Tackling diagnostic challenges during the first wave of COVID-19

Introduction: During the first wave of Coronavirus disease 2019 (COVID-19), a rule-out protocol was used at Ghent University Hospital to confirm or rule-out severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients admitted with symptoms suggestive of COVID-19.This step-wise testing approach included repeat nasopharyngeal swab (NFS) SARS-CoV-2 (real-time reverse transcription–polymerase chain reaction) rRT-PCR, respiratory multiplex RT-PCR, low-dose chest CT and bronchoscopy with bronchoalveolar lavage (BAL). Results: Between 19 March 2020 and 30 April 2020, 455 non-critically ill patients with symptoms of of upper or lower respiratory tract infection, suspect for COVID-19 were admitted at Ghent University Hospital. The diagnosis of COVID-19 was made in 118 cases (25.9%). The initial NFS SARS-CoV-2 rRT-PCR contributed to 66.9% of the total COVID-19 diagnoses, the second NFS and bronchoscopy with BAL yielded 25.4% and 5.9% of total COVID-19 diagnoses, respectively. Culture and respiratory multiplex PCR of BAL fluid revealed other respiratory pathogens in 65% (13/20) of the COVID-19 negative patients and only in 1/7 COVID-19 positive patients. Retrospective antibody testing showed a positive IgA or IgG in 42.9 % of the COVID-19 positive and 10.5% of the COVID-19 negative group at the time of bronchoscopy. In the COVID-19 positive group all patients developed anti-SARS-CoV-2 IgG antibodies in follow-up samples. In the COVID-19 negative group, follow-up serology showed 100% anti-SARS-CoV-2 IgG negativity. Conclusion: These results demonstrate that bronchoscopy with BAL can have an added value to rule-in or rule-out COVID-19 in patients with clinical and radiographical high-likelihood of COVID-19 and repeated negative NFS testing. Furthermore, culture and respiratory multiplex PCR on BAL fluid can aid to identify alternative microbial etiological agents in this group. Therefore, BAL can be a useful diagnostic tool in well-selected patients, provided that the necessary safety measures are taken. Retrospective antibody testing performed in the patients who underwent bronchoscopy suggests that the implementation of serology in the routine testing protocol will decrease the need for invasive procedures like bronchoscopy.