Plasma SARS-CoV-2 viral RNA as a valuable biomarker for SARS-CoV-2 infection in the lungs

In a recent study posted to the medRxiv* preprint server, researchers evaluated plasma and lower respiratory tract (LRT) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA) levels in longitudinal samples collected simultaneously from mechanically ventilated coronavirus disease 2019 (COVID-19) patients and analyzed their connections and relationships with clinical outcomes.

Study: Plasma SARS-CoV-2 RNA levels as a biomarker of lower respiratory tract SARS-CoV-2 infection in critically ill patients with COVID-19. Image Credit: CROCOTHERY/Shutterstock

Plasma SARS-CoV-2 vRNA levels are linked to COVID-19 outcomes in hospitalized patients, although it is uncertain if plasma vRNA reflects LRT vRNA levels.

About the study

The researchers prospectively enrolled COVID-19-positive hospitalized patients in this observational cohort study between April 2020 and May 2021. They included critically ill patients aged between 18 and 90 years who had been intubated and mechanically ventilated for acute hypoxemic respiratory failure due to COVID-19-related pneumonia and had been diagnosed with SARS-CoV-2 infection by a positive nasopharyngeal swab quantitative polymerase chain reaction (qPCR) test.

At the time of ICU admission, the researchers collected baseline demographics, COVID-19 timelines, severity indices, COVID-19-targeted treatments provided with probable effects on vRNA levels, 60-day survival, and time to removal of mechanical ventilation.

While the individuals were admitted to the ICU, the researchers collected serial blood samples and endotracheal aspirates (ETA) on day 1, and then again on days 5 and 10 post-enrollment. Statistically, in mixed linear regression models with random patient intercepts, the researchers looked at the temporal evolution of vRNA levels.

Key findings and conclusion

The researchers found a substantial correlation between SARS-CoV-2 viral RNA levels in plasma and LRT secretions in patients with severe COVID-19 early after ICU admission. This finding supports the use of plasma vRNA as a diagnostic for LRT viral burden and implies that plasma vRNA could be a valuable biomarker for lung SARS-CoV-2 infection.

In the current investigation, the researchers found a wide range of time intervals between symptom onset and ICU admission, indicating a very heterogeneous COVID-19 illness course. In comparison to ETA samples, a higher number of plasma samples had become undetectable for vRNA by the time patients were admitted to the ICU and included in the analysis.

The researchers found that both LRT and plasma vRNA decline over time, with larger levels and longer detection of LRT vRNA in non-survivors compared to survivors, which is consistent with previous results. Furthermore, they found statistically significant parallel reductions in LRT and plasma vRNA levels from the onset of symptoms, indicating that plasma vRNA might be used as a biomarker for LRT vRNA in critically ill patients. Given the diversity in timings of patient presentation and study enrolment across the clinical course of COVID-19, the findings underscore the necessity of controlling for time from symptom onset in survival studies.

The molecular processes underlying the tight relationship between vRNA levels in the LRT and the blood compartment are unknown. The disruption of the air-blood barrier due to inflammation and/or direct viral damage is one possible pathway for virions to travel from the lungs to the bloodstream, allowing virions to spill over into the bloodstream. The transit of virions from the LRT to the bloodstream, regardless of the method, may result in extrapulmonary infection; indeed, several studies have shown the presence of the extrapulmonary infectious virus.

In conclusion, the goal of this study was to look at LRT viral load and its connection with plasma vRNA levels in patients with severe COVID-19, because viral shedding in severe COVID-19 has been shown to be longer in the lower respiratory tract than in the upper. Given the rapid and dynamic drop of vRNA levels in both the LRT and blood compartments, the findings underscore the necessity of assessing the timing of vRNA biomarker testing in relation to the clinical timeline of COVID-19.

More research is needed to confirm the findings in additional cohorts and to investigate the biological mechanisms that underpin the relationship between lung and plasma viral burden, as well as to determine whether the persistence of plasma viremia in critically ill patients is associated with worse clinical outcomes using larger datasets.

We show that SARS-CoV-2 viral RNA levels in plasma and LRT secretions are strongly correlated in patients with severe COVID-19 early after ICU admission.”

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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