August 24, 2020

expert reaction to first reported case of COVID-19 re-infection in Hong Kong patient

There are reports of a case of COVID-19 re-infection in a Hong Kong patient, the case study of which has been submitted to the journal Clinical Infectious Diseases.

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.”

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.”

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.”

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.”

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.”

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).

• “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).”

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 understand that – it would actually be more interesting if there were no mutations cropping up.”

https://twitter.com/cwylilian/status/1297835718513815552, https://twitter.com/cwylilian/status/1297857565385093121 (Better source will be included once available)

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.