High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease

Abstract

Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood, also known as RNAemia, has been reported, but its prognostic implications are poorly understood. This study aimed to determine the frequency of SARS-CoV-2 RNA in plasma and its association with coronavirus disease 2019 (COVID-19) clinical severity. Methods An analytical cross-sectional study was performed in a single-center tertiary care institution and included consecutive inpatients and outpatients with confirmed COVID-19. The prevalence of SARS CoV-2 RNAemia and the strength of its association with clinical severity variables were examined and included intensive care unit (ICU) admission, invasive mechanical ventilation, and 30-day all-cause mortality. Results Paired nasopharyngeal and plasma samples were included from 85 patients. The median age was 55 years, and individuals with RNAemia were older than those with undetectable SARS-CoV-2 RNA in plasma (63 vs 50 years; P = .04). Comorbidities were frequent including obesity (37.6%), hypertension (30.6%), and diabetes mellitus (22.4%). RNAemia was detected in 28/85 (32.9%) of patients, including 22/28 (78.6%) who required hospitalization. In models adjusted for age, RNAemia was detected more frequently in individuals who developed severe disease including ICU admission (32.1 vs 14.0%; P = .04) and invasive mechanical ventilation (21.4% vs 3.5%; P = .02). All 4 deaths occurred in individuals with detectable RNAemia. An additional 121 plasma samples from 28 individuals with RNAemia were assessed longitudinally, and RNA was detected for a maximum duration of 10 days. Conclusions This study demonstrated a high proportion of SARS-CoV-2 RNAemia, and an association between RNAemia and clinical severity suggesting the potential utility of plasma viral testing as a prognostic indicator for COVID-19.

On the whereabouts of SARS-CoV-2 in the human body: A systematic review

“…One in vitro study used virus isolated from patients to test replication kinetics in PBMCs but could not find evidence of SARS-CoV-2 propagation in this heterogeneous population of cells, despite the observation of viral-like particles in primary CD4 + T cells by electron microscopy [ 53 ]. Detection of viral RNA has been observed in plasma of severe patients, but it remains questionable whether this RNA originates from actual virus particles or merely represents the potentially infectious viral genome [ 54 , 55 ]. Therefore, detecting RNA in plasma does not directly translate into the presence of infectious particles.…”

“…In line with this, SARS-CoV-2 components were also detected in a variety of body fluids such as mucus, saliva, urine, semen, faeces, cerebrospinal fluid and breast milk. Of note, although SARS-CoV-2 RNA has been detected in plasma of patients with severe disease [ 54 , 55 , 197 ], no study has as yet demonstrated the presence of infectious virus in blood. It therefore remains to be demonstrated that SARS-CoV-2 might infect organ systems by gaining access to the bloodstream.…”

Biodistribution and serologic response in SARS-CoV-2 induced ARDS: A cohort study

“…SARS-CoV2 RNAemia has been associated with more severe COVID-19, including a higher probability of ICU admission and mechanical ventilation. However, in these studies disease severity was either heterogenous [ 27 ] and ARDS severity remained undefined, respectively [ 28 ]. Only a minority of patients enrolled in these studies actually required intensive care, whereas our study only included critically ill ICU patients.…”

“…Cycle thresholds of positive samples differed between survivors and non-survivors: Median cycles of oropharyngeal swabs were 35 (30)(31)(32)(33)(34)(35)(36)(37) in survivors and 30 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) in non-survivors (p = 0.003). However, no significant difference was observed in tracheal swabs with 31 (25)(26)(27)(28)(29)(30)(31)(32)(33)(34) in survivors and 27 (24)(25)(26)(27)(28)(29)(30)(31)(32) in non-survivors (p = 0.11). Median cycles (IQR) in blood samples were equal in survivors and non-survivors (p = 0.613).…”

Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome

“…Viral RNAemia is detected in up to a third of COVID-19 patients, most often in patients with severe disease (3,31). RNAemia was evaluated in a subset of patients, and detected in 15 of 25 admitted patients, 13 of 15 ICU patients who recovered, and 2 of 2 patients who died of their disease.…”