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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