Viral etiology of severe acute respiratory infections in adults in Kuala Lumpur, Malaysia

Abstract

Background: Severe acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses in adults is relatively understudied in Asia. Emerging respiratory viruses, such as MERS-CoV and SARS-CoV have been reported in Asia, including in Malaysia. Methods and materials: From May 2017, adult patients with community-acquired SARI admitted to an urban teaching hospital in Kuala Lumpur were prospectively enrolled to comprehensively determine viral etiology. Respiratory samples were tested for 20 common respiratory pathogens (using the Luminex NxTAG-RPP assay) and MERS-CoV and SARS-CoV by RT-qPCR. Selected negative samples were further subjected to viral metagenomics analysis, using next-generation sequencing (NGS) using Illumina NextSeq 500 platform. Results: To date, 345 patients have been enrolled, with a median age of 65 years, 1.1:1 female:male ratio, and average hospital stay of 5.7 days. Sixty (17.4%) patients had severe disease, defined as admission to intensive care unit (5.5%, n = 19), requiring mechanical ventilation (13.9%, n = 48) or death (4.9%, n = 17). At least one respiratory virus was identified in 195 (56.5%) patients, of which 24 (7%) were co-infections. The most detected viruses were rhinovirus/enterovirus (51%, n = 176), influenza virus (7.5%, comprising 13 A/H3N2, 8 A/H1N1 and 5 influenza B), parainfluenza virus (2.3%, n = 8), respiratory syncytial virus (0.9%, n = 3), metapneumovirus (0.9%, n = 3), coronavirus OC43 (0.6%, n = 2) and adenovirus (0.3%, n = 1). Of 150 (43.5%) negative samples, 48 samples were selected for viral metagenomics analysis. At least one respiratory virus was detected in 14 (29.2%) NGS samples: rhinoviruses (18.8%, n = 9), influenza virus (8.3%, with 3 A/H3N2 and 1 influenza B), and enteroviruses (4.2%, n = 2). No avian influenza virus, MERS-CoV and SARS-CoV was detected in this study. Only 28 (8.1%) patients had significant positive blood cultures, most commonly Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus. Severe disease was independently associated with significant positive blood culture (OR 2.78, 95% CI 1.18–6.59, p = 0.02), but not with any viruses. Conclusion: Rhinovirus/enterovirus and influenza virus are the most frequently detected viruses in adults with SARI, although the clinical significance of the former is not certain. NGS showed that known respiratory viruses play an important etiologic role in unexplained SARIs cases and no emerging respiratory viruses were detected in this study.