Abstract
Background/Objectives: The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted global respiratory virus circulation, with sharp declines during 2020-2021, followed by a resurgence after the relaxation of public health measures. In South America, post-pandemic respiratory virus dynamics remain insufficiently characterized, particularly in ecologically diverse regions. Arequipa, a high-altitude city in southern Peru, has unique environmental conditions, including marked seasonal temperature variability, that may influence viral transmission. Methods: We performed a cross-sectional analysis of 21,784 nasopharyngeal swabs collected from symptomatic patients at four major hospitals between June 2021 and September 2023. All samples were tested for SARS-CoV-2 by RT-qPCR. Because routine screening for other respiratory viruses was implemented only in SARS-CoV-2-negative cases during the study period, a subset of SARS-CoV-2-negative samples was subsequently analyzed for influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV) using VIASURE assays. Viral circulation patterns were evaluated by year, month, and epidemiological week. Meteorological data were obtained from the SENAMHI-La Pampilla station. Logistic regression models were used to assess epidemiological and climatic predictors of viral detection. Results: SARS-CoV-2 positivity declined from 20.0% in 2021 to 8.8% in 2023. Conversely, detection of other respiratory viruses among SARS-CoV-2-negative samples increased from 0.8% in 2021 to 29.0% in 2023 (p < 0.01). Temporal increases in detection were observed during 2022-2023, particularly for IAV and RSV. In exploratory analyses, calendar year and relative humidity were associated with IAV and RSV detection, while age and temperature variables were associated with IBV. Conclusions: Climatic and demographic variables were associated with changes in viral detection for IAV, IBV, and RSV during the post-pandemic transition period in Arequipa. These findings describe patterns of viral detection within SARS-CoV-2-negative symptomatic patients and should be interpreted as surveillance-based observations rather than population-level estimates. Strengthened integrated epidemiological and genomic surveillance will be essential for vaccine planning and outbreak preparedness in the post-pandemic era.