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Coronavirus reinfection - Can you really get it again? The impacts for a second wave & vaccine development

SARS-CoV-2 virus (yellow) attacks dying human cell (red). Source: NIAID.

Covid-19 reinfection is a genetically proven fact. This Tuesday, European researchers documented two new cases of Covid-19 reinfection, just a day after the first genetically proven case of reinfection was reported in a 33-year old man in Hong Kong. The 33-year old had contracted two genetically distinct strains of Covid-19 over a period of four and a half months.

The potential for people to be reinfected with genetically distinct strains of Covid-19 months after recovering from their initial infection, has raised alarm bells among policymakers struggling to contain the virus, as well as among researchers racing to develop a vaccine. However, the frequency of such events, and their implications on coronavirus transmission, immunity, and the development of an effective vaccine, remain poorly understood.

Why is this important? The possibility that recovered Covid-19 patients can become reinfected further dashes hopes that the global population could develop a certain level of  “herd” immunity to the SARS-CoV-2 virus. Reinfection events also raise questions about whether a vaccine developed to treat one strain of the virus will be long lasting and effective against other viral strains.

“The unique Hong Kong case is puzzling and is a very unusual finding,” Barry Bloom, research professor at Harvard T.H. Chan School of Public Health, told Geneva Solutions this week, at a webinar hosted by the Harvard T.H. Chan School of Public Health.

In the viral world, reinfection is the rule not the exception. The reports add to a growing body of evidence that in the case of SARS-CoV-2, like other respiratory viruses - including influenza or common cold coronaviruses - true reinfection is possible. When recovered patients test positive again, it isn’t a result of prolonged viral shedding, or remnants of dead virus from the first infection.

“The Hong Kong report certainly looks like reinfection,” noted William Hanage, associate professor of epidemiology at Harvard T.H. Chan School of Public Health. “Whether it is rare or not is not clear at all.”

“First, this appears to be rare”, tweeted Ashish Jha, director of Harvard’s Global Health Institute. “Though we don't go looking [for reinfection] often enough so [it is] unclear.”

However, even if reinfection turns out to be more common than initially thought, its significance for Covid-19 transmission is unclear. 

It is possible that people reinfected with Covid-19 could spread as much virus as in their initial infection - even if they show no symptoms. And that has worrisome public health implications that require further exploration, said Hanage.

“We don’t know whether reinfected people transmit as much virus as compared to their first bout of infection,“ he added.

He also noted that the so-called ‘viral load’ during the second asymptomatic infection of the 33-year old Hong Kong patient was “reasonable”, and “neither very high nor very low”. But we’re not sure what that means yet.

“Just because reinfection can happen does not necessarily tell us how important it is for transmission of Covid-19,” said Hanage.

“A football team like Arsenal can beat Liverpool, but they have to keep beating Liverpool to make a meaningful difference at the end of football season.”

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Source: Harvard T.H. Chan School of Public Health.

Reinfection is a rare event, says the World Health Organization.  Despite the concerns raised by experts such as Hanage, other leading experts in Geneva and at the World Health Organization, offer more reassurance.

Based on available data, “Covid-19 reinfection is seemingly rare”, said Antoine Flahault, director of the Institute of Global Health at the University of Geneva, in an interview with Geneva Solutions.

He adds that reinfection is also known to occur in “most infectious diseases”, even in cases where strong immunity is developed. It tends to happen among people that have underlying conditions , whom also have weakened their immune systems.

That’s the view, as well, among experts at the World Health Organization.

“Of the 23 million cases of Covid-19 reported so far, only two or three cases of reinfection have been reported,” Jarbas Barbosa, assistant director of WHO’s Regional Office of the Americas/Pan American Health Organization (PAHO), emphasized at a press conference on Tuesday, in response to a question from Geneva Solutions.

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Jarbas Barbosa, assistant director of PAHO. Source: PAHO

According to virologist Marion Koopmans, one of the reinfected patients reported on Tuesday was an older Dutch man whose immune system was weakened, reported Dutch broadcaster NOS.

Can Covid-19 threaten vaccine development ? Hopefully not. Some scientists worry that reinfection with genetically distinct strains of SARS-CoV-2 could also threaten the development of an effective vaccine.

However, vaccines generally aim to target regions of the virus that do not mutate - such as the spikes of the virus that may attach itself to the body's ACE-2 receptors, said PAHO’s incident manager Sylvain Aldighieri on Tuesday.

“Even if a virus mutates, a vaccine may still confer perfect immunity because the vaccine may target a region of the virus that does not change.”

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He cautioned, however that, “genetic monitoring of circulating strains of the coronavirus must be maintained to keep a tab on any new mutations, and to study their effects.”

So far, over 3000 SARS-CoV-2 mutations have been identified, and yet they have not significantly changed the level of Covid-19 disease severity, and may thus not be an obstacle to the development of vaccine immunity, WHO experts say:

“We've not seen major changes in the way that [Covid-19] disease is presenting in populations”, said Catherine Smallwood, WHO’s senior emergency officer for the WHO Emergencies Programme, at a press conference last week.

“What we need to look at, is the clinical presentations [of mutations] to make sure that as the virus mutates - which is absolutely normal for viruses to do - that we track these mutations, and that we are able to interpret those mutations, and understand whether they are actually causing changes in the disease or not.”

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More generally, WHO notes that many vaccines are “primarily intended” to prevent disease symptoms, rather than protecting against infection itself sterilizing immunity.

Bottom line: immunity to Covid-19 still exists despite potential for reinfection. There seems to be some level of agreement that an initial COVID-19 infection in humans provides some level of protective immunity against a subsequent infection, though it may not be sufficient to block reinfection of the SARS-CoV-2 virus into human cells.

It is likely that an initial Covid-19 infection confers protection by muting disease symptoms in subsequent rounds of infection, just like the 33-year old in Monday’s Hong Kong report, whose second infection was asymptomatic - in contrast to his first, symptomatic infection that took him two weeks to recover from.

“This is exactly what one would want to see with immunity — that you can pick up virus again but that it won't cause serious illness," tweeted Jha.

However, it is unclear how long immunity to COVID-19 lasts.

“What we are learning about [Covid-19] infection is that people do develop an immune response, and what is not completely clear yet is how strong that immune response is, and for how long that immune response lasts,” said WHO’s coronavirus expert and technical lead for Covid-19 Maria Van Kerkhove on Monday, in response to reports of the Hong Kong reinfection case.

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Generally, common cold coronaviruses - including 229E, OC43 and NL63 strains - can reinfect individuals in less than a year, while protection against more serious coronaviruses, such as SARS-COV-1 and MERS seems to last for a few years.

A lack of data. Despite some disagreement on Covid-19 reinfection among leading scientists, there is consensus on at least one issue - the lack of data.

“Before making any recommendation, at this point, we need to take a better look at the evidence,” warned Barbosa.

“We need to understand reinfection better and evaluate if it is related to any modification in the virus or the immune system. It is very important to report these cases like the Hong Kong case.”

It will also be necessary to study reinfection at the “population level” to clarify whether it is a frequent or rare event, added Van Kerkhove.

According to Bloom, “serial blood samples” from reinfected individuals could help shine light on antibody responses to the coronavirus, and to understand whether they differ between the first and second bouts of infection - in terms of the quantity of antibodies produced, their affinity to the virus, and how long they last.

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Barry Bloom, research professor at Harvard T.H. Chan School of Public Health. Source: Harvard T.H. Chan School of Public Health