Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality

Abstract

While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection, work remains in identifying unifying correlates of coronavirus disease 2019 (COVID-19) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 inflammatory markers such as IL-6, IL-18, IL-10, and CXCL10, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19. Finally, patients with fatal COVID-19 exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load – as measured by saliva but not nasopharyngeal — is a dynamic unifying correlate of disease presentation, severity, and mortality over time.

SARS-CoV-2 infection of the oral cavity and saliva

“…Furthermore, minor SGs appear to be a relatively unexamined site for viral infection and replication, despite the detection of the virus throughout the functional unit for saliva production, which points to a mechanism whereby the acellular source of SARS-CoV-2 in saliva might be derived from these glands. The effect of this could be that SGs could propagate SARS-CoV-2 infection and sustain COVD-19 in other body sites 51 .…”

N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection

“…When analyzing N-protein in longitudinal saliva and DBS samples from an infected donor, we observed that N-protein presented in both saliva and blood before symptom onset and that N-protein levels correlate with Ct values for RNA in saliva, as has been recently observed for N-protein in NP swabs 26 . Recent work suggests that viral load in saliva is a predictor of mortality 27 .…”

Post-Disease Divergence in SARS-CoV-2 RNA Detection between Nasopharyngeal, Anterior Nares and Saliva/Oral Fluid Specimens - Significant Implications for Policy & Public Health

“…The FDA has moved rapidly to authorize hundreds of molecular tests for Emergency Use during the COVID-19 pandemic and has dramatically expanded access to testing (32). However, the number of tests authorized for alternative specimen types such as oral fluid or saliva which can provide easy, high-throughput access to regular testing, has remained small (33), despite these specimen types being shown to be highly effective (15, 34, 35, 36, 37). And in fact there still remains no test authorized for use in asymptomatic screening using saliva or oral fluid.…”