Clinical utility of SARS-CoV-2 whole genome sequencing in deciphering source of infection

Abstract

COVID-19 caused by SARS-CoV-2 is a worldwide problem. From the standpoint of hospital infection control, determining the source of infection is critical. We conducted the present study to evaluate the efficacy of using whole genome sequencing to determine the source of infection in hospitalized patients who do not have a clear infectious contact history. Recently, we encountered two seemingly separate COVID-19 clusters in a tertiary hospital. Whole viral genome sequencing distinguished the two clusters according to the viral haplotype. However, the source of infection was unclear in 14 patients with COVID-19 who were clinically unlinked to clusters #1 or #2. These patients, who had no clear history of infectious contact within the hospital (“undetermined source of infection”), had haplotypes similar to those in cluster #2 but did not have two of the mutations used to characterize cluster #2, suggesting that these 14 cases of “undetermined source of infection” were not derived from cluster #2. Whole viral genome sequencing can be useful for confirming that sporadic COVID-19 cases with an undetermined source of infection are indeed not part of clusters at the institutional level.

Healthcare workers acquired COVID-19 disease from patients? An investigation by phylogenomics

“…This estimation was supported by the observation that the viral genome of patient 1 remained identical to those of the locally acquired cases reported in October 2020. A similar evolutionary rate was also observed by the other studies [ 2 , 5 , 6 ]. As the interval of symptom onset between patients 1–3 and the HCWs was within one month ( Table I ), it is unlikely that the SARS-CoV-2 variant with this evolutionary rate accumulated three mutations in such short period.…”

“…Novel single nucleotide polymorphism (SNP) (also known as sample-unique variants) was defined as specific nucleotide substitution in viral genome present in the corresponding sample only. A similar approach has been used to determine intra-hospital transmission of SARS-CoV-2 [ 2 , 5 ]. Multiple sequence alignment for consensus genomes was performed by Clustal Omega 1.2.0 ( http://www.clustal.org/omega/ ).…”

“…A follow-up investigation to differentiate between hospital-acquired and community-acquired infection in these two HCWs was therefore important. Whole-genome sequencing (WGS) had been applied to study the genomic epidemiology of SARS-CoV-2 in hospitals with known outbreaks; infected patients/HCWs with epidemiological links and identical viral genomes would indicate that intra-hospital transmission had occurred [ [2] , [3] , [4] , [5] , [6] ]. Hong Kong is a densely populated city with >7.5 million residents.…”

Outbreak of Health Care-associated Novel Coronavirus (SARS-coV-2) COVID-19 infections in the Spring of 2020

“…8 The viral genetic analysis team was established by Professors of molecular biology, medical genetics, and public health to study effect of conduct molecular epidemiologic studies. 9 Research progressed at a very fast rate. Professor of the Division of Infectious Diseases and Infection Control, and Professor of the Clinical Testing Department verified a new method of serum diagnosis.…”

“…Analyses performed by the Keio Donner Project epidemiological and viral genetic analysis teams jointly formed by Department of Molecular Biology and Center for Medical Genetics also found that the cluster arising from another hospital and the cluster noted among the residents had different specific gene sequences, suggesting that they were not related to the other suspected cases of isolated occurrences and community-acquired infections. 8,9 As a result of the great efforts taken by the Division of Infectious Diseases and Infection Control, Department of Clinical Laboratory, epidemiological research team and viral genetic analysis team, along with an investigation of high-risk individuals, requests for individuals who were close contacts to self-isolate, repeated PCR testing and detailed epidemiological analysis, we were able to confirm cessation of health care-associated infections. PCR testing was performed in all 72 patients found to have fever of 37.5 °C or higher between 16th and 22nd April.…”