Circulating SARS-CoV-2 RNA detection in acute COVID-19 disease and post-COVID condition.

Abstract

Objectives: The study aimed to determine the clinical significance of circulating plasma SARS-CoV-2 RNA across acute COVID-19 and post-COVID condition (PCC) by investigating prevalence, determinants, and kinetics in a large longitudinal cohort, accounting for hospitalization and vaccination.

Methods: We consecutively enrolled individuals with confirmed SARS-CoV-2 infection. Acute COVID-19 was classified as mild, severe, or critical per WHO criteria. PCC was assessed 3 months after symptom onset, and plasma SARS-CoV-2 RNA (RNAemia) was quantified during acute infection (T0) and at follow-up (T1) by RT-qPCR. Associations between RNAemia and acute disease severity or PCC were evaluated using multivariable logistic regression. RNAemia was analysed as tertiles, binary detectability, and continuous levels.

Results: A total of 442 individuals with COVID-19 were included, of whom 195 (44.1%) had mild disease, 161 (36.4%) had severe illness, and 86 (19.5%) had critical illness. At a median of 3.2 (interquartile range, 2.7-3.9 months) months from symptom onset, 184 of 442 patients were followed up, and 144 of 184 (78.3%) reported at least one persistent symptom compatible with PCC, most commonly asthenia (22.9%), myalgic pain (26.4%), brain fog (19.4%), dyspnoea (31.3%), and cough (42.4%). RNAemia was detected in 67.4% of participants at baseline and in 53.6% at follow-up. RNAemia in the II-III tertiles or any detectable RNAemia was associated with critical COVID-19. Neither baseline nor follow-up RNAemia was associated with PCC, and results were unchanged in a sensitivity analysis excluding vaccinated individuals. RNAemia trajectories were not associated with PCC, PCC clusters, or upper respiratory tract viral clearance.

Conclusions: SARS-CoV-2 RNAemia was closely linked to acute COVID-19 severity but showed no association with PCC or PCC phenotype, which were assessed at 3 months from symptom onset in a cohort predominantly experiencing severe COVID-19 and hospitalization during acute infection. This dissociation may suggest that viral RNA in the peripheral blood is primarily involved in acute pathogenesis, whereas PCC likely arises from distinct biological mechanisms.