Covid-19 Sentry

Contents

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

From Preprints

• Longitudinal wastewater surveillance addressed public health priorities during the transition from “dynamic COVID-zero” to “opening up” in China: a population-based study -

  Background Wastewater surveillance provides real-time, cost-effective monitoring of SARS-CoV-2 transmission. We developed the first city-level wastewater warning system in mainland China, located in Shenzhen. Our study aimed to reveal cryptic transmissions under the “dynamic COVID-zero” policy and characterize the dynamics of the infected population and variant prevalence, and then guide the allocation of medical resources during the transition to “opening up” in China. Methods In this population-based study, a total of 1,204 COVID-19 cases were enrolled to evaluate the contribution of Omicron variant-specific faecal shedding rates in wastewater. After that, wastewater samples from up to 334 sites distributed in communities and port areas in two districts of Shenzhen covering 1.74 million people were tested daily to evaluate the sensitivity and specificity of this approach and were validated against daily SARS-CoV-2 screening. After the public health policy was switched to “opening up” in December 7, 2022, we conducted wastewater surveillance at wastewater treatment plants and pump stations covering 3.55 million people to estimate infected populations using model prediction and detect the relative abundance of SARS-CoV-2 lineages using wastewater sequencing. Findings In total, 82.4% of SARS-CoV-2 Omicron cases tested positive for faecal viral RNA within the first four days after the diagnosis, which was far more than the proportion of the ancestral variant. A total of 27,759 wastewater samples were detected from July 26 to November 30 in 2022, showing a sensitivity of 73.8% and a specificity of 99.8%. We further found that wastewater surveillance played roles in providing early warnings and revealing cryptic transmissions in two communities. Based on the above results, we employed a prediction model to monitor the daily number of infected individuals in Shenzhen during the transition to “opening up” in China, with over 80% of the population infected in both Futian District and Nanshan District. Notably, the prediction of the daily number of hospital admission was consistent with the actual number. Further sequencing revealed that the Omicron subvariant BA.5.2.48 accounted for the most abundant SARS-CoV-2 RNA in wastewater, and BF.7.14 and BA.5.2.49 ranked second and third, respectively, which was consistent with the clinical sequencing. Interpretation This study provides a scalable solution for wastewater surveillance of SARS-CoV-2 to provide real-time monitoring of the new variants, infected populations and facilitate the precise prediction of hospital admission. This novel framework could be a One Health system for the surveillance of other infectious and emerging pathogens with faecal shedding and antibiotic resistance genes in the future. Funding Sanming Project of Medicine in Shenzhen, Shenzhen Key Medical Discipline Construction Fund.

  🖺 Full Text HTML: Longitudinal wastewater surveillance addressed public health priorities during the transition from “dynamic COVID-zero” to “opening up” in China: a population-based study
• Seventy Years of Mortality Transition in India 1950-2021 -

  Mortality in India remains high by international standards. This paper analyses mortality transition in India during the 70 years since 1950 based on the annual estimates of age-specific probabilities of death prepared by the United Nations Population Division for the period 1950-2021. The analysis reveals that characterisation of mortality transition is sensitive to the summary index of mortality used. Mortality transition in India based on the geometric mean of the age-specific probabilities of death is found to be different from that based on the life expectancy at birth. The transition in mortality based on the geometric mean of age-specific probabilities of death accelerated during 2008-2019 but decelerated when based on the life expectancy at birth. The reason is that mortality transition in younger ages has been faster than mortality transition in older ages. The analysis also reveals that there were around 4.3 excess deaths associated with the COVID-19 epidemic in the country leading to a loss of around 3.7 years in the life expectancy at birth between 2019 and 2021.

  🖺 Full Text HTML: Seventy Years of Mortality Transition in India 1950-2021
• The impact of the Covid-19 pandemic on young people from black and mixed-ethnic groups’ mental health: A qualitative study -
  Author Notes This manuscript has been submitted for publication and is likely to be edited as part of the peer-review process. Correspondence regarding this paper should be addressed to Dr Keri Ka-Yee Wong, keri.wong@ucl.ac.uk Abstract Objectives The Covid-19 pandemic has disproportionately impacted vulnerable groups’ physical and mental health, especially young people and minority ethnic groups, yet little is known about how this is taking place and what support they would like. To address this gap, this qualitative study aims to uncover the effect of the Covid-19 outbreak on young people with ethnic minority backgrounds’ mental health, how this changed since the end of lockdown and what support they need to cope with these issues. Setting and Participants Ten 20-minute in-person semi-structured interviews were conducted with young people aged 12 to 17 years old from black and mixed-ethnic groups who regularly attend a community centre in West London. Results Through Interpretative Phenomenological Analysis, results indicated that the participants’ mental health was negatively impacted by the Covid-19 pandemic, with feelings of loneliness being the most common experience. However, positive effects were concurrently observed including improved well-being and better coping strategies post-lockdown, which is a testament to the young people’s resilience. That said, it is clear that young people from minority ethnic backgrounds lacked support during the Covid-19 pandemic and would now need psychological, practical and relational assistance to cope with these challenges. Conclusions Whilst future studies would benefit from a larger ethnically-diverse sample, this is a start. Study findings have the potential to inform future government policies around mental health support and access for young people from ethnic minorities, notably prioritising support for grassroots initiatives during times of crisis. Strengths and limitations • This qualitative interview study during Covid-19 gives voice to the experiences of young people from black and mixed-ethnic backgrounds in the UK • The in-person quality of the interviews helped build rapport between the researcher and the young people and sharing of sensitive issues around mental health access and support, increasing the results’ validity • This is a convenient sample, with girls and those aged 15 years and above being disproportionately represented in our data as they provided most of the answers. • The small sample size and lack of ethnic diversity limits the generalisability of the study to individuals from other ethnic minority groups.
  🖺 Full Text HTML: The impact of the Covid-19 pandemic on young people from black and mixed-ethnic groups’ mental health: A qualitative study
• Intra-Host Mutation Rate of Acute SARS-CoV-2 Infection During the Initial Pandemic Wave -
  Background: Our understanding of SARS-CoV-2 evolution and mutation rate is limited. The rate of SARS-CoV-2 evolution is minimized through a proofreading function encoded by NSP-14 and may be affected by patient comorbidity. Current understanding of SARS-CoV-2 mutational rate is through population based analysis while intra-host mutation rate remains poorly studied. Methods: Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) [≥]0.25, [≥]0.5 and [≥]0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with ({Delta}NSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Results: Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI:90.8-96.4], 40.7 (95%CI:38.9-42.6) and 34.7 (95%CI:33.0-36.4) substitutions/genome/year at AF [≥]0.25, [≥]0.5, [≥]0.75 respectively. Mutation rate in {Delta}NSP-14 were significantly elevated at AF>0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Discussion: Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.
  🖺 Full Text HTML: Intra-Host Mutation Rate of Acute SARS-CoV-2 Infection During the Initial Pandemic Wave
• Concerns about data integrity of 30 randomized clinical trials from one author. -
  Introduction In 2021, we learnt about the problems in studies on ivermectin and hydrocholoroquine in COVID-19. We noticed an appreciable number of unfunded randomised clinical trials (RCTs) on the treatment of COVID-19 conducted across three centres in Egypt (Tanta University, Assiut University, Ain-shams University) on COVID-19 patients with similar inclusion criteria and overlapping time frames. Dr Sherief M Abd-Elsalam ran seven such RCTs across these three centres; four of these RCTs have since been retracted. We therefore set out to systematically analyse the integrity of all RCTs (co-)authored by Dr Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. Methods We searched PubMed, Google Scholar, Scopus and clinical trial registries for RCTs published by Dr Sherief M Abd-Elsalam, affiliated with the Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt. We assessed trial registration, tables for identical data values, statistical errors, and improbable data trends. We assessed the probability of true randomization by assessing baseline characteristics through a Monte Carlo Analysis. Results We report on 30 published randomized control trials (RCTs) of Dr. Sherief Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. We found important issues in all RCTs examined. Of these 23 RCTs, 10 RCTs had substantial trial registration inconsistencies. Only one of these 10 RCTs has been retracted to date. We found nine RCTs with substantial statistical mistakes, five RCTs with similarities between tables unlikely to happen by chance, four RCTs with implausible Gaussian distributions, three RCTs in which almost all dichotomous variables had even values, while part of at least one study was plagiarized. Monte Carlo analysis indicated that the probability that distribution of baseline characteristics due to randomisation was 0.0000228. According to the trial registration, Dr. Abd-Elsalam is coordinating 76 clinical trials with 45 trials currently marked as ‘Recruiting’ and 17 trials marked as ‘Unknown Status’ as of November 2022. Interpretation We strongly recommend a thorough investigation of the data integrity of all RCTs by Dr Sherief M Abd-Elsalam by journal editors. Until the completion of such an investigation, we suggest that none of these studies are used to inform clinical practice.
  🖺 Full Text HTML: Concerns about data integrity of 30 randomized clinical trials from one author.
• False Information Literacy During the Covid-19 Pandemic -
  The COVID-19 pandemic is a confusing time. Because COVID-19 was a new evolution of a virus, much of the information surrounding it was ever-evolving. Although a vaccine was quickly developed, and it was approved by the FDA for emergency use, people were still skeptical of its efficacy and safety. Malicious internet users chose to spread mis- and disinformation about the vaccine. An explosion of information literacy has accompanied the spread of misinformation. Specifically, people used the internet to combat misinformation and spread true information about both the virus and its corresponding vaccine. By using a case study of an article, I choose to explore the methods in which malicious users spread misinformation and specifically the language used to spread this misinformation. While doctors and other public health experts have used the internet to argue against misinformation, malicious users have also used their medical qualifications, applicable or otherwise, to demonstrate credibility. Similarly, arguments such as “believe science” or “trust the evidence” have been twisted to spread misinformation. Finally, visualizations showing a false relationship between otherwise-unrelated topics spread quickly. While information literacy is an important tool, malicious users have co-opted the language used to obtain credibility. Identifying the forms that this false information literacy takes is one step in understanding how to combat it.
  🖺 Full Text HTML: False Information Literacy During the Covid-19 Pandemic
• The COVID-19 impact on tuberculosis incidence notification in India- A comparative study (2017-2022) -
  Abstract - Despite modern drugs treatment with 60 years of chemotherapy and 90 years of vaccination with various strategies to prevent and control tuberculosis (TB), globally TB ranks 13th in leading causes of mortality. In recent year 2021 Worldwide, TB ranks 2nd after COVID-19, in leading causes of infectious killer, killing about 1.6 million people in 2021 (including 187 000 people infected with HIV). During COVID-19 era 2020, very significant global reduction in TB incidence was detected, which suddenly reduced from 7.1 million in 2019, to 5.8 million in 2020 (–18 percent). Globally, India is listed among the top three countries accounting for 67percent of this global reduction in TB incidence, besides Indonesia and the Philippines. As per data of The World Bank, India’s annual TB incidence was falling continuously since 2000, rose again and reached 210/100,000 in 2021 from 204/100,000 in 2020. A modelling analysis study found that lockdown has induced 80 percent reduction in TB notification rates in India. India ranks fourth in infection and death from COVID-19; hence there is a possibility that slowing down of COVID-19 will unmask the TB cases and deaths leading to increase in the count of TB in future years. In spite of several similarities in manifestation and differences in aetiology, there is still lack of full knowledge about the epidemiological relationship between TB and COVID-19 .To know the real situation and scenario of TB cases this study was started with aim to alert policy maker for needful action to control TB effectively in time. This study aimed to know the impact of COVID-19 on annual TB notifications incidence in India. This is a cross-sectional, quantitative, retrospective, deductive study. This research study included all the 36 states and UTs of India. We performed a linear regression study of the existing data of pre pandemic years included in this study for calculating a counterfactual analysis in order to find out the possible real incidence of TB cases notifications, which may have been notified if the current natural intervention of COVID-19 had not taken place. The annual number of new (TB) cases detected during the pre-COVID-19 period as well as COVID-19 period of this study has shown similar trends separately. During both periods the number of new (TB) cases increased in consecutive years. Another significant finding of this study is that the number of new (TB) cases detected during the first two COVID-19 years i.e. 2020 and 2021 decreased in comparison to last pre-COVID-19 year i.e. 2019. The base year of this study i.e. 2017 are having least whereas the last year of this study i.e. 2022 are having the largest number of new (TB) cases detected in one individual year. There is an increase of 7.79 percent in TB case detection during the COVID-19 period of this study. This study revealed that during first COVID-19 year i.e. 2020 there is significant reduction in number of new (TB) cases detected by 580869 numbers or 24.29 percent in comparison to last pre-COVID-19 year i.e. 2019. The number of new (TB) cases detected increased continuously during pre-COVID-19 years by 29.59 percent in 2018 and 18.49 percent in 2019. The question arises from this study is that, is it possible to achieve the goal of NTEP by year 2025 in current scenario reality?
  🖺 Full Text HTML: The COVID-19 impact on tuberculosis incidence notification in India- A comparative study (2017-2022)
• Obesity and Smoking: A Tale of 2 Risk Factors with Implications for the Next Pandemic -

  Background: In 1990, two risk factors that would figure prominently in the COVID-19 pandemic were on divergent paths in the US. The smoking rate was 23.5% and dropped to 13.5% in 2021, while the obesity rate was 11.5% and increased 186% to 33.0%. Objective: The study objective was to compare the global impact of those risk factors on COVID deaths to help prepare the US for future pandemics. Methods: Stata and Excel were used to regress global COVID deaths on obesity and smoking before and after vaccines were available, and US deaths/day were compared pre-and post-vaccines. Results: Obesity was associated with global COVID deaths, with R2 as high as 0.87 for cumulative data with slightly lower R2 and coefficients for post-vaccines. For 9 regressions of deaths on obesity, all P values (overall and coefficients) were <0.05 while for regressions on smoking, no P values were < 0.05. Of the 1.1 million US deaths, the death rate/day post-vaccines was 59% of that pre-vaccines. If the US obesity rate had remained 11.5%, estimates suggest 800,000+ lives could have been saved. US smoking rate was reduced 42% by multiple strategies using support from a 1998 multi-billion-dollar settlement between states and tobacco companies. Conclusion: Vaccines have limited ability to reduce total COVID deaths, with obesity remaining a key factor in death rates. Results suggest that lower obesity rates are needed to further reduce US COVID deaths, potentially saving thousands of lives in future pandemics. Lessons from reducing smoking rates might prove useful.

  🖺 Full Text HTML: Obesity and Smoking: A Tale of 2 Risk Factors with Implications for the Next Pandemic
• Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study -

  Introduction: Three years into the pandemic, there remains significant uncertainty about the true infection and mortality burden of COVID-19 in the WHO-Africa region. High quality, population-representative studies in Africa are rare and tend to be conducted in national capitals or large cities, leaving a substantial gap in our understanding of the impact of COVID-19 in rural, low-resource settings. Here, we estimated the spatio-temporal morbidity and mortality burden associated with COVID-19 in a rural health district of Madagascar until the first half of 2021. Methods: We integrated a nested seroprevalence study within a pre-existing longitudinal cohort conducted in a representative sample of 1600 households in Ifanadiana District, Madagascar. Socio-demographic and health information was collected in combination with dried blood spots for about 6500 individuals of all ages, which were analysed to detect IgG and IgM antibodies against four specific proteins of SARS-CoV2 in bead-based multiplex immunoassay. We evaluated spatio-temporal patterns in COVID-19 infection history and its associations with several geographic, socio-economic and demographic factors via logistic regressions. Results: Eighteen percent of people had been infected by April-June 2021, with seroprevalence increasing with individuals age. COVID-19 primarily spread along the only paved road and in major towns during the first epidemic wave, subsequently spreading along secondary roads during the second wave to more remote areas. Wealthier individuals and those with occupations such as commerce and formal employment were at higher risk of being infected in the first wave. Adult mortality increased in 2020, particularly for older men for whom it nearly doubled up to nearly 40 deaths per 1000. Less than 10% of mortality in this period could be directly attributed to COVID-19 deaths given known infection fatality ratios and observed seroprevalence in the district. Conclusion: Our study provides a very granular understanding on COVID-19 transmission and mortality in a rural population of sub-Saharan Africa and suggests that the disease burden in these areas may have been substantially underestimated.

  🖺 Full Text HTML: Morbidity and mortality burden of COVID-19 in rural Madagascar: results from a longitudinal cohort and nested seroprevalence study
• “It’s no use saying it in English”: A qualitative study exploring community leaders’ perceptions of the challenges and opportunities with translating and interpreting COVID-19 related public health messaging to reach ethnic minorities in Australia -

  Background: The Australian Government implemented a range of public health response strategies and communication approaches to reduce the spread of COVID-19; however, concerns have been raised around a failure to consider culturally and linguistically diverse (CaLD) communities sufficiently in these processes. This research aimed to understand the factors that have impacted COVID-19 communication and engagement efforts during the pandemic from the perspective of key CaLD community stakeholders and community members. A further aim was to understand the processes that could be adopted to support future communication strategies, including the promotion of pandemic-related vaccines. Approach: This study included 29 key informant interviews with community and faith-based leaders in New South Wales, Australia. Results: The overwhelming message from community leaders was a sense of shared responsibility between their organisations and the government in communicating pertinent and accurate COVID-19 related information to CaLD communities. They expressed a sense of duty to keep their community members safe. While acknowledging this shared responsibility, community leaders and others shouldered significant costs related to resources and time that need to be acknowledged by governments in preparing for future disease outbreaks. They felt that governments should consider: 1) improving communication between governments and CaLD organisations; 2) responding to the specific CaLD needs with greater agility; 3) foregrounding social media in their communication strategy; 4) reinvesting in local public health units to know their population; 5) investing in a health ambassadors model program; 6) preparing a hybrid model of translators/interpreters to fill the gap; and, 7) reimagining vaccine information campaigns to better target CaLD communities. Conclusion: Given the technical details about the COVID-19 virus conveyed in government information campaigns and the media, ensuring the most vulnerable populations, including people from CaLD backgrounds, access clear, concise and timely public health messaging from both governments and community organisations requires further attention.

  🖺 Full Text HTML: “It’s no use saying it in English”: A qualitative study exploring community leaders’ perceptions of the challenges and opportunities with translating and interpreting COVID-19 related public health messaging to reach ethnic minorities in Australia
• SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses -

  Mucosal antibodies play a key role in the protection against SARS-CoV-2 infection in the upper respiratory tract, and potentially in limiting virus replication and therefore onward transmission. While systemic immunity to SARS-CoV-2 is well understood, little is known about the antibodies present on the nasal mucosal surfaces. In this study, we evaluated SARS-CoV-2 mucosal antibodies in response to infection, vaccination, or a combination of both. Paired nasal fluid and serum samples were collected from 136 individuals, which include convalescent, vaccinated, or breakthrough infections. We detected a high correlation between IgG responses in serum and nasal fluids, which were higher in both compartments in vaccinated compared to convalescent participants. Contrary, nasal and systemic SARS-CoV-2 IgA responses were weakly correlated, indicating a compartmentalization between the local and systemic IgA responses. SARS-CoV-2 secretory component IgA (s-IgA) antibodies, present exclusively on mucosal surfaces, were detected in the nasal fluid only in a minority of vaccinated subjects and were significantly higher in previously infected individuals. s-IgA binding antibodies showed significant correlation with neutralizing activity of nasal fluids against SARS-CoV-2 ancestral B.1 and Omicron-BA.5 variant, indicating that s-IgA is the crucial contributor to neutralization in the nasal mucosa. Neutralization against both SARS-CoV-2 strains was higher in the mucosa of subjects with previous SARS-CoV-2 infections compared to vaccinated participants. In summary, we demonstrate that currently available vaccines elicit strong systemic antibody responses, but SARS-CoV-2 infection generates more potent binding and neutralizing mucosal antibodies. Our results support the importance to develop SARS-CoV-2 vaccines that elicit mucosal antibodies.

  🖺 Full Text HTML: SARS-CoV-2 convalescence and hybrid immunity elicits mucosal immune responses
• Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients -

  Objective. To evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases. Methods. We collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogrens syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry. Results. Most of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable. Conclusion. Rheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.

  🖺 Full Text HTML: Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients
• Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial -

  Background: Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19. Methods: This phase 3, randomized, multicenter, open-label study tested non-inferiority of IM to IV administration using a 3.5% absolute non-inferiority margin. From June to August 2021, patients aged ≥12 years with COVID-19, not hospitalized or receiving supplemental oxygen, and at high risk for progression were randomized 1:1:1 to a single 500-mg IV sotrovimab infusion or 500-mg or 250-mg IM sotrovimab injection. The primary composite endpoint was progression to all-cause hospitalization for >24 hours for acute management of illness or all-cause death through day 29. Results: Sotrovimab 500 mg IM was non-inferior to 500 mg IV: 10/376 (2.7%) participants in the sotrovimab 500-mg IM group versus 5/378 (1.3%) in the sotrovimab 500-mg IV group met the primary endpoint (absolute adjusted risk difference: 1.06% [95% confidence interval [CI]: −1.15%, 3.26%]). The CI upper limit was lower than the prespecified non-inferiority margin of 3.5%. 250-mg IM group enrollment was discontinued early because a greater proportion of hospitalizations was seen in that group versus the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease related events and died (500 mg IM: 2/393 [<1%]; 250 mg IM: 2/195 [1%]). Conclusions: Sotrovimab 500-mg IM injection was well tolerated and non-inferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.

  🖺 Full Text HTML: Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial
• Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 antigen testing as a case study -

  In the era of living with COVID-19, the risk of localised SARS-CoV-2 outbreaks remains. Here, we develop a multi-scale modelling framework for estimating the local outbreak risk for a viral disease (the probability that a major outbreak results from a single case introduced into the population), accounting for within-host viral dynamics. Compared to population-level models previously used to estimate outbreak risks, our approach enables more detailed analysis of how the risk can be mitigated through pre-emptive interventions such as antigen testing. Considering SARS-CoV-2 as a case study, we quantify the within-host dynamics using data from individuals with omicron variant infections. We demonstrate that regular antigen testing reduces, but may not eliminate, the outbreak risk, depending on characteristics of local transmission. In our baseline analysis, daily antigen testing reduces the outbreak risk by 45% compared to a scenario without antigen testing. Additionally, we show that accounting for heterogeneity in within-host dynamics between individuals affects outbreak risk estimates and assessments of the impact of antigen testing. Our results therefore highlight important factors to consider when using multi-scale models to design pre-emptive interventions against SARS-CoV-2 and other viruses.

  🖺 Full Text HTML: Analysis of the risk and pre-emptive control of viral outbreaks accounting for within-host dynamics: SARS-CoV-2 antigen testing as a case study
• A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8 -
  Small animal models have been a challenge for the study of SARS-CoV-2 transmission, with most investigators using golden hamsters or ferrets. Mice have the advantages of low cost, wide availability, less regulatory and husbandry challenges, and the existence of a versatile reagent and genetic toolbox. However, adult mice do not robustly transmit SARS-CoV-2. Here we establish a model based on neonatal mice that allows for transmission of clinical SARS-CoV-2 isolates. We characterize tropism, respiratory tract replication and transmission of ancestral WA-1 compared to variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron BA.1 and Omicron BQ.1.1. We identify inter-variant differences in timing and magnitude of infectious particle shedding from index mice, both of which shape transmission to contact mice. Furthermore, we characterize two recombinant SARS-CoV-2 lacking either the ORF6 or ORF8 host antagonists. The removal of ORF8 shifts viral replication towards the lower respiratory tract, resulting in significantly delayed and reduced transmission in our model. Our results demonstrate the potential of our neonatal mouse model to characterize viral and host determinants of SARS-CoV-2 transmission, while revealing for the first time a role for an accessory protein in this context.
  🖺 Full Text HTML: A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8

From Clinical Trials

• Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test - Condition:   COVID-19
  Intervention:   Device: CareSuperb COVID-19 Antigen Home Test Kit
  Sponsor:   AccessBio, Inc.
  Recruiting

• Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MIR 19 ®;   Combination Product: Standart therapy
  Sponsor:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
  Completed

• LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™;   Drug: Placebo
  Sponsors:   Jose David Suarez, MD;   Sesderma S.L.;   Westchester General Hospital Inc. DBA Keralty Hospital Miami;   MGM Technology Corp
  Not yet recruiting

• MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Drug: MP0420;   Drug: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Molecular Partners AG;   University of Minnesota
  Active, not recruiting

• AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: AZD7442;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   AstraZeneca;   University of Minnesota
  Active, not recruiting

• PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Drug: PF-07304814;   Drug: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Pfizer;   University of Minnesota
  Suspended

• VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: VIR-7831;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Vir Biotechnology, Inc.;   GlaxoSmithKline;   University of Minnesota
  Completed

• BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: BRII-196;   Biological: BRII-198;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Brii Biosciences Limited;   University of Minnesota
  Completed

• LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition:   COVID-19
  Interventions:   Biological: LY3819253;   Biological: Placebo;   Biological: Remdesivir
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   International Network for Strategic Initiatives in Global HIV Trials (INSIGHT);   University of Copenhagen;   Medical Research Council;   Kirby Institute;   Washington D.C. Veterans Affairs Medical Center;   AIDS Clinical Trials Group;   National Heart, Lung, and Blood Institute (NHLBI);   US Department of Veterans Affairs;   Prevention and Early Treatment of Acute Lung Injury (PETAL);   Cardiothoracic Surgical Trials Network (CTSN);   Eli Lilly and Company;   University of Minnesota
  Completed

• Use of E-health Based Exercise Intervention After COVID-19 - Condition:   COVID-19
  Intervention:   Behavioral: Exercise training using an e-health tool
  Sponsors:   Norwegian University of Science and Technology;   University of Oslo
  Recruiting

• Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19. - Condition:   COVID-19
  Interventions:   Drug: P1101 (Ropeginterferon alfa-2b);   Procedure: SOC
  Sponsor:   National Taiwan University Hospital
  Active, not recruiting

• Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102) - Condition:   COVID-19
  Intervention:   Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102) - Condition:   COVID-19
  Interventions:   Biological: Recombinant variant COVID-19 vaccine (Sf9 cell);   Biological: Recombinant COVID-19 vaccine (CHO cell);   Biological: Recombinant COVID-19 vaccine (Sf9 cell)
  Sponsor:   WestVac Biopharma Co., Ltd.
  Not yet recruiting

• Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19 - Condition:   Post COVID-19 Condition
  Interventions:   Other: Pursed lip breathing;   Other: Cognitive Behavior Therapy;   Other: Diaphragmatic breathing exercise;   Other: Kinesio tape
  Sponsor:   Cairo University
  Not yet recruiting

• Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Calcitriol;   Other: Placebo
  Sponsor:   Universitas Sebelas Maret
  Completed

From PubMed

• Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis - The “Thalidomide tragedy” is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and…

• Antiviral drugs block replication of highly immune-evasive Omicron subvariants ex vivo, but fail to reduce tissue inflammation - The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and antiviral drugs against clinical specimens for SARS-CoV-2 Omicron BA.4/BA.5, BF.7 and BQ.1.1 employing an immunofluorescence neutralization assay. Further we explored treatment of BA.4/BA.5 infections with efficient antiviral drugs and monoclonal…

• Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332 - PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (M^(pro)) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with M^(pro)s of various coronaviruses reveal their inhibitory mechanisms against different M^(pro)s. However, the structural information on the lower pathogenic coronavirus M^(pro) with PF-07321332 or PF-07304814 is currently scarce, which hinders our…

• Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants - The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric…

• Role of heat shock protein 90 as an antiviral target for swine enteric coronaviruses - A variety of swine enteric coronaviruses (SECoVs) have emerged and are prevalent in pig populations, including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome (SADS)-CoV, a newly identified bat-origin CoV with zoonotic potential. Unfortunately, available traditional, inactivated and attenuated SECoV vaccines are of limited efficacy against the variants currently circulating in most pig…

• Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models - One of the major pathogenesis mechanisms of SARS-CoV-2 is its potent suppression of innate immunity, including blocking the production of type I interferons. However, it is unknown whether and how the virus interacts with different innate-like T cells, including NKT, MAIT and γδ T cells. Here we reported that upon SARS-CoV-2 infection, invariant NKT (iNKT) cells rapidly trafficked to infected lung tissues from the periphery. We discovered that the envelope (E) protein of SARS-CoV-2 efficiently…

• Protocol for an Implementation Science Evaluation of Roots of Hope: A Community Suicide Prevention Project - CONCLUSIONS: The evaluation results, including the identification of factors that facilitate and inhibit the implementation of RoH and adaptations to challenges, should be of use to the MHCC, current RoH communities and those who are considering adopting the RoH model.

• Levels of Complement Components in Children With Acute COVID-19 or Multisystem Inflammatory Syndrome - CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the complement system was associated with the pathogenesis of MIS-C and COVID-19 in children; complement inhibition could be further explored as a potential treatment option.

• The antiviral activity of a small molecule drug targeting the NSP1-ribosome complex against Omicron, especially in elderly patients - INTRODUCTION: With the emergence of SARS-CoV-2 mutant strains, especially the epidemic of Omicron, it continues to evolve to strengthen immune evasion. Omicron BQ. 1 and XBB pose a serious threat to the current COVID-19 vaccine (including bivalent mRNA vaccine for mutant strains) and COVID-19-positive survivors, and all current therapeutic monoclonal antibodies are ineffective against them. Older people, those with multimorbidity, and those with specific underlying health conditions remain at…

• Dynamics of factors associated with rates of COVID-19 cases and deaths in African countries - CONCLUSION: In African countries, internal movement restrictions enacted to inhibit COVID-19, had the opposite effect and enabled COVID-19 spread. Low Education levels and high unemployment were associated with having higher death rates from COVID-19. More studies are needed to understand the impact of tourism on COVID-19 and other infectious diseases arising from other regions on African countries, in order to put in place adequate control protocols.

• Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses - Great interest exists towards the discovery and development of broad-spectrum antivirals. This occurs due to the frequent emergence of new viruses which can also eventually lead to pandemics. A reasonable and efficient strategy to develop new broad-spectrum antivirals relies on targeting a common molecular player of various viruses. Heparan sulfate is a sulfated glycosaminoglycan present on the surface of cells which plays a key role as co-receptor in many virus infections. In previous work,…

• [Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19 - This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is…

• Cystic fibrosis transmembrane conductance regulator modulators attenuate platelet activation and aggregation in blood of healthy donors and COVID-19 patients - Cystic fibrosis transmembrane conductance regulator (CFTR) modulators reduce agonist-induced platelet activation and function. CFTR modulators, such as ivacaftor, present a promising therapeutic strategy in thrombocytopathies, including severe COVID-19. https://bit.ly/3HJykdt

• Intravenous ravulizumab in mechanically ventilated patients hospitalised with severe COVID-19: a phase 3, multicentre, open-label, randomised controlled trial - BACKGROUND: The complement pathway is a potential target for the treatment of severe COVID-19. We evaluated the safety and efficacy of ravulizumab, a terminal complement C5 inhibitor, in patients hospitalised with severe COVID-19 requiring invasive or non-invasive mechanical ventilation.

• Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (M^pro) and Papain-like Protease (PL^pro) - The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (M^(pro)) and the papain-like protease (PL^(pro)) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe)(2) which is an archetypal model of diselenides and a renowned potential therapeutic agent. The in vitro inhibitory concentration of (PhSe)(2) against…

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