Co-Infections Involving SARS-CoV-2 And Human Rhinovirus Typically Results In Severe Health Outcomes

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A new study involving researchers from the Institut Hospitalo-Universitaire Méditerranée Infection-France, Thai Binh University of Medicine and Pharmacy-Vietnam and Aix Marseille University-France has discovered that co-infections involving the SARS-CoV-2 coronavirus and the human Rhinovirus typically results in severe health outcomes

The study findings were published in the peer reviewed journal:

Viruses https://www.mdpi.com/1999-4915/13/12/2528

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in France at the end of January 2020. Since then, on 23 September 2021, the number of cases reached 6,905,071 and 115,517 associated deaths were recorded [1].

In our institute, the first case was diagnosed at the end of February 2020 and, since then (on 31 August 2021), 57,055 patients were found positive among the 525,464 patients tested. We have previously observed that the frequency of coinfections with several respiratory viruses and the type of respiratory viruses involved were a “matter of sampling time” [2].

Indeed, very important differences were reported according to the period of the study and the region of the world where it took place as the occurrence of viral coinfections requires a co-incidence of the viral epidemic periods [2,3,4,5,6].

Likewise, major differences were observed according to the epidemic mode of the respiratory viruses involved in coinfections, i.e., according to whether they showed a bell-shaped curve of incidence or circulated throughout the year with varying intensities [7].

Contrasting with our previous work that focused on the March-April 2020 period, we studied the diagnoses of infections with SARS-CoV-2 and/or other respiratory viruses over a whole year during the SARS-CoV-2 pandemic.

We centered our analyses on coinfections with SARS-CoV-2 and human rhinovirus (HRV) as this latter virus is the one that was found the most frequently associated with SARS-CoV-2 (in 41% of detected coinfections) in our center [2].

This predominance has also been reproducibly observed in several other previous studies conducted in various settings and geographical areas, with HRV being reported as the most frequent or among the most frequent respiratory viruses coinfecting COVID-19 patients [2,5,6,8,9,10,11,12,13].

Nonetheless, the clinical outcome of SARS-CoV-2 infection in patients co-infected with HRV remains unknown. In addition, HRV has a less marked seasonality compared to other respiratory viruses as it circulates throughout the year, although with various levels of incidence [7].

This is of particular interest in the study of respiratory virus coinfections with respect to the current SARS-CoV-2 pandemic. Here, we compared clinical severity in patients coinfected with a SARS-CoV-2 and HRV or monoinfected with a single of these viruses.

Discussion

Over a whole year from March 2020 through February 2021, rhinovirus was, by far, the most frequently diagnosed respiratory virus in our institute, either in association with SARS-CoV-2 or alone. To our knowledge, to date, no study systematically assessed the severity of infections with SARS-CoV-2 and rhinovirus, but prolonged SARS-CoV-2 persistence beyond the acute infection phase was significantly associated with HRV/enterovirus co-infection [11].

It could increase the capacity of viral transmission [11]. Previous reports were case reports [18,19]. Orozoco-Hermandez et al. reported increased severity of initially mild COVID-19 symptomatology in a 41-year-old patient with coinfection with rhinovirus or enterovirus who developed multilobar pneumonia requiring admission to ICU [18].

A case of SARS-CoV-2 and rhinovirus–enterovirus coinfection was also reported in a pregnant woman [19]. Our results notably suggest that patients coinfected with SARS-CoV-2 and rhinovirus were more likely to suffer dyspnea than those infected with rhinovirus only.

A trend toward increased risks for both transfer to an ICU and death was also seen in patients coinfected with SARS-CoV-2 and rhinovirus compared to those monoinfected with rhinovirus.

The putative interactions and clinical impact of HRV and SARS-CoV-2 co-infections were, thus, very scarcely addressed. Here, co-infected patients presented significantly more frequently cough, compared to those with mono-SARS-CoV-2 infection. Although the interaction between these viruses is still unclear, the co-detection of HRV has also been associated with mild COVID-19 [10,12].

One potential reason for this phenomenon is that viral coinfection is more common in young persons, aged between 15 and 64 years [10]. Besides, a recent in vitro study reported an indirect negative interaction between HRV and SARS-CoV-2 and hypothesized that HRV can trigger an interferon response that makes most cells nonpermissive to SARS-CoV-2 infection, blocking its replication [20].

The present study has some limitations. Not all patients diagnosed as infected with SARS-CoV-2 or HRV during the study period were systematically tested for the other respiratory virus. In addition, we were not able to classify these cases as concomitant infections or superinfections, as the study was not designed for this aim and same respiratory samples were tested for both viruses that have different incubation duration and may differ regarding their persistence duration.

In addition, several biomarkers known to be associated with respiratory disease severity, including lactate dehydrogenase level, D-dimers value, thrombocyte count, and troponin level [21], were not considered either. Moreover, we did not provide information on the duration of symptoms which could differ between patients who were co-or monoinfected with SARS-CoV-2 and rhinovirus. Additionally, we did not follow up the patient after discharge.

Finally, the duration and intensity of viral shedding were not evaluated. Since the future of the current SARS-CoV-2 pandemic is unknown, a close surveillance and investigation of the co-incidence and interactions of SARS-CoV-2 and other respiratory viruses are needed.

Further large-scale studies are needed to investigate the role of co-infection between SARS-CoV-2 and HRV in severity of COVID-19.

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