SARS-CoV-2 RNA in serum associated with poor prognosis and high mortality

The current coronavirus disease 2019 (COVID-19) pandemic has caused over 1.5 million deaths, though this accounts for a small fraction of the more than 76 million cases worldwide. The severity and mortality of the disease vary with several parameters, including age and sex, and the existence of other medical conditions. Prognostic factors are of great importance, therefore.

A new preprint on the medRxiv* server indicates the direct correlation between the presence of detectable viral RNA loads in serum, and clinical severity and death.  

The presence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is detected by the reverse-transcriptase polymerase chain reaction (RT-PCR) that reports the presence of viral RNA. It is typically performed on nasopharyngeal (NP) swab samples.

Earlier studies have shown that the viral load in such samples is highest at the time when symptoms set in, or within a few days. At about 2-3 weeks from this point, it diminishes beyond the limit of detection.

However, it is known that asymptomatic and symptomatic patients have similar viral loads in their airways, thus casting doubt on the relationship between viral load and severity.

A new study, therefore, aimed to study the correlation between the presence of the virus in blood and clinical severity. Some research suggests that viral RNA-emia is detectable in 15% of patients, though its significance remains unclear.


SARS-CoV-2. Image Credit: Dotted Yeti/

Study details

The researchers carried out a retrospective study of 56 consecutive patients admitted with COVID-19 at multiple centers in Japan, between April 13 and September 28, 2020, who were tested for viral RNA in serum. Paired samples were included if NP samples were collected within seven days of the serum sample.

The patients were classified as asymptomatic, mild (symptomatic patients without pneumonia), moderate (pneumonia patients who did not require supplemental oxygen), severe (required oxygen supplementation), and critically ill (required invasive mechanical ventilation, or developed shock, and/or multiple organ dysfunction).

With a median age of 55 years, and with ~43% being male, the patients were mostly found to have a moderate disease. About 20% had SARS-CoV-2 RNA in serum, and these patients had a higher median age of 78 compared to 50 for the remaining individuals.

Study findings show RNA-emia to be a high-risk indicator

Patients with RNA-emia made up 4% of moderate cases (1/25), but half of severe (6/12), while all critical patients (4/4) had viral RNA in blood. No patients with asymptomatic or mild infection had RNA-emia.

These patients had a 90% risk of oxygen supplementation vs 13% in the others, and ~82% risk of intensive care unit admission vs ~7% for the rest. Invasive mechanical ventilation was required by ~27% of them vs none of the others. The risk of dying in the hospital showed a trend towards an increase in this group, but not significantly, perhaps due to the small size of the group.

Interestingly, the NP viral load showed no correlation with viral RNA-emia, and neither did the number of days from symptom onset. Among the patients with viral RNA in the serum, however, the median viral load in NP swabs was more than twice as high, at 5.4 Log10 copies/μL, in critical patients, as in moderately or severely ill patients, at 2.6 Log10 copies/μL. This was despite a similar number of days from symptom onset to NP testing.

Additionally, when patients who died of the infection were compared to survivors, the difference is significant, at 6.2 Log10 copies/μL vs 3.9 Log10.

What are the implications?

Our results agree with those reported by other authors, thus suggesting an association with ICU admission, invasive mechanical ventilation, and mortality.”

Discrepancies between these findings and those of earlier studies, concerning the rate of viral RNA in serum, as well as the viral load in NP samples from patients with differing levels of clinical severity, may be attributable to differences in study methods, the timing of collection, and patient populations, among others.

The observed correlation between NP viral load and severity/risk of death deserves attention as a potential prognostic marker in COVID-19 patients.

It is noteworthy that in most cases, the NP samples and blood were obtained on or before the day of admission. This could indicate the possibility of using this test to detect patients at high risk for deterioration and death.

In addition to assessing the viral load of NP swabs, which is the technique that is most frequently used for COVID-19 diagnosis, serum tests may be considered a complementary modality for the early identification of individuals who are likely to develop severe COVID-19.”

Further studies will be necessary to understand the prognostic significance of RNA-emia, and whether this can be used to initiate early preventive management of those at particularly high risk of progressive disease and death.

*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.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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