Self-tests for COVID-19: what is the evidence? A living systematic review and meta-analysis (2020-2023) (preprint)

COVID-19 self-testing strategy (COVIDST) can rapidly identify symptomatic and asymptomatic SARS-CoV-2-infected individuals and their contacts, potentially reducing transmission. In this living systematic review, we evaluated the evidence for real-world COVIDST performance. Two independent reviewers searched six databases (PubMed, Embase, Web of Science, World Health Organization database, Cochrane COVID-19 registry, Europe PMC) for the period April 1st, 2020, to January 18th, 2023. Data on studies evaluating COVIDST against laboratory-based conventional testing and reported on diagnostic accuracy, feasibility, acceptability, impact, and qualitative outcomes were abstracted. Bivariate random effects meta-analyses of COVIDST accuracy were performed (n=14). Subgroup analyses (by sampling site, symptomatic/asymptomatic infection, supervised/unsupervised strategy, with/without digital supports) were conducted. Data from 70 included studies, conducted across 25 countries with a median sample size of 817 (range: 28-784,707) were pooled. Specificity was high overall, irrespective of subgroups (98.37-99.71%). Highest sensitivities were reported for: a) symptomatic individuals (73.91%, 95%CI: 68.41-78.75%; n=9), b) mid-turbinate nasal samples (77.79%, 95%CI: 56.03-90.59%; n=14), c) supervised strategy (86.67%, 95%CI: 59.64-96.62%; n=13), and d) presence of digital interventions (70.15%, 95%CI: 50.18-84.63%; n=14). Sensitivity was lower in asymptomatic populations (40.18%, 95% CI: 21.52-62.20%; n=4), due to errors in test conduct and absence of supervision or a digital support. We found no difference in COVIDST sensitivity between delta and omicron pre-dominant period. Digital supports increased confidence in COVIDST reporting and interpretation (n=16). Overall acceptability was 91.0-98.7% (n=2) with lower acceptability reported for daily self-testing (39.5-51.1%). Feasibility was 69.0-100.0% (n=5) with lower feasibility (35.9-64.6%) for serial self-testing. COVIDST decreased closures in school, workplace, and social events (n=4). COVIDST is an effective rapid screening strategy for home-, workplace- or school-based screening, for symptomatic persons, and for preventing transmission during outbreaks. This data is useful for updating COVIDST policy. Our review demonstrates that COVIDST has paved the way for the introduction of self-tests, worldwide.

SARS-CoV-2 viral replication persists in the human lung for several weeks after onset of symptomatic severe COVID-19 and is associated with attenuated pulmonary immunity and variant-specific clinical sequalae (preprint)

The immunopathogenesis of severe COVID-19 is incompletely understood. In contradistinction to the upper respiratory tract where replicating (culturable) SARS-CoV-2 is recoverable approximately ~ 4 to 8 days after symptom onset, there is paucity of data about the frequency or duration of replicating virus in the lower respiratory tract (the human lung). We undertook lung tissue sampling (needle biopsy), within ~2 hours of death, in 42 mechanically ventilated decedents during the Beta and Delta waves. Lung biopsy cores underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, immunohistochemistry and cell-based flow cytometry of deconstructed tissue. 38% (16/42) of patients had culturable virus in the lung (persisting for up to 4 weeks after symptom onset). This, hitherto, undescribed bio-phenotype of lung-specific persisting viral replication was associated with an enhanced pulmonary pro-inflammatory response and variant-specific increased rates of bacterial bronchopneumonia and accelerated death. These findings question existing paradigms and suggest that in a subset of patients, concurrent, rather than sequential active viral replication continues to drive a heightened pro-inflammatory response. Our findings have potential implications for the design of therapeutic interventional strategies and clinical management of severe COVID-19 disease.

Efficacy of the AZD1222 (ChAdOx1 nCoV-19) COVID-19 Vaccine Against SARS-CoV-2 Variants of Concern (preprint)

In this South African phase 1/2b study, we demonstrated vaccine efficacy (VE) of two doses of AZD1222 for asymptomatic and symptomatic SARS-CoV-2 infection: 90.6% against wild-type and 77.1% against the Delta variant [≥]9 months after vaccination. VE against infection with the Beta variant, which preceded circulation of Delta, was 6.7%. Clinical trial identifierCT.gov NCT04444674

Preliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant (preprint)

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use. Methods In this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 micrograms recombinant spike protein with 50 micrograms Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy greater than or equal to 7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants. Results A total of 4387 participants were randomized and dosed at least once, 2199 with NVX CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 cases in NVX CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: -0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX CoV2373; serious adverse events were rare in both groups. Conclusions The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection with the presumptive original SARS CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)