Background: Long Covid, characterised by symptoms after Covid-19 infection which persist for longer than 12 weeks, is becoming an important societal and economic problem. As Long Covid was novel in 2020, there has been debate regarding its aetiology and whether it is one, or multiple, syndromes. This study assessed risk factors associated with Long Covid and examined symptom clusters that might indicate sub-types. Methods: 4,040 participants reporting for >4 months in the Covid Symptom Study App were included. Multivariate logistic regression was undertaken to identify risk factors associated with Long Covid. Cluster analysis (K-modes and hierarchical agglomerative clustering) and factor analysis were undertaken to investigate symptom clusters. Results: Long Covid affected 13.6% of participants. Significant risk factors included being female (P < 0.01), pre-existing poor health (P < 0.01), and worse symptoms in the initial illness. A model incorporating sociodemographics, comorbidities, and health status predicted Long Covid with an accuracy (AUROC) of 76%. The three clustering approaches gave rise to different sets of clusters with no consistent pattern across methods. Conclusions: Our model of risk factors may help clinicians predict patients at higher risk of Long Covid, so these patients can rest more, receive treatments, or enter clinical trials; reducing the burden of this long-term and debilitating condition. No consistent subtypes were identified.
Background: SARS-CoV-2 immunity has declined with subsequent waves and accrual of viral mutations. In vitro studies raise concern for immune escape by BA.4/BA.5, and a study in Qatar showed moderate protection, but these findings have yet to be reproduced. Methods: This retrospective cohort study included individuals tested for COVID-19 by PCR during Delta or BA.1/BA.2 and retested during BA.4/BA.5. The preventable fraction (PF) was calculated as ratio of the infection/hospitalization rate for initially positive patients divided by infection/hospitalization rate for initially negative patients, stratified by age, and adjusted for age, gender, comorbidities, and vaccination using logistic regression. Results: 20,987 patients met inclusion criteria. Prior Delta infection provided no protection against BA.4/BA.5 infection (Adjusted PF: 11.9% (95% confidence interval [CI], 0.8-21.8); p=0.036) and minimal protection against hospitalization (Adjusted PF: 10.7% (95%CI, 4.9-21.7); p=0.003). In adjusted models, prior BA.1/BA.2 infection provided 45.9% (95%CI, 36.2-54.1) (p <0.001) protection against BA.4/BA.5 reinfection and 18.8% (95% CI, 10.3-28.3) (p<0.0001) protection against hospitalization. Up-to-date vaccination provided modest protection against reinfection with BA.4/BA.5 and hospitalization. Conclusions: Prior infection with BA.1/BA.2 and up-to-date vaccination provided modest protection against infection with BA.4/BA.5 and hospitalization, while prior Delta infection provided minimal protection against hospitalization, and no infection protection.
Background: Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. Methods: We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between January 1, 2020, and November 19, 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Results: Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [-0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. Conclusions: The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.
Aim: The present study discussed the humoral immune response and antibody dynamics after primary and booster immunity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic liver disease (CLD) in the real world. Thus, it provided data to develop SARS-CoV-2 vaccination strategy. Methods: Patients with confirmed CLD and completed primary or booster immunity of SARS-CoV-2 vaccines were enrolled. Serological specimens were collected after primary or booster immunity of SARS-CoV-2 vaccines to detect novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD). Thus, we could evaluate the humoral immune response and antibody dynamics after primary and booster immunity of SARS-CoV-2 vaccines among patients with CLD. Simultaneously, baseline demographics, liver disease-related situations, comorbidity-related situations, SARS-CoV-2 vaccination information, and laboratory examination-related indicators of patients were collected. Results: A total of 315 patients received SARS-CoV-2 vaccines, including 223 patients who completed the primary immunity of SARS-CoV-2 vaccines, 114 patients who completed booster immunity of SARS-CoV-2 vaccines, and 22 patients who underwent the antibody detection of SARS-CoV-2 vaccines after both primary and booster immunities. The positive rate of nCoV NTAb was 59.64% in Primary and 87.72% in Booster (P<0.001). The median level of nCoV NTAb was 11.53 AU/mL in Primary and 31.98 AU/mL in Booster (P<0.001). The positive rate of nCoV S-RBD was 69.06% in Primary and 91.23% in Booster (P<0.001). The median level of nCoV S-RBD was 21.60AU/mL in Primary and 112.65 AU/mL in Booster (P<0.001). After booster immunity of SARS-CoV-2 vaccines in 22 patients, the positive rate of nCoV NTAb increased from 59.09% to 86.36%, and that of nCoV S-RBD increased from 68.18% to 90.91%. The median level of nCoV NTAb increased from 11.24 AU /mL to 59.14 AU /mL after booster immunity. The median level of nCoV S-RBD increased from 27.28 AU/mL to 219.10 AU/mL. Compared to the antibody level of primary immunity, the median level of nCoV NTAb and nCoV S-RBD in 22 patients was increased by 5.26 and 8.03 times, respectively. Among 22 patients, 9 were negative for nCoV NTAb after primary immunity, while 6 were transformed positive after booster immunity, and the positive conversion rate of nCoV NTAb was 66.7%. On the other hand, 7 patients were negative for nCoV S-RBD after primary immunity, while 5 were transformed positive after booster immunity, and the positive conversion rate of nCoV S-RBD was 71.4%. Conclusion: Patients with CLD show improved humoral immune response after completing primary and booster immunity of SARS-CoV-2 vaccines, while booster immunity further improves the positive rate and antibody level of patients with CLD. Finally, the positive conversion rate among patients with primary immunity failure also can be improved after booster immunity. Keywords: immune response; primary and booster immunity; SARS-CoV-2 vaccination; chronic liver disease
Rapid classification and detection of SARS-CoV-2 variants have been critical in comprehending the virus9s transmission dynamics. Clinical manifestation of the infection is influenced by comorbidities such as age, immune status, diabetes, and the infecting variant. Thus, clinical management may differ for new variants. For example, some monoclonal antibody treatments are variant-specific. Yet, an FDA-approved test for detecting the SARS-CoV-2 variant is unavailable. A laboratory-developed test (LDT) remains a viable option for reporting the infecting variant for clinical intervention or epidemiological purposes. Accordingly, we have validated the Illumina COVID-Seq assay as an LDT according to the guidelines prescribed by the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). The limit of detection (LOD) of this test is Ct<30 (~15 viral copies) and >200X genomic coverage, and the test is 100% specific in the detection of existing variants. The test demonstrated 100% precision in inter-day, intra-day, and intra-laboratory reproducibility studies. It is also 100% accurate, defined by reference strain testing and split sample testing with other CLIA laboratories. Advanta Genetics LDT COVID Seq has been reviewed by CAP inspectors and is under review by FDA for Emergency Use Authorization.
Importance: The U.S. arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals and/or persons with a prior history of infection, comprehensive data describing infections among immunologically naïve adults is lacking. Objective: To examine COVID-19 acute and post-acute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave. Design: A prospective cohort undergoing high-resolution symptom and virologic monitoring between June 2021 and September 2022 Setting: Multisite recruitment of community-dwelling adults in 8 U.S. states Participants: Healthy, unvaccinated adults between 30 to 64 years of age without an immunological history of SARS-CoV-2 who were at high-risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 PCR testing. Exposure(s): Omicron (BA.1/BA.2 lineages) versus Delta SARS-CoV-2 infection, defined as a positive PCR that occurred during a period when the variant represented ≥50% of circulating SARS-CoV-2 variants in the participant9s geographic region. Main Outcome(s) and Measure(s): The main outcomes examined were the prevalence and severity of acute (≤28 days post-onset) and post-acute (≥5 weeks post-onset) symptoms. Results: Among 274 immunologically naïve participants, 166 (61%) contracted SARS-CoV-2. Of these, 137 (83%) and 29 (17%) infections occurred during the Omicron- and Delta-predominant periods, respectively. Asymptomatic infections occurred among 6.7% (95% CI: 3.1%, 12.3%) of Omicron cases and 0.0% (95% CI: 0.0%, 11.9%) of Delta cases. Healthcare utilization among Omicron cases was 79% (95% CI: 43%, 92%, P=0.001) lower relative to Delta cases. Relative to Delta, Omicron infections also experienced a 56% (95% CI: 26%, 74%, P=0.004) and 79% (95% CI: 54%, 91%, P<0.001) reduction in the risk and rate of post-acute symptoms, respectively. Conclusions and Relevance: These findings suggest that among previously immunologically naïve adults, few Omicron (BA.1/BA.2) and Delta infections are asymptomatic, and relative to Delta, Omicron infections were less likely to seek healthcare and experience post-acute symptoms.
Background: Since the beginning of the COVID-19 pandemic veterinary diagnostic laboratories have tested diagnostic samples for SARS-CoV-2 not only in animals, but in over five million human samples. An evaluation of the performance of those laboratories is needed using blinded test samples to ensure that laboratories report reliable data to the public. This interlaboratory comparison exercise (ILC3) builds on two prior exercises to assess whether veterinary diagnostic laboratories can detect Delta and Omicron variants spiked in canine nasal matrix or viral transport medium. Methods: Inactivated Delta variant at levels of 25 to 1,000 copies per 50 microliters of nasal matrix were prepared for participants by the ILC organizer, an independent laboratory, for blinded analysis. Omicron variant at 1,000 copies per 50 microliters of transport medium was also included. Feline infectious peritonitis virus (FIPV) RNA was used as a confounder for specificity assessment. A total of 14 test samples were prepared for each participant. Participants used their routine diagnostic procedures for RNA extraction and real-time RT-PCR. Results were analyzed according to International Organization for Standardization (ISO) 16140 - 2:2016. Results: The overall results showed 93% detection for Delta and 97% for Omicron at 1,000 copies per 50 microliters (22-200 copies per reaction). The overall specificity was 97% for blank samples and 100% for blank samples with FIPV. No differences in Ct values were significant for samples with the same virus levels between N1 and N2 markers, nor between the two variants. Conclusions: The results indicated that all ILC3 participants were able to detect both Delta and Omicron variants. The canine nasal matrix did not significantly affect SARS-CoV-2 detection.
The sudden emergence and spread of Monkeypox in non-endemic parts of the world is currently not well understood. Infections are often mis-diagnosed and surveillance strategies are scarce. Wastewater-based surveillance (WBS) of human Monkeypox virus (MPXV) can help supplement our current clinical surveillance and mitigation efforts. WBS has shown to be an effective tool in monitoring the spread of other infectious pathogens, such as SARS-CoV-2 and its variants, and has helped guide public health actions. In this study, we describe how WBS can be used to detect MPXV in wastewater. We conducted WBS for MPXV in 22 wastewater treatment plants (WWTPs) over a period of 14 weeks. Nucleic acids were extracted using the MagAttract PowerMicrobiome DNA/RNA extraction kit. Three real-time qPCR assays were assessed for the detection of MPXV in wastewater. These included the G2R assays (G2R_WA and G2R_G) developed by the Centers for Disease Control and Prevention (CDC) in 2010, as well as an in-house-developed assay (G2R_NML). The G2R_WA assay was designed to detect the West African clade of viruses while the G2R_G (generic) assay was designed to detect both the Congo and West African clades (re-named to clades 1 and 2 respectively). The G2R_NML assay was designed using reference genomes of the 2022 MPXV outbreak. Our results show that all three assays have similar limits of detection and are all able to detect the presence of MPXV in wastewater. Following detection through real time qPCR, Sanger sequencing was performed on the resulting amplicon products, with the assembled contigs then undergoing analysis using nucleotide Basic Local Alignment Search Tool (BLAST). Due in part to the longer amplicon size of the G2R_NML assay, a significantly greater number of positive detections were identified as originating from MPXV compared to the CDC G2R assays. The ability to detect trace amounts of MPXV in wastewater as well as obtain Sanger sequence confirmation, has allowed for the successful surveillance of this virus in wastewater.
Background Prone positioning (PP) is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods In an open-label randomized controlled trial, we enrolled patients hospitalized with mild COVID-19 pneumonia, whose PaO2/FiO2 ratio was >200 mmHg and who did not require mechanical ventilation (MV) or non-invasive ventilation (NIV) at hospital admission. Patients were randomized 1:1 to PP on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, MV, NIV and PaO2/FiO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results Sixty-one subjects were enrolled, 29 adjudicated to PP and 32 to the control group. By day 28, 11 patients required NIV, 4 MV and 3 died. Overall, 24/61 (39.3%) met the primary outcome. Using an intention-to-treat approach, 15/29 patients in PP group versus 9/32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomized to PP (HR 2.38 95%CI 1.04-5.43; P=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained PP for ≥3 hours/day, no significant differences were found between the two groups (HR 1.77; 95%CI 0.79-3.94; P=0.165). Also, we did not find any statistically difference in terms of time to oxygen weaning or hospital discharge between study arms, in any of the analyses conducted. Conclusions We observed no clinical benefit from awake PP among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.
COVID-19 Bivalent Booster Megastudy - Condition: COVID-19
Intervention: Behavioral: COVID Booster text messages
Sponsor: University of Pennsylvania
Enrolling by invitation
A Study on Utilization, Adherence, and Acceptability of Voluntary Routine COVID-19 Self-testing Among Students, Staff and Health Workers at Two Institutions in Mizoram, India. - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: COVID-19 Self testing and related messaging
Sponsors: PATH; UNITAID; Zoram Medical College; Pacchunga University College; ALERT India; Government of Mizoram
Not yet recruiting
Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities - Condition: COVID-19
Interventions: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)
Sponsors: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)
Active, not recruiting
Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing - Condition: COVID-19
Interventions: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control
Sponsors: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)
Not yet recruiting
Assessing Performance of the Testing Done Simple Covid 19 Antigen Test - Condition: COVID-19
Intervention: Diagnostic Test: Testing Done Simple SARS CoV-2 Antigen Test
Sponsors: Testing Done Simple; Nao Medical Urgent Care
Recruiting
A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older - Condition: COVID-19
Interventions: Biological: EuCorVac-19; Biological: ChAdOx1
Sponsor: EuBiologics Co.,Ltd
Recruiting
Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population - Condition: COVID-19
Interventions: Drug: nirmatrelvir/ritonavir; Drug: Standard of care
Sponsors: Promomed, LLC; Sponsor GmbH
Completed
Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Recruiting
The LAVA (Lateral Flow Antigen Validation and Applicability) 2 Study for COVID-19 - Condition: SARS-CoV-2 Infection
Intervention: Diagnostic Test: Innova Lateral Flow Test
Sponsor: Alder Hey Children’s NHS Foundation Trust
Completed
Q-POC COVID-19 Clinical Evaluation - Condition: COVID-19
Interventions: Diagnostic Test: RT-PCR Test; Diagnostic Test: Real-time PCR Test
Sponsors: QuantuMDx Group Ltd; EDP Biotech; Paragon Rx Clinical; PathAI; PRX Research and Development
Not yet recruiting
A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster - Condition: COVID-19
Interventions: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®
Sponsor: GreenLight Biosciences, Inc.
Not yet recruiting
Enhancing Protection Against Influenza and COVID-19 for Pregnant Women and Medically at Risk Children - Conditions: Influenza; COVID-19
Intervention: Behavioral: Nudge
Sponsor: University of Adelaide
Recruiting
Safety and Efficacy of Intranasal Administration of Avacc 10 Vaccine Against COVID-19 in Healthy Volunteers - Condition: COVID-19
Interventions: Biological: Avacc 10; Combination Product: Outer Membrane Vesicles (OMV) : OMV alone in vehicle; Other: Placebo
Sponsors: Intravacc B.V.; Novotech (Australia) Pty Limited
Not yet recruiting
COVID-19 Antibody Responses in Cystic Fibrosis - Conditions: COVID-19; Cystic Fibrosis
Intervention: Biological: Blood sample
Sponsors: Hospices Civils de Lyon; Queen’s University, Belfast
Recruiting
The Phase Ⅱ/Ⅲ Trial of LYB001 - Condition: COVID-19
Interventions: Biological: LYB001; Biological: Placebo
Sponsor: Yantai Patronus Biotech Co., Ltd.
Not yet recruiting