Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Questions of ethics during the Covid-19 pandemic emerging from problems of data fraud and health risks -
  In more than two years of the global health crisis of the Covid-19 pandemic, ethical issues regarding health data have been emerging quickly to the central focus of the global scientific community. Many papers have been retracted because of data problems, including those from prestigious journals. For example, two papers in The Lancet and the New England Journal of Medicine (NEJM) were retracted due to concerns regarding the veracity of datasets. Elisabeth Bik, an academic image sleuth, has found that 4% of more than 20000 biomedical papers she checked contained problematic image duplications; her efforts have led to at least 172 retractions. When the lives and well-being of countless people are at stake, and all eyes are on science, such mistakes could be (and have been) disruptive toward public trust, which might further fuel conspiracy theories, science-denying, and anti-vax attitudes. We require health data of good ethical standards, but who will be responsible if such standards are not met?
  🖺 Full Text HTML: Questions of ethics during the Covid-19 pandemic emerging from problems of data fraud and health risks
• Call for papers: Science lessons from the COVID-19 pandemic -
  The SM3D Portal invites colleagues to provide their perspectives, assessments, and analyses on science’s involvement in coping with the epidemic to the “Science lessons from the COVID-19 pandemic” collection. The collection is intended to supplement academic efforts to generate insightful lessons from the COVID-19 catastrophe and to create measures to safeguard our communities from future pandemics.
  🖺 Full Text HTML: Call for papers: Science lessons from the COVID-19 pandemic
• Republicans Discriminated Against Chinese-born Americans Throughout the COVID-19 Pandemic -
  Asian Americans became targets of increasingly hostile behavior during the COVID-19 pandemic. What motivated this? Fears of contagion arising from a behavioral immune system (BIS) may have motivated hostility toward Asian Americans, especially among those Americans vulnerable to COVID-19. Additionally, stigmatizing rhetoric from right-wing figures may have legitimated anti-Asian behavior among those Americans who held stronger anti-Asian sentiments to begin with or who were more receptive to right-wing rhetoric. We explore these possibilities using a behavioral game with a representative sample of Americans at two points: in May and October 2020. Participants were partnered with a US- or Chinese-born American in a give-or-take dictator game. The average American discriminated against Chinese-born Americans in May but not October 2020, when China was no longer a COVID-19 hotspot. But among Republicans, who may have held stronger anti-Asian sentiments to begin with and who were likely more receptive to right-wing rhetoric, discrimination—i.e., differential treatment—was both stronger in May compared to non-Republicans and persisted into October 2020. Notably, Americans who were more vulnerable to COVID-19 were not especially likely to discriminate.
  🖺 Full Text HTML: Republicans Discriminated Against Chinese-born Americans Throughout the COVID-19 Pandemic
• Comprehensive profiling of wastewater viromes by genomic sequencing -
  Genomic material in wastewater provides a rich source of data for detection and surveillance of microbes. Used for decades to monitor poliovirus and other pathogens, the SARS-CoV-2 pandemic and the falling costs of high-throughput sequencing have substantially boosted the interest in and the usage of wastewater monitoring. We have longitudinally collected over 100 samples from a wastewater treatment plant in Berlin/Germany, from March 2021 to July 2022, in order to investigate three aspects. First, we conducted a full metagenomic analysis and exemplified the depth of the data by temporal tracking strains and to a certain extent also variants of human astroviruses and enteroviruses. Second, targeting respiratory pathogens, a broad enrichment panel enabled us to detect waves of RSV, influenza, or common cold coronaviruses in high agreement with clinical data. Third, by applying a profile Hidden Markov Model-based search for novel viruses, we identified more than 100 thousand novel transcript assemblies likely not belonging to known virus species, thus substantially expanding our knowledge of virus diversity. Taken together, we present a longitudinal and deep investigation of the viral genomic information in wastewater that underlines the value of sewage surveillance for both public health purposes and planetary virome research.
  🖺 Full Text HTML: Comprehensive profiling of wastewater viromes by genomic sequencing
• Analysis of uptake, effectiveness and safety of COVID-19 vaccinations in pregnancy using the QResearch database: research protocol and statistical analysis plan -

  Background The COVID-19 pandemic has affected millions of people globally with major health, social and economic consequences, prompting development of vaccines for use in the general population. However, vaccination uptake is lower in some groups, including in pregnant women, because of concerns regarding vaccine safety. There is evidence of increased risk of adverse pregnancy and neonatal outcomes associated with SARS-CoV-2 infection, but fear of vaccine-associated adverse events on the baby both in short and longer term is one of the main drivers of low uptake for this group. Other vaccines commonly used in pregnancy include influenza and pertussis. These both have reportedly higher uptake compared with COVID-19 vaccination, which may be because they are perceived to be safer. In this study, we will undertake an independent evaluation of the uptake, effectiveness and safety of COVID-19 vaccinations in pregnant women using the QResearch primary care database in England. Objectives A. To determine COVID-19 vaccine uptake in pregnant women compared to uptake of influenza and pertussis vaccinations. B. To estimate COVID-19 vaccine effectiveness in pregnant women by evaluating the risk of severe COVID-19 outcomes following vaccination. C. To assess the safety of COVID-19 vaccination in pregnancy by evaluating the risks of adverse pregnancy and perinatal outcomes and adverse events of special interest for vaccine safety after COVID-19 vaccination compared with influenza and pertussis vaccinations. Methods This population-based study uses the QResearch database of primary health care records, linked to individual-level data on hospital admissions, mortality, COVID-19 vaccination, SARS-CoV-2 testing data and congenital anomalies. We will include women aged 16 to 49 years with at least one pregnancy during the study period of 30th December 2020 to the latest date available. Babies born during the study period will be identified and linked to the mothers record, where possible. We will describe vaccine uptake in pregnant women by trimester and population subgroups defined by demographics and other characteristics. Cox proportional hazards multivariable regression will be used to identify factors associated with vaccine uptake. The effectiveness of COVID-19 vaccines in pregnant women will be assessed using time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of severe COVID-19 outcomes after each vaccine dose compared with unvaccinated individuals. For the safety analysis, we will we use logistic regression analyses to determine unadjusted and adjusted odds ratios for the occurrence of maternal (e.g. miscarriage, ectopic pregnancy and gestational diabetes) and perinatal outcomes (e.g. stillbirth, small for gestational age and congenital anomalies) by vaccination status compared to unvaccinated individuals. For the adverse events of special interest for vaccine safety (e.g. venous thromboembolism, myocarditis and Guillain Barre syndrome), we will use time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of each outcome by vaccination status to unvaccinated individuals. Ethics and dissemination QResearch is a Research Ethics Approved Research Database with ongoing approval from the East Midlands Multi-Centre Research Ethics Committee (Ref: 18/EM/0400). This study was approved by the QResearch Scientific Committee on 9th June 2022. This research protocol has been developed with support from a patient and public involvement panel, who will continue to provide input throughout the duration of the study. Research findings will be submitted to pre-print servers such as MedRxIv, academic publication and disseminated more broadly through media releases and community groups and conference presentations.

  🖺 Full Text HTML: Analysis of uptake, effectiveness and safety of COVID-19 vaccinations in pregnancy using the QResearch database: research protocol and statistical analysis plan
• Transgenic Mouse Models Establish a Protective Role of Type 1 IFN Response in SARS-CoV-2 infection-related Immunopathology -
  Type 1 interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, however, the role of IFN-I in SARS-CoV-2 infections remained to be perplexing. Here, we developed two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1-/-) and the other with dampened IFN-I response (hACE2; Ifnar1-/-) to comprehend the role of IFN-I response during SARS-CoV-2 invasion. We found that hACE2; Irgm1-/- mice were resistant to lethal SARS-CoV-2 (including delta variant) infection with substantially reduced cytokine storm and immunopathology in the lungs and brain. In striking contrast, a severe SARS-CoV-2 infection along with immune cell infiltration, inflammatory response, and enhanced pathology was observed in the lungs of hACE2; Ifnar1-/- mice. Additionally, hACE2; Ifnar1-/- mice were highly susceptible to SARS-CoV-2 neuroinvasion in the brain accompanied by immune cell infiltration, microglia/astrocytes activation, cytokine response, and demyelination of neurons. The hACE2; Irgm1-/- Ifnar1-/- double knockout mice or hACE2; Irgm1-/- mice treated with STING or RIPK2 pharmacological inhibitors displayed loss of the protective phenotypes observed in hACE2; Irgm1-/- mice suggesting that heightened IFN-I response accounts for the observed immunity. Taken together, we explicitly demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against COVID-19.
  🖺 Full Text HTML: Transgenic Mouse Models Establish a Protective Role of Type 1 IFN Response in SARS-CoV-2 infection-related Immunopathology
• Effectiveness of the Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine -

  Background. The purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19. Methods. Employees of Cleveland Clinic in employment on the day the bivalent COVID-19 vaccine first became available to employees, were included. The cumulative incidence of COVID-19 was examined over the following weeks. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses received. Results. Among 51011 employees, 20689 (41%) had had a previous documented episode of COVID-19, and 42064 (83%) had received at least two doses of a COVID-19 vaccine. COVID-19 occurred in 2452 (5%) during the study. Risk of COVID-19 increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. In multivariable analysis, the bivalent vaccinated state was independently associated with lower risk of COVID-19 (HR, .70; 95% C.I., .61-.80), leading to an estimated vaccine effectiveness (VE) of 30% (95% CI, 20-39%). Compared to last exposure to SARS-CoV-2 within 90 days, last exposure 6-9 months previously was associated with twice the risk of COVID-19, and last exposure 9-12 months previously with 3.5 times the risk. Conclusions. The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19, while the virus strains dominant in the community were those represented in the vaccine.

  🖺 Full Text HTML: Effectiveness of the Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine
• Digital PCR discriminates between SARS-CoV-2 Omicron variants and immune escape mutations -

  As SARS-CoV-2 continues to evolve, mutations arise that will allow the virus to evade immune defenses and therapeutics. Assays that can identify these mutations can be used to guide personalized patient treatment plans. Digital PCR (dPCR) is a fast and reliable complement to whole genome sequencing that can be used to discriminate single nucleotide polymorphisms (SNPs) in template molecules. Here, we developed a panel of SARS-CoV-2 dPCR assays and demonstrate its applications for typing variant lineages and therapeutic monoclonal antibody resistance. We designed multiplexed dPCR assays for SNPs located at residue 3395 in the orf1ab gene and residue 143 of the spike gene that differentiate the Delta, Omicron BA.1, and Omicron BA.2 lineages. We demonstrate their validity on 596 clinical saliva specimens that were sequence-verified using Illumina whole genome sequencing. Next, we developed dPCR assays for spike mutations R346T, K444T, N460K, F486V, and F486S mutations that are associated with host immune evasion and reduced therapeutic monoclonal antibody efficacy. We demonstrate that these assays can be run individually or multiplexed to detect the presence of up to 4 SNPs in a single assay. We validate these dPCR assays on 81 clinical saliva SARS-CoV-2 positive specimens from Omicron subvariants BA.2.75.2, BM.1.1, BN.1, BF.7, BQ.1, BQ.1.1, and XBB. Thus, dPCR could serve as a useful tool to determine if clinical specimens contain therapeutically relevant mutations and inform patient treatment.

  🖺 Full Text HTML: Digital PCR discriminates between SARS-CoV-2 Omicron variants and immune escape mutations
• Association between SARS-CoV-2 Infection and Select Symptoms and Conditions 31 to 150 Days After Testing among Children and Adults -

  Background An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31 to 150 days following a SARS-CoV-2 test among adults (≥20 years) and children (<20 years) with positive and negative test results documented in the electronic health records (EHRs) of institutions participating in PCORnet, the National Patient-Centered Clinical Research Network. Methods and Findings This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test (nucleic acid amplification or rapid antigen) during March 1, 2020–May 31, 2021 documented in their EHR. We identified hospitalization status in the day prior through the 16 days following the SARS-CoV-2 test as a proxy for the severity of COVID-19. We used logistic regression to calculate the odds of receiving a diagnostic code for each symptom outcome and Cox proportional hazard models to calculate the risk of being newly diagnosed with each condition outcome, comparing those with a SARS-CoV-2 positive test to those with a negative test. After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) and shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥3 symptoms (aOR, 1.16[95% CI, 1.08 – 1.26]) and fatigue (aOR, 1.12[95% CI, 1.05 – 1.18]) compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (aHR, 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), and respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive SARS-CoV-2 test had higher odds of being diagnosed with fatigue (aOR, 1.11[95% CI, 1.05-1.16]) and shortness of breath (aOR, 1.22[95% CI, 1.15-1.29]), and had an increased risk (aHR, 1.12[95% CI, 1.02-1.23]) of being newly diagnosed with hematologic disorders (i.e., venous thromboembolism and pulmonary embolism) 31-150 days following SARS-CoV-2 test compared with those testing negative. The risk of being newly diagnosed with certain conditions, such as mental health conditions and neurological disorders, was lower among patients with a positive viral test relative to those with a negative viral test. Conclusions Patients with SARS-CoV-2 infection were at higher risk of being diagnosed with certain symptoms and conditions, particularly fatigue, respiratory symptoms, and hematological abnormalities, after acute infection. The risk was highest among adults hospitalized after SARS-CoV-2 infection.

  🖺 Full Text HTML: Association between SARS-CoV-2 Infection and Select Symptoms and Conditions 31 to 150 Days After Testing among Children and Adults
• How SARS-CoV-2 alters the regulation of gene expression in infected cells. -
  Non-structural accessory proteins in viruses play a key role in hijacking the basic cellular mechanisms, which is essential to promote the virus survival and evasion of the immune system. The immonuglobulin-like open reading frame 8 (ORF8) protein expressed by SARS-CoV-2 accumulates in the nucleus and may influence the regulation of the gene expression in infected cells. In this contribution, by using micro-second time-scale all-atom molecular dynamics simulations, we unravel the structural bases behind the epigenetic action of ORF8. In particular, we highlight how the protein is able to form stable aggregates with DNA through a histone tail-like motif, and how this interaction is influenced by post-translational modifications, such as acetylation and methylation, which are known epigenetic markers in histones. Our work not only clarifies the molecular mechanisms behind the perturbation of the epigenetic regulation caused by the viral infection, but also offers an unusual perspective which may foster the development of original antivirals.
  🖺 Full Text HTML: How SARS-CoV-2 alters the regulation of gene expression in infected cells.
• A versatile and interoperable computational framework for the analysis and modeling of COVID-19 disease mechanisms -
  The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Community-driven and highly interdisciplinary, the project is collaborative and supports community standards, open access, and the FAIR data principles. The coordination of community work allowed for an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework links key molecules highlighted from broad omics data analysis and computational modeling to dysregulated pathways in a cell-, tissue- or patient-specific manner. We also employ text mining and AI-assisted analysis to identify potential drugs and drug targets and use topological analysis to reveal interesting structural features of the map. The proposed framework is versatile and expandable, offering a significant upgrade in the arsenal used to understand virus-host interactions and other complex pathologies.
  🖺 Full Text HTML: A versatile and interoperable computational framework for the analysis and modeling of COVID-19 disease mechanisms
• Prewhitening and Normalization Help Detect a Strong Cross-Correlation Between Daily Wastewater SARS-CoV-2 RNA Abundance and COVID-19 Cases in a Community -
  Wastewater surveillance is a promising technology for real-time tracking and even early detection of COVID-19 infections in communities. Although correlation analysis between wastewater surveillance data and the daily clinical COVID-19 case numbers has been frequently conducted, the importance of stationarity of the time-series data has not been well addressed. In this study, we demonstrated that strong yet spurious correlation could arise from non-stationary time-series data in wastewater surveillance, and data prewhitening to remove trends helped to reveal distinct cross-correlation patterns between daily clinical case numbers and daily wastewater SARS-CoV-2 concentration during a lockdown period in 2020 in Honolulu, Hawaii. Normalization of wastewater SARS-CoV-2 concentration by the endogenous fecal viral markers in the same samples significantly improved the cross-correlation, and the best correlation was detected at a two-day lag of the daily clinical case numbers. The detection of a significant correlation between daily wastewater SARS-CoV-2 RNA abundance and clinical case numbers also suggests that disease burden fluctuation in the community should not be excluded as a contributor to the often observed weekly cyclic patterns of clinical cases.
  🖺 Full Text HTML: Prewhitening and Normalization Help Detect a Strong Cross-Correlation Between Daily Wastewater SARS-CoV-2 RNA Abundance and COVID-19 Cases in a Community
• Evaluation of bivalent Omicron BA.1 booster vaccination after different priming regimens in healthcare workers (SWITCH ON): a randomized controlled trial -

  Background Bivalent mRNA-based COVID-19 vaccines encoding the ancestral and Omicron spike protein were developed as a countermeasure against antigenically distinct SARS-CoV-2 variants. We compared the (variant-specific) immunogenicity and reactogenicity of mRNA-based bivalent Omicron BA.1 vaccines in individuals who were primed with adenovirus- or mRNA-based vaccines. Methods In this open-label, multicenter, randomized, controlled trial, healthcare workers primed with Ad26.COV2.S or mRNA-based vaccines were boosted with mRNA-1273.214 or BNT162b2 OMI BA.1. The primary endpoint was the fold change in S1-specific IgG antibodies pre- and 28 days after booster vaccination. Secondary outcomes were fast response, (antibody levels on day 7), reactogenicity, neutralization of circulating variants and (cross-reactive) SARS-CoV-2-specific T-cell responses. Findings No effect of different priming regimens was observed on bivalent vaccination boosted S1-specific IgG antibodies. The largest increase in S1-specific IgG antibodies occurred between day 0 and 7 after bivalent booster. Neutralizing antibodies targeting the variants in the bivalent vaccine (ancestral SARS-CoV-2 and Omicron BA.1) were boosted. In addition, neutralizing antibodies against the circulating Omicron BA.5 variant increased after BA.1 bivalent booster. T-cell responses were boosted and retained reactivity with variants from the Omicron sub-lineage. Interpretation Bivalent booster vaccination with mRNA-1273.214 or BNT162b2 OMI BA.1 resulted in a rapid recall of humoral and cellular immune responses independent of the initial priming regimen. Although no preferential boosting of variant-specific responses was observed, the induced antibodies and T-cells cross-reacted with Omicron BA.1 and BA.5. It remains crucial to monitor immunity at the population level, and simultaneously antigenic drift at the virus level, to determine the necessity (and timing) of COVID-19 booster vaccinations.

  🖺 Full Text HTML: Evaluation of bivalent Omicron BA.1 booster vaccination after different priming regimens in healthcare workers (SWITCH ON): a randomized controlled trial
• Bacillus Calmette-Guerin vaccine to reduce COVID-19 infections and hospitalisations in healthcare workers: a living systematic review and prospective ALL-IN meta-analysis of individual participant data from randomised controlled trials -

  BACKGROUND: The objective is to determine the impact of the Bacillus Calmette-Guerin (BCG) vaccine compared to placebo or no vaccine on COVID-19 infections and hospitalisations in healthcare workers. We are using a living and prospective approach to Individual-Participant-Data (IPD) meta-analysis of ongoing studies based on the Anytime Live and Leading Interim (ALL-IN) meta-analysis statistical methodology. METHODS: Planned and ongoing randomised controlled trials were identified from trial registries and by snowballing (final elicitation: Oct 3 2022). The methodology was specified prospectively – with no trial results available – for trial inclusion as well as statistical analysis. Inclusion decisions were made collaboratively based on a risk-of-bias assessment by an external protocol review committee (Cochrane risk-of-bias tool adjusted for use on protocols), expected homogeneity in treatment effect, and agreement with the predetermined event definitions. The co-primary endpoints were incidence of COVID-19 infection and COVID-19-related hospital admission. Accumulating IPD from included trials was analysed sequentially using the exact e-value logrank test (at level alpha = 0.5% for infections and level alpha = 4.5% for hospitalisations) and anytime-valid 95%-confidence intervals (CIs) for the hazard ratio (HR) for a predetermined fixed-effects approach to meta-analysis (no measures of statistical heterogeneity). Infections were included if demonstrated by PCR tests, antigen tests or suggestive lung CTs. Participants were censored at date of first COVID-19-specific vaccination and two-stage analyses were performed in calendar time, with a stratification factor per trial. RESULTS: Six trials were included in the primary analysis with 4 433 participants in total. The e-values showed no evidence of a favourable effect of minimal clinically relevance (HR < 0.8) in comparison to the null (HR = 1) for COVID-19 infections, nor for COVID-19 hospitalisations (HR < 0.7 vs HR = 1). COVID-19 infection was observed in 251 participants receiving BCG and 244 participants not receiving BCG, HR 1.02 (anytime-valid 95%-CI 0.78-1.35). COVID-19 hospitalisations were observed in 13 participants receiving BCG and 7 not receiving BCG, resulting in an uninformative estimate (HR 1.88; anytime-valid 95%-CI 0.26-13.40). DISCUSSION: It is highly unlikely that BCG has a clinically relevant effect on COVID-19 infections in healthcare workers. With only limited observations, no conclusion could be drawn for COVID-19 related hospitalisation. Due to the nature of ALL-IN meta-analysis, emerging data from new trials can be included without violating type-I error rates or interval coverage. We intend to keep this meta-analysis alive and up-to-date, as more trials report. For COVID-19 related hospitalisations, we do not expect enough future observations for a meaningful analysis. For BCG-mediated protection against COVID-19 infections, on the other hand, more observations could lead to a more precise estimate that concludes the meta-analysis for futility, meaning that the current interval excludes the HR of 0.8 predetermined as effect size of minimal clinical relevance. OTHER: No external funding. Preregistered at PROSPERO: CRD42021213069.

  🖺 Full Text HTML: Bacillus Calmette-Guerin vaccine to reduce COVID-19 infections and hospitalisations in healthcare workers: a living systematic review and prospective ALL-IN meta-analysis of individual participant data from randomised controlled trials
• Periodic epidemic outbursts explained by local saturation of clusters -

  Adding the notion of spatial locality to the susceptible-infected-recovered (or SIR) model, allows to capture local saturation of an epidemic. The resulting minimum model of an epidemic, consisting of five ordinary differential equations with constant model coefficients, reproduces slowly decaying periodic outbursts, as observed in the COVID-19 or Spanish flu epidemic. It is shown that if immunity decays, even slowly, the model yields a fully periodic dynamics.

  🖺 Full Text HTML: Periodic epidemic outbursts explained by local saturation of clusters

From Clinical Trials

• A Study for Immunocompromised Patients for Pre Exposure Prophylaxis of COVID-19 With AZD5156. - Condition:   COVID 19
  Interventions:   Biological: Placebo;   Biological: AZD5156;   Biological: AZD7442 (EVUSHELD™)
  Sponsor:   AstraZeneca
  Not yet recruiting

• 101-PGC-005 for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: 101-PGC-005;   Drug: Dexamethasone
  Sponsor:   101 Therapeutics
  Recruiting

• COVID-19 Huashi Baidu Formula Clinical Study - Condition:   COVID-19
  Interventions:   Drug: Huashi Baidu Granule;   Drug: Monapiravir
  Sponsors:   Xiyuan Hospital of China Academy of Chinese Medical Sciences;   Beijing YouAn Hospital;   Kossamak Hospital;   Kamuzu University of Health Sciences
  Not yet recruiting

• Shaping Care Home COVID-19 Testing Policy - Condition:   COVID-19
  Intervention:   Diagnostic Test: Lateral Flow Device
  Sponsor:   University College, London
  Not yet recruiting

• Baldachin: Ceiling HEPA-filtration to Prevent Nosocomial Transmission of COVID-19 - Condition:   COVID-19
  Intervention:   Device: Baldachin
  Sponsor:   University Hospital Inselspital, Berne
  Not yet recruiting

• Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease - Condition:   COVID-19
  Interventions:   Biological: Asunercept;   Other: Placebo
  Sponsor:   Apogenix AG
  Recruiting

• Study in Adults to Assess the Safety and Efficacy of Inhaled IBIO123, for Post-exposure Prophylaxis of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: IBIO123;   Other: Placebo
  Sponsor:   Immune Biosolutions Inc
  Not yet recruiting

• Comparative Study of the Efficacy and Safety of Ambervin and Standard Therapy in Hospitalized Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly;   Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled;   Drug: Standard of care
  Sponsor:   Promomed, LLC
  Completed

• Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: GST-HG171/Ritonavir;   Drug: Placebo
  Sponsor:   Fujian Akeylink Biotechnology Co., Ltd.
  Not yet recruiting

• A PhaseⅡ Study to Evaluate the Safety & Immunogenicity of SARS-CoV-2 Alpha/Beta/Delta/Omicron Variants COVID-19 Vaccine - Condition:   COVID-19 Pandemic
  Interventions:   Biological: SCTV01E;   Biological: Placebo (normal saline)
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• The Efficacy of Azvudine and Paxlovid in High-risk Patients With COVID-19: A Prospective Randomized Controlled Trial - Condition:   SARS-CoV-2 Infection
  Interventions:   Drug: Azvudine;   Drug: Paxlovid group
  Sponsors:   Southeast University, China;   Hohhot First Hospital, Hohhot, Inner Mongolia, China
  Recruiting

• ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening - Condition:   Depression and Anxiety Symptoms Related to the COVID-19 Pandemic
  Intervention:   Behavioral: Internet-based Cognitive Behavioral Therapy
  Sponsor:   Linkoeping University
  Not yet recruiting

• Effectiveness of Supportive Psychotherapy Through Internet-Based Teleconsultation on Psychological and Somatic Symptoms, Neutrophil-Lymphocyte Ratio, and Heart Rate Variability in Post Covid-19 Syndrome Patients - Condition:   Post-COVID-19 Syndrome
  Intervention:   Behavioral: Supportive Psychotherapy
  Sponsor:   Indonesia University
  Not yet recruiting

• Graphene Photothermal Adjuvant Therapy for Mild Corona Virus Disease 2019: A Prospective Randomized Controlled Trial - Condition:   COVID-19
  Intervention:   Device: Graphene spectrum light wave therapy room
  Sponsors:   Southeast University, China;   Hohhot First Hospital
  Recruiting

• ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine - Condition:   COVID-19 Vaccine
  Intervention:   Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)
  Sponsors:   Laboratorio Pablo Cassara S.R.L.;   Universidad Nacional de San Martín (UNSAM);   National Council of Scientific and Technical Research, Argentina
  Active, not recruiting

From PubMed

• A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies - No abstract

• Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19 - No abstract

• In silico evaluation of potential intervention against SARS-CoV-2 RNA-dependent RNA polymerase - No abstract

• Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern - No abstract

• UGTs-mediated metabolic interactions contribute to enhanced anti-inflammation activity of Jinhongtang - No abstract

• Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation - No abstract

• Identification of anti-SARS-CoV-2 agents based on flavor/fragrance compositions that inhibit the interaction between the virus receptor binding domain and human angiotensin converting enzyme 2 - No abstract

• Guanidinium-Perfunctionalized Polyhedral Oligomeric Silsesquioxanes as Highly Potent Antimicrobials against Planktonic Microbes, Biofilms, and Coronavirus - No abstract

• Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex - No abstract

• Nirmatrelvir plus ritonavir in COVID-19: a profile of its use - No abstract

• A highly sensitive bead-based flow cytometric competitive binding assay to detect SARS-CoV-2 neutralizing antibody activity - No abstract

• SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis - No abstract

• Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention - No abstract

• In-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2 - No abstract

• Predicting In Vitro and In Vivo Anti-SARS-CoV-2 Activities of Antivirals by Intracellular Bioavailability and Biochemical Activity - No abstract

From Patent Search