SARS-CoV-2 viral load is associated with increased disease severity and mortality

Abstract

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

Fig. 1. SARS-CoV-2 viral loads across sampling sites and detection rates by disease severity.

a Levels of SARS-CoV-2 viral loads at the time of initial sampling and across specimen types. The percent of samples with detectable viral loads are shown at the bottom. b Percent of participants with detectable plasma SARS-CoV-2 viral load by hospitalization status and disease severity. Symptomatic nasopharyngeal swab positive (NP+) and negative (NP−) individuals were evaluated at an outpatient respiratory infection clinic. Recovered individuals included participants who had previously been diagnosed with COVID-19, but whose symptoms have since resolved. P values are from a Χ² analysis.

Fig. 2. SARS-CoV-2 viral load is associated with markers of inflammation and disease severity.

a Heat map of Spearman correlation values with bold numbers indicating P  <  0.05. Absolute lymphocyte count, c-reactive protein (CRP), and interleukin-6 (IL-6) levels in hospitalized participants with and without detectable plasma (b), nasopharyngeal (c), and sputum (d) viral loads. NP nasopharyngeal, OP oropharyngeal, VL viral load. P values are from a two-tailed Wilcoxon rank sum test.

Fig. 3. SARS-CoV-2 viral load and risk of death.

a–d Participants who died had higher initial viral loads compared to those who survived to discharge. The center line depicts the median value, the whiskers depict the 10–90 percentile. P values are from a two-tailed Wilcoxon rank sum test. e–h Percent of participants who eventually died categorized by detectable viral load and disease severity at the time of initial sampling. VL viral load, cps copies. P values are from a two-tailed Fishers exact test.

Fig. 4. Longitudinal viral load measurements.

Samples were obtained from plasma (a, b), nasopharyngeal swab (c, d), oropharyngeal swab (e, f), or sputum (g, h). Red dots and lines show viral loads in those who died. Two-tailed Wilcoxon signed rank test P values showing significant changes over time are reported in an analysis of viral loads at the first and second available time points (TPs) from plasma (n = 13), nasopharyngeal (n = 16), oropharyngeal (n = 10), sputum (n = 12). Cps copies.