In our cohort, we found no significant correlation between disease severity as indicated by respiratory indices, and viral load, as indicated by Ct values. As per a systematic review, eight (57%) out of 14 studies assessing a correlation between Ct value or viral loads and disease severity reported a significant association; our study would be the largest cohort (6 times the size of the largest one reported in the systematic review) to report no association . Conversely, according to one study, patients with severe symptoms presented with 60 times higher viral load and prolonged viral shedding than patients with mild symptoms . Additionally, a recent prospective cohort study showed an independent relationship between high viral load and mortality .
The fact that patients presenting more severely on admission relatively had both higher and lower Ct values in comparison to those presenting less severely may be more sensible when placed in the context of disease screening and time since symptom onset. Patients who were tested in our cohort were either contacts of positive cases, individuals with symptoms who got tested, or cases presenting to the Emergency Department. Patients presenting with severe cases on admission are likely to have progressed over a period of time while at home, before deciding that admission was necessary. This was specifically observed in the subpopulation of migrant workers, who formed a majority of our cohort in the initial months. In fact, our multivariate regression pointed out Bahraini’s to have significantly lower odds of presenting with severe disease on admission than non-Bahraini’s, which may support the hypothesised confounding nature of time since onset of symptoms rather than being an indicator of underlying biologic differences. As such, viral shedding may have been taking place for a longer period of time, thus leading to the patient’s Ct values being higher on admission compared to patients who only recently acquired the infection. The relationship between time since symptom onset and higher Ct values has already been well documented . On the other hand, a study of 205 patients showed an inverse correlation between viral load and disease severity, which they also pointed out may have been a reflection of time from onset of infection . Hence, time since symptom onset could be an important confounder when studying the association between Ct value and disease severity on admission. Nonetheless, without stratifying the two groups and accounting for bias and error in sample collection no such conclusion can be made with certainty. As such, although it may be the case that the correlation between viral load and disease severity is confounded by the time since symptom onset, it may also be that no inherent correlation exists. With a cohort of this size however, we can conclude that RT-PCR Ct values do not seem to be a viable metric to use as a simple, unprocessed, independent indicator of disease severity.
In the multivariate model, age was reported to be significantly associated with disease severity on presentation, which corroborates global findings . Likewise, fever and shortness of breath also seem to indicate disease severity on admission, in terms of requirement for oxygen support. Overall, comorbidities (i.e. chronic diseases) have been established as an important prognostic indicator of disease severity, as we have shown in a previous study , and should be considered as a potential confounder when examining correlations with other variables. As such, they were controlled for in this study.
As mentioned earlier, our study suggests that RT-PCR Ct value as a simple unprocessed metric is not associated with disease severity on admission. More prospective studies of diverse cohorts are needed to shed light on this controversial topic.