Importance: Successive waves of infection by SARS-CoV-2 have left little doubt that COVID-19 will transition to an endemic disease, yet the future seasonality of COVID-19 remains one of its most consequential unknowns. Foreknowledge of spatiotemporal surges would have immediate and long-term consequences for medical and public health decision-making. Objective: To estimate the impending endemic seasonality of COVID-19 in temperate population centers via a phylogenetic ancestral and descendent states approach that leverages long-term data on the incidence of circulating coronaviruses. Design: We performed a comparative evolutionary analysis on literature-based monthly verified cases of HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43 infection within populations across the Northern Hemisphere. Ancestral and descendent states analyses on human-infecting coronaviruses provided projections of the impending seasonality of endemic COVID-19. Setting: Quantitative projections of the endemic seasonality of COVID-19 were based on human endemic coronavirus infection incidence data from New York City (USA); Denver (USA); Tampere (Finland); Trondelag (Norway); Gothenburg (Sweden); Stockholm (Sweden); Amsterdam (Netherlands); Beijing (China); South Korea (Nationwide); Yamagata (Japan); Hong Kong; Nakon Si Thammarat (Thailand); Guangzhou (China); and Sarlahi (Nepal). Main Outcome(s) and Measure(s): The primary projection was the monthly relative frequency of SARS-CoV-2 infections in each geographic locale. Four secondary outcomes consisted of empirical monthly relative frequencies of the endemic human-infecting coronaviruses HCoV-NL63, -229E, -HKU1, and -OC43. Results: We project asynchronous surges of SARS-CoV-2 across locales in the Northern Hemisphere. In New York City, SARS-CoV-2 incidence is projected in late fall and winter months (Nov.-Jan.), In Tampere, Finland; Yamagata, Japan; and Sarlahi, Nepal incidence peaks in February. Gothenburg and Stockholm in Sweden reach peak incidence between November and February. Guangzhou, China; and South Korea. In Denver, incidence peaks in early Spring (Mar.). In Amsterdam, incidence rises in late fall (Dec.), and declines in late spring (Apr.). In Hong Kong, the projected apex of infection is in late fall (Nov.-Dec.), yet variation in incidence is muted across other seasons. Seasonal projections for Nakhon Si Thammarat, Thailand and for Beijing, China are muted compared to other locations. Conclusions and Relevance: This knowledge of likely spatiotemporal surges of COVID-19 is fundamental to medical preparedness and expansions of public health interventions that anticipate the impending endemicity of this disease and mitigate COVID-19 transmission. These results provide crucial guidance for adaptive public health responses to this disease, and are vital to the long-term mitigation of COVID-19 transmission.
Introduction This study compares the clinical characteristics and disease progression of vaccinated and unvaccinated pregnant and postpartum women positive for the original, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Brazilian epidemiological data. Methods Data of pregnant or postpartum patients with coronavirus disease 2019 (COVID-19) SARS-CoV-2 confirmed using polymerase chain reaction from February 2020 to July 2022 were extracted from a Brazilian national database. The patients were divided based on vaccination status and viral variant (original, Gamma, Delta, and Omicron). The patients demographic data, clinical characteristics, comorbidities, signs, symptoms, and outcomes were retrospectively compared. Results Data from 10,003 pregnant and 2,361 postpartum women were extracted from the database. Among unvaccinated patients, postpartum women were more likely to be admitted to the intensive care unit (ICU). These patients were more likely to require invasive ventilation when infected with the original, Gamma, and Omicron variants and were more likely to die when infected with the original and Gamma variants. Patients who were vaccinated had reduced adverse outcomes including ICU admission, requirement for invasive ventilation, and death. Conclusion Postpartum women were more likely to develop severe COVID-19 that required ICU admission or invasive ventilatory support or led to death, among all variants, especially when the patients were unvaccinated. Therefore, the risk of severe COVID-19 should not be underestimated after delivery. Vaccinated patients had a lower risk of severe outcomes. Vaccination should be a top priority in pregnant and postpartum patients.
Abstract Objective To assess whether there is an association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infection and the incidence of immune mediated inflammatory diseases (IMIDs). Design Matched cohort study. Setting Primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. Participants The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS CoV-2 infection by reverse transcriptase polymerase chain reaction (RT-PCR) or lateral flow antigen test, and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults in the unexposed cohort with no diagnosis of confirmed or suspected SARS CoV-2 infection and no prior diagnosis of IMIDs. Main Outcome Measures The primary outcome measure was a composite of the incidence of any of the following IMIDs: 1. autoimmune thyroiditis, 2. coeliac disease, 3. inflammatory bowel disease (IBD), 4. myasthenia gravis, 5. pernicious anaemia, 6. psoriasis, 7. rheumatoid arthritis (RA), 8. Sjogrens syndrome, 9. systemic lupus erythematosus (SLE), 10. type 1 diabetes mellitus (T1DM), and 11. vitiligo. The secondary outcomes were the incidence of each of these conditions separately. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes comparing the exposed to the unexposed cohorts, and adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. Results 537 patients (0.11%) in the exposed cohort developed an IMID during the follow-up period over 0.29 person years, giving a crude incidence rate of 3.54 per 1000 person years. This was compared 1723 patients (0.09%) over 0.29 person years in the unexposed cohort, with an incidence rate of 2.82 per 1000 person years. Patients in the exposed cohort had a 22% relative increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.10 to 1.34). The incidence of three IMIDs were statistically significantly associated with SARS CoV-2 infection. These were T1DM (aHR 1.56, 95% CI 1.09 to 2.23), IBD (1.52, 1.23 to 1.88), and psoriasis (1.23, 1.05 to 1.42). Conclusions SARS CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19, including Long COVID and matched controls.
Importance: Characterizing the effect of vaccination on long COVID allows for better healthcare recommendations. Objective: To determine if, and to what degree, vaccination prior to COVID-19 is associated with eventual long COVID onset, among those a documented COVID-19 infection. Design, Settings, and Participants: Retrospective cohort study of adults with evidence of COVID-19 between August 1, 2021 and January 31, 2022 based on electronic health records from eleven healthcare institutions taking part in the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative, a project of the National Covid Cohort Collaborative (N3C). Exposures: Pre-COVID-19 receipt of a complete vaccine series versus no pre-COVID-19 vaccination. Main Outcomes and Measures: Two approaches to the identification of long COVID were used. In the clinical diagnosis cohort (n=47,752), ICD-10 diagnosis codes or evidence of a healthcare encounter at a long COVID clinic were used. In the model-based cohort (n=199,498), a computable phenotype was used. The association between pre-COVID vaccination and long COVID was estimated using IPTW-adjusted logistic regression and Cox proportional hazards. Results: In both cohorts, when adjusting for demographics and medical history, pre-COVID vaccination was associated with a reduced risk of long COVID (clinic-based cohort: HR, 0.66; 95% CI, 0.55-0.80; OR, 0.69; 95% CI, 0.59-0.82; model-based cohort: HR, 0.62; 95% CI, 0.56-0.69; OR, 0.70; 95% CI, 0.65-0.75). Conclusions and Relevance: Long COVID has become a central concern for public health experts. Prior studies have considered the effect of vaccination on the prevalence of future long COVID symptoms, but ours is the first to thoroughly characterize the association between vaccination and clinically diagnosed or computationally derived long COVID. Our results bolster the growing consensus that vaccines retain protective effects against long COVID even in breakthrough infections.
Intensive care unit (ICU) staff continue to face recurrent work-related traumatic events throughout the COVID-19 pandemic. Intrusive memories (IMs) of such traumatic events comprise sensory image-based memories. Harnessing research on preventing IMs with a novel behavioural intervention on the day of trauma, here we take critical next steps in developing this approach as a treatment for ICU staff who are already experiencing IMs days, weeks, or months post-trauma. To address the urgent need to develop novel mental health interventions, we used Bayesian statistical approaches to optimise a brief imagery-competing task intervention to reduce the number of IMs. We evaluated a digitised version of the intervention for remote, scalable delivery. We conducted a two-arm, parallel-group, randomised, adaptive Bayesian optimisation trial. Eligible participants worked clinically in a UK NHS ICU during the pandemic, experienced at least one work-related traumatic event, and at least three IMs in the week prior to recruitment. Participants were randomised to receive immediate or delayed (after four weeks) access to the intervention. Primary outcome was the number of IMs of trauma during week 4, controlling for baseline week. Analyses were conducted on an intention-to-treat basis as a between-group comparison. Prior to final analysis, sequential Bayesian analyses were conducted (n=20,23,29,37,41,45) to inform early stopping of the trial prior to the planned maximum recruitment (n=150). Final analysis (n=75) showed strong evidence for a positive treatment effect (Bayes factor, BF=1.25 × 106): the immediate arm reported fewer IMs (median=1, IQR=0-3) than the delayed arm (median=10, IQR=6-16.5). With further digital enhancements, the intervention (n=28) also showed a positive treatment effect (BF=7.31). Sequential Bayesian analyses provided evidence for reducing IMs of work-related trauma for healthcare workers. This methodology also allowed us to rule out negative effects early, reduced the planned maximum sample size, and allowed evaluation of enhancements. Trial Registration NCT02044809 (www.clinicaltrials.gov).
Objective: Vaccination decreases the risk of severe COVID-19 but its impact on post-acute sequelae of COVID-19 (PASC) is unclear among patients with systemic autoimmune rheumatic diseases (SARDs) who may have blunted vaccine immunogenicity and be vulnerable to PASC. Methods: We prospectively enrolled SARD patients from a large healthcare system who survived acute infection to complete surveys. The symptom-free duration and the odds of PASC (any symptom lasting ≥ 28 or 90 days) were evaluated using restricted mean survival time and multivariable logistic regression, respectively, among those with and without breakthrough infection (≥ 14 days after initial vaccine series). Results: Among 280 patients, the mean age was 53 years, 80% were female, and 82% were white. The most common SARDs were inflammatory arthritis (59%) and connective tissue disease (24%). Those with breakthrough infection had more upper respiratory symptoms, and those with non-breakthrough infection had more anosmia, dysgeusia, and joint pain. Compared to those with non-breakthrough COVID-19 infection (n=164), those with breakthrough infection (n=116) had significantly more symptom-free days over the follow-up period (+28.9 days, 95% CI: 8.83, 48.89; p=0.005) and lower odds of PASC at 28 and 90 days (aOR 0.49, 95% CI: 0.29, 0.83 and aOR 0.10, 95% CI: 0.04, 0.22, respectively). Conclusion: Vaccinated patients with SARDs were less likely to experience PASC compared to those not fully vaccinated. These findings support the benefits of vaccination for patients with SARDs and suggest that the immune response to acute infection is important in the pathogenesis of PASC in SARD patients.
A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir - Condition: COVID-19
Interventions: Drug: nirmatrelvir; Drug: ritonavir; Drug: placebo for nirmatrelvir
Sponsor: Pfizer
Not yet recruiting
COVID-19 iCura SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Device: iCura COVID-19 Antigen Rapid Home Test; Diagnostic Test: RT-PCR Test
Sponsors: EDP Biotech; Paragon Rx Clinical, Inc.; iCura Diagnostics, LLC
Recruiting
FMT for Post-acute COVID-19 Syndrome - Conditions: Post-Acute COVID19 Syndrome; COVID-19
Intervention: Procedure: Faecal Microbiota Transplantation
Sponsor: Chinese University of Hong Kong
Recruiting
Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia - Condition: COVID-19
Intervention: Drug: DILTIAZEM TEVA 60 mg or placebo
Sponsors: Hospices Civils de Lyon; Signia Therapeutics
Not yet recruiting
COVID-19 Booster Dose Reminder/Recall for Adolescents - Condition: COVID-19 Vaccines
Intervention: Behavioral: Reminder/Recall Sent Via Preferred Method of Communication
Sponsor: Marshfield Clinic Research Foundation
Active, not recruiting
VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination - Conditions: Immunization; Infection; Pregnancy Related; COVID-19
Interventions: Behavioral: VAX-MOM COVID-19 Intervention; Other: Standard of Care
Sponsors: University of Rochester; Centers for Disease Control and Prevention; University of California, Los Angeles
Not yet recruiting
Research on Community Based ATK Test Study to Control Spread of COVID-19 in Migrant Community - Condition: COVID-19 Pandemic
Intervention: Device: STANDARD Q COVID-19 Ag Test
Sponsor: University of Oxford
Active, not recruiting
Personalized Computerized Training Program for Cognitive Dysfunction After COVID-19 - Conditions: Post-Acute COVID-19; Long COVID
Intervention: Device: CogniFit’s CCT Post COVID-19
Sponsor: Universidad Antonio de Nebrija
Completed
Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families - Condition: Psychological Disorder
Intervention: Other: Qualitative research interview
Sponsor: Assistance Publique - Hôpitaux de Paris
Not yet recruiting
3EO Health SARS-CoV-2 OTC At Home Test - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: In Vitro
Sponsor: 3EO Health
Recruiting
Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial - Conditions: HIV; Organ Transplantation; Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia; Multiple Myeloma; COVID-19 Vaccines
Interventions: Biological: BNT162b2; Biological: mRNA-1273; Biological: NVX-COV2373
Sponsors: Bayside Health; Monash University
Not yet recruiting
Sequential Enhanced Safety Study of a Novel Coronavirus Messenger RNA (mRNA) Vaccine in Adults Aged 18 Years and Older. - Condition: Corona Virus Disease 2019(COVID-19)
Intervention: Biological: 0.3ml of mRNA vaccine
Sponsor: Yu Qin
Enrolling by invitation
PAPR: PAP + MBSR for Front-line Healthcare Provider COVID-19 Related Burnout - Conditions: Depression; Burnout, Professional
Interventions: Drug: Psilocybin; Behavioral: Mindfulness-Based Stress Reduction (MBSR)
Sponsors: University of Utah; Heffter Research Institute; Usona Institute
Not yet recruiting
Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity - Condition: Post-acute Sequelae of SARS-CoV-2 Infection
Intervention: Behavioral: Exercise
Sponsor: University of Colorado, Denver
Not yet recruiting
Scaling Well-Being for Educators During COVID-19 - Conditions: Anxiety; Depression
Intervention: Behavioral: Healthy Minds Program Foundations Training
Sponsors: University of Wisconsin, Madison; Chan Zuckerberg Initiative
Not yet recruiting
Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate - Recent reports demonstrate that SARS-CoV-2 utilizes cell surface heparan sulfate as an attachment factor to facilitate the initial interaction with host cells. Heparan sulfate interacts with the receptor binding domain of SARS-CoV-2 spike glycoprotein, and blocking this interaction can decrease cell infection. We and others reported recently that the family of compounds of 2,5-dihydroxyphenylic acid interferes with the binding of the positively charged groove in growth factor molecules to…
Combating the SARS-CoV-2 Omicron (BA.1) and BA.2 with potent bispecific antibodies engineered from non-Omicron neutralizing antibodies - The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion from most anti-SARS-CoV-2 neutralizing antibodies (NAbs). In this study, we explored the possibility of combating the Omicron and BA.2 by constructing bispecific antibodies based on non-Omicron NAbs. We engineered 10 IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and…
The use of adenoviral vectors in gene therapy and vaccine approaches - Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles,…
Therapeutic potential of metal ions for COVID-19: insights from the papain-like protease of SARS-CoV-2 - Coronaviruses have been responsible for multiple challenging global pandemics, including coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing. Consequently, PLpro…
Comparison of Intracellular Transcriptional Response of NHBE Cells to Infection with SARS-CoV-2 Washington and New York Strains - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial…
Inhibition of nonstructural protein 15 of SARS-CoV-2 by golden spice: A computational insight - The quick widespread of the coronavirus and speedy upsurge in the tally of cases demand the fast development of effective drugs. The uridine-directed endoribonuclease activity of nonstructural protein 15 (Nsp15) of the coronavirus is responsible for the invasion of the host immune system. Therefore, developing potential inhibitors against Nsp15 is a promising strategy. In this concern, the in silico approach can play a significant role, as it is fast and cost-effective in comparison to the trial…
Apelin as a new therapeutic target for COVID-19 treatment - CONCLUSION: Apelin is a potential therapeutic candidate against SARS-CoV-2 infection.
Two Cases of Acute Myocarditis in Young Male Adults After mRNA Vaccines Against COVID-19: Similarities and Differences - CONCLUSION: The benefits of vaccination against Covid-19 outweigh possible untoward effects and especially myocarditis. Health workers must close monitor the vaccinated patients for possible future cardiovascular complications.
Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System - Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the…
The Integral Membrane Protein ZMPSTE24 Protects Cells from SARS-CoV-2 Spike-Mediated Pseudovirus Infection and Syncytia Formation - COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on global public health, emphasizing the importance of understanding innate immune mechanisms and cellular restriction factors that cells can harness to fight viral infections. The multimembrane-spanning zinc metalloprotease ZMPSTE24 is one such restriction factor. ZMPSTE24 has a well-characterized proteolytic role in the maturation of prelamin A, precursor of the nuclear…
Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV - CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs.
Body Weight is Inversely Associated with Anti-SARS-CoV-2 Antibody Levels after BNT162b2 mRNA Vaccination in Young and Middle Aged Adults - CONCLUSION: Anti-SARS-CoV-2 antibody was inversely correlated with weight and BMI, which may be used as a marker to predict immune response of BNT162b2 mRNA vaccination in young and middle aged adults.
A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo - “Pan-coronavirus” antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations….
Assessment of Practices Affecting Racial and Ethnic COVID-19 Vaccination Equity in 10 Large US Cities - CONCLUSIONS: Lack of consistent public reporting and transparency of COVID-19 vaccination data has likely hindered public health responses by impeding the ability to track the effectiveness of strategies that target vaccine equity.
SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376 - Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first protease inhibitor against the SARS-CoV-2 protease 3CL^(pro) that has been licensed for clinical use. To identify mutations that confer resistance to this protease inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a polyprotein composed of the VSV glycoprotein G, the SARS-CoV-2 3CL^(pro), and the VSV polymerase L. Viral replication was thus dependent on the autocatalytic…