COVID-19: saliva could predict the course of the disease

While many countries continue to fight the pandemic, doctors and virologists are trying to improve the screening tools made available to populations in order to better detect and prevent the transmission of COVID-19. Recently, American researchers have shown that the viral load of saliva is a relatively reliable predictor of the course of the disease; a high salivary viral load being correlated with a subsequent hospitalization. If these results were to be confirmed, saliva tests could be used by caregivers to manage patients at risk early.

Several new tests are already looking for SARS-CoV-2 in saliva, and this study reveals a striking correlation between elevated saliva virus levels and subsequent hospitalization or death. If the results are confirmed, saliva tests could help doctors determine which patients in the early stages of the disease should receive viral load-lowering treatments.

These findings are not the first to link viral load and disease progression. Several research groups have found a correlation between high viral levels in the nasal passages at the time of a patient’s admission to hospital and the severity of the disease. But other groups have failed to find the same link.

Saliva tests: more reliable predictors than nasopharyngeal swabs?

The standard test to detect the coronavirus uses samples of nasal mucus collected using nasopharyngeal (NP) swabs. The procedure is unpleasant, but it is the usual way of sampling respiratory pathogens. In recent months, however, several research groups have developed and received emergency use authorization for the Food and Drug Administration from the United States for saliva detection tests.

Researchers at Yale University were among the first, and university hospitals use both saliva tests and NP swabs. In both cases, the labs analyze the samples using quantitative reverse transcription polymerase chain reaction tests, which can detect the genetic material of SARS-CoV-2 and quantify the number of viral particles in each milliliter of ‘sample.

Graphs showing viral load as a function of A) out-of-hospital and in-hospital patients; B) moderate and severe forms of the disease; C) living and deceased persons. Above for salivary viral load and below for nasopharyngeal viral load. © Julio Silva et al. 2021

The team, led by Yale immunologist Akiko Iwasaki, compared viral loads in saliva and NP swabs from 154 patients and 109 uninfected people. The authors divided the patients into groups that had low, medium, and high viral loads, as determined by the two types of tests. Then they compared those results to the severity of the symptoms that the patients developed later.

They found that patients who developed a severe form, were hospitalized, or died were more likely to have had high viral loads in their saliva tests, but not in their NP swabs. The viral load in saliva and nasal mucus decreased over time in patients who recovered, but not in those who died.

Salivary viral load and the immune system

When Iwasaki and his colleagues examined electronic patient medical records for markers of disease in the blood, they found that high salivary viral loads correlated with high levels of immune signals such as cytokines and chemokines, nonspecific molecules that increase in response to viral infections and have been linked to tissue damage.

chart immune system viral load saliva
Graphs showing the level of immune cells targeting the virus as a function of salivary viral load. The control group is indicated in black in graph A. © Julio Silva et al. 2021

People with a high salivary viral load also gradually lost certain cells that develop an immune response against viral targets, had lower levels of antibodies targeting the spike protein that the virus uses to enter cells, and were slower to develop the strong immune response necessary to neutralize the virus in cases where they have recovered.

Iwasaki and colleagues argue that saliva may be a better predictor of disease outcome than nasal mucus because the latter comes from the upper respiratory tract, while severe disease is associated with deep damage to the lungs. ” Saliva may better represent what is happening in the lower airways Says Iwasaki, because the cilia lining the airways naturally move mucus from the lungs to the throat, where it mixes with saliva; coughing has the same effect.

Early identification of patients at risk

The results do not have enough statistical power to reveal just how more likely a person with a high salivary viral load is to develop a severe form of COVID-19. The researchers also want other groups to replicate the results, especially because efforts to link high NP swab viral loads with disease progression have yielded mixed results.

If further research confirms the finding, “that would clear up a lot of the fog” around this disease, Crotty says. Monica Gandhi, an infectious disease specialist at the University of California, adds that if saliva tests are predictive, they could help doctors identify patients to treat early with antibodies to lower the viral load or steroids to lessen the symptoms. nonspecific hyperactive immune responses.

Sources: mediRxiv

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