The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6–11.5) and 56.8% (95% CI, 56.3–57.3) in the period 8–59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9–80.7) and 86.0% (95% CI, 84.5–87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4–39.7) against Covid-19, 55.1% (95% CI, 46.6–62.2) against hospitalization, and 61.8% (95% CI, 48.9–71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2–84.2) against Covid-19, 87.6% (95% CI, 78.2–92.9) against hospitalization, and 93.6% (95% CI, 81.9–97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.

Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent (“leaky”) protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25–0.54]; 0.57 [0.42–0.78]; 0.24 [0.15–0.39]; respectively) and with cellblock exposures (0.61 [0.49–0.75]; 0.69 [0.58–0.83]; 0.41 [0.31–0.55]; respectively) but not with cell exposures (0.89 [0.58–1.35]; 0.96 [0.64–1.46]; 0.80 [0.46–1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.

Efforts to reduce the impact of stunting have been largely independent of interventions to reduce the impact of wasting, despite the observation that the conditions can coexist in the same child and increase risk of death. To optimize the management of malnourished children—who can be wasted, stunted, or both—the relationship between stunting and wasting should be elaborated. We aimed to describe the relationship between concurrent weight and height gain during and after rehabilitation from severe wasting. We conducted a secondary analysis of a randomized trial for the outpatient treatment of severe wasting, including 1,542 children who recovered and were followed for 12 weeks. We described the overlap of stunting and severe wasting and the change in stunting over time. We showed the relationship between concurrent weight and height gain using adjusted generalized estimating equations and calculated the mean rate of change in weight‐for‐height z score (WHZ) and height‐for‐age z score (HAZ) during and after rehabilitation. At baseline, 79% (n = 1,223/1,542) and 49% (n = 757/1,542) of children were stunted and severely stunted, respectively. Prevalence increased over time among children <24 months. During rehabilitation when weight was not yet fully recovered, we found rapid WHZ gain but limited HAZ gain. Following successful rehabilitation, WHZ gain slowed. The rate of HAZ gain was negative after rehabilitation but increased relative to the period during treatment. The potential relationship between weight and height gain calls for increased coverage of wasting treatment to not only prevent child mortality but also reduce linear growth faltering.