In August, the first confirmed case of “re-infection” of COVID-19 was reported in Hong Kong, shortly followed by more in the Netherlands, Belgium and the United States. Currently, over 28 million people are reported to be infected with COVID-19, and questions still remain about re-infection and the possibility of long-lasting immunity to COVID-19. 

So can we be re-infected with COVID-19? The short answer is yes.

The recent case emerging out of the University of Hong Kong was the first recorded case of a COVID-19 patient who had been infected with two distinct COVID-19 virus strains (while other “re-infections” had been reported, they could not be confirmed because of the potential of persistent viral shedding from the first infection). His infections occurred 142 days apart, and while he had been hospitalized with symptoms in the first case, he was asymptomatic in the second. The similar cases reported shortly afterwards in the Netherlands and Belgium were considered mild. While many re-infection cases appear to be less severe, a 25 year-old man in Nevada required hospitalization during his second infection after a period of 48 days.

To understand what this means, we first need to understand how the immune system works. Dr. Sydney Ramirez, a researcher at La Jolla Institute for Immunology, compares the immune response to an arms race between the virus and immune system.

“Almost all viruses have a variety of genes that they encode that are designed to evade the immune system, to get around recognition by the body that they’re there and then also [to] counteract whatever immune response the body might make. They’re usually very good at this because that’s how they’re able to survive and make more viruses and spread,” she said.

Our immune response consists of two primary systems of defense against viruses: the innate and adaptive immune system. The innate immune system is the first line of defense and indiscriminately provides protection against foreign pathogens and particles within hours of exposure, working to slow down and stop the spread of the virus.

“The basic concept of the immune system is it should be able to define what is me versus what is not me, and everything that’s not me should be gotten rid of,” Ramirez said.

If the innate immune system fails to stop the viral infection, the adaptive immune system kicks in, generating a more specific response to the virus.

Dr. Akiko Iwasaki, a professor of immunobiology at Yale School of Medicine, explained that an important component of the adaptive immune system is B-cells and the neutralizing antibodies that they produce, which prevents the virus from being able to get into cells and actually prevents infection from occurring.

Transmission electron microscope image showing SARS-CoV2 viruses. Neutralizing antibodies can recognize the spike proteins on the surface of the viruses. Image courtesy of NIAID-RML.

Another component, killer T-cells, recognize and destroy infected cells to prevent the spread of the virus. After clearing out the viruses, the adaptive immune system also employs another key mechanism, known as memory, that protects against future infection from the same virus.

“These B-cells and T-cells become what’s known as memory cells and they just remember all the features of the virus. So the second time you encounter the same virus, these memory T-cells and B-cells become reactivated and they get engaged to attack the virus much more quickly and [at a] much higher level than if you had never seen the virus,” Iwasaki said.

This immune system “memory” is what provides protection against repeated infection and illness from viruses, usually obtained after infection or vaccination. For some diseases, catching the virus or being vaccinated is “one-and-done” (like chicken pox, measles or mumps), while others have a certain period of immunity (or even just partial immunity) and require regular vaccinations to maintain protection (like tetanus). 

The most common example is the flu, which requires annual vaccines due to its high mutation rate that can trick the immune system. 

“The flu is interesting because it can really accumulate mutations quickly so that every year, the virus comes out with a variant that escapes immune recognition. That’s why we need to do annual vaccines—because the virus changes every year,” Iwasaki said.

While scientists aren’t sure exactly why COVID-19 has been able to bypass our immune system memory, mutations don’t appear to be the reason. The SARS-CoV-2 virus and other coronaviruses have been found to mutate at a much slower rate than the influenza virus. 

Scientists have already looked into re-infection of common cold coronaviruses and found that some individuals were still susceptible to re-infection a year later with the same species of coronavirus. With COVID-19 only emerging within the last 10 months, scientists have not had much time to determine correlates of protection—a measure that signifies a person is immune (i.e. the levels of antibodies)—that may confer immunity to SARS-CoV-2.

“So we don’t actually know what level of antibodies is protective and it can differ from virus to virus what that means,” Ramirez said, “So from our standpoint, the assumption is that you’re not going to have 100% protective immunity from COVID-19. Your body is going to make an immune response to SARS-CoV-2, but it probably will not prevent you from getting re-infected, which is what we’re starting to see with the case in Hong Kong.”

That’s not to say all hope is lost, however, because having had an immune response to the virus previously does mean you may be better equipped to fight off the virus or, once infected again, experience less severe symptoms. 

“From what we can see it seems as though the people with the best protection are the ones who have all of the adaptive immune response, who have antibodies including the neutralizing antibodies that the B-cells make and who have the killer and helper T-cell responses,” Ramirez said.

How will re-infection change the trajectory of the pandemic?
As of mid-September, there were over six million recorded cases of COVID-19 in the U.S.,  amounting to around 2% of the country’s population. While some had originally hoped that widespread infection would at least result in herd immunity (still a far cry anyway, requiring 70-90% to have immunity to effectively dwindle the spread of the virus), the discovery that humans can be infected with COVID-19 more than once means that herd immunity without a vaccine is less likely than ever.

The concept of herd immunity. Risk of transmission greatly decreases as the percentage of people with immunity increases. Graphic by Alex Lim for Midstory.

In terms of protection, vaccines provide a safer means of immunization.

“Herd immunity is only achievable by a vaccine in a safe and effective manner. We shouldn’t be relying on herd immunity that is generated by natural infection because there’s so much variability amongst the population of whether they have become resistant to second infection or not,” Iwasaki said.

There are multiple types of vaccines, and their effectiveness varies depending on a few different factors. Live attenuated vaccines, which use a weakened version of the disease, like those for measles and chickenpox, give life-long protection from the disease after one or two doses. Other types of vaccines, which may use parts or segments of pathogen proteins like COVID-19’s spike protein, may only confer partial protection and require multiple doses or boosters to improve immunity. 

Very few vaccines offer high levels of protection greater than 90% (namely chicken pox and polio), and some, like the annual flu vaccine, can vary all the way from 19% to 60%. According to a study in the American Journal of Preventive Medicine, even with 100% of the population being vaccinated, vaccine effectiveness still needs to be 60% to achieve herd immunity. At 75% vaccine coverage, vaccine effectiveness would need to be 70%. 

There are currently 38 vaccines undergoing different stages of trials to ensure safety and effectiveness. One pharmaceutical company has paused its own phase III vaccine trials when one patient fell ill. Iwasaki says that we shouldn’t be rushing to approve a vaccine without a clear understanding of its effectiveness and health risks.

“We really need to understand if they’re safe first and then distribute to the population,” Iwasaki said.

While we are consulting experts in the field to get answers to important questions during this crisis, new information and studies come out almost every day and much remains unknown regarding COVID-19. Midstory encourages everyone to follow all public health and safety protocols and exercise extreme caution. 


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