Discussion
In Mexico, as in many parts of the world, respiratory infections are the
health conditions with the highest morbidity and mortality each
year12,13. According to previous studies conducted by
our research group, there is evidence that at least 16 respiratory
viruses co-circulate in Mexico (RV, HRSV, HMpV, HMdV, EV, PBpV 1, HPIV
1, HPIV 3, HPIV 4, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, Inf
A/H1N1pdm09, Inf A/H3N2, and Inf B)14,15, aside from
the recently introduced SARS-CoV-2. These viruses frequently cause cases
of coinfections within the Mexican population, where the same patient
can be infected with up to four different respiratory viruses at the
same time14.
Since shortly after the identification of this novel virus in Wuhan,
China, demographic groups and risk factors have been reported that
predispose to a more severe COVID-19 progression, but serious cases and
even deaths that are not explained by these factors continue to appear.
In this study, we verified the presence of 16 respiratory viruses in
COVID-19-positive patients in Mexico to determine the existence of
coinfections, as well as the relationship that coinfections may have
with more severe manifestations of the disease.
After analysing 103 samples, 14 coinfections (13.6%) were identified.
This percentage was slightly lower than that found by Navarro-MarĂ et
al.16 in Spain, who retrospectively looked for the
presence of other respiratory viruses during the 2009 influenza pandemic
and reported 15% coinfection in the more than 18,000 analysed
samples15. Although their study addressed other
important topics on the behaviour of some respiratory viruses, the
clinical data associated with coinfections were not
analysed16.
In our study, contrary to what would be expected, the group of patients
with co-infections presented evidently less severe manifestations of
COVID-19, since 92.9% of these cases developed mild forms of the
disease and the patients did not require hospitalization (outpatient
cases). Additionally, comorbidities considered risk factors were equally
prevalent in both groups, and the two groups had similar mean ages
(Table 4), which shows that both groups presented the same
predisposition to developing complications.
Of all the coinfections detected, only the case of coinfection with
influenza A resulted in the death of the patient, which led us to
investigate antecedents on whether the severity of the coinfection could
depend on the specific type of virus that causes it or what other
factors could explain our findings. In 2016, Pinky and Dobrovolny
published one of the few existing studies on coinfections with different
combinations of respiratory viruses. In their study, using a
mathematical model, they demonstrated that viral interference can be
explained mainly by competition for the resources of the host cell.
Apparently, this interference also depends on which infection occurs
first, and the authors predicted that viruses with higher growth rates
can outperform viruses with lower growth rates, since the
fastest-growing virus would consume more target cells at the beginning
of infection17.
When measuring the SARS-CoV-2 viral load in the cases analysed, we
observed, although without statistical significance
(P>0.05), that the mean viral load was lower in the
coinfected patients (Fig. 2). This could suggest that there are viruses
whose replication rates are higher than those of SARS-CoV-2, directly
influencing its replication and resulting in a milder case of COVID-19.
Even though we cannot affirm that the virus with a higher replication
rate is the one that dictates the clinical manifestations of the
coinfected patient, it seems not to be random that the seven viruses
that were detected simultaneously in mild cases of COVID-19 (HCoV-229E,
RSV, RV, HPIV1, HPIV2, HPIV4, and HCoV-OC43) cause generally
self-limited respiratory infections that resolve in an average of 15
days and that, unlike these viruses, Inf A is associated with higher
rates of complications and mortality than the other viruses and may have
been the cause of death of the coinfected patient.
In any case, the interactions of two or more viruses when they
simultaneously infect a host are more complex than they seem. In
addition to competition for the resources of the host cell, other
mechanisms are linked to the immune response and production of
cytokines, such as interferons, that may also have some role in the
viral interference phenomenon18-20. Therefore, larger
and more targeted studies are required to corroborate the observations
described in this work and to determine if coinfection with some viruses
could lead to a better prognosis for patients diagnosed with COVID-19.