Unexpected: Higher Viral Loads Seen in Less Severe COVID-19

Damian McNamara

July 17, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Testing in the emergency department (ED) at a New York City hospital revealed, unexpectedly, that people with higher viral loads of the novel coronavirus were less likely to require hospital admission, new evidence reveals.

"It was surprising as it is counterintuitive, but the reason became clear when we analyzed the onset and duration of symptoms," co-lead investigator Paolo Cotzia, MD, assistant professor, Department of Pathology, and assistant director, Center for Biospecimen Research and Development at NYU Langone Health in New York City, told Medscape Medical News.

The finding points to an early peak in viral load, a time when people with mild or asymptomatic disease could carry a higher potential for viral shedding and infecting others.

"Promoting social distancing and recommending the use of masks even to patients that are asymptomatic is of paramount importance to reduce the spreading of the virus. Patients with mild symptoms could be mistakenly perceived as carriers of a low amount of virus and being overlooked as a vector," co-lead investigator George Jour, MD, told Medscape Medical News.

"However, our study showed that there is a good number of mildly symptomatic patients with high levels of virus especially during the early phase of infection," added Jour, assistant professor, Department of Pathology and Department of Dermatology and associate director of Molecular Pathology at NYU Langone.

The study was published online July 2 in The American Journal of Pathology.

This is the first report to investigate how SARS-CoV-2 viral levels might correspond to clinical symptoms and outcomes in a US population, the researchers note.

Interestingly, they linked higher viral loads with significantly shorter symptom duration in all patients, regardless of hospitalization, and with shorter length of stay for hospitalized patients. No significant association, however, emerged regarding intensive care unit (ICU) admission, length of oxygen support, or overall survival.

An association between history of cancer or cardiovascular disease and higher viral loads, even after adjusting for age, was another notable finding.

International studies appear to lack consensus regarding viral loads and clinical severity. For example, a study in Lombardy, Italy revealed no difference in viral loads between asymptomatic carriers and symptomatic patients with COVID-19. In contrast, previous findings from Asian cohorts revealed similar trends to the current study, where patients with mild disease had the highest copy numbers during the first and second week after symptom onset.

Hospitalized Patients Older

To get a clearer picture, investigators studied 205 adults with confirmed COVID-19 who presented to the NYU Langone Medical Center emergency department in New York City. Investigators took nasopharyngeal swabs and measured SARS-CoV-2 viral load using qualitative and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assays.

The retrospective observational study population included 165 adults discharged from the ED and another 40 admitted to the hospital. The groups were similar in terms of sex, race, and body mass index (BMI). Age differed significantly — median age was 45 years in the nonhospitalized group compared with 60 years in the hospitalized group.

The nonhospitalized participants reported a median 3 days from symptom onset to time of nasopharyngeal swab collection vs a median 5 days among the hospitalized group. "Patients with severe symptoms and requiring hospitalization displayed lower diagnostic viral loads but their samples were taken at a later time point in the disease course. We believe that the viral load reflects the time from onset of infection," Cotzia said.

The median length of stay for hospitalized patients was 6.5 days.

ICU Admission and Deaths

Diagnostic viral load titers were 4.0 log10 in the nonhospitalized cohort vs 3.3 log10 in those ultimately hospitalized, a significant difference (P = .014). This finding remained regardless of sex, race, comorbidities, or BMI in a multilinear regression analysis.

Higher viral loads were associated with significantly shorter symptom duration in all patients (P < .001). Again, this was confirmed by a multivariate analysis controlling for age, sex, race, BMI, and comorbidities.

A total of 14 people were admitted to the ICU, including 35% of the hospitalized patients. Nine people in the hospitalized group died.

The investigators report a significant association between higher viral loads at time of diagnosis in the ED and history of cancer (P = .033). The same relationship was reported between viral load and cardiovascular disorders including coronary artery disease, arrhythmias, and chronic heart failure but excluding hypertension (P = .022).

After adjusting for age, the association with history of cancer remained significant (P = .019), as did the association with cardiovascular disease (P = .005).

Clinical Implications

The results of the study could guide triage decisions, such as determining which patients should be assigned to a negative-pressure room, the researchers note. For outpatient management, "clinicians can utilize viral load as a quantitative metric to reinforce the importance of self-isolation and face coverings to reduce the risk of spreading the infection."

The initially high viral load finding aligns with previous findings that people with severe COVID-19 experience high morbidity late in the disease process. This suggests that severe symptoms are likely unrelated to high viral titers, the current investigators note.

Going forward, the researchers plan to work on "collaborative efforts that focus on viral sequencing to identify mutations in the viral genome that can be useful for case tracing and for the correlation with clinical outcome," Cotzia said. "We hope that our contribution will be useful to achieve a better understanding of the viral biology and will give us more tools to face this pandemic."

More Research Warranted

"Overall, I think that more studies on the viral load are certainly needed and will be important for the correct comprehension of the interplay between this new virus and our immune system, especially as far [as] the most severe complications of COVID-19 are concerned," Nicasio Mancini, MD, told Medscape Medical News.

"The viral load is certainly not the only parameter to consider, but its possible role in stratifying patients belonging to higher-risk categories and presenting with worse symptoms should be carefully evaluated in future larger studies," added Mancini, who is affiliated with the Laboratory of Medical Microbiology and Virology, University "Vita Salute" San Raffaele in Milan, Italy.

Mancini and colleagues conducted a pilot study comparing 100 samples taken in April — at the height of the pandemic in Italy — with 100 samples taken the following month. They found significantly lower viral loads in May, suggesting a time-dependent decrease in viral load levels over time.

Similar to the NYU research, the Italian investigators found a trend toward higher viral loads in participants not admitted to the hospital. However, the difference disappeared in a multiple regression model "especially because of strikingly significant difference in age between hospitalized vs non-hospitalized patients."

The study was supported by the NYU Cancer Center NIH Support Grant and the NYU Melanoma NCI SPOREJour, Cotzia, and Mancini have disclosed no relevant financial relationships.

Am J Pathol. Published online July 2, 2020. Full text

Follow Damian McNamara on Twitter: @MedReporter.

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