Importance: Removing the epidemic waves and reducing the instability level of an endemic critical point of COVID-19 dynamics are fundamental to the control of COVID-19 in the US. Objective: To develop new mathematic models and investigate when and how will the COVID-19 in the US be evolved to endemic. Design, Setting, and Participants: To solve the problem of whether mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic, we defined a set of nonlinear ordinary differential equations as a mathematical model of transmission dynamics of COVID-19 with vaccination. Multi-stability analysis was conducted on the data for the daily reported new cases of infection from January 12, 2021 to December 12, 2022 across 50 states in the US using the developed dynamic model of COVID-19 and limit cycle theory. Main Outcomes and Measures: Eigenvalues and the reproduction number under the disease-free equilibrium point and endemic equilibrium point were used to assess the stability of the disease-free equilibrium point and endemic equilibrium point. Both analytic analysis and numerical methods were used to determine the instability level of new cases of COVID-19 in the US under the different types of equilibrium points and to investigate how the system moves back and forth between stable and unstable states of the system and how the pandemic COVD-19 will evolve to endemic in the US. Results: Multi-stability analysis identified two types of critical equilibrium points, disease-free endemic equilibrium points in the COVID-19 transmission dynamic system. The transmissional, recovery, vaccination rates and vaccination effectiveness during the major transmission waves of COVID-19 across 50 states in the US were estimated. These parameters in the model varied over time and across the 50 states. The eigenvalues and the reproduction numbers R0 and R0end in the disease-free equilibrium point and endemic equilibrium point were estimated to assess stability and classify equilibrium points. They also varied from state to state. The impacts of the transmission and vaccination parameters on the stability of COVID-19 were simulated, and stability attractor regions of these parameters were found and ranked for all 50 states in the US. The US experienced five major epidemic waves, endemic equilibrium points of which across 50 states were all in unstable states. However, the combination of re-infection and vaccination (hybrid immunity) may provide strong protection against COVID-19 infection, and stability analysis showed that these unstable equilibrium points were toward stable points. Theoretical analysis and real data analysis showed that additional epidemic waves may be possible in the future, but COVID-19 across all 50 sates in the US is rapidly moving toward stable endemicity. Conclusions and Relevance: Both stability analysis and observed epidemic waves in the US indicated that the pandemic might not end with the disappearance of the virus. However, after enough people gained immune protection from vaccination and from natural infection, COVID-19 would become an endemic disease, as the stability analysis showed. Educating the population about multiple epidemic waves of the transmission dynamics of COVID-19 and designing optimal vaccine rollout are crucial for controlling the pandemic of COVID-19 and its evolving to endemic.
Background: To characterize interferences between Streptococcus pneumoniae and SARS-CoV-2 we investigated the longitudinal patterns of viral infection and pneumococcal carriage in households infected with SARS-CoV-2. Methods: SARS-CoV-2 and pneumococcus were detected with quantitative molecular methods in saliva from members of eighty participating households. Samples were collected between October 2020 and January 2021 from n=197 adults and n=118 children of which n=176 adults and n=98 children had a complete set of ten samples collected within 42 days since enrolment. Time-dependent Cox models were used to evaluate the associations between SARS-CoV-2 and pneumococcal carriage. Results: In the entire cohort, cumulative pneumococcal carriage and SARS-CoV-2 infection rates were 58% and 65%, respectively. Pneumococcal abundances were associated with an increased risk of SARS-CoV-2 infection (HR 1.14, 95% CI, 1.01-1.29, P=0.04) and delayed clearance of SARS-CoV-2 infection (HR 0.90, 95% CI, 0.82-0.99, P=0.03). Elevated viral loads were observed among pneumococcal carriers and individuals with high overall bacterial 16S abundances, however, there were no longitudinal differences in viral loads in linear mixed-effects models. Individuals with high 16S abundances displayed delayed viral clearance (HR 0.65, 95% CI 0.55-0.78, P<0.0001). Conclusions: Although we found insufficient evidence for a strong impact of SARS-CoV-2 infection on pneumococcal carriage. Results from the current study suggest that pneumococcal carriers may have an increased risk of SARS-CoV-2 infection and high pneumococcal abundances and 16S abundances may be associated with elevated viral loads and delayed clearance of SARS-CoV-2 infection.
Background: Understanding severity of infections with SARS-CoV-2 and its variants is crucial to inform public health measures. Here we used COVID-19 patient data from Hong Kong to characterise the severity profile of COVID-19 and to examine factors associated with fatality of infection. Methods: Time-varying and age-specific effective severity measured by case-hospitalization risk and hospitalization risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through to 26 October 2022 over six epidemic waves, in comparison with estimates of influenza A(H1N1)pdm09 during the 2009 pandemic. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections. Factors potentially associated with the fatality risk of hospitalized Omicron patients were also examined. Results: With 32,222 COVID-19 hospitalizations and 9,669 deaths confirmed over 6 epidemic waves in Hong Kong, the time-varying hospitalization fatality risk dramatically increased from below 10% before the largest fifth wave of Omicron BA.2, to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, the highest fatality risk was amongst unvaccinated patients aged ≥80 years and the risk was inversely associated with the number of vaccination doses received. Conclusions: Omicron has comparable intrinsic severity to the ancestral Wuhan strain although the effective severity is substantially lower in Omicron cases due to vaccination. With a moderate-to-high coverage of vaccination, hospitalized COVID-19 patients caused by Omicron subvariants appeared to have similar age-specific risks of fatality to patients hospitalized with influenza A(H1N1)pdm09.
Background and aim: Lay people and medical professionals have suggested a link between (mRNA) COVID-19 vaccination and a purported increase in sudden cardiac arrest (SCA) and death (SCD) among athletes. We aimed to compare the athlete death rate in 2021-2022 with pre-pandemic estimates and investigate the role of vaccination. Methods: A comprehensive, much referenced, publicly available list of health issues, emergencies, and SCA/SCD in athletes from January 2021 to December 2022 was analysed. Demographic data, country, type of sport, vaccination status, and possible association between reported medical events and vaccination were evaluated for the complete set of athletes. The following data were specifically assessed for cases of SCD in young US athletes and compared to matched data from pre-pandemic studies: average annual SCD number, mean age, male/female ratio, sports with highest death toll, cause and scene of death, and relation to exercise. Descriptive statistics were used. Results: The list contained 1653 entries. (Former) athletes, aged 5-86 years, from 99 countries, participated in 61 different sports. In multiple cases, causes of and circumstances surrounding medical events were irretrievable. Many cases involved non-cardiovascular, exercise-unrelated aetiologies. Vaccination details were scarce. In 63 (3.8%) cases, including 9 fatal events, there was a plausible association with COVID-19 vaccination. In US athletes aged 9-40 (mean 22.7) years, 166 SCD cases were identified (average 83/year), mainly in males (83%) and in football (39.8%) and basketball (16.9%). Main causes of death were non-cardiovascular exercise-unrelated (22.9%) or unknown (50.6%). Deaths primarily occurred at rest (32.5%) or under unknown circumstances (38.6%). SCD characteristics were similar to those of two pre-pandemic studies with comparable datasets. Conclusion: SCD rate among young US athletes in 2021-2022 was comparable to pre-pandemic estimates. There is currently no evidence to substantiate a link between (mRNA) COVID-19 vaccination and SCD in (young) athletes.
Study objectives: Millions of COVID-19 survivors experience a wide range of long-term symptoms after acute infection, giving rise to serious public health concerns. To date, few risk factors for post-COVID-19 conditions have been determined. This study evaluated the role of pre-infection sleep quality/duration and insomnia severity in the incidence of long-term symptoms after COVID-19. Methods: This prospective study involved two assessments (April 2020 and 2022). At baseline, sleep quality/duration and insomnia symptoms in participants without current/prior SARS-CoV-2 infection were measured using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). At follow-up, we evaluated the presence of twenty-one symptoms (psychiatric, neurological, cognitive, bodily, and respiratory) one month (n=713, infection in April 2020-February 2022) and three months after COVID-19 (n=333, infection in April 2020-December 2021). Zero-inflated negative binomial models were used to estimate the effect of previous sleep on the number of long-term symptoms. Binomial logistic regressions were performed to evaluate the association between sleep outcomes and the incidence of each post-COVID-19 symptom. Results: Analyses highlighted a significant effect of pre-infection sleep on the number of symptoms one/three months after COVID-19. Previous higher PSQI and ISI scores, and shorter sleep duration significantly increased the risk of almost every long-term symptom at one/three months from COVID-19. Conclusion: This study suggested a prospective dose-dependent association between pre-infection sleep quality/quantity and insomnia severity with the manifestation of post-COVID-19 symptoms. Promoting sleep health may represent an effective preventive approach to mitigate the COVID-19 sequelae, with substantial public health and societal implications.
Background: To cope with the persistence of the Covid-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially, and the heterologous ChadOx1-S/BNT162b2 regimen had shown better efficacy and immunogenicity than the homologous BNT162b2/BNT162b2 regimen. Aim : We wanted to determine if this benefit was retained after the third dose. Methods: We combined an observational study of SARS-COV-2 infections among vaccinated healthcare workers at the University-Hospital of Lyon, France, with an analysis of immunological parameters before and after the third mRNA vaccine dose. Results: Following the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens, but this was no longer the case after the third dose. RBD-specific IgG levels and serum neutralization capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group. Conclusion: The advantage conferred by heterologous vaccination is lost after the third dose in terms of both protection and immunogenicity. Immunological measurements one month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.
Background: Medical oxygen is an essential component of modern healthcare, with a wide variety of applications ranging from supplemental use in surgery and trauma patients to the primary medication in oxygen therapy. This is the most effective treatment for any respiratory illness. Despite the importance of oxygen for public health and its demand as a life-saving drug, research on the subject is limited, with the majority of studies conducted following the outbreak of the COVID-19 pandemic. Due to the lack of empirical studies, we aimed to compile the recent research efforts with the current state of the field through a systematic review. Methods: We have performed a systematic review targeting the medical oxygen ecosystem, following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). For the study, we have limited our scope to healthcare facilities and domiciliary applications of medical oxygen. We considered the articles published in the last twenty years, starting from the SARS outbreak in November 2002 to 15th May 2022. Results: Our systematic search resulted in forty-one preliminary articles, with three more articles appended for a complete outlook on the topic. Based on the selected articles, the current state of the topic was presented through detailed discussion and analysis. Conclusion: We have presented an in-depth discussion of the research works found through the systematic search while extrapolating to provide insights on the current subject scenario. We have highlighted the areas with inadequate contemporary studies and presented some research gaps in the field.
MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance - Condition: COVID-19
Intervention: Drug: Manzi Guben granules
Sponsors: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine
Not yet recruiting
Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial - Condition: COVID-19
Intervention: Procedure: Pilates Exercises
Sponsor: Michele de Aguiar Zacaria
Recruiting
Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 subunit protein recombinant vaccine
Sponsors: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran
Not yet recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone) - Condition: Covid19
Interventions: Drug: Fluticasone; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400) - Condition: Covid19
Interventions: Drug: Ivermectin; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages - Condition: COVID-19
Intervention: Behavioral: Persuasive Appeal
Sponsor: University of Calgary
Completed
Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19 - Condition: COVID-19
Intervention: Diagnostic Test: Blood sampling
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Completed
Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19 - Condition: COVID-19
Interventions: Drug: N-Acetylcysteine; Drug: Placebo
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Active, not recruiting
Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2 - Condition: COVID-19
Intervention: Drug: AZD 1222
Sponsors: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health
Completed
Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Not yet recruiting
Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis - Condition: COVID-19
Interventions: Drug: Double-Stranded RNA sodium salt; Drug: Placebo
Sponsor: Promomed, LLC
Completed
Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19) - Condition: COVID-19
Interventions: Drug: STI-1558; Drug: STI-1558 placebo
Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd.
Not yet recruiting
Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19 - Condition: Long COVID-19
Intervention: Biological: UC-MSCs
Sponsor: Shanghai East Hospital
Not yet recruiting
CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents - Condition: COVID-19 Vaccination
Intervention: Behavioral: CONFIDENCE
Sponsors: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health
Not yet recruiting
Cognitive Rehabilitation for People With Cognitive Covid19 - Condition: Long Covid19
Intervention: Behavioral: Cognitive rehabilitation
Sponsors: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust
Recruiting