By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Whole genome sequencing confirmed that repeat infection with SARS-CoV-2 is possible, something that has consequences for vaccine use and for public health.

SOURCE: To KK, Hung IF, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis 2020; Aug. 25. doi:10.1093/cid/ciaa1275. [Online ahead of print].

A previously healthy 33-year-old male resident of Hong Kong developed fever, a sore throat, and a productive cough. SARS-CoV-2 nucleic acid was detected by polymerase chain reaction (PCR) on a swab of his posterior oropharynx on March 26, 2020. He was hospitalized on March 29, by which time he was asymptomatic. He was discharged on April 14 after two negative PCR tests on samples obtained 24 hours apart.

A screening swab obtained from his posterior oropharynx at the Hong Kong airport on Aug. 15 upon his return from a trip to Spain and the United Kingdom was once again PCR positive. Although asymptomatic, he was hospitalized again, with repeat PCR positive with a cycle threshold (Ct) of 26.69. Although his C-reactive protein (CRP) was slightly elevated, he remained asymptomatic throughout his inpatient stay, during which the Ct gradually rose, indicating decreasing amounts of viral ribonucleic acid (RNA). He received no antiviral therapy.

Serum anti-SARS-CoV-2 nucleoprotein IgG antibody was undetectable in samples obtained 10 days after the onset of symptoms during his first episode, as were serial specimens during his second hospitalization. However, antibody was detected five days after hospital discharge.

Whole genome sequencing (WGS) performed on the clinical specimens obtained during the first and second episodes found that they belonged to different clades/lineages. Differences included a 58 amino acid truncation in the first specimen, the two differed by an additional 23 nucleotides, with 13 changes being non-synonymous and resulting in amino acid changes. Analysis using a basic local alignment search tool (BLAST) found that the first viral genome was most closely related to strains that had been collected previously in the United States and England, while the second was most related to strains collected in England and Switzerland in July and August.


Although repeat COVID-19 infection has been suspected based on the recurrence of positive PCR tests after negativity had been documented, demonstration of a distinct virus in the second specimen has not been reported previously. Previous “second” cases have not been associated with symptoms, and the viruses from each episode have not been genetically compared. The report reviewed here has been widely accepted as evidence of a second SARS-CoV-2 infection, albeit asymptomatic, and the WGS provides strong evidence in this regard. This observation is said to be consistent with reports of waning antibody titers over just months after infection and to raise concern that, as with seasonal coronaviruses, immunity is not persistent — something that also raises concern regarding the effectiveness of vaccines in this disease.

I might add one other possibility in this instance that the episode 1 virus tested was not recovered from this patient but was the result of a specimen mix-up and that episode 1 was not, in fact, due to SARS-CoV-2 infection.