key: cord-0767035-wfe44dbd authors: C Dopico, X.; Muschiol, S.; Christian, M.; Hanke, L.; Sheward, D. J.; Grinberg, N. F.; Bogdanovic, G.; Mcinerney, G.; Allander, T.; Wallace, C.; Murrell, B.; Albert, J.; Karlsson Hedestam, G. B. title: Seropositivity in blood donors and pregnant women during 9-months of SARS-CoV-2 transmission in Stockholm, Sweden date: 2020-12-26 journal: nan DOI: 10.1101/2020.12.24.20248821 sha: b292a087ce38c9f2630feb2c7f813a1985ece746 doc_id: 767035 cord_uid: wfe44dbd Public 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. Densely populated areassuch as Stockholm countyfacilitate the spread of SARS-CoV-2 66 and evidence suggests that transmission can be curtailed by temporary restriction of leisure and 67 business activities, and track and trace 1 . In contrast to the vast majority of European, American 68 and Asian countries, Sweden has favored a strategy in which individuals are encouraged to 69 adhere to a set of basic public health instructions, while society has remained largely open -70 drawing numerous criticisms. The country has reported a significantly higher burden on the 71 healthcare system than its Scandinavian neighbors (Fig. 1A) . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The plasmid for expression of the SARS-CoV-2 prefusion-stabilized spike ectodomain with a 117 C-terminal T4 fibritin trimerization motif was obtained from 2 . The plasmid was used to 118 transiently transfect FreeStyle 293F cells using FreeStyle MAX reagent (Thermo Fisher 119 Scientific). The ectodomain was purified from filtered supernatant on Streptactin XT resin 120 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 26, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 26, 2020. ; https://doi.org/10.1101/2020.12.24.20248821 doi: medRxiv preprint Prior to analysis, each sample OD was standardized by dividing by the mean OD of "no sample 160 controls" on that plate or other plates run on the same day. This resulted in more similar 161 distributions for 2019 blood donor samples with 2020 blood donors and pregnant volunteers. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 26, 2020. Table 1 ). We validated the 210 estimates from our Bayesian approach with an equal-weighted (cut-off-independent) learner 211 from the output of support vector machines and linear discriminant analysis that we previously 212 optimized for ELISA measurements (Fig. 1G) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 26, 2020. ; https://doi.org/10.1101/2020.12.24.20248821 doi: medRxiv preprint To characterize immunological responses to SARS-CoV-2 and safeguard public health, it is 227 critical to monitor the level of population immunity after natural infection 14 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 26, 2020. ; https://doi.org/10.1101/2020.12.24.20248821 doi: medRxiv preprint supports that Stockholm has fared worse in terms of infections (following the first wave) than 259 the majority of study locations 26-28 , with the exception of Lombardy, Italy (23% seropositivity, 260 an early European center of infection) 29 , and comparable to London, UK (13%) 30 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted December 26, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Anti-RBD IgG Health policy and leadership models during the COVID-19 pandemic: 304 A review Cryo-EM structure of the 2019-nCoV spike in the prefusion 306 conformation Discriminative Bayesian Serology: Counting Without 308 Cutoffs A probability-based approach for identifying low-titer antibody 310 responses against SARS-CoV-2 Viral epitope profiling of COVID-19 patients reveals cross-reactivity 312 and correlates of severity The cost of dichotomising continuous variables Systemic and mucosal antibody responses specific to SARS-CoV-2 316 during mild versus severe COVID-19 Phase I/II study of COVID-19 RNA vaccine BNT162b1 in 319 adults An mRNA Vaccine against SARS-CoV-2 -Preliminary Report Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate Identification of sequence variants influencing immunoglobulin 326 levels Human immune system variation Widespread seasonal gene expression reveals annual differences in 330 human immunity and physiology The important role of serology for COVID-19 control The Lancet Infectious Diseases Spread of SARS-CoV-2 in the Icelandic Population Clinical and immunological assessment of asymptomatic SARS-336 CoV-2 infections SARS-CoV-2 infection protects against rechallenge in rhesus 338 macaques Primary exposure to SARS-CoV-2 protects against reinfection in 340 rhesus macaques Convergent Antibody Responses to SARS-CoV-2 Infection in 342 Convalescent Individuals Robust neutralizing antibodies to SARS-CoV-2 infection persist 344 for months Human neutralizing antibodies elicited by SARS-CoV-2 infection Immunological memory to SARS-CoV-2 assessed for greater than 348 eight months after infection Repeated cross-sectional sero-monitoring of SARS-CoV-2 in New 350 Burden and prevalence of prognostic factors for severe COVID-19 in 352 Estimating the infection-fatality risk of SARS-CoV-2 City during the spring 2020 pandemic wave: a model-based analysis SARS-CoV-2 seroprevalence worldwide: a systematic review and