SARS-CoV-2 Viral Load – Can it predict COVID-19 mortality?
An interesting letter in The Lancet Respiratory Medicine published August 6, 2020 by Pujadas and others reports on the association of viral load and COVID-19 mortality.
Currently SARS-CoV-2 PCR swabs do not allow for the quantitative assessment of viral load. The tests are purely qualitative.
However, technology based on RT-PCR does allow for the calculation of viral load, which is associated with transmission risk and disease severity in other viral illnesses.
Viral load in COVID-19 might correlate with infectivity, disease phenotype, morbidity, and mortality.
To date, there have been no studies that have assessed the association between viral load and mortality in a large patient cohort.
This group reported on SARS-CoV-2 viral load at diagnosis as an independent predictor of mortality in a large hospitalised cohort of 1145 patients.
They prospectively evaluated nasopharyngeal swab samples for SARS-CoV-2 by real-time RT-PCR on the Roche test. Positive samples were assessed by laboratory-developed quantitative RT-PCR test approved for clinical use and the viral loads were calculated with standard curves.
Viral loads for symptomatic, hospitalised patients who tested positive for SARS-CoV-2 were measured on samples collected within a two-month period in March and May. Patients with complete data were included. The mean age was 64.6 years with 651 male patients (56.9%) and a self-reported racial distribution of 31.2% African American patients, 29.3% white patients, 3.7% Asian patients, 32·8% patients of other race, and 3·1% patients of unknown race.
The overall mean log viral load was 5.6 copies per ml and the median log was 6.2 copies per ml. The mean viral load significantly differed between patients who were alive with a viral load of 5.2 copies per ml versus those who had died with a viral load of 6.4 copies per ml by the end of the study period.
Using a Cox proportional hazards model which adjusted for age, sex, asthma, atrial fibrillation, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, heart failure, hypertension, stroke, and race yielded a significant independent association between viral load and mortality.
A univariate survival analysis revealed a significant difference in survival probability between those with high viral load and those with low viral load.
Early risk stratification in COVID-19 remains a challenge. Here, they showed an independent relationship between high viral load and mortality.
Transforming qualitative testing into a quantitative measurement of viral load will assist clinicians in risk-stratifying patients and choosing among available therapies and trials.
Viral load might also affect isolation measures on the basis of infectivity.
Future work is needed to address whether SARS-CoV-2 viral load dynamics and the quantitative relationship with neutralising antibodies, cytokines, pre-existing conditions, and treatments received, among other covariates in order to predict integrative algorithms for risk prediction.