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First confirmed case of COVID-19 reinfection – Expert Reaction

A man in Hong Kong is the first confirmed case to have been infected with SARS-Co-V2 for a second time.

Researchers in Hong Kong sequenced the virus genomes from both of the man’s infections and found significant differences, suggesting that the patient had been infected with two different strains. The patient mounted an immune response to the new infection, but did not experience symptoms.

The SMC asked experts to comment on this news. 

Dr Nikki Turner, Director, Immunisation Advisory Centre, University of Auckland, comments:

“This is a single case and is of scientific interest, but it is important not to assume at this point that rapid waning immunity is a frequent occurrence across populations.

“For any infectious disease there is the potential to get it a second time, and this is more common for some infectious diseases than others. We know that repeat infections occur with other coronaviruses, influenza viruses and other common respiratory illnesses. The duration of immunity following the first infection varies both with the type of organism and the immune response from the person infected.

“But there are also important factors relating to the individual exposed. For example, people who are on medications that may affect their immune response, or have certain medical conditions that affect their immune response, may have a shorter duration of protection than others.

“When someone does get sick again from the same virus, it is usually more mild as there is some existing immunity, but the immunity is not adequate to fully protect. I understand that is what was seen in this case.

“There is still a lot unknown about the duration of immunity following infection with COVID-19, and over time more will become established about how long duration of immunity is expected to be.”

No conflict of interest.

Professor David Murdoch, Clinical Microbiologist and Infectious Diseases Physician, Dean and Head of Campus, University of Otago, Christchurch, Co-Director, One Health Aotearoa, comments:

“A major unanswered question about COVID-19 is the magnitude and duration of immunity after infection.

“Hence, there has been considerable interest in an early report about a man from Hong Kong who was apparently infected for a second time with SARS-CoV-2, the virus that causes COVID-19, over four months after the first episode. Details of the case have yet to be published in the scientific literature, so this report needs to be interpreted with caution until full results are available.

“The report indicated that the man was infected a second time with a different strain of SARS-CoV-2 than the first episode as determined by genome sequencing. He supposedly had mild symptoms after the first episode, after which no detectable antibodies were detected in his blood. In contrast, he had no symptoms with his second episode, but did produce antibodies this time.

“These findings are consistent with an expected immune response to a new virus, and suggests that a first infection may protect a person from moderate or severe disease a second time. However, this is still one unpublished case and we need much more information in order to understand immunity to COVID-19.”

No conflict of interest

Associate Professor Helen Petousis-Harris, Vaccinologist, University of Auckland, comments:

“I would not make too many assumptions based on this finding for two reasons: evidence of reinfection does not mean that the person was not immune to getting sick or to transmitting the virus to others; and this is but one individual, so it could be unusual, we do not know.

“This finding does not necessarily have bearing on the vaccines under development because they are not mimicking natural infection. In the case of this coronavirus, natural infection actually interferes with the immune response, something that vaccines will not have to contend with. I am inclined to keep an open mind and not jump to conclusions.”

No conflict of interest declared.

Associate Professor James Ussher, Department of Microbiology and Immunology, University of Otago, comments:

“Regarding the reports of a reinfection, based on the limited information available (it is not yet published), it seems that reinfection is possible – which is not a great surprise.

“The researchers confirmed that it was reinfection rather than prolonged shedding of non-infectious virus (which is now well described) by showing this virus differed from the one the person was originally infected with by genome sequencing. Given that reinfection with endemic human coronaviruses, which cause a significant proportion of colds, is well described, it is not surprising that reinfection can also occur with SARS-CoV-2.

“It remains unknown how common reinfection will be, what will be the median duration between infection and reinfection, and whether the clinical course of patients who are reinfected with SARS-CoV-2 differs from primary infection (is asymptotic and mild disease more common? Can severe disease still occur?). It complicates the idea of achieving herd immunity through natural infection.”

No conflict of interest.

All the following comments have been gathered by the UK Science Media Centre:

Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:

“The significant thing here is that being re-infected with a mutated strain demonstrates that it is more likely to be re-infection, 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. The finding of a mutant strain is absolutely nothing to be shocked or surprised by and I think that some journalists don’t quite get that – it would actually be more interesting if there were no mutations cropping up.”

No conflict of interest.

Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, said:

“With over 3 million cases of COVID-19 worldwide, the first reported case of a potential re-infection with SARS-CoV-2 needs to be taken into context. It appears that the young and healthy adult has been re-infected 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 re-infection and it should not negate the global drive to develop COVID-19 vaccines.”

No conflict of interest.

Dr David Strain, Clinical Senior Lecturer, University of Exeter and chair of the British Medical Association’s Medical Academic Staff Committee, said:

“This is a worrying finding for several reasons. The first, as is laid out in this manuscript, is that it suggests that previous infection is not protective. The second is that it raises the possibility that vaccinations may not provide the hope that we have been waiting for. Vaccinations work by simulating infection to the body, thereby allowing the body to develop antibodies. If antibodies don’t provide lasting protection, we will need to revert to a strategy of viral near-elimination in order to return to a more normal life.”

No conflict of interest.

Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“The report from Hong Kong of a re-infection in a man by COVID-19 that was genetically different from the first infection should not be too surprising. It is, however, important that this is documented.

“Of particular note was that the case was a young and otherwise healthy person and that the second infection was diagnosed 4.5 months after the initial episode.

“Commentators have been saying for some time that immunity is unlikely to be permanent and may only last a few months. Given the different intensity of the antibody response in people with mild or severe illness and the subsequent decay in levels, it is likely that those with a mild illness will have a shorter duration of immunity than those with severe illness. Although the press release does not discuss the patient’s clinical illness, given the reported fact that the person was young this probably means that he had a mild illness and so would be expected to have a shorter duration of immunity. The press release also gives no mention of the severity of the second illness. No indication is given in the press release on whether the person, even if otherwise healthy, may have indications of any immune deficit.

“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.”

No conflict of interest.

Dr Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:

“This is a fascinating report. Assuming that it truly represents re-infection, and the sequence evidence for this is compelling, it highlights a number of critical unknowns regarding SARS-CoV-2 infection.

“First, does infection always lead to a protective immune response?

“Second, if the answer to the first question is yes, how long does immunity last?

“Third, can the virus change to permit escape from an initial immune response?

“If serum samples were taken at diagnosis of the second bout of infection, it would be of considerable interest to test for the presence of neutralising antibodies to both viruses. Absence of a neutralising response to the first virus could be taken as evidence for a waning response. Reactivity to the first virus but not to the second might suggest virus evolution to escape immune responses. Reactivity with both viruses would raise questions about the nature of protective responses.”

No conflict of interest.

Dr Julian Tang, Honorary Associate Professor in Respiratory Sciences, University of Leicester, said:

“The tweets from this Hong Kong team refer to an accepted paper in Clinical Infectious Diseases, an American journal, that gives a fairly standard phylogenetic (viral sequence) analysis of SARS-COV-2 full Genome sequences obtained from Hong Kong’s 1st (Jan 22-Mar 9, n=24), 2nd (13 Mar-21 May, n=42) and 3rd (22 Jun-14 Jul, n=50) COVID-19 waves.

“This shows how the virus has changed over time – into different strains (clades), with 2 distinct HK1 and HK2 viral clusters appearing in the most recent 3rd wave within the GR/20B clade.

“The tweet also mentions (presumably within this study cohort though not mentioned directly in the paper above) a patient with possible re-infection with two different classes of SARS-CoV-2.

“In fact, there are several papers published with patients that may have been re-infected – based on clinical features with/without supporting routine lab diagnostic testing, i.e. seeing a PCR POS-NEG-POS results pattern with corresponding clinical illness-recovery-illness/asymptomatic infection patterns. But these other reported potential reinfection cases have not yet been proven by additional sequencing.

“There are not many details in the tweet from the Hong Kong team, but it looks like they have found at least one case that has been infected with at least two SARS-CoV-2 strains over time. However, we need to see more clinical information on this case as well as a clear timeline to see if this SARS-CoV-2 re-infection case makes clinical as well as temporal sense, i.e. it is not just an initial co-infection with two different SARS-CoV-2 viral clades, with one initial predominant clade, then with the other minority clade just persisting longer than the predominant one.”

No conflict of interest.

Dr Jeffrey Barrett FMedSci, Senior Scientific Consultant for COVID-19 Genome Project, Wellcome Sanger Institute, said:

“It is very hard to draw firm conclusions from the press release alone (i.e. without the paper that it relates to). Some of the paper has been published on social media, which fills in some gaps (though we’re still waiting for the full paper). With those caveats:

  • “This is certainly stronger evidence of re-infection 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).
  • “An important point about this one case, which is not mentioned in the press release, is that the second infection is asymptomatic. It was caught by screening tests on returning passengers at HK airport, and the individual never developed any symptoms from their second infection.
  • “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 their second episode).”

No conflict of interest.