Covid-19 Sentry

Contents

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

From Preprints

• Impact of the COVID-19 pandemic on the circulation of other pathogens in England -

  The COVID-19 pandemic and the associated prevention measures did not only impact on the transmission of COVID-19 but also on the spread of other infectious diseases in an unprecedented natural experiment. Here, we analysed the transmission patterns of 22 different infectious diseases during the COVID-19 pandemic in England. Our results show that the COVID-19 prevention measures generally reduced the spread of pathogens that are transmitted via the air and the faecal-oral route. Moreover, the COVID-19 prevention measures resulted in the sustained suppression of vaccine-preventable infectious diseases also after the removal of restrictions, while non-vaccine preventable diseases displayed a rapid rebound. Despite concerns that a lack of exposure to common pathogens may affect population immunity and result in large outbreaks by various pathogens post-COVID-19, only four of the 22 investigated diseases and disease groups displayed higher post- than pre-pandemic levels without an obvious causative relationship. Notably, this included chickenpox for which an effective vaccine is available but not used in the UK, which provides strong evidence supporting the inclusion of the chickenpox vaccination into the routine vaccination schedule in the UK. In conclusion, our findings provide unique, novel insights into the impact of non-pharmaceutical interventions on the spread of a broad range of infectious diseases.

  🖺 Full Text HTML: Impact of the COVID-19 pandemic on the circulation of other pathogens in England
• Development of Loop-mediated Isothermal Amplification (LAMP) Assays Using Five Primers Reduces the False-positive Rate in COVID-19 Diagnosis -

  The reverse-transcription loop-mediated isothermal amplification (RT-LAMP) is a cheaper and faster testing alternative for detecting SARS-CoV-2. However, high false-positive rate due to misamplification is one of the major limitations. To overcome misamplifications, we developed colorimetric and fluorometric RT-LAMP assays. The assay performances was verified by the gold-standard RT-qPCR technique on 150 clinical samples. Compared to other primer sets with six primers (N, S, and RdRp), E-ID1 primer set, including five primers, performed superbly on both colorimetric and fluorometric assays, yielding sensitivities of 89.5% and 100%, respectively, with a limit of detection of 20 copies/uL. The colorimetric RT-LAMP had a specificity of 97.2% and an accuracy of 94.5%, while the fluorometric RT-LAMP obtained 96.9% and 98%, respectively. No misamplification was evident even after 120 minutes, which is crucial for the success of this technique. These findings are important to support the use of RT-LAMP in the healthcare systems in fighting COVID-19.

  🖺 Full Text HTML: Development of Loop-mediated Isothermal Amplification (LAMP) Assays Using Five Primers Reduces the False-positive Rate in COVID-19 Diagnosis
• Comparison of the risk of hospitalisation among BA.1 and BA.2 COVID-19 cases treated with Sotrovimab in the community in England -

  Objectives Sotrovimab is one of several therapeutic agents that have been licensed to treat people at risk of severe outcomes following COVID-19 infection. However, there are concerns that it has reduced efficacy to treat people with the BA.2 sub-lineage of the Omicron (B.1.1.529) SARS-CoV-2 variant. We compared individuals with the BA.1 or BA.2 sub-lineage of the Omicron variant treated Sotrovimab in the community to assess their risk of hospital admission. Methods We performed a retrospective cohort study of individuals treated with Sotrovimab in the community and either had BA.1 or BA.2 variant classification. Results Using a Stratified Cox regression model it was estimated that the hazard ratios (HR) of hospital admission with a length of stay of two or more days was 1.17 for BA.2 compared to BA.1 (95% CI 0.74-1.86) and for such admissions where COVID-19 ICD-10 codes was recorded the HR was 0.98 (95% CI 0.58-1.65). Conclusion These results suggest that the risk of hospital admission is similar between BA.1 and BA.2 cases treated with Sotrovimab in the community.

  🖺 Full Text HTML: Comparison of the risk of hospitalisation among BA.1 and BA.2 COVID-19 cases treated with Sotrovimab in the community in England
• Design of effective outpatient sentinel surveillance for COVID-19 decision-making: a modeling study -

  Background: Decision-makers impose COVID-19 mitigations based on public health indicators such as reported cases, which are sensitive to fluctuations in supply and demand for diagnostic testing, and hospital admissions, which lag infections by up to two weeks. Imposing mitigations too early has unnecessary economic costs, while imposing too late leads to uncontrolled epidemics with unnecessary cases and deaths. Sentinel surveillance of recently-symptomatic individuals in outpatient testing sites may overcome biases and lags in conventional indicators, but the minimal outpatient sentinel surveillance system needed for reliable trend estimation remains unknown. Methods: We used a stochastic, compartmental transmission model to evaluate the performance of various surveillance indicators at reliably triggering an alarm in response to, but not before, a step increase in transmission of SARS-CoV-2. The surveillance indicators included hospital admissions, hospital occupancy, and sentinel cases with varying levels of sampling effort capturing 5, 10, 20, 50 or 100% of incident mild cases. We tested 3 levels of transmission increase, 3 population sizes, and condition of either simultaneous transmission increase, or lagged increase in older population. We compared the indicators9 performance at triggering alarm soon after, but not prior, to the transmission increase. Results: Compared to surveillance based on hospital admissions, outpatient sentinel surveillance that captured at least 20% of incident mild cases could trigger alarm 2 to 5 days earlier for a mild increase in transmission and 6 days earlier for moderate or strong increase. Sentinel surveillance triggered fewer false alarms and averted more deaths per day spent in mitigation. When transmission increase in older populations lagged increase in younger populations by 14 days, sentinel surveillance extended its lead time over hospital admissions by an additional 2 days. Conclusions: Sentinel surveillance of mild symptomatic cases can provide more timely and reliable information on changes in transmission to inform decision-makers in an epidemic like COVID-19.

  🖺 Full Text HTML: Design of effective outpatient sentinel surveillance for COVID-19 decision-making: a modeling study
• Perceptions of COVID-19 risk, vaccine access, and confidence: a qualitative analysis of South Asians in Canada -

  Objectives: In the first full year of the COVID-19 pandemic (2020), South Asians living in the Greater Toronto Hamilton and Vancouver Areas experienced specific barriers to accessing SARS-CoV-2 testing and receiving reliable health information. However, between June 2021 and February 2022, the proportion of people having received at least 1 dose of a COVID-19 vaccine was higher among this group (96%) than among individuals who were not visible minorities (93%). A better understanding of successful approaches and the challenges experienced by those who remain unvaccinated among this highly vaccinated group may improve public health outreach in subsequent waves of the current pandemic or for future pandemic planning. Using qualitative methods, we sought to explore the perceptions of COVID-19 risk, vaccine access, uptake, and confidence among South Asians living in Canada. Methods: In this qualitative study, we interviewed 25 participants between July 2021 and January 2022 in the Greater Toronto Hamilton and Greater Vancouver Areas (10 community members, 9 advocacy group leaders, 6 public health staff). We conducted initial and focused coding in duplicate and developed salient themes. Throughout this process, we held frequent discussions with members of the study9s advisory group to guide data collection as it relates to community engagement, recruitment, and data analysis. Results: Access to and confidence in the COVID-19 vaccine was impacted by individual risk perceptions; sources of trusted information (ethnic and non-ethnic); impact of COVID-19 and the pandemic on individuals, families, and society; and experiences with COVID-19 mandates and policies (including temporal and generational differences). Approaches that include community-level awareness and tailored outreach as it relates to language and cultural context were considered successful. Conclusion: Understanding factors and developing strategies that build vaccine confidence can guide our approach to increase vaccine acceptance in the current and future pandemics.

  🖺 Full Text HTML: Perceptions of COVID-19 risk, vaccine access, and confidence: a qualitative analysis of South Asians in Canada
• Predicting COVID-19 mortality in Zambia - an Application of Machine Learning -
  Background: The Corona virus, has caused havoc all over the world, it has left no country untouched resulting in millions of cases and deaths. In an effort to fight back, scientist and public health professionals have used every form of advancing technology to curb the spread, predict the unforeseen adverse events, improve preparedness, and bring the world under control once more. Objective: The objective of this study was to predict mortality in hospitalized COVID-19 patients in Zambia using ML methods from a number of predictors that have been shown to be predictive of mortality. Methods: This research used powerful ML models in predicting COVID-19 mortality in 1,433 hospitalized patients in Zambia. The feature importance analysis helped in identification of important factors. The ML models GB, RF, SVM, DT, LR, and NB were used the performance metrics checked for each model were accuracy, recall, specificity, precision, F1 Score, ROC-AUC, and PRC-AUC. Results: The feature importance analysis found that hospital length of stay (LOS) and white blood cell count were the most influential features, other factors arranged in order of reducing importance included: age, wave, diabetes, hypertension, and sex. The GB achieved accuracy of 91.5%, recall of 93.6%, F1 Score of 91.7%, and ROC-AUC of 96.9%. The RF achieved accuracy of 90.9%, recall of 93.8%, F1 Score of 91.2%, and ROC-AUC of 96.8%. The SVM achieved accuracy of 87.8%, recall of 91.2%, F1 Score of 88.2%, and ROC-AUC of 94.1%. The accuracy and ROC-AUC of other models were 88.2% and 90.7% respectively for DT, 81.9% and 90.1% respectively for LR, and 79.2% and 86.9% respectively for NB. Conclusion: The study successfully derived and validated multiple ML models that predicted mortality effectively with reasonably high performance in stated metrics. The GB was the best suited for the data in our study. GB was thus recommended for similar studies with RF as best alternative. Knowledge of underlying health conditions about patients (length of hospitalization (LOS), white blood cell count, age, sex, hypertension, diabetes, and other factors) can help healthcare providers offer lifesaving services on time, improve preparedness and decongest health facilities.
  🖺 Full Text HTML: Predicting COVID-19 mortality in Zambia - an Application of Machine Learning
• Robust Machine Learning predicts COVID-19 Disease Severity based on Single-cell RNA-seq from multiple hospitals -

  Coronavirus disease 2019 (COVID-19) has a highly variable disease severity. Possible associations between peripheral blood signatures and disease severity have been investigated since the emergence of the pandemic. Although several signatures were identified based on exploratory analyses of single-cell omics data, there are no state-of-the-art validated models to predict COVID-19 severity from comprehensive transcriptome profiling of Peripheral Blood Mononuclear Cells (PBMCs). In this paper, we present a computational workflow based on a Multilayer perceptron network that predicts the necessity of mechanical ventilation from PBMCs single-cell RNA-seq data. The study includes patient cohorts from Bonn, Berlin, Stanford, and three Korean medical centers. Training and model validation are performed using Berlin and Bonn samples, while testing is performed on completely unseen samples from the Stanford and Korean datasets. Our model shows a high area under the receiver operating characteristic (AUROC) curve (Korea: 1 (CI:1-1), Stanford: 0.86 (CI:0.81-0.9)), proving our models robustness. Moreover, we explain our models performance by identifying gene loci and cell types, which are most critical for the classification task. In summary, we could show that the expression of 15 genes and the cell type proportion of 29 PBMC classes distinguish between COVID-19 disease states.

  🖺 Full Text HTML: Robust Machine Learning predicts COVID-19 Disease Severity based on Single-cell RNA-seq from multiple hospitals
• Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US -

  Objective: The growing number of Coronavirus Disease-2019 (COVID-19) survivors who are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS) represent a worldwide public health challenge. Yet, the novelty of this condition and the resulting limited data on underlying pathomechanisms so far hampered the advancement of effective therapies. Using electronic health records (EHR) data, we aimed to characterize PASC-associated diagnoses and to develop risk prediction models. Methods: In our cohort of 63,675 COVID-19 positive patients seen at Michigan Medicine, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case control study design comparing PASC cases with 17,205 matched controls and performed phenome-wide association studies (PheWASs) to characterize enriched phenotypes of the post-COVID-19 period and potential PASC pre-disposing phenotypes of the pre-, and acute-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance. Results: In the post-COVID-19 period, cases were significantly enriched for known PASC symptoms (e.g., shortness of breath, malaise/fatigue, and cardiac dysrhythmias) but also many musculoskeletal, infectious, and digestive disorders. We found seven phenotypes in the pre-COVID-19 period (irritable bowel syndrome, concussion, nausea/vomiting, shortness of breath, respiratory abnormalities, allergic reaction to food, and circulatory disease) and 69 phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological, digestive, and mental health phenotypes) that were significantly associated with PASC. The derived pre-COVID-19 PheRS and acute-COVID-19 PheRS had low accuracy to differentiate cases from controls; however, they stratified risk well, e.g., a combination of the two PheRSs identified a quarter of the COVID-19 positive cohort at a 3.5-fold increased risk for PASC compared to the bottom 50% of their distributions. Conclusions: Our agnostic screen of time stamped EHR data uncovered a plethora of PASC-associated diagnoses across many categories and highlighted a complex arrangement of presenting and likely pre-disposing features — the latter with a potential for risk stratification approaches. Yet, considerably more work will need to be done to better characterize PASC and its subtypes, especially long-term consequences, and to consider more comprehensive risk models.

  🖺 Full Text HTML: Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US
• Global prediction for monkeypox epidemic -

  The monkeypox epidemic has now spread all over the world and has become an epidemic of widespread concern in the international community. Before the emergence of targeted vaccines and specific drugs, it is necessary to numerically simulate and predict the epidemic. In order to better understand and grasp its transmission situation, and put forward some countermeasures accordingly, we predicted and simulated monkeypox transmission and vaccination scenarios using models developed for COVID-19 predictions. The results suggest the monkeypox epidemic will spread to almost all countries in the world by the end of 2022 based on modified SEIR model prediction. The total number of people infected with monkeypox will reach 100,000. The top five countries will be the United States, Brazil, Germany, France and Britain with more than 28000, 20000, 4000, 4500 and 4000 cases respectively. If 30% of the population is vaccinated, the number of infected people will drop by 35%.

  🖺 Full Text HTML: Global prediction for monkeypox epidemic
• Receipt of COVID-19 and seasonal influenza vaccines in California (USA) during the 2021-2022 influenza season -

  Background Despite lower circulation of influenza virus throughout 2020-2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood. Methods We assessed predictors of receipt of 2021-2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination. Results Among 1261 eligible participants recruited between 22 October 2021 - 22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and >1 dose of a COVID-19 vaccine, 34% (426) received >1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of >1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15-6.43); this association was stronger among participants receiving >1 COVID-19 booster dose (aOR=16.50 [10.10-26.97]). Compared with participants testing negative for SARS-CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR=0.64 [0.50-0.82]). Conclusions Recipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021-2022 season. Factors associated with individuals9 likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis.

  🖺 Full Text HTML: Receipt of COVID-19 and seasonal influenza vaccines in California (USA) during the 2021-2022 influenza season
• Abnormal renal function tests at presentation in severe COVID 19 pneumonia and its effect on clinical outcomes -

  Aim To determine the incidence of abnormal renal function tests at presentation in South Asian patients admitted with severe COVID 19 pneumonia and determine its effect on disease severity and clinical outcomes Methods This was a retrospective cross-sectional study conducted at the COVID Intensive care unit of a large tertiary care government hospital in Karachi, Pakistan. 190 patients admitted over five months from 1/5/2021 till 30/6/2021 were included in the study. Patient demographic characteristics, comorbidities, and clinical manifestations of COVID 19 infection were recorded. Laboratory values at the time of presentation, including Hemoglobin, NLR, platelets, blood urea nitrogen, glomerular filtration rate (GFR), inflammatory markers, liver function tests, and electrolytes were recorded. Patient outcome and need for mechanical ventilation were assessed 28 days after admission and compared with the incidence of abnormal renal functions at presentation. Results Mean GFR and BUN at presentation were 69.7 and 28.4 respectively. 109 (50.4%) patients had abnormal renal function tests at the time of presentation. 76 (40.0%) patients had low GFR and 33 (17.4%) had only raised BUN with normal GFR. Mean GFR was lower in non-survivors vs survivors (p-value 0.000) and in patients who required mechanical ventilation (p-value 0.008). Patients who had low GFR showed greater mortality than those with normal GFR (p-value 0.04) and were more likely to require mechanical ventilation (p-value 0.04). Conclusion Low GFR at presentation is common in patients with severe COVID 19 pneumonia and is associated with a higher in-hospital mortality rate and need for mechanical ventilation.

  🖺 Full Text HTML: Abnormal renal function tests at presentation in severe COVID 19 pneumonia and its effect on clinical outcomes
• Association of viral variant and vaccination status with the occurrence of symptoms compatible with post-acute sequelae after primary SARS-CoV-2 infection -

  Importance: Disentangling the effects of different SARS-CoV-2 variants and of vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and potentially reduce the future burden of PASC. Objective: To determine the association of primary SARS-CoV-2 infection on the frequency of PASC symptoms by viral variant and vaccination status. Design: Cross-sectional questionnaire and SARS-CoV-2 serology (May/June 2022) performed within a prospective healthcare worker cohort (SURPRISE study). Setting: Multicenter study in nine healthcare networks from North-Eastern Switzerland. Participants: Volunteer sample of healthcare workers (HCW) from participating institutions. Of approximately 20000 eligible participants, 3870 registered for the cohort and 2912 were included in this analysis. Exposures: SARS-CoV-2 infection documented by positive nasopharyngeal swab (>4 weeks ago), stratified by viral variant and vaccination status at time of infection, compared to absence of documented infection (no positive swab, negative serology). Main Outcome: Sum score of eighteen self-reported PASC symptoms. Results: Among 2912 participants (median age 44 years, 81.3% female), SARS-CoV-2 infection was reported by 1685 (55.9%) participants, thereof 315 (18.7%) during Wild-type, 288 (17.1%) during Alpha/Delta, and 1082 (64.2%) during Omicron circulation. Mean symptom number in previously infected participants significantly exceeded that of uninfected controls (0.39), but decreased with recency of the viral variant: 1.12 (p<0.001) for Wild-type (median time since infection 18.5 months), 0.67 (p<0.001) for Alpha/Delta (6.6 months), and 0.52 (p=0.005) for Omicron BA.1 (3.1 months) infected participants. After Omicron BA.1 infection, the mean symptom score was 0.49 (p=0.30) for those with at least 3 prior vaccinations and 0.71 (p=0.028) with 1-2 previous vaccinations compared to 0.36 for unvaccinated individuals. Adjusting for confounders, Wild-type (adjusted risk ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) showed significant associations with the outcome, whereas Omicron BA.1 infection (aRR 1.29, 95% CI 0.69-2.43) and vaccination before infection (aRR 1.27, 95% CI 0.82-1.94) did not. Conclusions and Relevance: Previous infection with pre-Omicron variants was the strongest risk factor for reporting PASC symptoms in this HCW cohort. A definite influence of prior vaccination on the prevention of PASC after Omicron BA.1 infection was not measurable.

  🖺 Full Text HTML: Association of viral variant and vaccination status with the occurrence of symptoms compatible with post-acute sequelae after primary SARS-CoV-2 infection
• Psychological Distress and Perceived Discrimination Among Chinese International Students One Year into COVID-19: A Preregistered Comparative Study -
  Background and Objectives: During the COVID-19 pandemic, Chinese international students (CISs) experienced increased distress associated with a combination of unique and universal stressors, among which discrimination against Chinese is especially harmful. Therefore, studying correlates of distress among CISs, including the association between discrimination and distress and factors intensifying or attenuating this link, may yield important insights into prevention and intervention efforts. Design: We adopted a cross-sectional self-report design. Methods: Our study compared depression and anxiety between CISs (N = 381) and Chinese students in Chinese colleges (CSCCs; N = 306) and examined correlates of distress including the association between discrimination and distress as well as moderators on this link within CISs. Results: Compared to CSCCs, CISs reported greater depression and anxiety. Depression was associated with being female, older, non-heterosexual, increased discrimination, decreased self- esteem, coping flexibility, perceived social support, and satisfaction with online learning. Anxiety was associated with being female, heterosexual, in undergraduate years, increased discrimination, decreased self-esteem, subjective socioeconomic status, coping flexibility, and satisfaction with online learning. High perceived social support and being heterosexual weakened the association between discrimination and distress (anxiety and depression). Conclusions: Our study underscored the impact of the pandemic and related discrimination on CISs and highlighted individual differences that may warrant attention.
  🖺 Full Text HTML: Psychological Distress and Perceived Discrimination Among Chinese International Students One Year into COVID-19: A Preregistered Comparative Study
• Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 regions sequences -
  Background: Studies on the role of the oral microbiome in SARS-CoV-2 infection and severity of the disease are limited. We aimed to characterize the bacterial communities present in the saliva of patients with varied COVID-19 severity to learn if there are differences in the characteristics of the microbiome among the clinical groups. Methods: We included asymptomatic subjects with no previous COVID-19 infection or vaccination; patients with mild respiratory symptoms, positive or negative for SARS-CoV-2 infection; patients that required hospitalization because of severe COVID-19 with oxygen saturation below 92%, and fatal cases of COVID-19. Saliva samples collected before any treatment were tested for SARS-CoV-2 by PCR. Oral microbiota in saliva was studied by amplification and sequencing of the V1-V3 variable regions of 16S gene using a Illumina MiSeq platform. Results: We found significant changes in diversity, composition, and networking in saliva microbiota of patients with COVID-19, as well as patterns associated with severity of disease. The presence or abundance of several commensal species and opportunistic pathogens were associated with each clinical stage. Patterns of networking were also found associated with severity of disease: a highly regulated bacterial community (normonetting) was found in healthy people whereas poorly regulated populations (disnetting) were characteristic of severe cases. Conclusions: Characterization of microbiota in saliva may offer important clues in the pathogenesis of COVID-19 and may also identify potential markers for prognosis in the severity of the disease.
  🖺 Full Text HTML: Diversity, composition, and networking of saliva microbiota distinguish the severity of COVID-19 episodes as revealed by an analysis of 16S rRNA variable V1-V3 regions sequences
• SARS-CoV-2 nsp3-4 suffice to form a pore shaping replication organelles -
  Coronavirus replication is associated with the remodeling of cellular membranes resulting in the formation of double-membrane vesicles (DMVs). Recently, a pore spanning DMV was identified as a putative portal for viral RNA transcription and replication products providing a novel target for antiviral intervention. However, the exact components and the structure of the SARS-CoV-2 pore remain to be determined. Here, we investigate the structure of DMV pores by in situ cryo-electron tomography combined with subtomogram averaging. We reveal non-structural proteins (nsp) 3 and 4 as minimal components forming a DMV spanning pore and show that nsp3 Ubl1-Ubl2 domains are critical for inducing membrane curvature and DMV formation. Altogether, SARS-CoV-2 nsp3-4 has a dual role by driving the biogenesis of replication organelles and forming DMV-spanning replicopores.
  🖺 Full Text HTML: SARS-CoV-2 nsp3-4 suffice to form a pore shaping replication organelles

From Clinical Trials

• Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant Omicron-Delta COVID-19 Vaccine (CHO Cell);   Biological: Inactivated COVID-19 vaccine (Vero Cell)
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   First Affiliated Hospital Bengbu Medical College
  Active, not recruiting

• A Phase III Study to Evaluate Immunogenicity and Safety of COVID-19 Vaccine EuCorVac-19 in Healthy Adults - Condition:   COVID-19
  Interventions:   Biological: EuCorVac-19;   Biological: ChAdOx1
  Sponsor:   EuBiologics Co.,Ltd
  Recruiting

• COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: Tri-City COVID Attitudes Study
  Sponsor:   University of Kansas Medical Center
  Recruiting

• JT001 (VV116) for the Treatment of COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: JT001;   Drug: Placebo
  Sponsors:   Shanghai Vinnerna Biosciences Co., Ltd.;   Sponsor GmbH
  Not yet recruiting

• Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Reminder that facilitates action;   Behavioral: Consistency framing;   Behavioral: Information provision about the uniqueness of the bivalent booster;   Behavioral: Information provision about bivalent booster eligibility;   Behavioral: Information provision about the severity of COVID-19 symptoms
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Respiratory Muscles After Inspiratory Muscle Training After COVID-19 - Conditions:   COVID-19;   Diaphragm Injury
  Intervention:   Device: Inspiratory Muscle Training (IMT)
  Sponsors:   RWTH Aachen University;   Philipps University Marburg Medical Center
  Recruiting

• COVID-19 Simulation Education on Nursing Students - Conditions:   COVID-19 Pandemic;   Simulation of Physical Illness
  Interventions:   Behavioral: Simulation training;   Other: Control Group
  Sponsor:   Mehmet Akif Ersoy University
  Completed

• OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial - Conditions:   COVID-19;   Immunodeficiency
  Interventions:   Drug: Paxlovid 5 days;   Drug: Paxlovid 10 days;   Drug: Tixagevimab and Cilgavimab
  Sponsors:   ANRS, Emerging Infectious Diseases;   University Hospital, Geneva
  Not yet recruiting

• Boost Intentions and Facilitate Action to Promote Covid-19 Booster Take-up - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Eligibility reminder;   Behavioral: Link to a narrow set of vaccine venues;   Behavioral: Link to a broad set of vaccine venues;   Behavioral: Doctors’ recommendation and value of vaccine
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Effects of Prompt to Bundle Covid-19 Booster and Flu Shot - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Reminder to boost protection against COVID-19;   Behavioral: Flu Tag Along;   Behavioral: COVID-19 Booster & Flu Bundle
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions:   SARS-CoV2 Infection;   COVID-19
  Interventions:   Device: iCura COVID-19 Antigen Rapid Home Test;   Device: RT-PCR Test
  Sponsors:   MP Biomedicals, LLC;   EDP Biotech
  Completed

• COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability - Conditions:   Sars-CoV-2 Infection;   COVID-19
  Intervention:   Device: Rapid SARS-CoV-2 Antigen Test
  Sponsors:   MP Biomedicals, LLC;   EDP Biotech
  Completed

• Safety and Immunogenicity of AdCLD-CoV19-1 OMI as a Booster: A SARS-CoV-2 (COVID-19) Preventive Vaccine - Conditions:   COVID-19;   Vaccines
  Interventions:   Biological: AdCLD-CoV19-1 OMI (Part A);   Biological: AdCLD-CoV19-1 OMI (Part B);   Other: Placebo (Part B)
  Sponsor:   Cellid Co., Ltd.
  Active, not recruiting

• Safety and Dosage of a Computerized Cognitive Training Program for Cognitive Dysfunction After COVID-19 - Conditions:   Post-Acute COVID-19;   Post Acute COVID-19 Syndrome;   Cognitive Dysfunction;   Cognitive Impairment
  Intervention:   Behavioral: CCT Long COVID
  Sponsor:   Universidad Antonio de Nebrija
  Not yet recruiting

• A Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5 - Condition:   COVID-19 Pandemic
  Interventions:   Biological: V-01/V-01-B5;   Biological: V-01-351/V-01-B5;   Biological: V-01
  Sponsor:   Livzon Pharmaceutical Group Inc.
  Active, not recruiting

From PubMed

• Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion - CONCLUSIONS: GMI, an FDA-approved dietary ingredient, acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 and could become a promising candidate for preventing or treating SARS-CoV-2 associated diseases.

• Therapeutic use of calpeptin in COVID-19 infection - This perspective considers the benefits of the potential future use of the cell permeant calpain inhibitor, calpeptin, as a drug to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Recent work has reported calpeptin’s capacity to inhibit entry of the virus into cells. Elsewhere, several drugs, including calpeptin, were found to be able to inhibit extracellular vesicle (EV) biogenesis. Unsurprisingly, because of similarities between viral and EV release mechanisms,…

• Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1 - ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as…

• Post COVID-19 neuropsychiatric complications and therapeutic role for TNF-α inhibitors: a case series study - CONCLUSIONS: To our knowledge, this report is the first case series study that suggests TNF inhibitors in the treatment of post-COVID-19 syndrome, especially neuropsychological complications. However, future studies should evaluate the best therapeutic options for this syndrome.

• Gossypol Broadly Inhibits Coronaviruses by Targeting RNA-Dependent RNA Polymerases - Outbreaks of coronaviruses (CoVs), especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have posed serious threats to humans and animals, which urgently calls for effective broad-spectrum antivirals. RNA-dependent RNA polymerase (RdRp) plays an essential role in viral RNA synthesis and is an ideal pan-coronaviral therapeutic target. Herein, based on cryo-electron microscopy and biochemical approaches, gossypol (GOS) is identified from 881 natural products to directly block…

• Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases - CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as…

• Potent inhibition of diverse Omicron sublineages by SARS-CoV-2 fusion-inhibitory lipopeptides - The emergence and rapid spreading of SARS-CoV-2 variants of concern (VOCs) have posed a great challenge to the efficacy of vaccines and therapeutic antibodies, calling for antivirals that can overcome viral evasion. We recently reported that SARS-CoV-2 fusion-inhibitory lipopeptides, IPB02V3 and IPB24, possessed the potent activities against divergent VOCs, including Alpha, Beta, Gamma, Delta, and the initial Omicron strain (B.1.1.529); however, multiple Omicron sublineages have emerged and…

• Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature - Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body’s defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress,…

• Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2 - SARS-CoV-2 infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA-approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that…

• Combined Molnupiravir and Nirmatrelvir Treatment Improves the Inhibitory Effect on SARS-CoV-2 in Rhesus Macaques - The periodic emergence of SARS-CoV-2 variants of concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, and nirmatrelvir (PF-07321332), a 3C-like protease inhibitor, have each recently been approved as monotherapy for use in high risk COVID-19 patients. As preclinical data are only available for rodent and ferret models, we…

• Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection - Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and tissue injury and be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro…

• A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases - CONCLUSION: IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.

• Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19 - The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. To…

• SARS-CoV-2 Vaccination in Kidney Transplant Recipients-Stratified Analysis of the Humoral Immune Response - CONCLUSIONS: Apart from immunosuppressive therapy, the humoral vaccination response is largely affected by nonmodifiable factors in kidney transplant recipients. With the currently leading and clinically easier Omicron variant, this puts into perspective the strategy to significantly enhance the protective efficacy of the available vaccines by reducing or temporarily stopping proliferation inhibitors, not least considering the inherent rejection risk with a possible deterioration of graft…

• Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients co-morbidly affected by type 2 diabetes - CONCLUSIONS: The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those co-morbid patients. This article is protected by…

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