Measurement of the amount of virus in humans infected with SARS-CoV-2 is one of the main factors in the evaluation of infectivity in COVID-19 patients. Viral load can be affected by the infectious SARS-CoV-2 variant as well as the patient’s vaccination status.
A research team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) measured the amount of infectious virus in almost 600 symptomatic patients to detect possible differences between the original virus, Delta and Omicron sublineage BA.1, and according to vaccination status . They discovered that Delta causes a higher viral load than the original virus and the Omicron variant. For Delta and Omicron breakthrough infections, vaccination drastically reduces the viral load. In the case of Omicron, however, the decrease was only observed after three doses of vaccine. Furthermore, Omicron’s very high infectivity is apparently related to factors other than viral load alone. These results can be read in the journal Natural medicinehighlight the benefits of vaccination for public health in addition to individual protection against the serious form of the disease, and remind us that variants of the virus must be closely monitored to prevent further massive outbreaks.
The diagnosis COVID-19 consists of a PCR test performed on a nasopharyngeal or saliva inoculation. “This test is very effective in identifying infected people, but does not indicate whether they are contagious, that is, able to transmit the virus to other people,” says Isabella Eckerle, professor at the Department of Medicine at UNIGE Faculty of Medicine and head of the HUG-UNIGE Center for Emerging Viral Diseases, who led this work. “However, the concept of contagion is crucial in making decisions about collective prevention measures, such as periods of isolation.”
PCR tests can only detect the presence of viral RNA, but do not indicate whether the virus is still intact and able to spread. The measurement of the amount of infectious virus necessarily involves culturing the virus for several days in a biosafety level 3 laboratory, a procedure that is impossible to perform routinely.
Lower viral load due to vaccination
Since the beginning of the pandemic, samples taken at the HUG screening center have been kept for research purposes with the permission of the persons concerned. “We were able to re-analyze samples from previous waves of the disease,” explains Benjamin Meyer, a researcher at the Center for Vaccinology at the Department of Pathology and Immunology at UNIGE Faculty of Medicine. We measured the infectious viral load of 3 cohorts of patients during the first 5 symptomatic days to compare the viral load caused by the original virus (118 samples, spring 2020), the Delta variant (293 samples, autumn 2021) and The omicron variant sublineage BA.1 (154 samples, winter 2022), as well as, for the last two cohorts, whether a significant difference could be detected in vaccinated and unvaccinated individuals. “
Overall, the infectious viral load for the Delta cohort was significantly higher than for the cohort with the original virus. However, individuals infected with Delta who received two doses of mRNA vaccine had a significantly lower infectious viral load than unvaccinated humans. “For the Omicron cohort, contrary to what one might assume due to its rapid spread, the infectious viral load was generally lower than the Delta cohort,” says Isabella Eckerle. In contrast, only individuals who were boosted (i.e., having received three doses of the vaccine) had their viral volume reduced; individuals who received only two doses had no benefit in this regard compared to unvaccinated people. “This is immunologically consistent: many vaccines require 3 doses at intervals of several months to elicit a sustained immune response, such as that against the hepatitis B virus,” explains Isabella Eckerle.
Omicron: a variant far removed from the former
Why is the Omicron variant so contagious if the viral load it induces is lower than its predecessors? “We still do not know, but our data suggest that other infectious mechanisms are at play,” explains Pauline Vetter, clinic director at the HUG-UNIGE Center for Emerging Diseases. “It is now clear that the mutations of Omicron strongly distinguish it from other variants, enabling it to partially escape the vaccine and diminish the effectiveness of some antiviral treatments that have been used so far.” However, vaccination has been shown to be useful in limiting the occurrence of severe symptoms and most likely also transmission of the virus. In countries where the population, especially the elderly, are poorly vaccinated, Omicron has been shown to be just as deadly.
The Geneva study also shows that the knowledge gained for previous variants needs to be updated each time a new variant emerges in order to adapt the means to combat COVID-19. “In the light of our findings, the utmost caution should be exercised in relation to a virus whose development is not fully understood and which currently existing treatments are losing some of their effectiveness against,” the authors conclude.
This work was carried out thanks to grants from the Swiss National Science Foundation (SNSF), the Pictet Group’s Foundation Ancrage bienfaisance and the HUG Private Foundation.