Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021-September 2022.

Since June 2020, the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study has conducted routine PCR testing in UK healthcare workers and sequenced PCR-positive samples. SIREN detected increases in infections and reinfections during Omicron subvariant waves contemporaneous with national surveillance. SIREN's sentinel surveillance methods can be used for variant surveillance.

Comparison of maternal and neonatal outcomes of COVID-19 before and after SARS-CoV-2 omicron emergence in maternity facilities in Malawi (MATSurvey): data from a national maternal surveillance platform.

BACKGROUND: Outcomes of omicron-associated COVID-19 in pregnancy have not been reported from low-resource settings, and data from sub-Saharan Africa before the emergence of omicron are scarce. Using a national maternal surveillance platform (MATSurvey), we aimed to compare maternal and neonatal outcomes of COVID-19 in Malawi during the omicron wave to the preceding waves of beta and delta. METHODS: All pregnant and recently pregnant patients, up to 42 days following delivery, admitted to 33 health-care facilities throughout Malawi with symptomatic, test-proven COVID-19 during the second (beta [B.1.351]: January to April, 2021), third (delta [B.1.617.2]: June to October, 2021), and fourth (omicron [B.1.1.529]: December 2021 to March, 2022) waves were included, with no age restrictions. Demographic and clinical features, maternal outcomes of interest (severe maternal outcome [a composite of maternal near-miss events and maternal deaths] and maternal death), and neonatal outcomes of interest (stillbirth and death during maternal stay in the health-care facility of enrolment) were compared between the fourth wave and the second and third waves using Fisher's exact test. Adjusted odds ratios (ORs) for maternal outcomes were estimated using mixed-effects logistic regression. FINDINGS: Between Jan 1, 2021, and March 31, 2022, 437 patients admitted to 28 health-care facilities conducting MATSurvey had symptoms of COVID-19. SARS-CoV-2 infection was confirmed in 261 patients; of whom 76 (29%) had a severe maternal outcome and 45 (17%) died. These two outcomes were less common during the fourth wave (omicron dominance) than the second wave (adjusted OR of severe maternal outcome: 3·96 [95% CI 1·22-12·83], p=0·022; adjusted OR of maternal death: 5·65 [1·54-20·69], p=0·0090) and the third wave (adjusted OR: 3·18 [1·03-9·80], p=0·044; adjusted OR: 3·52 [0·98-12·60], p=0·053). Shortness of breath was the only symptom associated with poor maternal outcomes of interest (p<0·0001), and was less frequently reported in the fourth wave (23%) than in the second wave (51%; p=0·0007) or third wave (50%; p=0·0004). The demographic characteristics and medical histories of patients were similar across the three waves. During the second and third waves, 12 (13%) of 92 singleton neonates were stillborn or died during maternal stay in the health-care facility of enrolment, compared with 0 of the 25 born in the fourth wave (p=0·067 vs preceding waves combined). INTERPRETATION: Maternal and neonatal outcomes from COVID-19 were less severe during the fourth wave of the SARS-CoV-2 pandemic in Malawi, during omicron dominance, than during the preceding beta and delta waves. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and the National Institute for Health and Care Research. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study.

OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

Burden of SARS-CoV-2 infection in healthcare workers during second wave in England and impact of vaccines: prospective multicentre cohort study (SIREN) and mathematical model.

OBJECTIVE: To describe the incidence of, risk factors for, and impact of vaccines on primary SARS-CoV-2 infection during the second wave of the covid-19 pandemic in susceptible hospital healthcare workers in England. DESIGN: Multicentre prospective cohort study. SETTING: National Health Service secondary care health organisations (trusts) in England between 1 September 2020 and 30 April 2021. PARTICIPANTS: Clinical, support, and administrative staff enrolled in the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study with no evidence of previous infection. Vaccination status was obtained from national covid-19 vaccination registries and self-reported. MAIN OUTCOME MEASURE: SARS-CoV-2 infection confirmed by polymerase chain reaction. Mixed effects logistic regression was conducted to determine demographic and occupational risk factors for infection, and an individual based mathematical model was used to predict how large the burden could have been if vaccines had not been available from 8 December 2020 . RESULTS: During England's second wave, 12.9% (2353/18 284) of susceptible SIREN participants became infected with SARS-CoV-2. Infections peaked in late December 2020 and decreased from January 2021, concurrent with the cohort's rapid vaccination coverage and a national lockdown. In multivariable analysis, factors increasing the likelihood of infection in the second wave were being under 25 years old (20.3% (132/651); adjusted odds ratio 1.35, 95% confidence interval 1.07 to 1.69), living in a large household (15.8% (282/1781); 1.54, 1.23 to 1.94, for participants from households of five or more people), having frequent exposure to patients with covid-19 (19.2% (723/3762); 1.79, 1.56 to 2.06, for participants with exposure every shift), working in an emergency department or inpatient ward setting (20.8% (386/1855); 1.76, 1.45 to 2.14), and being a healthcare assistant (18.1% (267/1479); 1.43, 1.16 to 1.77). Time to first vaccination emerged as being strongly associated with infection (P<0.001), with each additional day multiplying a participant's adjusted odds ratio by 1.02. Mathematical model simulations indicated that an additional 9.9% of all patient facing hospital healthcare workers would have been infected were it not for the rapid vaccination coverage. CONCLUSIONS: The rapid covid-19 vaccine rollout from December 2020 averted infection in a large proportion of hospital healthcare workers in England: without vaccines, second wave infections could have been 69% higher. With booster vaccinations being needed for adequate protection from the omicron variant, and perhaps the need for further boosters for future variants, ensuring equitable delivery to healthcare workers is essential. The findings also highlight occupational risk factors that persisted in healthcare workers despite vaccine rollout; a greater understanding of the transmission dynamics responsible for these is needed to help to optimise the infection prevention and control policies that protect healthcare workers from infection and therefore to support staffing levels and maintain healthcare provision. TRIAL REGISTRATION: ISRCTN registry ISRCTN11041050.

SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).

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 history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. FUNDING: Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.