Co-infection of SARS-CoV-2 with human coronavirus OC43 in a patient with underlying lung disease: A case report

Abstract

Co-infections with SARS-CoV-2 remain relatively rare and there is limited published data on the consequences of these events. We present the case of a 26-year-old man with SARS-CoV-2 and human coronavirus OC43 who had a severe infection resulting in prolonged hospitalization. Consideration of co-infections should be considered in high-risk patients.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Co-infections of SARS-CoV-2 with other respiratory pathogens are reported infrequently and testing for other respiratory viruses in non-severe cases of COVID-19 is not routinely done (1). With the easing of the COVID-19 pandemic restrictions, an increased incidence of respiratory viruses transmitted via droplet and contact means is expected. Herein, we describe a case of an immunocompromised patient with underlying pulmonary disease co-infected with SARS-CoV-2 and human coronavirus OC43 (HCoV-OC43).

Case Presentation

A 28-year-old male was admitted to the respirology service at a tertiary care hospital with a productive cough, acute dyspnea, and new onset hypoxia of 4 days duration. He required 4 L/minute of oxygen via nasal prongs to maintain a pO2 > 90%, having previously maintained adequate oxygen saturations on room air. He had been diagnosed with interstitial lung disease in the preceding 3 months and had started prednisone therapy at 50 mg orally daily 2 weeks prior to his admission. He had received two doses of an mRNA SARS-CoV-2 vaccine 5 months prior to his admission. He reported a close contact with a symptomatic relative (fever and pharyngitis) 24 hours prior to the onset of his symptoms. He denied any preceding upper respiratory tract symptoms. On exam, he was afebrile and normotensive, without tachycardia. Physical examination was notable for dyspnea and hypoxia with bilateral basilar crackles without wheeze heard on respiratory auscultation. The rest of his examination was non-contributory.

Biochemical work-up was notable for an elevated white blood cell count at 19.9 × 10⁹/L with neutrophilia and a C-reactive protein level of 91.3 mg/L. A nasopharyngeal swab specimen was positive for SARS-CoV-2, Omicron BA.1 variant (via real-time polymerase chain reaction), and HCoV-OC43 (via nucleic acid amplification). The tests were ordered using the Molecular Testing Requisition by Provincial Laboratory for Public Health. A chest X-ray showed bilateral hazy and reticular opacities with air bronchograms in the lung bases. Superimposed bacterial pneumonia was not suspected via X-ray (Figure 1).

Figure 1:

Anterior-posterior and lateral chest X-ray view of the patient at admission

During his admission, he continued his home dose of prednisone 50 mg daily and was treated with intravenous Remdesivir (200 mg loading dose on day 1 followed by 100 mg daily for 4 more days) (2). Repeat nasopharyngeal swabs on day 5 of Remdesivir treatment yielded persistent positivity of SARS-CoV-2 but was negative for HCoV-OC43.

Tocilizumab was used during the first week of his admission as his respiratory status worsened with an increase of his oxygen requirements from 4 L/min via nasal prongs to 15 L/min via a non-rebreather, to maintain a >90% SaO₂. Subsequently, his respiratory status gradually stabilized and improved by the last week of his admission. He was ultimately discharged home after a 29-day admission on 4 L/min of oxygen via nasal prongs and prednisone 40 mg daily.

Discussion

Rates of co-infection of SARS-CoV-2 with other respiratory viruses reportedly range from 2% to 10%, while bacterial and fungal infections, either co-infection or secondary, are more commonly described (1). Co-infections by respiratory viruses in children and the elderly have previously been demonstrated to result in greater symptomatology (i.e., dyspnea, cough), with limited effect on hospitalizations (3). While there is a paucity of data on the effect of co-infections of endemic human coronaviruses like HCoV-OC43, and SARS-CoV-2, the reported cases have indicated mild differences in clinical presentation in persons with and without co-infections (4).

To our knowledge, this is the first report of SARS-CoV-2 co-infection with HCoV-OC43 in a person with underlying pulmonary dysfunction and with significant immunocompromise. Human coronavirus OC43 typically results in upper respiratory tract symptomatology (5). Lower respiratory tract and other clinically relevant infections are infrequently reported but have been observed in children, the elderly or the immunocompromised (3). An infection with HCoV-OC43 may increase the susceptibility to other infections (3). An immunocompromised state along with recent corticosteroid usage and co-infection may increase the risk of moderate-to-severe outcomes (6).

While the contribution of HCoV-OC43 to the patient's protracted course remains unclear, in vivo studies of HCoV-43 are associated with greater inflammatory cytokine production, particularly, Interleukin-6 (IL-6) (3). It is possible that greater levels of IL-6 may associate with the severity of respiratory distress (3). Remdesivir targets viral RNA-dependent-RNA polymerase, and has activity against SARS-CoV-2 and potentially HCoV-OC43 (7), and has been demonstrated to decrease mortality in persons requiring low flow oxygen (8). It is possible that treatment with remdesivir in our patient may have led to a more rapid resolution of OC43 and its associated IL-6 response (9).

With the easing of pandemic restrictions, there is likely to be an increase in the prevalence of respiratory viral coinfections with SARS-CoV-2. While infection with less virulent pathogens may not significantly affect disease severity in healthy individuals, those with underlying pulmonary disease and/or immunocompromised states may have a greater risk of death or morbidity (3). Similarly, infection with HCoV-OC43 in children, elderly, and immunocompromised individuals has indicated a high likelihood of mortality. Considerations should be made for testing for co-infections in SARS-CoV-2 patients, particularly in at-risk individuals or those with unusual or more severe presentations. Accurate diagnosis can assist clinicians with explaining disease severity, particularly in at-risk individuals and may have implications for drug or vaccine strategies to treat the presenting infection or for preventing future infections respectively. Additionally, the association between severity of symptoms and inflammatory cytokines such as IL-6 in co-infection states should be explored.

Conclusion

The epidemiology of respiratory viral co-infections of SARS-CoV-2 and their associated clinical severity is increasingly being reported, with greater efforts underway to understand their infection mechanisms and clinical presentations (10,11). Reported data on viral respiratory co-infections have suggested more severe clinical states in patients. More detailed studies are required to gain a richer understanding of the presence of respiratory co-infections during the current pandemic and the consequent impact on clinical severity. With the easing of pandemic-related social restrictions, an increase in respiratory co-infections is likely to occur. Those with underlying pulmonary disease or immunocompromised may be at higher risk of co-infection and should be evaluated for this phenomenon so that optimal therapeutic decisions can be made.

Contributors:

Conceptualization, K Mponponsuo, A Tremblay, J Conly, R Somayaji; Methodology, J Conly, R Somayaji; Validation, Y Murthy, J Kanji, A Tremblay, D Khan, R Somayaji; Resources, K Mponponsuo, J Kanji, A Tremblay; Supervision, A Tremblay; Software, D Khan, J Conly, R Somayaji; Writing – Original Draft, K Mponponsuo, Y Murthy, D Khan; Writing – Review & Editing, J Kanji, A Tremblay, D Khan, J Conly, R Somayaji; Data Curation, K Mponponsuo, Y Murthy, J Kanji, D Khan; Project Administration, Y Murthy, A Tremblay, D Khan, J Conly, R Somayaji.

Ethics Approval:

N/A

Informed Consent:

We confirm that informed patient consent has been secured from all patients whose personal information is included in the manuscript or the parents or guardians of minors.

Registry and the Registration No. of the Study/Trial:

N/A

Data Accessibility:

All data will not be made publicly available. Researchers who require access to the study data can contact the corresponding author for further information.

Funding:

N/A

Disclosures:

R Somayaji received clinical research grants from Cystic Fibrosis Foundation, Canadian Institutes of Health Research, Snyder Institute for Chronic Disease, and the Department of Surgery at the University of Calgary, received educational payments from Vertex Pharmaceuticals, and was a DSMB member on the Oncovir Phase II trial and an advisory board member for Vertex Pharmaceuticals. The other authors have nothing to disclose.

Peer Review:

This manuscript has been peer-reviewed.

Animal Studies:

N/A