HKU first to confirm distinct strain SARS-CoV-2 reinfection by whole genome sequencing

Researchers from the Department of Microbiology at the University of Hong Kong (HKU) are the first to document a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection with a phylogenetically distinct strain of the virus using whole genome sequencing.

“Although neutralizing antibodies develop rapidly after infection [with SARS-CoV-2], recent studies showed that antibody titres start to decline as early as 1–2 months after acute infection,” wrote the researchers. [Lancet Infect Dis 2020, doi: 10.1016/S1473-3099(20)30196-1; Emerg Microbes Infect 2020;9:1664-1670; Nat Med 2020;26:1200-1204; Nature 2020, doi: 10.1038/s41586-020-2456-9]

While there have been case reports suggesting possible reinfection with SARS-CoV-2, viral genome analysis was not performed, leading to lack of clarity on whether positive results are due to persistent viral shedding from the original infection or due to an actual reinfection. [Am J Emerg Med 2020, doi: 10.1016/j.ajem.2020.06.079] So as to differentiate re-infection from persistent viral shedding, HKU researchers conducted comparative genome analysis of respiratory specimens during two episodes of coronavirus disease-19 (COVID-19) in one patient. [Clinical Infectious Diseases 2020, doi: 10.1093/cid/ciaa1275]

“The patient was a 33-year-old male resident of Hong Kong, who presented with cough and sputum, sore throat, fever and headache for 3 days during the first episode in late March 2020. He was hospitalized and subsequently discharged in mid-April 2020, following two negative SARS-CoV-2 reverse transcriptase-polymerase chain reaction [RT-PCR] assays on nasopharyngeal and throat swabs taken 24 hours apart,” reported the researchers.

The patient’s second asymptomatic episode of COVID-19 was detected when he returned to Hong Kong from Spain via the UK. On screening at the Hong Kong airport in mid-August 2020 (142 days after the onset of the first episode), he tested positive by SARS-CoV-2 RT-PCR on his posterior oropharyngeal saliva sample. He was hospitalized again and, despite having an acute infection as evidenced by an elevated C-reactive protein level, remained asymptomatic until discharge when there was no detectable virus in his specimens. “A previous study of re-infection in rhesus macaque also showed milder illness during the reinfection,” noted the researchers. [Science 2020;369:812-817]

Whole-genome sequencing was performed with the patient’s posterior oropharyngeal saliva specimens collected during the first episode in March and from the second episode in August. “Genomic analysis showed that the first viral genome belonged to a different clade/lineage from the second viral genome. A blast search for the first and second genomes suggested that the first viral genome is most closely related to strains from the US or England collected in March and April 2020, while the second viral genome is most closely related to strains from Switzerland and England collected in July and August 2020,” reported the researchers.

“The confirmation of reinfection has several important implications,” they wrote. “Firstly, it is unlikely that herd immunity can eliminate SARS-CoV-2, although it is possible that subsequent infections may be milder than the first infection, as in this patient. COVID-19 will likely continue to circulate in the human population, as is the case of other human coronaviruses. Secondly, vaccines may not be able to provide lifelong protection against COVID-19. Furthermore, vaccine studies should also include patients who recovered from COVID-19.”