SARS-CoV-2 (COVID-19), viral load and clinical outcomes; lessons learned one year into the pandemic: A systematic review

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, Log 10 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.

A simple risk score for mortality including the PCR Ct value upon admission in patients hospitalized due to COVID-19

“…Different findings about the predictive value of the Ct value have been reported. There are systematic reviews [ 16 , 18 ] indicating a predictive role for morbidity and mortality, but studies have also pointed to a number of weaknesses, such as inter-individual differences in sample-taking, which may result in varying outcomes for specimens [ 19 ]. Moreover, Ct values change over the course of the disease, which renders them dependent on the time of sampling [ 23 , 44 ].…”

“…The higher is the Ct value, the lower the virus load, and vice versa [ 15 ]. A number of studies found the Ct value to be predictive for mortality and ICU admission [ 16 – 18 ]. However, respiratory virus load is known to change during the course of infection, indicating the degree of virus shedding in an individual patient.…”

A COVID-19 primer for primary care clinicians

“…In adults, there is a correlation between viral load at onset of symptoms and the severity of symptoms of COVID-19. 11 Children have been found to have similar viral loads compared to adults and are known to be efficient spreaders of SARS-CoV-2. 12 …”

Gut microbiome, Vitamin D, ACE2 interactions are critical factors in immune-senescence and inflammaging: key for vaccine response and severity of COVID-19 infection

“…Systemic immune-senescence and inflammaging also have damaging effects on the GI tract and dysfunctional gut immune system is associated with severity of lung infections, pneumonia and sepsis through gut lung axis [9,15,28]. The state of gut function and its physiological health, such as dysbiosis, vitamin D deficiency, poor nutrition, obesity, along with COVID-19-related factors, such as viral load, may determine the outcome associated with COVID-19 sepsis [3,12,18].…”

“…This current COVID-19 pandemic has established that our understanding of the pathophysiology of sepsis remains incomplete and further research is needed to fill these gaps. It has been demonstrated that combinations of risk factors, such as medical comorbidities, older age group, mitochondrial dysfunction, along with high nasopharyngeal viral load, are predictors for worse outcomes [3,4].…”