Temporal Dynamics of SARS-CoV-2 Detection in Household Contacts: Divergences Between Time to First Positive Test, Symptom Onset, and Maximum Viral Load.

Abstract

Introduction: Understanding the temporal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for optimizing diagnostic strategies. This prospective cohort study aimed to quantify the temporal viral transmission dynamics and biomarker profiles among households containing a SARS-CoV-2-positive index patient (IP) and uninfected household contacts (HHCs).

Methods: IPs entered the study within 48 h after confirmation of SARS-CoV-2 through reverse transcription polymerase chain reaction (RT-PCR). During 10-13 follow-up visits at days 0-7, and every 3-4 days thereafter until day 30 (± 6 days), nasopharyngeal swab and saliva samples were collected from participants (IP and HHC), and quantified via RT-PCR. Viral loads were estimated from cycle threshold values using three independently validated reference curved. Temporal viral dynamics for HHCs were evaluated as median times to first positive test (T_f+), symptom onset (T_so), and peak viral load (T_pvl), using a within-host target cell-limited framework.

Results: We prospectively screened 30 households with SARS-CoV-2-negative index cases; nine had a subsequent index-HHC conversion to PCR-positive, and 89 samples were generated. The results revealed a median T_f+ of 2 days, T_so of 4 days, and T_pvl of 5 days, which underscores significant gaps between viral detection and peak viral load. Nasal samples exhibited higher viral replication rates (β = 0.77/day) and prolonged virus production as compared to saliva samples, while infected cells in saliva cleared more rapidly (δ = 0.65 day^-1 vs 0.25 day^-1).

Conclusion: These findings suggest that SARS-CoV-2 viral RNA is detectable before symptom onset, and emphasize the need for testing immediately after exposure with repeated testing in the first week. This study provides critical insights into the temporal interplay of viral kinetics, aiding the development of targeted diagnostic and public health interventions. Further research is needed to validate these findings across larger, diverse cohorts and evolving viral variants. Testing immediately after exposure, with repeat testing during the first week may improve case detection.