After earlier anecdotal reports, the first case of COVID-19 reinfection has been formally documented and studied by Hong Kong University. The researchers say a 33-year old man was diagnosed with coronavirus more than four months after he recovered from a first bout of the disease, with genomic sequencing finding the man had been infected with two different strains. The research has been accepted for publication in the journal Clinical Infectious Diseases.
What is the significance of their findings, and what might it mean for vaccine development? Australian experts respond.
Professor Peter McIntyre is a Professor of Child and Adolescent Health at the Children’s Hospital, Westmead and the University of Sydney. He is also a Professor in the Department of Women’s and Children’s Health at the University of Otago, New Zealand.
“I think this is a perfect example of the thinking that isn’t happening regarding COVID vaccines. There seems to be an expectation on the part of many in the media that a ‘successful’ COVID vaccine will only be one that is 100 percent effective at eliminating COVID infection and transmission and rewinds the clock to October 2019.
A more realistic expectation would be a vaccine, which prevents you getting sick on re-exposure to COVID-19, including different strains, and reduces, but probably doesn’t eliminate, your propensity to transmit infection to others. We’ve seen increasing examples of this happening with measles vaccine as reported from Victoria in 2019 and California a bit earlier. There we saw infection with much milder symptoms occurring in people who received two doses but some time ago and occasionally may transmit to others.
If this young man’s recent symptomatic infection turned his recent exposure into an an asymptomatic infection, then great. In the current environment however, not knowing his capacity to transmit (function of viral load and nature of contact) and not being able to protect potential vulnerable contacts by vaccines, pre or therapeutics post exposure to him, then he has to be treated exactly the same as someone with no history of vaccination or infection – quarantined etc. Whither immunity passports?”
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Associate Professor Taghrid Istivan is Associate Professor of Microbiology and Senior Program Leader – Biosciences at RMIT University.
“Some viral infections are known to generate life-long immune responses, such as measles, while others will only provide limited immunity for few months, such as the common cold and the flu viruses. As COVID-19 infections are new in humans, we do not know much about the nature of immune responses against SARS-CoV2. It was hoped that this virus will generate long lasting immune responses like its close relatives, the SARS and MERS viruses, but it seems to be different.
This current re-infection case highlights two main issues in my opinion. The first, is the importance of vaccination and probably the need of multiple doses to generate the desired antibody level that can protect us from infection. Or for a vaccination system similar to the flu vaccination, when each year a new selection of active variants of the virus are included.
The second issue is that the 33 years old man had some symptoms in the first infection, but antibodies were not detected after recovery, yet in the second infection antibodies against the virus were detected and he was asymptomatic. Usually immune responses in second infections are generated from the activation of B and T memory cells, which will act against the viral antigen and generate an army of antibodies to fight the infection.
This patient was infected with a slightly different strain of the virus in the second time, but his immune response were capable of balancing the viral load and keeping it under control, as it did not develop to the symptomatic stage.
This may make us think if this is a reason behind the mystery cases that are driving community infections in Victoria, for example, as recovered individuals may get infected for a second time and spread the virus without noticing any symptoms. Therefore, PCR testing of asymptomatic individuals in hot spot areas and probably screening for immune responses in recovered patients may contribute to further knowledge on this.”
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Associate Professor Sanjaya Senanayake is a specialist in Infectious Diseases and Associate Professor Of Medicine at The Australian National University.
“The occurrence of reinfection by SARS-CoV-2 in a 33-year-old man from Hong Kong is helpful in some ways, but also leaves a number of unanswered questions. Trying to determine if reinfection with SARS-CoV-2 was possible on the basis of antibody levels in blood and other markers of immunity was always an exercise in speculation. The only way to prove this was to see if someone actually became reinfected; now that it has happened, we definitely know that reinfection with SARS-CoV-2 can occur. It is also pleasing to see that the second infection was associated with an antibody response and with no illness, suggesting that subsequent infections can be associated with a more robust immune response and a milder illness.
Of the limitations, we don’t know if he was infectious to others. Secondly, the fact that this occurred after such a short period between infections is disappointing. Also, this was only one case; therefore, we don’t know how common or rare reinfection is. This apparently is a young and healthy man: will the second illness be as mild in an older person or someone with a chronic disease? This man had a mild first illness: will someone with a more severe illness have a more durable immune response that means reinfection won’t occur for over a year? Could cross-immunity to other coronaviruses modify the risk of reinfection? Certainly, this case of reinfection is an important discovery but there is still much to be discovered.”
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Professor Nigel McMillan is the Director in Infectious Diseases and Immunology at Menzies Health Institute Queensland, Griffith University.
“The finding that a person in Hong Kong has been confirmed to be reinfected with SARS-CoV-2 is not unexpected. Recent published work on people naturally infected with the virus have shown their antibody levels start to fall soon after and 20 per cent of people infected have baseline antibody levels after two months. This is how our normal common cold coronavirus strain behaves and is why we are continually infected with them year after year.
These two findings mean that any country who is relying on natural herd immunity as a way to deal with COVID-19 is on the wrong path as this will not be effective.
Going forward what we need to know is how long T cell immunity lasts in naturally infected people and more importantly how long vaccine responses last as this will determine how often we need to be vaccinated.”
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Professor Sarah Palmer is the Co-Director of the Centre for Virus Research at The Westmead Institute for Medical Research and Professor in the Faculty of Medicine at the University of Sydney.
“The finding that a person was re-infected with a different strain of COVID-19 reminds us yet again not to get ahead of ourselves, not to be complacent, and recognise we are still learning about the pathology of this virus.
In terms of policy, it underscores the need for continuing strict preventative measures until an effective vaccine is available and widely distributed. Counting on ‘herd immunity’, to the extent it was ever a good strategy, is now seriously called in to question.
It also should give pause as to the effectiveness of vaccines. We will need to develop vaccines that are effective against all global strains of the virus and ensure extended antibody and cellular immunity. This will be especially important for those with compromised immune systems, such as the elderly or individuals with co-morbidities.”
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Professor Raina MacIntyre is Head of the Biosecurity Program at the Kirby Institute at the University of NSW. She is an expert in influenza and emerging infectious diseases.
“There have been reports of reinfection from early in the pandemic but investigations in the past, such as in South Korea, have shown that many of these may have been persistent viral shedding in people who recovered clinically, and also shedding of non-infectious viral fragments after recovery. However, we do know re-infection is possible with other coronaviruses because immunity is not long-lasting, so it may also be possible with SARS-CoV-2. The body of evidence to date also suggests that people with an asymptomatic or mild infection may not mount a strong antibody response.
In this case, reported prior to publication (the paper is scheduled to be published in Clinical Infectious Diseases), a man in Hong Kong who had a mild case of COVID-19 in March was reinfected with a genetically different strain of SARS-CoV-2 in August. The fact it was a genetically distinct strain, and the long time lag between the first and second infection are strong evidence of reinfection. The first time, he did not develop antibodies. So, this tells us reinfection is possible, especially in people who have mild infection and do not develop antibodies. Other research also suggests that asymptomatic or mild infections may not result in a robust antibody response. This may also explain why serological surveys of young children show low rates of infection – not because they are not getting infected, but because they are infected, have mild infection and are not developing antibodies. This means that vaccines for COVID-19 should produce a strong antibody response to make sure people can fight off infection.”
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Professor Jeremy Nicholson is Pro-Vice Chancellor for Health Sciences and Director of the Australian National Phenome Center at Murdoch University.
“We do not really know the extent of the SARS-CoV-2 reinfection problem for many reasons. The fact that it can happen at all a few months after ‘recovery’ is disturbing, as it has possible implications for vaccine development.
There is nothing simple about this disease. The SARS-CoV-2 virus infection presents in many different forms, including of course the well-recognised and potentially life-threatening respiratory version. But many people appear asymptomatic, are mildly affected, or have other manifestations of the disease, including new onset diabetes, heart, brain/stroke liver, gut, skin and kidney problems. Some of those can be difficult to spot and the true proportions of the population affected is still hard to assess.
Reinfection probably does occur, but it is still difficult to know exactly how often this happens with current testing levels, but so far it seems to be a rare event. The problem is further complicated by the concurrent circulation of several SARS-CoV-2 viral strains with different levels of infectivity and severity, each with possible variable manifestations and complications.
We are still lacking data, but there is no intrinsic reason to think that immunity to one strain of the coronavirus confers immunity to infection by another strain (influenza is the perfect example where we need to develop new flu vaccines regularly to cope with strain variation). Again, we don’t know if this will be a problem for SARS-CoV-2 because we are yet to produce a proven effective vaccine. The fact is that antibodies and cell-mediated immunity have complex and variable individual patterns, which means that some people may lose immunity quite quickly and others won’t. It is not safe to make assumptions about the properties of this virus, we are on a steep learning curve to try and understand the deep biology of the disease. Despite the massive ongoing international scientific efforts to investigate COVID-19, it is still going to take time to figure it all out.”
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Dr Mainthan Palendira is from the University of Sydney and is Head of the Human Viral and Cancer Immunology Laboratory at the Centenary Institute.
“We should be careful in interpreting too much out of a single case of reinfection, however, it is the first lab-confirmed case of reinfection that we know of. This case is interesting because the person had a mild infection the first time and remained asymptomatic the second time. The virus that caused the infection the second time appears to be completely different from the original virus. Interestingly there were no detectable antibody responses after the first infection, however, a boosting of antibody response was seen after the second infection.
I would look at the positive side of the story. He was asymptomatic and there was a boosting of his antibody responses. This tells us that immunity can be enhanced by reinfection and that could potentially mitigate the severity of the disease when we get it the second time. This is good news for vaccine development and this is what we would expect vaccines to do.”
