Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection

The incidence of long COVID is substantial, even in people who did not require hospitalization for acute COVID-19. The pathobiological mechanisms of long COVID and the role of early viral kinetics in its development are largely unknown. Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long- COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset. Brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). This work indicates that at least two long COVID symptoms - brain fog and muscle pain – at 90+ days from acute COVID-19 onset are specifically associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract. ### Competing Interest Statement Dr. Manabe has received research grant support to Johns Hopkins University from Hologic, Cepheid, Roche, ChemBio, Becton Dickinson, miDiagnostics, and has provided consultative support to Abbott, none of which constitute a conflict of interest with this study. No other authors have commercial or financial relationships that could be construed as a potential conflict of interest. ### Funding Statement Drs Blair and Manabe received support for this study from the Henry M. Jackson Foundation for the Advancement of Military Medicine (contract number 1007957) and the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program. Dr. Antar is supported by the National Institutes of Health (grant number K08AI143391). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the Johns Hopkins University School of Medicine gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.