key: cord-308831-u5bj1sod
authors: Chaung, Jenna; Chan, Douglas; Pada, Surinder; Tambyah, Paul A.
title: Coinfection with COVID‐19 and Coronavirus HKU1 – the critical need for repeat testing if clinically indicated
date: 2020-04-15
journal: J Med Virol
DOI: 10.1002/jmv.25890
sha: 
doc_id: 308831
cord_uid: u5bj1sod

COVID‐19 is the latest global pandemic caused by severe acute respiratory syndrome coronavirus ‐2 (SARS‐CoV‐2). There have been seven pathogenic Human Coronaviruses (HCoVs) which cause respiratory infections. Common cold coronaviruses HCoV‐229E, HCoV‐OC43, HCoV‐NL63, HCoV‐HKU1 are the four endemic HCoVs. SARS‐CoV‐1, MERS‐CoV, SARS‐CoV‐2 are zoonotic emerging epidemic pathogens with significant morbidity, mortality and economic impact. The endemic HCoVs have been known to cause co‐infections or can be co‐detected with each other or with other respiratory viruses. In general, respiratory viral co‐infections are recognized more commonly today with the use of respiratory multiplex molecular diagnostic panels. Clinicians need to be aware of co‐infections among HCoVs. A high degree of suspicion in this rapidly evolving outbreak is required in order to make the diagnosis. This is vital if we are to try and contain and control the spread of the COVID‐19. This article is protected by copyright. All rights reserved.

COVID-19 is the latest global pandemic caused by the severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). There have been seven pathogenic Human Coronaviruses (HCoVs). The four endemic HCoVs (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) can cause respiratory infections ranging from common cold and croup to lower respiratory tract infections 1 . SARS-CoV-1, MERS-CoV, SARS-CoV-2 are zoonotic emerging epidemic pathogens with significant morbidity, mortality and economic impact.

The endemic HCoVs have been known to cause co-infections, sequential infections or can be co-detected with each other or with other respiratory viruses 2, 3,4, 5 . In general, respiratory viral co-infections are recognized more commonly today with the use of respiratory multiplex molecular diagnostic panels.

We describe a case of endemic HCoV co-infection with SARS-CoV-2 in a patient with COVID-19.

Case details:

A 34-year-old Filipino domestic worker presented with dry cough and sore throat of four days duration on 28 Feb 2020. She also had a low grade fever on the previous day, with maximal temperature recorded at 38°C. She had travelled to Batam, Indonesia, 3 days before the admission with seven other people from two separate households. Three of them subsequently were found to be confirmed cases of COVID-19 disease.

At presentation, she was afebrile, and her throat was mildly injected. Otherwise, the physical examination, including respiratory exam was unremarkable. Full blood counts, renal and liver function tests and lactate dehydrogenase were within normal limits. Of note, no leukopenia, lymphopenia or thrombocytopenia was observed. Nasopharyngeal swabs were sent on day 1 of admission, one was positive for HCoV-HKU1 on the FilmArray Respiratory Panel (RP) (BioFire Diagnostics, bioMerieux) but another was negative for SARS-CoV-2 by RT-PCR (in-house-laboratorydeveloped test detecting the N and ORF1ab genes by primers, with LightCycler 2.0 instrument from Roche, RotKreuz, Switzerland a ) 6 . Chest radiography revealed illdefined air space opacities bilaterally in the lower zones. As her travel companions had been confirmed to have COVID-19, and she remained symptomatic, we persisted in testing her for SARS-CoV-2 despite having an "alternative" diagnosis for her initial symptoms. SARS-CoV-2 was eventually detected on day 3 of admission. She made an uneventful recovery without any desaturation and had improvements in her chest radiography. She was discharged on day 20 of her admission; 24 days after onset of symptoms. Endemic HCoVs cause mild to severe respiratory infections or severe pneumonia with acute respiratory distress syndromes (ARDS) primarily in immunocompromised patients 5 HCoVs are known to co-infect human hosts with other respiratory viruses, including influenza A/B, RSV, metapneumovirus, enterovirus, adenovirus 2, 3, 4, 5 . Even among the four endemic HCoVs, co-infections may sometimes occur 2, 3, 4, 5 . In this case, our immediate concern was whether there was cross reactivity of SARS-CoV-2 virus with the CoV-HKU1 target on the FilmArray RP. This was definitively ruled out when a repeat nasopharyngeal swab positive for SARS-CoV-2 on day 18 of admission was subjected to testing again on the FilmArray RP and found to be negative for all pathogens on the panel. Hence, we believe that our patient experienced co-infection with both endemic HCoV-HKU1 and pandemic SARS-CoV-2.

It is also possible that she had sequential infections. The patient was infected first with HCoV-HKU1 then later with SARS-CoV-2 with the FilmArray RP picking up the remnant or colonizing HCoV-HKU1 RNA that subsequently disappeared.

Our case illustrates the importance of maintaining a high degree of suspicion and to note that positivity for a known virus on any respiratory multiplex assay does not exclude the possibility of co-infection with SARS-CoV-2 in a patient with a compatible clinical presentation and epidemiological history.

Clinicians need to be aware of co-infections among HCoVs. Testing protocols need to allow for repeat testing (our patient only turned positive on her third test) and testing in individuals with a possible alternative diagnosis. A high degree of suspicion in this rapidly evolving outbreak is required in order to make the diagnosis. This is vital if we are to try and contain and control the spread of the COVID-19.

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Thermal cycling was performed at 50C for 20 minutes for reverse transcription, 95C for 15 minutes for denaturation followed by 50 cycles of 94C for 5 seconds, 50C for 20 seconds and 72C for 20 seconds. For both assays, each 20uL reaction contained 5uL RNA template, 1uL each of forward and reverse primer, 0.5uL probe and 0.2 uL QuantiTect RT mix (QuantiTect Probe RT-PCR kit, Qiagen). Detection of endogenous RNAse