Project description:The introduction of effective vaccines in December 2020 marked a significant step forward in the global response to COVID-19. Given concerns with access, acceptability, and hesitancy across Africa, there is a need to describe the current status of vaccine uptake in the continent. An exploratory study was undertaken to investigate these aspects, current challenges, and lessons learnt across Africa to provide future direction. Senior personnel across 14 African countries completed a self-administered questionnaire, with a descriptive analysis of the data. Vaccine roll-out commenced in March 2021 in most countries. COVID-19 vaccination coverage varied from low in Cameroon and Tanzania and up to 39.85% full coverage in Botswana at the end of 2021; that is, all doses advocated by initial protocols versus the total population, with rates increasing to 58.4% in Botswana by the end of June 2022. The greatest increase in people being fully vaccinated was observed in Uganda (20.4% increase), Botswana (18.5% increase), and Zambia (17.9% increase). Most vaccines were obtained through WHO-COVAX agreements. Initially, vaccination was prioritised for healthcare workers (HCWs), the elderly, adults with co-morbidities, and other at-risk groups, with countries now commencing vaccination among children and administering booster doses. Challenges included irregular supply and considerable hesitancy arising from misinformation fuelled by social media activities. Overall, there was fair to reasonable access to vaccination across countries, enhanced by government initiatives. Vaccine hesitancy must be addressed with context-specific interventions, including proactive programmes among HCWs, medical journalists, and the public.
Project description:BackgroundDespite their effectiveness, coronavirus disease 2019 (COVID-19) vaccines have been associated with adverse effects, underscoring the importance of continuous surveillance to ensure vaccine safety and effective management of public health. Herein, the characteristics and risk factors of vaccine-related adverse events (AEs) were identified to gain an in-depth understanding of vaccine safety by investigating the impact of the vaccination dose on changes in post-vaccination AEs.MethodsHerein, a linked database of COVID-19 vaccination records from the Korea Disease Control and Prevention Agency, AE reports from the COVID-19 Vaccination Management System, and healthcare claims from the National Health Insurance Service, targeting ≥ 5-year-old individuals, was utilized (study duration = February 26, 2021, to January 31, 2023). The frequency and severity of reported post-vaccination AEs were evaluated. Furthermore, we specifically explored AEs in relation to the cumulative dosage of vaccines administered while evaluating associated risk factors.ResultsDuring the observation period, 42,804,523 individuals completed the COVID-19 vaccination series, with 365,900 reporting AEs, with headache, muscle pain, and fever being the most frequently reported. Notably, the AE reports were approximately twice as high for women than for men, which was further exacerbated following both doses. Analysis by age group revealed that AE reports were lower among children, adolescents, and older adults than in the middle-aged cohort (age = 50-64 years), with higher reports observed for 18-49-year-old individuals. Additionally, a higher risk of reporting was identified among individuals with lower socioeconomic status compared with those of middle socioeconomic status. Excluding dementia, the risk of reporting AEs was high in individuals with underlying diseases compared with those without, for instance, the risk of reporting AEs following two-dose vaccinations was approximately twice as high in individuals with chronic obstructive pulmonary disease and asthma.ConclusionThese findings indicate that women, younger people, those with a lower socioeconomic status, and those with underlying health conditions reported a higher incidence of AEs following COVID-19 vaccinations. This emphasizes the need for continued monitoring to ensure safe vaccination and address vaccine-related anxiety and fear, especially within the aforementioned groups.
Project description:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an enveloped, single-stranded RNA virus. Humans infected with SARS-CoV-2 develop a disease known as coronavirus disease 2019 (COVID-19) with symptoms and consequences including acute respiratory distress syndrome (ARDS), cardiovascular disorders, and death. SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2). The process of virus entry into endosomes and its release from endolysosomes are key features of enveloped viruses. Thus, it is important to focus attention on the role of endolysosomes in SARS-CoV-2 infection. Indeed, coronaviruses are now known to hijack endocytic machinery to enter cells such that they can deliver their genome at replication sites without initiating host detection and immunological responses. Hence, endolysosomes might be good targets for developing therapeutic strategies against coronaviruses. Here, we focus attention on the involvement of endolysosomes in SARS-CoV-2 infection and COVID-19 pathogenesis. Further, we explore endolysosome-based therapeutic strategies to restrict SARS-CoV-2 infection and COVID-19 pathogenesis.
Project description:BackgroundCOVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear.MethodsWe included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant.ResultsThe median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy.ConclusionsWe present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.
Project description:ObjectivesPatients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management.DesignWe adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings.SettingInterdisciplinary Collaboration in Systems Medicine Research Network.SubjectsThe simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation.InterventionsNone.Measurements and main resultsAn acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model.ConclusionsOur model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.
Project description:Acute hypoxemic respiratory failure is the major complication of coronavirus disease 2019, yet optimal respiratory support strategies are uncertain. We aimed to describe outcomes with high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation in coronavirus disease 2019 acute hypoxemic respiratory failure and identify individual factors associated with noninvasive respiratory support failure.DesignRetrospective cohort study to describe rates of high-flow oxygen delivered through nasal cannula and/or noninvasive positive pressure ventilation success (live discharge without endotracheal intubation). Fine-Gray subdistribution hazard models were used to identify patient characteristics associated with high-flow oxygen delivered through nasal cannula and/or noninvasive positive pressure ventilation failure (endotracheal intubation and/or in-hospital mortality).SettingOne large academic health system, including five hospitals (one quaternary referral center, a tertiary hospital, and three community hospitals), in New York City.PatientsAll hospitalized adults 18-100 years old with coronavirus disease 2019 admitted between March 1, 2020, and April 28, 2020.InterventionsNone.Measurements and main resultsA total of 331 and 747 patients received high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation as the highest level of noninvasive respiratory support, respectively; 154 (46.5%) in the high-flow oxygen delivered through nasal cannula cohort and 167 (22.4%) in the noninvasive positive pressure ventilation cohort were successfully discharged without requiring endotracheal intubation. In adjusted models, significantly increased risk of high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation failure was seen among patients with cardiovascular disease (subdistribution hazard ratio, 1.82; 95% CI, 1.17-2.83 and subdistribution hazard ratio, 1.40; 95% CI, 1.06-1.84, respectively). Conversely, a higher peripheral blood oxygen saturation to Fio2 ratio at high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation initiation was associated with reduced risk of failure (subdistribution hazard ratio, 0.32; 95% CI, 0.19-0.54, and subdistribution hazard ratio 0.34; 95% CI, 0.21-0.55, respectively).ConclusionsA significant proportion of patients receiving noninvasive respiratory modalities for coronavirus disease 2019 acute hypoxemic respiratory failure achieved successful hospital discharge without requiring endotracheal intubation, with lower success rates among those with comorbid cardiovascular disease or more severe hypoxemia. The role of high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation in coronavirus disease 2019-related acute hypoxemic respiratory failure warrants further consideration.
Project description:BackgroundOlder age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19.MethodsIn this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses.ResultsThe cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65-2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71-1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine.ConclusionsBCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection.Clinical trials registrationEU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335.
Project description:BackgroundSignificant concerns have been raised regarding the overuse of antibiotics among patients hospitalized for coronavirus disease 2019 (COVID-19) and the broad impact of the pandemic on antimicrobial stewardship in acute care. We sought to compare potentially unnecessary antibiotic prescribing over time among patients admitted with symptomatic COVID-19 and non-COVID-19 viral acute respiratory tract infections (ARTIs).MethodsWe conducted a repeated cross-sectional analysis of the monthly antibiotic prescribing rate from March 2020 to December 2023 for COVID-19 admissions and from January 2019 to December 2023 for other viral ARTI admissions to 803 acute care hospitals in the United States that contributed data to the Premier Healthcare Database. Our primary outcome was the receipt of ≥1 dose of an antibiotic during the first 5 days of the admission. Secondary outcomes included days and duration of antibiotic therapy.ResultsThis study included 513 698 COVID-19 and 106 932 non-COVID-19 viral ARTI admissions from March 2020 to December 2023. At the onset of the pandemic, >80% of patients admitted for COVID-19 received antibiotics, and antibiotic prescribing for other viral ARTIs increased to nearly 70%. Antibiotic prescribing for these viral infections declined over time, with prescribing for COVID-19 stabilizing around 35% in 2022-2023 and prescribing for other viral ARTIs returning to 2019 seasonal patterns in 2023, with average monthly prescribing around 50%.ConclusionsDespite improvements since the early part of the COVID-19 pandemic, potentially unnecessary antibiotic prescribing for inpatients with COVID-19 and non-COVID-19 viral ARTIs remains an important antibiotic stewardship target.