High SARS-CoV-2 genomic load at time of hospital admission may predict adverse outcomes
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The amount of RNA, or genomic load, of SARS-CoV-2 detected in swab tests of patients admitted to the hospital with viral pneumonia is associated with more severe outcomes, researchers reported in the Annals of the American Thoracic Society.
“We demonstrated that for patients admitted to the hospital with COVID-19 pneumonia, SARS-CoV-2 load, as reflected by the cycle threshold value of the polymerase chain reaction, should be looked at as a predictor of adverse outcomes,” Ioannis M. Zacharioudakis, MD, infectious disease specialist in the department of medicine at the New York University Grossman School of Medicine, said in a press release. “High viral load was shown to be a predictor of poor outcomes above and beyond age, other medical problems and severity of illness on presentation, indicating that it can be used to risk-stratify, or triage, patients.”
The retrospective cohort study included 314 patients (mean age, 64 years; 44.6% men; median BMI, 28.3 kg/m2) hospitalized at NYU Langone Medical Center in March and April with results of viral pneumonia and positive screening for SARS-CoV-2. Researchers gathered respiratory samples analyzed by molecular diagnostic technology from each patient by nasopharyngeal swabs.
The researchers categorized cycle threshold values into SARS-CoV-2 genomic load groups: 107 patients were in the low group (> 34.2), 103 patients in the intermediate group (27.7-34.2) and 104 patients in the high group (< 27.7).
The primary outcome was the association between genomic load and COVID-19-related pneumonia outcomes such as death, discharge to hospice care, mechanical ventilation use or extracorporeal membrane oxygenation use.
Mean Charlson Comorbidity Index was 3, 37.3% of patients had obesity, 15.9% had at least one pulmonary comorbidity, (23.5% were current or former smokers, 6.7% were transplant recipients and 1.2% had HIV. Mean symptom duration before presentation was 7 days. Patients were classified based on Pneumonia Severity Index (PSI), with nine (2.9%) patients classified in class 1, 78 (24.8%) in class 2, 84 (26.8%) in class 3, 102 (32.5%) in class 4 and 41 (13%) in class 5.
Patients with high SARS-CoV-2 genomic load had higher Charlson Comorbidity Index scores (P = .006) and PSI (P = .03) and these patients were more likely to be transplant recipients (P < .001) and have short duration of symptoms (P = .004). In multivariate analysis, the significant association between high genomic load and transplant history (OR = 5.37; 95% CI, 1.15-25) and symptom duration (OR = 0.93; 95% CI, 0.88-0.97) remained.
After a median follow-up of 25 days, the primary outcome was achieved in 23.6% of patients, with a median time to primary outcome of 3.5 days. Patients with high genomic load had a higher risk for mortality (P < .001) and for the composite outcome of death, intubation or ECMO (P = .004) compared with those with low genomic load. High genomic load remained an independent risk factor for adverse outcomes after the researchers controlled for other variables (P = .02). Duration of symptoms (P = .05) and PSI at time of admission (P < .01) were associated with adverse outcomes.
Researchers estimated the average probability of adverse outcomes to be 24% if all patients had a high genomic load compared with 11% if all patients had a low genomic load. In those with a high PSI, the expected probability of adverse outcomes was 49% for those with a high genomic load compared with 31% for those with a low genomic load.
“Our study provides a justification for using patients’ SARS-CoV-2 load at the time of hospital admission to assess their risk of adverse outcomes. In an era when the availability of antiviral medications proven effective against COVID might be limited and the capacity for intensive monitoring is finite, it is of utmost importance to be able to prioritize the patients who will benefit the most from early treatment or a higher level of care,” Zacharioudakis said. “Further studies are needed to evaluate whether a decrease in viral load of patients hospitalized with COVID-19 who may or may not be treated with antiviral medications such as remdesivir (Veklury, Gilead Sciences) correlate with an improvement in clinical status.”