Discussion

In this large monocentric prospective cohort study, including 508 and 596 consecutive ILI patients attending the ED during the RV and SARS-CoV-2 periods, respectively, we identified several clinical features associated with positive viral PCR. This allowed us to identify the highest COVID-19 suspicions among all respiratory viral infections.
The ability to distinguish COVID-19 from other RVs will become an increasingly important issue in northern-hemisphere countries as circulation of SARS-CoV-2 could be expected to continue during the upcoming year and the next epidemic of winter-associated viruses’5. The importance of such co-circulation is difficult to predict. Few countries in the southern hemisphere are currently describing high co-circulation of other RVs with SARS-CoV-2. However, several countries at the beginning of the SARS-CoV-2 outbreaks in Northern America or Europe reported such co-circulation6,7.
The features observed in our cohort for COVID-19 patients are in line with previous reports 14. Most of these clinical features are also associated with other respiratory viral infections observed in our study and previous works 15,16. By analyzing the comparative strength of these clinical features’ associations with SARS-CoV-2 positivity in relation to other RVs, we were able to define a limited set of markers associated with a higher risk of being infected by SARS-CoV-2: being male, of a younger age, with feverishness and in the absence of expectoration is predictive of a SARS-CoV-2 infection, while having chronic lung diseases is predictive of non-SARS-CoV-2 RVs. Our results were confirmed under several SARS-CoV-2 prevalence conditions and are in line with the only other study available to date comparing features associated with SARS-CoV-2 to those associated with other respiratory viral infections. The latter study described anosmia, dysgeusia, diarrhoea, frontal headache and bilateral crackling sounds as being more frequently associated with COVID-19 than other RVs 17. Our results confirm the findings of this smaller retrospective work on a large prospective cohort, except for diarrhea, which was not associated with COVID-19 diagnosis in our population. In both this previous work and our study, no biological findings upon ED admission allowed for a discrimination between SARS-CoV-2 and non-SARS-CoV-2 respiratory infections. An interesting point highlighted in our work is the impact of SARS-CoV-2 and the other RVs relative prevalence on the clinical scoring with PPVs ranging from 57 to 92% and NPVs ranging from 45 to 88% depending on the proportion of SARS-CoV-2 among RVs. As those relative prevalence cannot be predicted and will probably evolve during the RV epidemic period, any clinical scoring of COVID-19 suspicion will have to be monitored in real time and will not eliminate the need for rapid molecular assays.
Our study presents several limitations. first, it is a monocentric study, and the RV period was designed before the emergence of SARS-CoV-2 for analyzing other RV features. Therefore, a few key characteristics, such as diarrhea, anosmia and ageusia, or procalcitonin, which was initially not known to be associated with COVID-19, could not be included in the present work. Their collection could help in future works to improve the clinical scoring of COVID-19 suspicions. As the French COVID-19 initial outbreak began at the end of the winter season, a few other RVs were identified during the SARS-CoV-2 period, alone or in association with SARS-CoV-2. The small numbers of co-infections observed in our work did not allow for an individual assessment of their clinical and biological presentations. Finally, the proposed clinical score requires an external validation before being used for patient management. Moreover, the identified features may evolve in the upcoming years with the ongoing immunization of the general population. A surveillance of the disease’s evolution will be therefore, required in the future.
In conclusion, symptoms associated with SARS-CoV-2 and with other respiratory viral infections are frequently shared 8. This poses potential challenges in patient management in case of a large co-circulation of all these viruses, as it may be expected in the upcoming months in most northern countries. Despite this overlap, COVID-19 patients present several clinical characteristics less frequently identified among those infected by other RVs such as influenza. Based on these data, we developed a clinical tool to aid in screening SARS-CoV-2 infection among all viral respiratory infections. These observations were confirmed in various ratios of SARS-CoV-2 and other RVs. As having an efficient, reliable and rapid patient’s triage system upon ED entrance, clinical scoring could be a tempting and useful tool depending on one’s local environment and constraints, especially due to the large PCR turnaround time or poor single room availability either in the ED or in the hospital. However, this tool needs to be prospectively evaluated before any potential use and, as we demonstrated, the performances may be strongly impacted by the relative prevalence of SARS-CoV-2 and other RVs. As this relative prevalence is impossible to predict in the near future, no clinical scoring will waive the need for molecular assays. Therefore, our main efforts, on the eve of the next respiratory viruses epidemic period, should still focus on having a large availability, accessibility and optimized use of rapid molecular testing.
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