Abstract

During early 2021, Peru had the highest COVID-19-associated per-capita mortality rate. Socioeconomic inequality, insufficiently prepared healthcare, and surveillance systems are factors explaining the mortality rate, which can be severely worsened by early undetected SARS-CoV-2 circulation. We tested 1,441 individuals with fever sampled during August 2019-May 2021, several months before the first SARS-CoV-2 seroprevalence study available so far in Lima, Peru, for SARS-CoV-2-specific antibodies. The testing algorithm included a chemiluminescence immunoassay and surrogate virus neutralization test. Early positive samples (N = 24) from January-March 2020 were further tested using a plaque-reduction neutralization test (PRNT) and avidity test against the SARS-CoV-2 spike and nucleoprotein. None of the early samples were PRNT-confirmed, in contrast to 81.8% (18/22) of a subsample from April 2020 onward (Fisher exact test; P <0.0001). Therefore, we excluded non-PRNT-confirmed samples from subsequent analyses. The SARS-CoV-2 antibody detection rate was 0.9% in mid-April 2020 (1/104; 95% CI: 0.1-5.8%), suggesting viral circulation in early-middle March 2020, consistent with the first molecular detection of SARS-CoV-2 in Peru on March 2020. Mean avidity increase of 62-77% to 81-94% from all PRNT-confirmed SARS-CoV-2-positive samples during early 2020 were consistent with onset of SARS-CoV-2 circulation during late February/March 2020. Early circulation was also confirmed in a susceptible, exposed, infected, and recovered mathematical model that calculated an effective reproduction number >1 during February-March 2020. Early introduction of SARS-CoV-2 thus contributed to the high COVID-19 mortality rate in Peru. Emphasizing the role of diagnostic confirmation in understanding the pandemic's trajectory, this study highlights the importance of early detection and accurate testing in managing infectious disease outbreaks.

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