Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19

Shona C Moore; Rebekah Penrice-Randal; Muhannad Alruwaili; Xiaofeng Dong; Steven T Pullan; Daniel Carter; Kevin Bewley; Qin Zhao; Yani Sun; Catherine Hartley; En-min Zhou; Tom Solomon; Michael B. J. Beadsworth; James Cruise; Debby Bogaert; Derrick W T Crook; David A Matthews; Andrew D. Davidson; Zana Mahmood; Waleed Aljabr; Julian Druce; Richard T Vipond; Lisa Ng; Laurent Renia; Peter Openshaw; J Kenneth Baillie; Miles W Carroll; Calum Semple; Lance Turtle; Julian Alexander Hiscox

Mechanisms of life-threatening disease in COVID-19 including factors associated with morbidity and mortality. Middle East respiratory syndrome (MERS) can provide important parallels: one of the risk factors associated with severe disease and/or a fatal outcome is the presence of other infections [1, 2] . Other infections may therefore exacerbate COVID-19. A case study in China identified the presence of other microorganisms in patients with COVID-19 and included specific nucleic acid based detection for six common respiratory virus and the use of culture [3] . No viruses were identified but the study identified Acinetobacter baumannii, Klebsiella pneumoniae, and Aspergillus flavus in a single patient and several cases of fungal infection were diagnosed including Candida albicans and Candida glabrata. The ability to rapidly identify both the primary pathogen and other infections that may be present early in disease may provide opportunities for targeted intervention in patients suspected or confirmed with COVID-19. The advantage of both laboratory [4] and field-based sequencing approaches [5] was illustrated in the West African Ebola virus outbreak in characterising viral infection and also providing an assessment of the contribution of potential co-infections to outcome [6] . Rapid sequencing of SARS-CoV-2 itself provides utility in two main areas. First, specific amplicon-based sequencing of SARS-CoV-2 allows for potential contact tracing, molecular epidemiology and studies of viral evolution. Second, the use of metagenomic approaches like SISPA provides a check on sequence divergence for amplicon-based approaches. This is particularly important for SARS-CoV-2 as the virus could undergo recombination with other human coronaviruses and mutation and this may also affect both vaccine and antiviral efficacy.