A case of coronavirus reinfection in Hong Kong confirmed by genome sequencing

Using genome sequencing, researchers at the University of Hong Kong have found a rare instance of reinfection with novel coronavirus for the second time, four-and-a-half months after the first infection. The first viral genome belongs to GISAID clade V, while the second genome belongs to GISAID clade G.

Using genome sequencing, researchers at the University of Hong Kong have found a rare instance of reinfection with novel coronavirus for the second time, four-and-a-half months after the first infection; the adult who was reinfected was 33 years old.

The first infection was confirmed on March 26; the patient was hospitalised on March 29 and discharged on April 14 after two RT-PCR tests turned negative. The second round of infection, which was asymptomatic, was confirmed on August 15 when the adult was returning from Spain to Hong Kong via UK, and was screened at the airport. The reason for asymptomatic infection when infected for the second time, the researchers guess may be due to the patient’s adaptive immunity during the re-infection.

Earlier reports of reinfection from South Korea

Earlier reports, including cases from South Korea suggested reinfection after recovering from COVID-19. By end-April, 263 people in South Korea who had recovered from COVID-19 had once again tested positive for the virus, raising concerns about reinfection or reactivation. However, by end of April, infectious disease experts in South Korea confirmed that dead virus fragments still present in recovered people when tested with RT-PCR had led to false positive results even weeks after making a full recovery.

The Korea Centers for Disease Control and Prevention (KCDC) had investigated three cases from the same family where patients tested positive after recovering. But scientists were unable to grow (culture) the virus.

But so far genome sequencing has not been performed to verify if people harboured the virus for a longer time (up to three months) or were genuinely reinfected.  

Advantage genome sequencing

Genome sequencing found that the adult was infected for the second time with a strain that is “clearly different” from the genome sequence of the virus strain from the first infection. The viral genomes from the first and second infections belonged to different clades/lineages.

“A total of 24 nucleotides were different between the two viruses from the first and second episodes. Amino acid differences can be found in nine proteins, including a 58-amino acid truncation of a particular protein that was present only in the virus from the first infection,” a press release from the University says. The first viral genome belongs to GISAID clade V, while the second genome belongs to GISAID clade G.

The differences in the amino acids between the two genome sequences are located in spike protein, nucleoprotein, non-structural proteins and accessory proteins.

A paper based on this has been accepted for publication in the journal Clinical Infectious Diseases, the release says.

Implications of reinfection  

“The significant thing here is that being reinfected with a mutated strain demonstrates that it is more likely to be reinfection, rather than the same infection that has hung around because the virus has not actually been got rid of, as some people have suggested happens,” Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading tells the Science Media Centre.

“The implications of this finding should not be over-stated. It is quite likely that subsequent infections do not cause as severe an illness as the first episode because of some degree of residual immunity which may not be sufficient to stop the infection but be enough to reduce the risk of severe illness. Also it is unclear how likely such people are to pose a risk to others. For example, is the viral load as great in the second infection as in the first? This report is not necessarily an indication that immunisation may not be effective. We need more information about this case and other cases of re-infection before we can really understand the implications,” Prof Paul Hunter, The Norwich School of Medicine, University of East Anglia tells the Science Media Centre.

More evidence from the patient

The elevated C-reactive protein, relatively high viral load with gradual decline, and seroconversion of coronavirus IgG during the second episode, the authors write in the paper suggests that this is a case of a genuine episode of acute infection. Also, there was a gap of 142 days between the first and second episodes, they say. The patient traveled to Europe, where there is resurgence of the virus since late July. “The viral genome obtained during the second episode is phylogenetically closely related to strain collected from Europe in July and August,” they write.

Although SARS-CoV-2 antibody was not detected initially during the second infection, the residual low levels of antibody from previous infection might have controlled the virus. Neutralising antibodies target the spike protein. But variations in spike proteins, as seen in the second infection, might have rendered the virus less susceptible to neutralising antibodies that were induced during the first infection, they write. Screenshots of the paper were posted by Lilian Cheng, a Local Reporter at the South China Morning Post.

What the reinfection means

“This is certainly stronger evidence of reinfection than some of the previous reports because it uses the genome sequence of the virus to separate the two infections. It seems much more likely that this patient has two distinct infections than a single infection followed by a relapse (due to the number of genetic differences between the two sequences),” Dr Jeffrey Barrett, Senior Scientific Consultant for COVID-19 Genome Project, Wellcome Sanger Institute, tells the Science Media Centre.  

Dr Barrett adds: “It is very hard to make any strong inference from a single observation! Given the number of global infections to date, seeing one case of reinfection is not that surprising even if it is a very rare occurrence. I think their ‘implications’ are far too broad given that they have seen just one instance. This may be very rare, and it may be that second infections, when they do occur, are not serious (though we don’t know whether this person was infectious during the second episode).”

“With over three million cases of COVID-19 worldwide, the first reported case of a potential reinfection with SARS-CoV-2 needs to be taken into context. It appears that the young and healthy adult has been reinfected with a slight SARS-CoV-2 variant from the initial infection three months previously. It is to be expected that the virus will naturally mutate over time. This is a very rare example of reinfection and it should not negate the global drive to develop COVID-19 vaccines,” Prof. Brendan Wren from the London School of Hygiene & Tropical Medicine was quoted as saying by the Science Media Centre.

UPDATE: The paper was published online on August 25.