NEW YORK (Reuters Health) – SARS-CoV-2 RNA in plasma was associated with intensive care unit (ICU) admission and mortality in a single-center study of patients hospitalized with COVID-19.
“The frequency and clinical significance of extrapulmonary spread of SARS-CoV-2 has yet to be established,” Dr. Jan-Erik Berdal of Akershus University Hospital in Lorenskog, Norway, told Reuters Health by email. “We suggest that circulating RNA may be a useful prognostic marker in COVID-19, particularly to identify patients who may benefit from future antiviral and/or immunomodulatory therapeutics.”
Dr. Berdal and colleagues studied SARS-CoV-2 RNA levels in plasma and upper airway samples from 123 patients recruited between March 18 and May 4. Plasma and serum samples were taken at baseline (enrollment), day three and day nine in patients who were still hospitalized.
The predefined primary endpoint was a composite of ICU admission >24 hours and in-hospital mortality.
As reported in Clinical Infectious Diseases, 28% of patients reached the primary endpoint: 31 were admitted to the ICU, 29 received mechanical ventilation and four died. Another four patients with do-not-intubate orders died on regular wards. All ICU admissions and deaths were attributable to COVID-19.
Patients admitted to the ICU or who died had a mean age of 64 and about 71% were men (vs. 53% who were hospitalized but did not require ICU admission).
SARS-CoV-2 RNAemia was detected in at least one sample in 47% patients, and in a significantly higher proportion of patients who were admitted to the ICU or died (80% vs. 34%,). RNAemia was detected in 39% patients at baseline, shortly before ICU admission.
RNAemia was significantly more frequent at all time points in patients who reached the primary endpoint, whereas RNA loads were significantly higher at baseline and day three.
Further analysis showed that baseline RNAemia and RNA load were both significantly associated with ICU admission and/or death, and the association persisted after adjustment for age, sex, race, BMI, diabetes mellitus and symptom duration.
By contrast, there was no association between upper respiratory RT-PCR Ct (cycle threshold) values and the primary endpoint. In addition, there was no correlation between upper respiratory Ct values and RNAemia frequency or plasma RNA loads, meaning that RT-PCR Ct values in upper respiratory swabs obtained at admission yielded no prognostic information.
Dr. Berdal said, “More research is needed to ascertain whether SARS-CoV-2 RNA in the circulation truly represents a systemic infection, or whether it is merely spillover from an intense pulmonary infection.”
“Our research group is currently investigating the role of cardiac and inflammatory biomarkers in risk prediction for patients hospitalized with COVID-19, and in characterizing the immune response through the course of disease,” he added.
Dr. John Mellors of the University of Pittsburgh School of Medicine, coauthor of a related editorial, commented by email to Reuters Health, “The study and others dispels the ‘myth’ that viremia is rare in COVID-19. It can spread from the respiratory tract (upper or lower) to anywhere in the body and it does so not infrequently.”
“Virus in the bloodstream appears to be a biomarker of more severe COVID-19,” as in HIV, Ebola and other infectious diseases, he said. “Spread of the virus out of the respiratory tract into the blood stream is likely to be a sign that the virus is ‘winning’ the battle versus the host and that the host needs help in the form of therapy, although more data are required to confirm the need for therapy.”
“Measuring the amount of virus in blood before and after therapy may be useful to assess the effectiveness of therapies to block further spread of the virus,” he noted, as testing nose swabs or saliva for virus may not provide a complete picture.
“We have much to learn about how the virus is able to spread into the bloodstream and other organs,” he said. “Documenting that it happens is just the beginning.”
SOURCE: https://bit.ly/35PEBDd and https://bit.ly/35KqgYP Clinical Infectious Diseases, online September 5, 2020.