High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes

“…We previously classified 448 patients (Fundación Jiménez Díaz [FJD] cohort, Madrid, Spain, April 2020) according to the COVID-19 severity into three categories, mild, moderate, and severe COVID-19, based on a number of demographic and clinical parameters, and we found a positive association between viral load in nasopharyngeal swabs and disease severity ( 37 ). For the present study, we have chosen 30 of the nasopharyngeal samples based on three criteria: (i) the COVID-19 category, including 10 patients who developed mild symptoms, 10 patients who developed moderate disease, and 10 patients who progressed to severe disease and exitus, (ii) patients whose diagnostics (real-time PCR RNA samples) displayed similar cycle threshold [ C T ] values (average C T of 25.37 ± 3.9 for mild, C T of 21.81 ± 2.4 for moderate, and C T of 20.38 ± 2.9 for exitus patients), and (iii) similar time interval between symptom onset and swab collection (average 5.78 ± 4.2 days for mild, 4.89 ± 3.1 days for moderate, and 4.5 ± 2.6 days for exitus patients).…”

“…The cohort of the study included 30 patients admitted to the Fundación Jiménez Díaz Hospital (FJD, Madrid, Spain) from 3 to 29 April 2020. All patients were confirmed to be positive for SARS-CoV-2 by a specific real-time PCR (VIASURE) with a C T (cycle threshold, which is inversely correlated with viral RNA level) range of 15.6 to 28.5; the samples are a subset from the cohort that has been described previously in reference 37 . Data collected included patient demographics, risk factors for COVID-19, and clinical information at the time of SARS-CoV-2 diagnosis (Table S1 in https://saco.csic.es/index.php/s/8GH5aJgritCjEx5 ).…”

Molecular and Clinical Prognostic Biomarkers of COVID-19 Severity and Persistence

“…pDCs link innate and adaptive immunity and one of their key functions is the production of IFN-I in response to viral or bacterial infections [ 59 ]. Depletion of pDCs could therefore result in a reduced ability to detect and limit viraemia since high viral loads have been associated with severe disease [ 60 ]. Changes in the composition of adaptive immune cells are associated with disease progression and it is reported that severe and critical COVID-19 patients present dramatically decreased natural killer cells (NK cells) on admission to hospital [ 43 , 49 , 53 ].…”

Comparison of Abbott ID NOW COVID-19 Rapid Molecular Assay to Allplex 2019-nCoV and VIASURE SARS-CoV-2 Detection in Nasal Swabs

“…Many studies have suggested that the SARS-CoV-2 viral load might predict the potentiality of disease severity and transmission. In the 2020 SARS-CoV epidemic, a higher viral load was related to increase emergency care requirements, intensive care, and overall poor prognosis [30], [31]. [32].…”