 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05-1.08, p<0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) vs. 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08-1.10, p<0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified. Conclusions: Relying on specific long COVID diagnostic codes results in significant under-reporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285742v1" target="_blank">Long COVID in Elderly Patients: An Epidemiologic Exploration Using a Medicare Cohort</a>
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<li><strong>Functional comparisons of the virus sensor RIG-I from humans, the microbat Myotis daubentonii, and the megabat Rousettus aegyptiacus, and their response to SARS-CoV-2 infection</strong> -
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Bats (order Chiroptera) are a major reservoir for emerging and re-emerging zoonotic viruses. Their tolerance towards highly pathogenic human viruses led to the hypothesis that bats may possess an especially active antiviral interferon (IFN) system. Here, we cloned and functionally characterized the virus RNA sensor, Retinoic Acid-Inducible Gene-I (RIG-I), from the “microbat” Myotis daubentonii (suborder Yangochiroptera) and the “megabat” Rousettus aegyptiacus (suborder Yinpterochiroptera), and compared them to the human ortholog. Our data show that the overall sequence and domain organization is highly conserved and that all three RIG-I orthologs can mediate a similar IFN induction in response to viral RNA at 37{degrees} and 39{degrees}C, but not at 30{degrees}C. Like human RIG-I, bat RIG-Is were optimally activated by double stranded RNA containing a 5’-triphosphate end and required Mitochondrial Antiviral-Signalling Protein (MAVS) for antiviral signalling. Moreover, the RIG-I orthologs of humans and of R. aegyptiacus, but not of M. daubentonii, enable innate immune sensing of SARS-CoV-2 infection. Our results thus show that microbats and megabats express a RIG-I that is not substantially different from the human counterpart with respect to function, temperature dependency, antiviral signaling, and RNA ligand properties, and that human and megabat RIG-I are able to sense SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.08.527785v1" target="_blank">Functional comparisons of the virus sensor RIG-I from humans, the microbat Myotis daubentonii, and the megabat Rousettus aegyptiacus, and their response to SARS-CoV-2 infection</a>
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<li><strong>Defining Cities in the New Normal: A Conjoint Experiment of Livability Attributes</strong> -
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This paper examines attributes of cities that people prefer to live in after the outbreak of the COVID-19. Using an online survey of approximately 700 respondents in the Philippines conducted from December 2020 to March 2021 that incorporated conjoint experiments, we investigate the relative importance of various attributes of a city – such as neighborhood, healthcare, infrastructure, and governance – in influencing people’s willingness to live in the city under the new normal.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/a7ezj/" target="_blank">Defining Cities in the New Normal: A Conjoint Experiment of Livability Attributes</a>
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<li><strong>Population genetics in the early emergence of the Omicron SARS-CoV-2 variant in the provinces of South Africa.</strong> -
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Population genetic analyses of viral genome populations provide insight into the emergence and evolution of new variants of SARS-CoV-2. In this study, we use a population genetic approach to examine the evolution of the Omicron variant of SARS-CoV-2 in four provinces of South Africa (Eastern Cape, Gauteng, KwaZulu-Natal, and Mpumalanga) during the first months before emergence and after early spread. Our results show that Omicron polymorphisms increase sharply from September to November. We found differences between SARS-CoV-2 populations from Gauteng and Kwazulu-Natal and viruses from the Eastern Cape, where allele frequencies were higher, suggesting that natural selection may have contributed to the increase in frequency or that this was the site of origin. We found that the frequency of variants N501Y, T478K, and D614G increased in the spike in November compared with other mutations, some of which are also present in other animal hosts. Gauteng province was the most isolated, and most genetic variation was found within populations. Our population genomic approach is useful for small-scale genomic surveillance and identification of novel allele-level variants that can help us understand how SARS-CoV-2 will continue to adapt to humans and other hosts.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.09.527920v1" target="_blank">Population genetics in the early emergence of the Omicron SARS-CoV-2 variant in the provinces of South Africa.</a>
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<li><strong>Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p</strong> -
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The stem loop 2 motif (s2m), a highly conserved 41-nucleotide hairpin structure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, serves as an attractive therapeutic target that may have important roles in the virus life cycle or interactions with the host. However, the conserved s2m in Delta SARS-CoV-2, a previously dominant variant characterized by high infectivity and disease severity, has received relatively less attention than that of the original SARS-CoV-2 virus. The focus of this work is to identify and define the s2m changes between Delta and SARS-CoV-2 and subsequent impact of those changes upon the s2m dimerization and interactions with the host microRNA miR-1307-3p. Bioinformatics analysis of the GISAID database targeting the s2m element reveals a greater than 99% correlation of a single nucleotide mutation at the 15th position (G15U) in Delta SARS-CoV-2. Based on 1H NMR assignments comparing the imino proton resonance region of s2m and the G15U at 19{degrees}C, we find that the U15-A29 base pair closes resulting in a stabilization of the upper stem without overall secondary structure deviation. Increased stability of the upper stem did not affect the chaperone activity of the viral N protein, as it was still able to convert the kissing dimers formed by s2m G15U into a stable duplex conformation, consistent with the s2m reference. However, we find that the s2m G15U mutation drastically reduces the binding affinity of the host miR-1307-3p. These findings demonstrate that the observed G15U mutation alters the secondary structure of s2m with subsequent impact on viral binding of host miR-1307-3p, with potential consequences on the immune response.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528014v1" target="_blank">Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p</a>
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<li><strong>Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2</strong> -
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Analyses of the genomic diversity of SARS-CoV-2 found that some sites across the genome appear to have mutated independently multiple times with frequency significantly higher than four-fold sites, which can be either due to mutational bias, i.e., elevated mutation rate in some sites of the genome, or selection of the variants due to antagonistic pleiotropy, a condition where mutations increase some components of fitness at a cost to others. To examine how different forces shaped evolution of SARS-CoV-2 in 2020-2021, we analyzed a large set of genome sequences (~ 2 million). Here we show that while evolution of SARS-CoV-2 during the pandemic was largely mutation-driven, a group of nonsynonymous changes is probably maintained by antagonistic pleiotropy. To test this hypothesis, we studied the function of one such mutation, spike M1237I. Spike I1237 increases viral assembly and secretion, but decreases efficiency of transmission in vitro. Therefore, while the frequency of spike M1237I may increase within hosts, viruses carrying this mutation would be outcompeted at the population level. We also discuss how the antagonistic pleiotropy might facilitate positive epistasis to promote virus adaptation and reconcile discordant estimates of SARS-CoV-2 transmission bottleneck sizes in previous studies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527437v1" target="_blank">Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2</a>
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<li><strong>Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2</strong> -
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Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple omics assays (CyTOF, RNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.09.527892v1" target="_blank">Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2</a>
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<li><strong>SARS-CoV-2 NSP5 Antagonizes the MHC II Antigen Presentation Pathway by Hijacking Histone Deacetylase 2</strong> -
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The clearance of SARS-CoV-2 requires a multi-faceted immune response that is initiated by innate immune cells, with infection ultimately resolved by adaptive immune mechanisms. Induction of adaptive immunity to SARS-CoV-2 is dependent on the presentation of viral antigens on MHC II by professional antigen presenting cells such as dendritic cells and macrophages, to induce robust activation of CD4+ T cells. SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on the antigen presenting cells of COVID-19 patients, but the molecular mechanism mediating this process is unelucidated. In this study, analysis of protein and gene expression in human antigen presenting cells reveals that the expression of MHC II is inhibited by the SARS-CoV-2 main protease, NSP5. Suppression of MHC II expression occurs via downregulation of the transcription factor CIITA, which is required for MHC II expression. This downregulation of CIITA is independent of NSP5’s proteolytic activity, and rather, NSP5 delivers HDAC2 to the CIITA promoter via interactions with IRF3, Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a novel mechanism by which SARS-CoV-2 can limit antigen presentation on MHC II, thereby delaying or weakening the subsequent adaptive immune response.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528032v1" target="_blank">SARS-CoV-2 NSP5 Antagonizes the MHC II Antigen Presentation Pathway by Hijacking Histone Deacetylase 2</a>
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<li><strong>Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico</strong> -
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Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.05.498834v3" target="_blank">Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico</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>MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Manzi Guben granules<br/><b>Sponsors</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine<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>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., Ltd.<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>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Plitidepsin<br/><b>Sponsor</b>: PharmaMar<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>Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Persuasive Appeal<br/><b>Sponsor</b>: University of Calgary<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>Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AZD 1222<br/><b>Sponsors</b>: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health<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>Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<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>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>: Cairo 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>A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 nasal spray; Drug: Placebo Comparator<br/><b>Sponsor</b>: Huahui Health<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>Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Double-Stranded RNA sodium salt; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<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>Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: VV116+SOC; Drug: SOC<br/><b>Sponsor</b>: Chengdu Zenitar Biomedical Technology Co., Ltd<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>Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-1558; Drug: STI-1558 placebo<br/><b>Sponsor</b>: Zhejiang ACEA Pharmaceutical Co. Ltd.<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>Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Pilates Exercises<br/><b>Sponsor</b>: Michele de Aguiar Zacaria<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>Pirfenidone in Adult Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo<br/><b>Sponsor</b>: Capital Medical University<br/><b>Active, not 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 and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Biological: UC-MSCs<br/><b>Sponsor</b>: Shanghai East Hospital<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>CONFIDENCE: A Pilot Randomized Control Trial With Waitlist Condition to Test a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccination<br/><b>Intervention</b>: Behavioral: CONFIDENCE<br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health<br/><b>Not yet recruiting</b></p></li>
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</ul>
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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>Remdesivir Use in Low Weight, Premature, and Renally Impaired Infants With SARS-CoV-2 Infection in Sheikh Khalifa Medical City, UAE: Case Series</strong> - Remdesivir possesses in vitro inhibitory effect against severe acute respiratory syndrome coronavirus 2 and the Middle East respiratory syndrome. It works by inhibiting severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase that is essential for viral replication. Remdesivir is approved by Food and Drug Administration for treating COVID-19 in hospitalized adult and pediatric patients aged 28 days and more and weighing 3 kg and more. This case series is describing two cases…</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>Can Internet penetration curb the spread of infectious diseases among regions?-Analysis based on spatial spillover perspective</strong> - Based on the outbreak of COVID-19, this paper empirically studied the impact of internet penetration on the incidence of class A and B infectious diseases among regions in spatial Dubin model, by using health panel data from 31 provinces in China from 2009 to 2018. The findings showed that: (1) The regional spillover effect of incidence of class A and B infectious diseases was significantly positive, and that is most obvious in the central regions. (2) Internet penetration not only has a…</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 comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic</strong> - Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all…</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>Stress adaptation signature into the functional units of spike, envelope, membrane protein and ssRNA of SARS-CoV-2</strong> - Pandemic coronavirus causes respiratory, enteric and sometimes neurological diseases. Proteome data of individual coronavirus strains were already reported. Here we investigated of SARS-CoV-2 ssRNA and protein of spike, envelope and membrane to determine stress adaptation profile. Thermodynamic properties, Physicochemical behaviour and, amino acid composition along with their RMSD value was analysed. Thermodynamic index of SARS-CoV2 spike, envelope and membrane ssRNA is unstable in higher…</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>Extensive blood transcriptome analysis reveals cellular signaling networks activated by circulating glycocalyx components reflecting vascular injury in COVID-19</strong> - CONCLUSIONS: Circulating glycocalyx components in COVID-19 have distinct biologic feedback effects on immune and endothelial cells and result in upregulation of key regulatory transcripts leading to further immune activation and more severe systemic inflammation. These consequences are most pronounced during the early hospital phase of COVID-19 before pulmonary failure develops. Elevated levels of circulating glycocalyx components may early identify patients at risk for microvascular injury 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>The evaluation of <em>in vitro</em> antichagasic and <em>anti</em>-SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone</strong> - The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to…</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 review article on neuroprotective, immunomodulatory, and anti-inflammatory role of vitamin-D3 in elderly COVID-19 patients</strong> - Vitamin D3 is a secosteroid, broad-spectrum immunomodulatory, antioxidant, and anti-inflammatory hormone produced either by the internal subcutaneous pathway in the presence of ultraviolet B (UVB) rays or by the external pathway in the form of supplements. Vitamin D3 deficiency is a common and reversible contributor to mortality and morbidity among critically ill patients, including Coronavirus Disease 2019 (COVID-19) and other viral infections. The major functions of vitamin D3 are inhibiting…</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>Multigenerational effects of microplastic fragments derived from polyethylene terephthalate bottles on duckweed Lemna minor: Size-dependent effects of microplastics on photosynthesis</strong> - The 2019 global coronavirus disease pandemic has led to an increase in the demand for polyethylene terephthalate (PET) packaging. Although PET is one of the most recycled plastics, it is likely to enter the aquatic ecosystem. To date, the chronic effects of PET microplastics (MPs) on aquatic plants have not been fully understood. Therefore, this study aimed to investigate the adverse effects of PET MP fragments derived from PET bottles on the aquatic duckweed plant Lemna minor through a…</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>Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 Main Protease</strong> - SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (M^(pro)) is an attractive target for antivirals. The clinically approved drug nirmatrelvir, and the clinical candidate ensitrelvir have so far showed great potential for treatment of viral infection. However, the broad use of antivirals is often associated with resistance generation. Herein, we enzymatically characterized 14 naturally occurring M^(pro) polymorphisms that are close to the binding site of these antivirals….</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>Comparison study of Beninese and Chinese herbal medicines in treating COVID-19</strong> - CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.</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>The influence of facemasks on communication in healthcare settings: a systematic review</strong> - CONCLUSIONS: Despite considerable complexity and heterogeneity in outcome measure, 93% (14 of 15) articles suggest respiratory protective equipment negatively affects speech understanding in normal hearing and hearing-impaired adults.</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>Inhibitory Activity of <em>Saussurea costus</em> Extract against Bacteria, Candida, Herpes, and SARS-CoV-2</strong> - Medicinal herbs have long been utilized to treat various diseases or to relieve the symptoms of some ailments for extended periods. The present investigation demonstrates the phytochemical profile, molecular docking, anti-Candida activity, and anti-viral activity of the Saussurea costus acetic acid extract. GC-MS analysis of the extract revealed the presence of 69 chemical compounds. The chemical compounds were alkaloids (4%), terpenoids (79%), phenolic compounds (4%), hydrocarbons (7%), 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>3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors</strong> - The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study…</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><em>N</em>-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents</strong> - New N-containing xanthone analogs of α-mangostin were synthesized via one-pot Smiles rearrangement. Using cesium carbonate in the presence of 2-chloroacetamide and catalytic potassium iodide, α-mangostin (1) was subsequently transformed in three steps to provide ether 2, amide 3, and amine 4 in good yields at an optimum ratio of 1:3:3, respectively. The evaluation of the biological activities of α-mangostin and analogs 2-4 was described. Amine 4 showed promising cytotoxicity against 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>Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells</strong> - Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety of wild Pu’er tea plants were two major ingredients responsible for the anti-influenza activity. As the COVID-19 outbreak is still lurking, developing safe and cost-effective therapeutics is an urgent need. This study aimed to evaluate the effects of these tea compounds on the infection of mouse hepatitis virus (MHV), a β-coronavirus serving as a surrogate for SARS-CoV. Treatment with strictinin (100 μM), but not…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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