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.