The number of plasma SARS-CoV-2 viral RNA (vRNA) copies detected in patients hospitalized with COVID-19 (RNAemia) were found to be significantly associated with disease severity, length of hospitalization, and mortality, according to results of a small study published in Clinical Infectious Diseases.

In this observational, prospective study, researchers investigated whether SARS-CoV-2 RNAemia is an indicator of viremia, associated with COVID-19 clinical outcomes including mortality, and the relationship between SARS-CoV-2 RNAemia and host immune responses, including neutralizing antibody and inflammatory biomarkers in outpatients and patients hospitalized with COVID-19. Patients were categorized into groups A, B, or C: group A included included those in an intensive care unit (ICU) who required mechanical ventilation or significant oxygenation support (severely ill patients); group B included those in a non-ICU setting (moderately ill patients); and group C included those who remained in an outpatient or at-home setting throughout the study period (outpatients with mild illness).

Of the 51 patients included in the analysis, 23 were in group A, 19 were in group B, and 9 were in group C. At baseline, SARS-CoV-2 RNAemia was detected among all patients in group A, 10 in group B, and 1 in group C (P <.0001). Patients in group A had more than a 3000-fold increase in the median number of vRNA copies/mL compared those in group B (P <.0001). In regard to the study patients who were hospitalized, those in group A had increased baseline severity of illness vs those in group B, as quantified by the World Health Organization (WHO) 10-point ordinal scale (median WHO score, 7.0 vs 5.0; P <.001). In addition, the researchers noted a significant association between SARS-CoV-2 RNAemia and peak WHO scores among patients in Group A measured during hospitalization (P =.002) as well as discharge disposition (death vs discharge to inpatient facility or home care, P =.037).

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Among patients in groups A and B who were hospitalized, a receiver operating characteristic curve analysis showed that a cut-off of more than 6000 vRNA copies/mL was associated with significantly increased mortality and length of hospitalization. After adjustment for age, sex, and treatment, increased plasma vRNA concentrations remained strongly associated with increased mortality (hazard ratio [HR], 10.7; 95% CI, 1.49-76.9) and length of hospitlization (HR, 5.12; 95% CI, 1.65-15.88).

To determine if SARS-CoV-2 RNAemia is an indicator of viremia, the researchers used electron tomography and immunostaining to visualize virions in pelleted plasma. On analysis of a subset of plasma samples with a wide range of  vRNA measurements (6720–304,333 copies/ml) with sufficient sample volume, the researchers found that “a median of 76% of total recovered vRNA was detected in the pellet fraction.”

Although plasma neutralizing antibody titers were not associated with SARS-CoV-2 RNAemia measurements, SARS-CoV-2 RNAemia was significantly associated with markers of innate immunity (interleukin 6, 8, and 10) and inflammation (procalcitonin and pentraxin-3).

Despite the study being limited by its small sample size, the researchers observed a moderate decrease in SARS-CoV-2 RNAemia during a 10-day period among patients who survived; however, no measureable decrease was observed among those who died.

Larger studies that include an increased follow-up duration of patients with varying disease severity are needed to gain “additional insight into the usefulness of SARS-CoV-2 plasma RNA as a prognostic marker and a means to guide antiviral therapy,” the researchers concluded.

Disclosure: Some study author(s) declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Jacobs JL, Bain W, Naqvi A, et al. SARS-CoV-2 viremia is associated with COVID-19 severity and predicts clinical outcomes. Clin Infect Dis. Published online August 10, 2021. doi:10.1093/cid/ciab686