Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants

Abstract

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented public health crisis in the 21st century. As the pandemic evolves, the emergence of SARS-CoV-2 has been characterized by the emergence of new variants of concern (VOCs), which resulted in a catastrophic impact on SARS-CoV-2 infection. In light of this, research groups around the world are unraveling key aspects of the associated illness, coronavirus disease 2019 (COVID-19). A cumulative body of data has indicated that the SARS-CoV-2 viral load may be a determinant of the COVID-19 severity. Here we summarize the main characteristics of the emerging variants of SARS-CoV-2, discussing their impact on viral transmissibility, viral load, disease severity, vaccine breakthrough, and lethality among COVID-19 patients. We also provide a rundown of the rapidly expanding scientific evidence from clinical studies and animal models that indicate how viral load could be linked to COVID-19 prognosis and vaccine efficacy among vaccinated individuals, highlighting the differences compared to unvaccinated individuals.

Global m6A RNA Methylation in SARS-CoV-2 Positive Nasopharyngeal Samples in a Mexican Population: A First Approximation Study

“…Interestingly, the two most contagious variants (delta and omicron)—with omicron being the most contagious globally—[ 22 ] showed the lowest methylation levels. These differences are unlikely to reflect variation in disease severity across variants, as COVID-19 patients with beta and delta variants generally are at higher risk of developing severe disease compared to patients with alpha, gamma [ 23 ], and omicron variant(s), whose mutations have been suggested to contribute to the host immune escape [ 24 ]. Interestingly, DRACH motifs are highly conserved among SARS-CoV-2 variants [ 25 ], thus the contribution of DRACH motifs to differential methylation levels among variants remains unclear and require further research.…”

Comparing studies of SARS‐CoV‐2 viral loads requires caution

“…A probable answer is the use of RT‐qPCR C t values instead of true quantitative determinations. 18 , 19 …”

“… 20 However, C t values cannot be directly compared across RT‐qPCR assays and, therefore, they must be interpreted with caution. 20 Notably, the exclusive use of C t value to assess viral load can represent a bias during the statistical analysis since many technical issues that might impact and alter the C t value during RT‐qPCR reactions—including differences in protocols, threshold values, viral target, primers, enzymes, and research kits, calibration of RT‐qPCR machine, type of biological samples, and period of sample collection, 19 which means that the C t value not represent the best parameter to assess viral load in COVID‐19 patients. With this in mind, I suggest that further studies should consider a combination of C t values and RNA copies/ml for viral load analysis among COVID‐19 patients.…”

“…This new perspective, combined with the evaluation of host‐related factors (e.g., age, sex, comorbidities, etc.) 19 , 21 will be critical to understand the real impact of SARS‐CoV‐2 viral load on COVID‐19 disease severity.…”

“…A probable answer is the use of RT-qPCR C t values instead of true quantitative determinations. 18,19 At present, most studies just considered the C t value for analysis viral load among COVID-19 patients, instead of the number of RNA copies/ml. In fact, C t values are correlated with the amount of viral RNA in a sample.…”