Serologic evidence for early SARS-CoV-2 circulation in Lima, Peru, 2020

Abstract During early 2021, Peru had the highest COVID-19-associated per-capita mortality rate globally. Socioeconomic inequality and insufficiently prepared healthcare and surveillance systems likely contributed to high mortality, potentially coupled with early SARS-CoV-2 introduction. We tested 1,441 individuals with fever sampled during August 2019-May 2021 in Lima, Peru, for SARS-CoV-2-specific antibodies. Serologic testing included a chemiluminescence immunoassay and confirmatory surrogate virus neutralization testing. Early positive samples (n=24) from January-March 2020 were further tested using a plaque-reduction neutralization and avidity tests based on SARS-CoV-2 spike and nucleoprotein antigens. None of the early samples were PRNT-confirmed, in contrast to 81.8% (18/22) of a subsample from April 2020 onwards (Fischer-exact test, p<0.0001). SARS-CoV-2 antibody detection rate was 0.9% in mid-April 2020 (1/104; 95% confidence interval (CI), 0.1-5.8%), suggesting onset of viral circulation in early-mid March 2020, consistent with the first molecular detection of SARS-CoV-2 in Peru on March 6th. Mean avidity increase of 62-77% to 81-94% from all PRNT-confirmed samples during early 2020, were consistent with onset of SARS-CoV-2 circulation during late February/March 2020. Early circulation of SARS-CoV-2 was confirmed in a Susceptible, Exposed, Infected and Recovered mathematical model that projected an effective reproduction number >1, during February-March 2020. Robust serologic testing thus confirmed that early SARS-CoV-2 introduction contributed to high COVID-19 mortality in Peru. Emphasizing the role of diagnostic confirmation, our study highlights the importance of early detection and accurate testing in managing infectious disease outbreaks. Importance Latin America was hard hit by the COVID-19 pandemic. Reasons include inadequate healthcare preparation and socio-economic vulnerabilities, likely exacerbated by early undetected SARS-CoV-2 circulation. Diagnostic testing for early SARS-CoV-2 circulation requires exhaustive diagnostic validation due to unspecific reactivity. We used a cohort of circa 1400 febrile patients from August 2019 until May 2021, months earlier than the first seroprevalence study in Lima, Peru, using a two-step diagnostic algorithm. Early 2020 positive samples were further tested with neutralization tests and avidity testing. We confirmed SARS-CoV-2-specific antibodies from April 2020 onwards, suggesting undetected viral circulation circa March 2020, consistent with the first SARS-CoV-2-detection. Early circulation was further confirmed by the significant increase in avidity in positive samples during early 2020 and the modeled peak of reproduction number of >1 during February-March 2020. Using exhaustive diagnostic validation, we detected early SARS-CoV-2 circulation that likely contributed to the severe impact of COVID-19 in Peru.