Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous histo...

Background BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. MethodsThe SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing.Findings 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46•1 years (IQR 36•0-54•1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infecti...

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

The number of marine environments known to harbor dinitrogen (N 2)-fixing (diazotrophic) microorganisms is increasing, prompting a reassessment of the biogeography of marine diazotrophs and N 2 fixation rates (NFRs). Here, we investigate the diversity, abundance, and activity of diazotrophic microorganisms in the North Pacific Subtropical Gyre (NPSG), a diazotrophic habitat, and the North Pacific Transition Zone (NPTZ), a region characterized by strong physical, chemical, and biological gradients. Samples were collected on two springtime meridional cruises during 2016 and 2017, spanning from 23.5 N to 41.4 N along 158 W. We observed an abrupt decrease in diazotrophic abundances near the southern edge of the NPTZ, which coincided with a salinity front and with a $10-fold increase in Synechococcus abundance, but without a concomitant change in phosphate or nitrate concentrations. In NPSG waters south of this diazotrophic boundary, nifH genes and NFRs were consistently detected and diazotrophic communities were dominated by UCYN-A, an uncultivated, symbiotic cyanobacterium (2.8 × 10 3 to 1.0 × 10 6 nifH gene copies L −1). There was a significant positive relationship between quantitative polymerase chain reaction-derived UCYN-A nifH gene abundances and community NFRs in the NPSG, suggesting a large contribution of UCYN-A to community NFRs. In the NPTZ waters to the north, NFRs were low or undetected and nifH genes were rare, with the few detected sequences represented by UCYN-A and noncyanobacterial diazotrophs. The patterns we observed in UCYN-A abundance in the context of local biogeochemistry suggest that the environmental controls of this organism may differ from those of cultivated marine cyanobacterial diazotrophs.

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