Associations Found Between Plasma SARS-CoV-2 Viral RNA and COVID-19 Severity, Mortality

TURIN, ITALY – FEBRUARY 28: Blood and plasma samples used for the evaluation swabs for Coronavirus in the research laboratory of the Amedeo di Savoia hospital in Turin during of the Northern Italy In The Grip Of Covid-19 Coronavirus on February 28, 2020 in Turin, Italy. (Photo by Stefano Guidi/Getty Images)
Researchers conducted a study to determine whether SARS-CoV-2 viral RNA detected in the bloodstreams of patients with COVID-19 is reflective of viremia or related to host immune responses and outcomes.

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).

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