Early SARS-CoV-2 dynamics and immune responses in unvaccinated participants of an intensely sampled longitudinal surveillance study

Manjula Gunawardana; Simon Webster; Sofia Rivera; John M Cortez Jr; Jessica Breslin; Cristian Pinales; Christopher Buser; F Javier Ibarrondo; Otto O Yang; Michael Bobardt; Philippe A Gallay; Amy P Adler; Christina M Ramirez; Peter A Anton; Marc M Baum

doi:10.1038/s43856-022-00195-4

Early SARS-CoV-2 dynamics and immune responses in unvaccinated participants of an intensely sampled longitudinal surveillance study

Commun Med (Lond). 2022 Oct 11:2:129. doi: 10.1038/s43856-022-00195-4. eCollection 2022.

Authors

Manjula Gunawardana¹, Simon Webster^#¹, Sofia Rivera^#¹, John M Cortez Jr^#¹, Jessica Breslin^#¹, Cristian Pinales¹, Christopher Buser¹, F Javier Ibarrondo², Otto O Yang^{2

3}, Michael Bobardt⁴, Philippe A Gallay⁴, Amy P Adler⁵, Christina M Ramirez⁶, Peter A Anton¹, Marc M Baum¹

Affiliations

¹ Department of Chemistry, Oak Crest Institute of Science, 128-132W. Chestnut Ave., Monrovia, CA USA.
² University of California, Los Angeles (UCLA), Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
³ University of California, Los Angeles (UCLA), Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
⁴ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA USA.
⁵ Jumpstart Research Consulting, LLC, Santa Fe, NM USA.
⁶ University of California, Los Angeles (UCLA), Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA USA.

^# Contributed equally.

Abstract

Background: A comprehensive understanding of the SARS-CoV-2 infection dynamics and the ensuing host immune responses is needed to explain the pathogenesis as it relates to viral transmission. Knowledge gaps exist surrounding SARS-CoV-2 in vivo kinetics, particularly in the earliest stages after exposure.

Methods: An ongoing, workplace clinical surveillance study was used to intensely sample a small cohort longitudinally. Nine study participants who developed COVID-19 between November, 2020 and March, 2021 were monitored at high temporal resolution for three months in terms of viral loads as well as associated inflammatory biomarker and antibody responses. CD8 + T cells targeting SARS-CoV-2 in blood samples from study participants were evaluated.

Results: Here we show that the resulting datasets, supported by Bayesian modeling, allowed the underlying kinetic processes to be described, yielding a number of unexpected findings. Early viral replication is rapid (median doubling time, 3.1 h), providing a narrow window between exposure and viral shedding, while the clearance phase is slow and heterogeneous. Host immune responses different widely across participants.

Conclusions: Results from our small study give a rare insight into the life-cycle of COVID-19 infection and hold a number of important biological, clinical, and public health implications.

Keywords: Medical research; Viral infection.