Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Jul 9, 2021; 10(4): 132-150
Published online Jul 9, 2021. doi: 10.5492/wjccm.v10.i4.132
SARS-CoV-2 (COVID-19), viral load and clinical outcomes; lessons learned one year into the pandemic: A systematic review
Santosh Shenoy
Santosh Shenoy, Department of General and Colorectal Surgery, KCVA and University of Missouri at Kansas City, Missouri, MO 64128, United States
Author contributions: Shenoy S designed the study, performed the literature search, wrote and analyzed the data, revised and approved the final manuscript.
Conflict-of-interest statement: The author declares that he has no competing interests.
PRISMA 2009 Checklist statement: The author has read the PRISMA 2009 checklist, and the manuscript was prepared and revised according to the PRISMA 2009 checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Noncommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Santosh Shenoy, MD, Professor, Department of General and Colorectal Surgery, KCVA and University of Missouri at Kansas City, 4801 E Linwood Blvd., Missouri, MO 64128, United States. shenoy2009@hotmail.com
Received: February 5, 2021
Peer-review started: February 5, 2021
First decision: March 17, 2021
Revised: March 21, 2021
Accepted: June 15, 2021
Article in press: June 15, 2021
Published online: July 9, 2021
Processing time: 151 Days and 22.7 Hours
Abstract
BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is diagnosed via real time reverse transcriptase polymerase chain reaction (RT-PCR) and reported as a binary assessment of the test being positive or negative. High SARS-CoV-2 viral load is an independent predictor of disease severity and mortality. Quantitative RT-PCR may be useful in predicting the clinical course and prognosis of patients diagnosed with coronavirus disease 2019 (COVID-19).

AIM

To identify whether quantitative SARS-CoV-2 viral load assay correlates with clinical outcome in COVID-19 infections.

METHODS

A systematic literature search was undertaken for a period between December 30, 2019 to December 31, 2020 in PubMed/MEDLINE using combination of terms “COVID-19, SARS-CoV-2, Ct values, Log10 copies, quantitative viral load, viral dynamics, kinetics, association with severity, sepsis, mortality and infectiousness’’. After screening 990 manuscripts, a total of 60 manuscripts which met the inclusion criteria were identified. Data on age, number of patients, sample sites, RT-PCR targets, disease severity, intensive care unit admission, mortality and conclusions of the studies was extracted, organized and is analyzed.

RESULTS

At present there is no Food and Drug Administration Emergency Use Authorization for quantitative viral load assay in the current pandemic. The intent of this research is to identify whether quantitative SARS-CoV-2 viral load assay correlates with severity of infection and mortality? High SARS-CoV-2 viral load was found to be an independent predictor of disease severity and mortality in majority of studies, and may be useful in COVID-19 infection in susceptible individuals such as elderly, patients with co-existing medical illness such as diabetes, heart diseases and immunosuppressed. High viral load is also associated with elevated levels of TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and C reactive protein contributing to a hyper-inflammatory state and severe infection. However there is a wide heterogeneity in fluid samples and different phases of the disease and these data should be interpreted with caution and considered only as trends.

CONCLUSION

Our observations support the hypothesis of reporting quantitative RT-PCR in SARS-CoV-2 infection. It may serve as a guiding principle for therapy and infection control policies for current and future pandemics.

Keywords: COVID-19, SARS-CoV-2, Viral load, Severe sepsis, Dynamics, Mortality

Core Tip: High viral load in Coronavirus-2 infections is an independent predictor of disease severity, mortality and prognosis. However there is a wide heterogeneity in fluid samples at different phases of the disease and data should be interpreted with caution. In aggregate, observations support the hypothesis of checking and reporting viral load by quantitative real time reverse transcriptase polymerase chain reaction, instead of binary assessment of a test being positive or negative. Longitudinal analysis with viral loads should be conducted for interpretation of outcome data. This may be the guiding principle for therapy and infection control policies for future pandemics.