Abstract Background: Diagnosis of SARS-CoV-2 infection in Liberia has primarily relied on polymerase chain reaction (PCR)-based testing at the country National Reference Laboratory. This centralized approach caused reporting delays, prompting evaluation of point-of-care antigen-based tests. We assessed the test performance of the LumiraDx SARS-CoV-2 Ag test (LumiraDx, London, UK) in this setting. Methods: We tested ambulatory individuals screened for enrollment into an observational cohort study of COVID-19 sequelae in Monrovia in 2021. We compared the results of LumiraDx testing of anterior nasal swab specimens to the results of PCR BioFire R2.1P (bioMerieux, Salt Lake City, Utah) on eluent from nasopharyngeal swabs. Results: We evaluated 348 individuals. Among the 274 persons with symptoms, 49.3% were PCR-positive and 36.5% were antigen-positive. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of LumiraDx in this group were 72.6% (95% CI: 64.3%-79.9%), 98.6% (95% CI: 94.9%-99.8%), 78.7% (CI: 71.9%-84.6%), and 98.0% (CI: 93.0%-99.8%), respectively. Among the 74 asymptomatic individuals, 12.2% were positive by PCR, and 5.5% by antigen testing, resulting in a sensitivity, specificity, NPV, and PPV of LumiraDx of 44.4% (95% CI: 13.7%-78.8%), 100% (95% CI: 94.5%-100%), 92.9% (CI: 84.1%-97.6%), and 100% (CI: 39.8%-100%), respectively. Conclusion: Although the specificity and PPV of LumiraDx for diagnosing SARS-CoV-2 were high among persons with and without symptoms, the sensitivity was unacceptably low in both groups, and much less than that reported by the manufacturer. Before new point-of-care diagnostics are adopted, test performance needs to be assessed in the local setting.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza viruses can be transmitted by infected persons who are pre-symptomatic or symptomatic. To assess impact of the COVID-19 pandemic on work attendance during illness, we analyzed prospectively collected data from persons with acute respiratory illness (ARI) enrolled in a multi-state study during 2018-2022. Persons with prior experience working from home were significantly less likely than those without this experience to work onsite on the day before illness and during the first 3 days of illness; the effect was more pronounced for the COVID-19 pandemic period than the pre-pandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other ARIs. Among persons for whom positive COVID-19 test results were available by the second or third day of illness, few worked onsite. Work-from-home policies may reduce the likelihood of workplace exposures to respiratory viruses.
Background: As SARS-CoV-2 has transitioned from a pandemic to endemic disease, the majority of new infections have been among previously infected individuals. To manage the risks and benefits of ongoing COVID-19 policies, it is important to understand whether prior infection modifies the severity of subsequent infections. Methods: We used data from first and second COVID-19 episodes in the National COVID Cohort Collaborative (N3C), a collection of health systems who provide de-identified electronic health records for research purposes. Our analysis was a sequential series of nested trial emulations. In the first of two analytic stages, we created a month-specific model of the probability of prior infection for each individual. In the second stage, we used an ordinal logistic regression with inverse probability weights calculated in the first stage to simulate a series of monthly trials comparing severity between the cohorts of first and second infections. In addition to cohort-wide effect estimates, we also conducted analyses among race/ethnicity, sex, and age subgroups. Results: From an initial cohort of 7,446,481 combined first and second infections, we identified a cohort of 2,227,484 infections, among which 7.6% were second infections. Ninety-four percent of patients with two recorded infections experienced mild disease for both. The overall odds ratio (OR) for more severe disease with prior infection was 1.06 (95% confidence interval [CI]: 1.03 to 1.10). Monthly point estimates of the OR ranged from 0.56 (95% CI: 0.37 to 0.84) in October 2020 to 1.64 (95% CI: 1.33 to 2.00) in February 2023. In most subgroups, the effect of prior infection was significant. In 8 out of 10 subgroups, the maximum monthly OR occurred after the minimum monthly OR, suggesting that protection has waned throughout the pandemic. Conclusion: Overall, prior infection was associated with a significant slightly elevated risk of severe disease. This effect varied month to month. As the pandemic proceeded, the effect of prior infection tended to evolve from generally protective during the pre-Omicron era to unprotective during the Omicron era. This points to the need for continued strategies to avert and minimize the harms of COVID-19, rather than relying upon immunity acquired through previous infection.
Background: Pandemic response and preparedness plans aim at mitigating the spread of infectious diseases and protecting public health, but migrants are often side-lined. Evidence amounted early that migrants are disproportionately affected by the COVID-19 pandemic and its consequences. However, synthesised evidence is lacking that quantifies the inequalities in infection risk and disease outcomes, or contextualises the consequences of pandemic measures and their underlying mechanisms. Methods: Systematic review searching 25 databases and grey literature (12/2019 to 11/2021). We considered empirical articles covering migrants, refugees, asylum-seekers, and internally displaced persons reporting SARS-CoV-2 cases, hospitalisation, ICU admission, mortality, COVID-19 vaccination rates or health consequences of pandemic measures. Random-effects meta-analysis of observational studies and qualitative analysis were performed for evidence synthesis. A Protocol was registered with PROSPERO (CRD42021296952). Findings: Out of 6956 studies, we included 241 in the review. For the quantitative studies (n=46), meta-analysis with over 40 million study participants showed that compared to non-migrants, migrants have an elevated risk of infection (RR = 2.33; 95%-CI: 1.88-2.89) but similar risk for hospitalisation (RR = 1.05; 0.80-1.37), while the likelihood of ICU admission was higher (RR = 1.36; 1.04-1.78). Among those hospitalised, migrants had a lower risk of mortality (RR = 0.47; 0.30-0.73), while their population-based excess mortality tended to be higher (RR = 1.31; 0.95-1.80). The qualitative synthesis (n=44) highlighted the complex interplay of social and COVID-19-related factors at different levels. This involved increased exposure, risk, and impact of pandemic measures that compromised the health of migrants. Interpretation: Even in the advanced stages of the pandemic, migrants faced higher infection risks and disproportionately suffered from the consequences of COVID-19 disease, including deaths. Population-level interventions in future health emergencies must better consider socio-economic, structural and community-level exposures to mitigate risks among migrants and enhance health information systems, to close coverage gaps in migrant groups.
Background: Surveillance of communicable diseases typically relies on case counts for estimates of risk, and counts can be strongly influenced by testing rates. In the Canadian province of Ontario, testing rates varied markedly by age, sex, geography and time over the course of the SARS-CoV-2 pandemic. We applied a standardization-based approach to test-adjustment to better understand pandemic dynamics from 2020 to 2022, and to better understand when test-adjustment is necessary for accurate estimation of risk. Methods: SARS-CoV-2 case counts by age, sex, public health unit and week were obtained from Ontarios Case and Contact Management system (CCM), which includes all SARS-CoV-2 cases from March 2020 to August 2022. Complete data on testing volumes was obtained from the Ontario Laboratory Information System (OLIS). Case counts were adjusted for under-testing using a previously published standardization-based approach that estimates case numbers that would have been expected if the entire population was tested at the same rate as most-tested age and sex groups. Logistic regression was used to identify threshold testing rates beyond which test-adjustment was unnecessary. Results: Testing rates varied markedly by age, sex, public health unit and pandemic wave. After adjustment for under-testing, overall case counts increased threefold. Adjusted epidemic curves suggested, in contrast to reported case counts, that the first two pandemic waves were equivalent in size, and that there were three distinct pandemic waves in 2022, due to the emergence of Omicron variants. Under-reporting was greatest in children and young males, and varied significantly across public health units, with variation explained partly by testing rates and prevalence of multigenerational households. Test adjustment resulted in little change in the epidemic curve during pandemic waves when testing rates were highest; we found that test-adjustment did not increase case counts once weekly per capita testing rates exceeded 6.3%. Conclusions: Standardization-based adjustment for differential testing by age and sex, and for dynamic changes in testing over time, results in a different picture of infection risk during the SARS-CoV-2 pandemic in Ontario; test-adjusted epidemic curves are concordant with observed patterns of mortality during the pandemic and have face validity. This methodology offers an alternative to sero-epidemiology for identification of true burden of infection when reinfection, sero-reversion, and non-specificity of serological assays make sero-epidemiology challenging.
Background: The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities. Method and findings: In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP <=140/90mmHg; 80 or more years old: <=150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using 9blood pressure control9 (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively. The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control. Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study. Conclusion: The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.
ABSTRACT: Introduction: SARS-CoV-2 is responsible for global pandemic that originates from Wuhan, China (1). Patients presentation van be varied from asymptomatic to severe ARDS and multiorgan dysfunction likely due the dysregulated systemic inflammation (2). Glucocorticoids inhibits the inflammation by down streaming of cytokine receptor and promote resolution (3). The role of corticosteroid in COVID-19 still remains controversial. Corticosteroids associated with many long terms side effects. Previous MARS outbreak had experienced avascular necrosis with corticosteroid use (4). Objectives: The aim of the study was to evaluate the outcome of covid-19 patients on the corticosteroid therapy and estimate mortality rate with corticosteroid therapy and investigate potential long-term adverse events associated with its use. Methods: We did a longitudinal follow up study at the AIIMS Rishikesh to assess the side effects of corticosteroids in COVID-19 patients. Patients with moderate to severe COVID-19 pneumonia requiring the oxygen support were included in the study. According to the institutional protocol patients received conventional dose steroids versus pulse dose steroids. (Based on CT/ X-ray findings). Patients were followed up in the hospital till discharge/death for assessment of adverse events due to corticosteroids and all other biochemical parameters (Inflammatory markers) and SOFA score were obtained during hospitalisation till discharge. And at the 6 month follow up patient was assessed for infection and avascular necrosis of the femur. Results: A total of 600 patients were screened out of which 541 patients who received corticosteroids were included in this study. 71.3% were male and 26.6 % were females. Most prevalent comorbidity was systemic hypertension (38.8%) followed by diabetes mellitus (38%). Most common presenting symptoms was dyspnoea followed by fever and cough. Majority patients received dexamethasone (95%). 65.8 % patients received conventional dose while 34.2% of patients received pulse dose. Mortality was more associated with pulse dose (44%) then a conventional dose (30%) (p-value 0.0015). the median duration of the corticosteroids was 10 days with an IQR of 7-13 days. During the hospitalisation 142 patients (26.2%) develops hyperglycaemia. Hyperglycaemia was more prevalent in the pulse dose steroid group (16.8% versus 9.4%). One patient develops pancreatitis. There was a significant reduction in the levels of inflammatory markers (p<0.005) after steroid initiation. At the 6th month of follow patients were assessed for AVN and suspected infection. 25 patients (8.25%) had infection out of which 19 received pulse dose. Out of 25 patients cultures was available for 7 patients and 2 patients grows pathogenic organism in the urine (pseudomonas and E. coli). 02 patients develop non-specific joint pain at 6 months. No patient had AVN during the follow up.
Background: Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative. Methods: Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients. Results: The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate, respectively. Conclusions: Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.
The Orthocoronaviridae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 (COVID-19) pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly crossreactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, betacoronaviruses including Middle Eastern respiratory syndrome coronavirus (MERS CoV), and extending to alpha-, gamma- and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these crossreactive antibodies, they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential.
Objectives: Compared to long-term expatriates, the health issues of short-term international business travellers are less clear. Particularly, there are no reports on the impact of the COVID-19 pandemic. We explored the changes in health challenges faced by Japanese international business travellers owing to the COVID-19 pandemic. Design: Cross-sectional survey research using questionnaires Setting: We surveyed 3,845 listed public companies in Japan in September 2021. Participants: A total of 251 companies responded (response rate: 6.5%), of which 131 (52%) had foreign travel requirements for their business. Primary and secondary outcome measures: The survey included questions regarding company size, business type, necessity for foreign travel, destination and number of trips, common health issues that arise, and the importance of business travel before and after the COVID-19 pandemic. Results: Among the companies, 44% replied that they could not predict the number of foreign business trips after the pandemic. However, 64% of companies responded that business travel would continue to be important in the future. Before the COVID-19 pandemic, the most important health concerns faced by business travellers were illness during travel (42%), followed by the prevention of infectious diseases and lifestyle disease management. Post-pandemic, 48% of the responses were for infectious diseases, including COVID-19, followed by 40% for travel-related diseases, and 25% for lifestyle-related diseases. Conclusions: Owing to global economic and social activities, business travel will continue to be necessary in the post-COVID-19 era. Comprehensive health management including prevention of infectious diseases is desirable for business travel.
Background: Little research has examined within/between group predictors and mediators of race/ethnic differences or disparities in mental and sleep health outcomes arising from the experience of the COVID-19 pandemic. Objectives: This study sought to evaluate the effect of COVID-19 experiences on trauma-related symptoms and sleep quality among a multiracial/ethnic sample in New York. Method: This is a cross-sectional study conducted online among multiethnic adults (n=541) who experienced the pandemic in New York from September to November 2020. Comparisons of characteristics and mean scores by race/ethnicity status were conducted using one-way ANOVA and independent samples t-tests for continuous variables and chi-square tests for categorical variables. Multilinear regression was used for associations between social determinants of health and/or SES, trauma-related symptoms, coping, and sleep. Results: Compared to Whites [Mean (SD)= (24.1(7.6)] and other group [Mean (SD)=24.9(8.2), Blacks [Mean (SD)=(26.3(6.4)] and Hispanics [Mean(SD)=(27.2(8.2)] reported higher level of peritraumatic distress [ df= 3; F=4273; p=0.005). The prevalence of clinically significant PTSD symptoms was 21.4%(n=113): [Whites=31(16.3%); Blacks=28(25.7%); Hispanics=24(25%); and other groups=30(22.4%); x2 =4.93; p=0.177]. This rate doubled [48.3%(257)] when it comes to the overall clinically significant depression level. Compared to all subcategories, [Blacks=52(47.7%); Hispanics =62(64.6%); other group=66(49.3%)], depression symptoms were lower among Whites [77(39.9%; x2 =15.71; p=0.001]. We found a prevalence of insufficient sleep <6 hours of 41%(198): [Whites=69(39.4%); Blacks=43(41.7%); Hispanics=46(52.3%); other groups=40(34.2%); x2=12.21; p=0.057]. Several unique demographic predictors of PTSD emerged for distinct racial/ethnic groups. Among Blacks, sex [β = −0.22; p < .01] and employment [β = −0.159; p < .05] emerged as significant predictors for PTSD, but for no other racial/ethnic group. Interestingly, among Hispanics [β = −0.144; p = .064] and Blacks [β = −0.174; p = .0.076], coping strategies did not mitigate PTSD or depressive symptoms. Conclusion: As New York and the rest of the world are trying to bounce back from the COVID-19 consequences, mental health outcomes are devastating, particularly among historically marginalized communities. This study provides insight into the emergency for policymakers to invest in racial justice programs and provide free access to culturally responsive mental health care for the most vulnerable groups.
Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.
Background Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial healthcare resource burden. This study aimed to describe healthcare resource utilization (HCRU) and costs associated with COVID-19 in pediatrics aged 1-17 years in England. Methods A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care (HES APC) secondary care data. HCRU and associated costs to the National Health Service (NHS) were stratified by age, risk of severe COVID-19, and immunocompromized status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). Results This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those aged 1-4 years (face-to-face: 4.3%; telephone: 6.0%) compared to those aged 5-11 (2.0%; 2.1%) and 12-17 years (2.2%; 2.5%). In the hospitalized cohort, mean [SD] length of stay was longer (5.0 [5.8] days) among those aged 12-17 years (n=24) than those aged 1-4 (n=15; 1.8 [0.9] days) and 5-11 years (n=21; 2.8 [2.1] days). Conclusions Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those aged 12-17 years. Our results may help optimize the management and resource allocation of COVID-19 in this population.
COVID-19 is a rapidly spreading infectious disease caused by the SARS-CoV-2 virus. Although several therapeutic interventions have been developed, the mortality rate of the disease remains high, and effective treatment options are urgently needed. Host-directed therapies targeting enzymes involved in the immune response represent a promising strategy for the development of novel therapeutics against COVID-19. This study aims to conduct a systematic review and meta-analysis of the literature to evaluate the potential of drug candidates targeting host enzymes involved in the immune response for the treatment of COVID-19. We will conduct a systematic search of electronic databases including PubMed, Embase, and Cochrane Library, as well as preprint servers and clinical trial registries for relevant studies. We will include randomized controlled trials, observational studies, and preclinical studies evaluating the efficacy of drug candidates targeting host enzymes involved in the immune response in COVID-19. Two reviewers will independently screen articles, extract data, and assess study quality. The primary outcome will be the effect of drug candidates on mortality, while secondary outcomes will include time to recovery, adverse events, and changes in immune markers. A meta-analysis will be performed to estimate pooled effect sizes of the interventions, and a narrative synthesis will be conducted for studies that are not amenable to quantitative analysis. This study will provide a comprehensive evaluation of the potential of host-directed therapies targeting enzymes involved in the immune response for the treatment of COVID-19. The results of this study may guide the development of novel therapeutics against COVID-19 and inform clinical practice.
Background Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity. Methods A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Findings There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5 to 56.0%), 29.7% (95% C.I.; 7.5 to 46.6%) and 52.7% (95% C.I.; 24.6 to 70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5 to 9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77 to 0.99) and 0.88 (95% C.I.; 0.75 to 1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71 to 1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44 to 1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Interpretation Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. Funding None.
Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients - Condition: COVID-19
Intervention: Dietary Supplement: Freeze-dried Mare Milk (Saumal)
Sponsor: Asfendiyarov Kazakh National Medical University
Not yet recruiting
Effects of Exercise Training on Patients With Long COVID-19 - Condition: Long COVID-19
Intervention: Behavioral: Exercise training
Sponsor: Guangdong Provincial People’s Hospital
Recruiting
Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly - Conditions: Vaccination; Infection; COVID-19
Intervention: Biological: Comirnaty
Sponsor: Radboud University Medical Center
Not yet recruiting
A Phase 2/3 Open-Label Study to Evaluate the Safety and Immunogenicity of an XBB.1.5 (Omicron Subvariant) SARS CoV-2 rS Vaccine. - Condition: COVID-19
Interventions: Biological: XBB.1.5 Vaccine (Booster); Biological: XBB.1.5 Vaccine (single dose)
Sponsor: Novavax
Not yet recruiting
A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults - Condition: COVID-19
Interventions: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo
Sponsor: GlaxoSmithKline
Not yet recruiting
A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adolescents Previously Vaccinated With mRNA COVID-19 Vaccines - Condition: COVID-19
Interventions: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)
Sponsor: Novavax
Not yet recruiting
Hyperbaric on Pulmonary Functions in Post Covid -19 Patients. - Condition: Post COVID-19 Patients
Interventions: Device: hyperbaric oxygen therapy; Device: breathing exercise; Drug: medical treatment
Sponsor: Cairo University
Completed
Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome - Conditions: Post-Acute COVID-19 Syndrome; Fatigue
Interventions: Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome; Other: Attention Control
Sponsor: University of Maryland, Baltimore
Not yet recruiting
Non-ventilated Prone Positioning in the COVID-19 Population - Conditions: COVID-19; Proning; Oxygenation; Length of Stay
Interventions: Other: Proning group; Other: Control group
Sponsor: Baylor St. Luke’s Medical Center
Completed
HD-Tdcs and Pharmacological Intervention For Delirium In Critical Patients With COVID-19 - Conditions: COVID-19; Delirium; Critical Illness
Interventions: Combination Product: Active HD-tDCS; Combination Product: Sham HD-tDCS
Sponsors: Suellen Andrade; City University of New York
Completed
RECOVER-VITAL: Platform Protocol, Appendix to Measure the Effects of Paxlovid on Long COVID Symptoms - Conditions: Long COVID-19; Long COVID
Interventions: Drug: Paxlovid 25 day dosing; Drug: Paxlovid 15 day dosing; Drug: Control
Sponsor: Kanecia Obie Zimmerman
Not yet recruiting
A Study on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults - Condition: SARS-CoV-2
Interventions: Biological: CV0701 Bivalent High dose; Biological: CV0701 Bivalent Medium dose; Biological: CV0701 Bivalent Low dose; Biological: CV0601 Monovalent High dose; Biological: Control vaccine
Sponsors: GlaxoSmithKline; CureVac
Not yet recruiting
RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms - Conditions: Long COVID; Long Covid19; Long Covid-19
Interventions: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham
Sponsor: Duke University
Not yet recruiting
Directed Topical Drug Delivery for Treatment for PASC Hyposmia - Condition: Post Acute Sequelae Covid-19 Hyposmia
Interventions: Drug: Beclomethasone; Other: Placebo; Device: Microsponge
Sponsor: Duke University
Not yet recruiting
RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms - Conditions: Long COVID; Long Covid19; Long Covid-19
Interventions: Other: BrainHQ/Active Comparator Activity; Other: BrainHQ; Other: PASC CoRE; Device: tDCS-active; Device: tDCS-sham
Sponsor: Duke University
Not yet recruiting
The Role of the Tyrosine-Based Sorting Signals of the ORF3a Protein of SARS-CoV-2 on Intracellular Trafficking, Autophagy, and Apoptosis - The open reading frame 3a (ORF3a) is an accessory transmembrane protein that is important to the pathogenicity of SARS-CoV-2. The cytoplasmic domain of ORF3a has three canonical tyrosine-based sorting signals (YxxΦ; where x is any amino acid and Φ is a hydrophobic amino acid with a bulky -R group). They have been implicated in the trafficking of membrane proteins to the cell plasma membrane and to intracellular organelles. Previous studies have indicated that mutation of the ^(160) YSNV ^(163)…
Discovery of Hybrid Thiouracil-Coumarin Conjugates as Potential Novel Anti-SARS-CoV-2 Agents Targeting the Virus’s Polymerase “RdRp” as a Confirmed Interacting Biomolecule - The coronavirus (COVID-19) pandemic, along with its various strains, has emerged as a global health crisis that has severely affected humankind and posed a great challenge to the public health system of affected countries. The replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly depends on RNA-dependent RNA polymerase (RdRp), a key enzyme that is involved in RNA synthesis. In this regard, we designed, synthesized, and characterized hybrid thiouracil and coumarin…
Transfer and biotransformation of the COVID-19 prodrug molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-placenta barrier - BACKGROUND: Molnupiravir is an orally bioavailable prodrug of the nucleoside analogue β-D-N4-hydroxycytidine (NHC) and is used to treat coronavirus disease 2019 (COVID-19). However, the pharmacokinetics and transplacental transfer of molnupiravir in pregnant women are still not well understood. In the present study, we investigated the hypothesis that molnupiravir and NHC cross the blood-placenta barrier into the fetus.
Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19 - PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in…
SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters - ABSTRACTPrevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with…
Novel computational and drug design strategies for inhibition of monkeypox virus and Babesia microti: molecular docking, molecular dynamic simulation and drug design approach by natural compounds - CONCLUSION: These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo…
Reflections on access to care for heavy menstrual bleeding: Past, present, and in times of the COVID-19 pandemic - The symptom of heavy menstrual bleeding (HMB) affects at least a quarter of reproductive-age menstruators. However, given the variance in diagnosing the underlying causes, barriers, and inequity in access to care for HMB, and therefore reporting of HMB, this figure is likely to be a gross underestimate. HMB can have a detrimental impact on quality of life. From the limited reports available it is estimated that around 50%-80% of people with HMB do not seek care for this debilitating symptom, and…
Inhibition by components of Glycyrrhiza uralensis of 3CLpro and HCoV-OC43 proliferation - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). 3CLpro is a key enzyme in coronavirus proliferation and a treatment target for COVID-19. In vitro and in silico, compounds 1-3 from Glycyrrhiza uralensis had inhibitory activity and binding affinity for 3CLpro. These compounds decreased HCoV-OC43 cytotoxicity in RD cells. Moreover, they inhibited viral growth by reducing the amounts of the necessary proteins (M, N,…
An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen - The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains 3 linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein. It was…
Structural-Based Virtual Screening of FDA-Approved Drugs Repository for NSP16 Inhibitors, Essential for SARS-COV-2 Invasion Into Host Cells: Elucidation From MM/PBSA Calculation - NSP16 is one of the structural proteins of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) necessary for its entrance to the host cells. It exhibits 2’O-methyl-transferase (2’O-MTase) activity of NSP16 using methyl group from S-adenosyl methionine (SAM) by methylating the 5-end of virally encoded mRNAs and shields viral RNA, and also controls its replication as well as infection. In the present study, we used in silico approaches of drug repurposing to target and inhibit the SAM…
Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease - Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that…
Crystal structures of main protease (Mpro) mutants of SARS-CoV-2 variants bound to PF-07304814 - There is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (M^(pro)) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 M^(pro) with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment…
Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo - COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles’ ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five…
Chicoric Acid Presented NLRP3-Mediated Pyroptosis through Mitochondrial Damage by PDPK1 Ubiquitination in an Acute Lung Injury Model - Chicoric acid (CA), a functional food ingredient, is a caffeic acid derivative that is mainly found in lettuce, pulsatilla, and other natural plants. However, the anti-inflammatory effects of CA in acute lung injury (ALI) remain poorly understood. This study was conducted to investigate potential drug usage of CA for ALI and the underlying molecular mechanisms of inflammation. C57BL/6 mice were given injections of liposaccharide (LPS) to establish the in vivo model. Meanwhile, BMDM cells were…
Therapeutic effects of tea polyphenol-loaded nanoparticles coated with platelet membranes on LPS-induced lung injury - Patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) are often septic and with poor prognosis, which leads to a high mortality rate of 25-40%. Despite the advances in medicine, there are no effective pharmacological therapies for ALI/ARDS due to the short systemic circulation and poor specificity in the lungs. To address this problem, we prepared TP-loaded nanoparticles (TP-NPs) through the emulsification-and-evaporation method, and then the platelet membrane vesicles…