ABSTRACT
Introduction: Flexible bronchoscopy with bronchoalveolar lavage (FB+BAL) is routinely used for diagnostic evaluation in immunocompromised patients with pulmonary infiltrates. However, during the current COVID-19 pandemic, this procedure has usually been deferred in those with suspected or known diagnosis of COVID-19, given the risk of aerosolization and subsequent transmission of SARS-CoV-2 to healthcare personnel. We report the case of an immunosuppressed teenager with persistent fever and progressive respiratory symptoms after an initial diagnosis of COVID-19 in whom the need of FB+BAL represented a clinical dilemma. Description: A 14-year-old female on treatment for relapsed acute lymphoblastic leukemia was diagnosed with SARS-CoV-2 infection by polymerase chain reaction (PCR) in a nasal sample after having a positive household contact. Her symptoms were initially mild until she developed fever, cough, and dyspnea ∼2 weeks after diagnosis. Her laboratory evaluation was notable for lymphopenia and her chest CT revealed extensive lower lobe consolidations with scattered ground-glass opacities (Figure A), prompting hospitalization. Despite broad-spectrum antibiotics, her respiratory status worsened and she eventually required high-flow nasal cannula support. Pediatric pulmonology was consulted for consideration of FB+BAL to rule out opportunistic infections. Her repeat SARSCoV-2 PCR nasal test at that time, done ∼3 weeks after her initial diagnosis, was inconclusive. Because of this, as well as her tenuous respiratory status, it was decided not to proceed with FB+BAL. She then received steroids, remdesivir, and immunoglobulin, with gradual resolution of her hypoxemia. She was subsequently discharged home. Unfortunately, her fever and dyspnea returned ∼1 week after, prompting re-admission. Her repeat SARS-CoV-2 PCR nasal test was positive and her chest CT demonstrated shifting consolidative and ground-glass opacities, now more predominant in the upper and mid-lung fields (Figure B). We then proceeded with FB+BAL, which was unremarkable. Evaluations for a broad range of viral, bacterial, and fungal pathogens were negative, except for positive SARS-CoV-2 by PCR from BAL fluid. Her symptoms slowly improved with supportive treatment, so she was again discharged home. Her SARS-CoV-2 PCR nasal testing ∼2 months after initial diagnosis continued to be positive. Discussion: There is limited evidence regarding the safety and utility of FB+BAL in those with suspected or diagnosed COVID-19, particularly in the pediatric population. This case highlights an immunosuppressed child with prolonged viral shedding and emphasizes that in certain clinical situations FB+BAL may be required for further microbiologic data, especially when illness is protracted, the differential diagnosis is broad, and imaging findings are non-specific for COVID-19.
ABSTRACT
RATIONALE: The upper respiratory tract (URT) is the portal of entry and an active site of replication of SARS-CoV-2 and thus of critical importance in the pathogenesis of COVID-19. However, little is known about the relationships between SARS-CoV-2 and the URT microbiome. To fill this gap in knowledge, we 1) compared the URT microbiome between SARS-CoV-2-infected and-uninfected adults, and 2) examined the association of SARS-CoV-2 viral load with the URT microbiome during COVID-19. Methods: We characterized the URT microbiome using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild-to-moderate COVID-19 and 21 asymptomatic, uninfected controls). In those with COVID-19, we measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 infection status and its viral load with the α-diversity i.e., richness ± evenness), β-diversity (i.e, overall structure), and abundance of bacterial taxa of the URT microbiome using common microbial ecology analyses. Our main models were all adjusted for age and sex. Results: The median (interquartile range) age was 30 (27-45) years and none of the participants had recently used antibiotics or intranasal steroids. The observed species -diversity index was higher in SARS-CoV-2-infected than in-uninfected adults (β=7.53, 95%CI=0.17-14.89, p=0.045). There were no differences in the Bray-Curtis β-diversity index between groups (permutational multivariate analysis of variance p>0.05). In DESeq2 testing, 21 amplicon sequence variants (ASVs) were differentially abundant between groups, with 13 being more abundant (including Brevundimonas, Corynebacterium, Granilucatella, Anaerococcus, and Peptoniphulus ASVs) and 8 being less abundant (including Corynebacterium-1, Prevotella, Staphylococcus, Anaerostipes, and Neisseria ASVs) in SARSCoV-2-infected vs.-uninfected adults (p<0.05 for all comparisons). In the adults with COVID-19, there were no associations of viral load with -or β-diversity indices of the URT microbiome (p>0.05 for all comparisons). However, 21 ASVs were differentially abundant between groups in DESeq2 analyses, with 9 being more abundant (including Neisseriacea, Anaerococcus, Peptoniphulus, Campylobacter, and Enterococcus ASVs) and 12 being less abundant (including Corynebacterium-1, Staphylococcus, Granilucatella, Neisseria, and Prevotella ASVs) in those with high viral load when compared to those with low viral load (p<0.05 for all comparisons) (Figure 1). Conclusions: Our findings suggest complex associations between SARS-CoV-2 and the URT microbiome in adults. Our study is a stepping stone in examining the role of the URT microbiome in SARS-CoV-2-related outcomes and in understanding the development of bacterial co-infections during COVID-19. We are now examining longitudinal associations of SARS-CoV-2 viral load with the URT microbiome over time.