An Outbreak of Human Coronavirus OC43 Infection and Serological Cross-reactivity with SARS Coronavirus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095096/
Abstract
Background
In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV).
Methods
Cases at a care facility were epidemiologically characterized and sequentially investigated for conventional agents of respiratory infection, SARS-CoV and other human CoVs. Serological cross-reactivity between SARS-CoV and human CoV-OC43 (HCoV-OC43) was investigated by peptide spot assay.
Results
Ninety-five of 142 residents (67%) and 53 of 160 staff members (33%) experienced symptoms of respiratory infection. Symptomatic residents experienced cough (66%), fever (21%) and pneumonia (12%). Eight residents died, six with pneumonia. No staff members developed pneumonia. Findings on reverse transcriptase-polymerase chain reaction assays for SARS-CoV at a national reference laboratory were suspected to represent false positives, but this was confounded by concurrent identification of antibody to N protein on serology. Subsequent testing by reverse transcriptase-polymerase chain reaction confirmed HCoV-OC43 infection. Convalescent serology ruled out SARS. Notably, sera demonstrated cross-reactivity against nucleocapsid peptide sequences common to HCoV-OC43 and SARS-CoV.
Conclusions
These findings underscore the virulence of human CoV-OC43 in elderly populations and confirm that cross-reactivity to antibody against nucleocapsid proteins from these viruses must be considered when interpreting serological tests for SARS-CoV.
Microbiological Testing
Respiratory specimens were tested for adenovirus, parainfluenza virus, respiratory syncytial virus, enterovirus and influenza virus by immunofluorescence microscopy and isolation in cell culture (10). Serological testing was carried out for Mycoplasma pneumoniae, Chlamydophila pneumoniae and Chlamydophila psittaci. Respiratory specimens were cultured for bacterial pathogens and, together with urine specimens, were evaluated for Legionella antigen using standard methods
Epidemiology
Of the residents who met the case definition, 66% experienced cough, 21% fever, 66% rhinitis and 12% pneumonia. Twelve residents were admitted to hospital, eight for pneumonia. There were eight deaths among patients with respiratory symptoms. During the preceding six months, there was a mean of three deaths per month. None of the 53 affected staff members died, was hospitalized or developed pneumonia.
Microbiology Findings
No pathogenic organisms were identified on routine testing from any of the residents. The exception was the finding of hMPV in respiratory specimens from four of 17 residents tested by RT-PCR. Molecular or serological testing for SARS-CoV was performed on specimens from 51 of 95 affected residents, the results of which are summarized in the final column of Table 1.
Findings from Nucleic Acid Testing for SARS-CoV
Specimens from nine patients had a signal on one or more RT-PCR assays at the NML and were suspected of being false positives. These included two of the patients who had tested positive for hMPV by PCR at the NML. Analysis of the sequences of amplicons from three suspected false-positive PCR specimens at the NML (lung, stool and respiratory) showed homology to sequences of SARS-CoV (14,15). No specimens were positive for SARS-CoV by RT-PCR at the BCCDC.
While initial RT-PCR findings at the NML were suspected to be false-positive because they did not fit the epidemiological picture, early signals on serological testing meant that SARS precautions were prudent as the investigation progressed. The outbreak was observed for 60 days, during which no severe illness among staff and no change toward a pattern reminiscent of SARS occurred. Subsequent molecular and serological investigations conducted at three laboratories ruled against a role for SARS-CoV and in favour of HCoV-OC43 as the etiological agent for this outbreak. Consultation among the BCCDC, Health Canada and the WHO concluded that the outbreak was not SARS, and was unlikely to have involved SARS-CoV.
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