ABSTRACT
Background There is continuing uncertainty regarding the longevity of immunological responses to both SARS-CoV-2 natural infection and COVID-19 vaccines. Methods We analysed data from two serological cohorts in Singapore among residents of a COVID-19 affected migrant worker dormitory between May-July 2020, and among mRNA COVID-19 vaccine recipients between May 2021 and January 2022. We compared SARS-CoV-2 neutralising antibody levels by age group, sex, presence of pre-existing medical conditions, type of mRNA vaccine received and number of doses received. We investigated the effect of time since infection or vaccination on antibody levels in naturally infected individuals and two- and three-dose vaccinees. Results After two vaccine doses, neutralising antibody responses were higher in Spikevax (Moderna) recipients, females, younger individuals and those with no underlying medical conditions. However, antibody levels waned to similar levels in all groups over time. A third dose boosted these to similarly high levels in all groups. Waning was apparent among two-dose but not three-dose recipients over a period of six months. Both two and three-dose vaccine recipients showed consistently higher neutralising antibody levels compared with naturally infected individuals over the 12-week period following infection or vaccination. Conclusions Our findings support the broad use of booster doses to improve population protection from COVID-19. However, recent increases in transmission of new SARS-CoV-2 variants, even in the presence of high levels of neutralising antibody in a highly vaccinated population, point to vaccine breakthrough as an important mechanism for maintaining SARS-CoV-2 circulation and indicate the need for variant-specific or universal COVID-19 vaccines.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
From January 2020, Singapore implemented comprehensive measures to suppress SARS-CoV-2. Community transmission has been limited, although explosive outbreaks have occurred in migrant worker dormitories. We conducted longitudinal SARS-CoV-2 serology studies among 478 residents of a SARS-CoV-2 affected migrant worker dormitory between May and July 2020, and 937 community-dwelling adult Singapore residents with sera collected before September 2019 and in November/December 2020. By end 2020, <2 per 1000 (0.16%, 95% CrI: 0.008% - 0.72%) adult residents in the community were infected with SARS-CoV-2, approximately 4 times higher than the national notified case incidence. In contrast, in the migrant worker cohort, nearly two-thirds 63.8% (95% CrI: 57.9% - 70.3%) had been infected by July 2020; no symptoms were reported in >90% of these infections. SARS-CoV-2 suppression is feasible with rapid implementation of comprehensive control measures. However, the risk of large-scale epidemics in densely-populated environments requires specific consideration in preparedness planning.
ABSTRACT
The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-{gamma}, IL-4, IL-6, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma} and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF- and IL-1{beta}) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.