Structured abstractO_ST_ABSObjectivesC_ST_ABSAs Sweden did not enforce social lockdown in response to the pandemic, it is critical to establish seropositivity to SARS-CoV-2 in healthy, active adults - here represented by blood donors and pregnant women. Random sampling was carried out in Stockholm, the countrys most populous region, and the study ran from virus emergence (March 2020) until the end of 2020, shortly prior to the first round of vaccinations, allowing for an estimate of population seropositivity in response to natural infection. DesignIn this cross-sectional prospective study, otherwise-healthy blood donors (n=2,100) and pregnant women (n=2,000) were sampled at random for consecutive weeks (at three intervals) between 14th March and 11th December 2020. Sera from all participants and a large cohort of historical controls (n=595) were screened for IgG responses against the SARS-CoV-2 spike (S) trimer and the receptor-binding domain (RBD). As a complement to standard approaches to analyze the data, a probabilistic Bayesian approach that assigns likelihood of past infection was used to analyze the population data. The study was carried out in accordance with Swedish Ethical Review Authority registration no. 2020-01807. SettingHealthy participant samples were selected from their respective pools at random through the Karolinska University Hospital. ParticipantsNone of the participants were symptomatic at the time of sampling and none had previously been hospitalized for COVID-19. No additional metadata was available from the samples. ResultsBlood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second-wave of infections, approaching 15% of all individuals surveyed by 11th December 2020. Importantly, 96% of antibody-positive healthy donors screened (n=56) developed neutralizing antibody responses at titers comparable to or higher than those observed in clinical trials of SARS-CoV-2 spike mRNA vaccination, supporting that mild infection engenders a competent B cell response. ConclusionsIn agreement with currently rising COVID-19 cases and ICU occupancy during a second winter wave of infections, these data demonstrate that the metropolitan Stockholm area was far from herd immunity nine months after the outbreak, with approximately one-in-six persons in the examined cohort seropositive for SARS-CoV-2. General abstractPublic health strategies to contain the pandemic continue to vary markedly across the world. In Sweden, compared to most advanced economies, social restrictions have primarily relied upon voluntary adherence to a set of recommendations and strict lockdowns have not been enforced. To better understand the development of humoral immunity to SARS-CoV-2 in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n=4,100) were sampled at random between 14th March-11th December 2020. All individuals (n=200/sampling week) were screened for anti-SARS-CoV-2 spike (S) trimer- and RBD-specific IgG responses with highly sensitive and specific ELISA assays, and the results were compared with those from historical controls (n=595). Data were modelled using a probabilistic Bayesian framework that considered individual responses to both antigens. We found that after a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second-wave of infections, approaching 15% of all individuals surveyed by 11th December. In agreement with the high transmission rate observed in the Stockholm area, seroprevalence in this cohort of active adults increased during the 9 months from the start of the outbreak, but was far from that required for herd immunity at the end of 2020.

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