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Following the news this week of what appears to have been the first confirmed case of a Covid-19 reinfection, other researchers have been coming forward with their own reports. One in Belgium, another in the Netherlands. And now, one in Nevada.

What caught experts’ attention about the case of the 25-year-old Reno man was not that he appears to have contracted SARS-CoV-2 (the name of the virus that causes Covid-19) a second time. Rather, it’s that his second bout was more serious than his first.

Immunologists had expected that if the immune response generated after an initial infection could not prevent a second case, then it should at least stave off more severe illness. That’s what occurred with the first known reinfection case, in a 33-year-old Hong Kong man.

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Still, despite what happened to the man in Nevada, researchers are stressing this is not a sky-is-falling situation or one that should result in firm conclusions. They always presumed people would become vulnerable to Covid-19 again some time after recovering from an initial case, based on how our immune systems respond to other respiratory viruses, including other coronaviruses. It’s possible that these early cases of reinfection are outliers and have features that won’t apply to the tens of millions of other people who have already shaken off Covid-19.

“There are millions and millions of cases,” said Michael Mina, an epidemiologist at Harvard’s T.H. Chan School of Public Health. The real question that should get the most focus, Mina said, is, “What happens to most people?”

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But with more reinfection reports likely to make it into the scientific literature soon, and from there into the mainstream press, here are some things to look for in assessing them.

What’s the deal with the Nevada case?

The Reno resident in question first tested positive for SARS-CoV-2 in April after coming down with a sore throat, cough, and headache, as well as nausea and diarrhea. He got better over time and later tested negative twice.

But then, some 48 days later, the man started experiencing headaches, cough, and other symptoms again. Eventually, he became so sick that he had to be hospitalized and was found to have pneumonia.

Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first.

What happens when we get Covid-19 in the first case?

Researchers are finding that, generally, people who get Covid-19 develop a healthy immune response replete with both antibodies (molecules that can block pathogens from infecting cells) and T cells (which help wipe out the virus). This is what happens after other viral infections.

In addition to fending off the virus the first time, that immune response also creates memories of the virus, should it try to invade a second time. It’s thought, then, that people who recover from Covid-19 will typically be protected from another case for some amount of time. With other coronaviruses, protection is thought to last for perhaps a little less than a year to about three years.

But researchers can’t tell how long immunity will last with a new pathogen (like SARS-CoV-2) until people start getting reinfected. They also don’t know exactly what mechanisms provide protection against Covid-19, nor do they know what levels of antibodies or T cells are required to signal that someone is protected through a blood test. (These are called the “correlates of protection.”)

Why do experts expect second cases to be milder?

With other viruses, protective immunity doesn’t just vanish one day. Instead, it wanes over time. Researchers have then hypothesized that with SARS-CoV-2, perhaps our immune systems might not always be able to prevent it from getting a toehold in our cells — to halt infection entirely — but that it could still put up enough of a fight to guard us from getting really sick. Again, this is what happens with other respiratory pathogens.

And it’s why some researchers actually looked at the Hong Kong case with relief. The man had mild to moderate Covid-19 symptoms during the first case, but was asymptomatic the second time. It was a demonstration, experts said, of what you would want your immune system to do. (The case was only detected because the man’s sample was taken at the airport when he arrived back in Hong Kong after traveling in Europe.)

“The fact that somebody may get reinfected is not surprising,” Malik Peiris, a virologist at the University of Hong Kong, told STAT earlier this week about the first reinfection. “But the reinfection didn’t cause disease, so that’s the first point.”

The Nevada case, then, provides a counterexample to that.

What kind of immune response did the person who was reinfected generate initially?

Earlier, we described the robust immune response that most people who have Covid-19 seem to mount. But that was a generalization. Infections and the immune responses they induce in different people are “heterogeneous,” said Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago.

Older people often generate weaker immune responses than younger people. Some studies have also indicated that milder cases of Covid-19 induce tamer immune responses that might not provide as lasting or as thorough of a defense as stronger immune responses. The man in Hong Kong, for example, did not generate antibodies to the virus after his first infection, at least to the level that could be detected by blood tests. Perhaps that explains why he contracted the virus again just about 4 1/2 months after recovering from his initial infection.

In the Nevada case, researchers did not test what kind of immune response the man generated after the first case.

“Infection is not some binary event,” Cobey said. And with reinfection, “there’s going to be some viral replication, but the question is how much is the immune system getting engaged?”

What might be broadly meaningful is when people who mounted robust immune responses start getting reinfected, and how severe their second cases are.

Are people who have Covid-19 a second time infectious?

As discussed, immune memory can prevent reinfection. If it can’t, it might stave off serious illness. But there’s a third aspect of this, too.

“The most important question for reinfection, with the most serious implications for controlling the pandemic, is whether reinfected people can transmit the virus to others,” Columbia University virologist Angela Rasmussen wrote in Slate this week.

Unfortunately, neither the Hong Kong nor the Reno studies looked at this question. But if most people who get reinfected don’t spread the virus, that’s obviously good news.

What happens when people broadly become susceptible again?

Whether it’s six months after the first infection or nine months or a year or longer, at some point, protection for most people who recover from Covid-19 is expected to wane. And without the arrival of a vaccine and broad uptake of it, that could change the dynamics of local outbreaks.

In some communities, it’s thought that more than 20% of residents have experienced an initial Covid-19 case, and are thus theoretically protected from another case for some time. That is still below the point of herd immunity — when enough people are immune that transmission doesn’t occur — but still, the fewer vulnerable people there are, the less likely spread is to occur.

On the flip side though, if more people become susceptible to the virus again, that could increase the risk of transmission. Modelers are starting to factor that possibility into their forecasts.

A crucial question for which there is not an answer yet is whether what happened to the man in Reno, where the second case was more severe than the first, remains a rare occurrence, as researchers expect and hope. As the Nevada researchers wrote, “the generalizability of this finding is unknown.”

  • They need tp do blood draws on those that have been infected to see how much of the residual antibodies they have remaining checking after months of infection giving everyone a better idea of how long you could maintain immunity or how long it will last with the different strains

  • The real question is: is it more or less deadly the second/third/fourth time around for those over the age of 60?

    If equal or more deadly for subsequent infections, this virus has the potential of lowering human life expectancy worldwide.

  • This is the fifth case of COVID-19 reinfection in the US that I’ve read about in the news. Apparently these other cases were not analyzed in depth they way they were in Hong Kong, Europe and Reno. One was in Washington DC, two in New Jersey, and a fourth in Massachusetts at Holyoak Soldiers Home.
    https://www.vox.com/2020/7/12/21321653/getting-covid-19-twice-reinfection-antibody-herd-immunity

    https://dailyvoice.com/new-jersey/monmouth/news/central-jersey-doctor-reports-patients-reinfected-with-coronavirus/790555/

    Hopefully, dealing with the different strains or variants of SARS-CoV-2 is not like dealing with the four strains of Dengue Fever. In the case of Dengue Fever, unfortunately having had one strain, gives one zero immunity to the other strains. I immagine it would probably mean a yearly COVID-19 vaccine based on the latest mutations. There is no vaccine for Dengue Fever yet, but not for lack of trying.

  • Why is this just being made public now…3 months after the fact? Who was this man that he could get 4 tests done in less than 60 days when most people at that time couldn’t get one test done in a timely matter…let alone 4.

    • My mother received five tests in less than three weeks back in April. In her case, she was a cancer patient and everyone in our household — three people including my mother — were infected. She needed three negative tests and her first two were positive. She ended up taking a sixth test about a month later when she got her chest port removed.

  • This is nonsense and meaningless. Why is it meaningless?
    Why is it nonsense? For it to be a reinfection it must be the identical strain of the virus. We were told that the virus does not mutate. This was the ultimate in scientific nonsense. All viruses mutate and they mutate extremely rapidly in reference to human cells. And RNA viruses mutate the fastest of all. The mutation rate is so fast that in many cases the immune system cannot keep up.

    We have great models for this. The flu. Each flu season I am vaccinated against the anticipated strain. If the vaccine is correct, I am protected. If the strain is not as expected, the vaccine may be less effective or not effective. if there are two strains of flu in a season, and I am not vaccinated I may get the first strain and then the second strain. It is true to say I was re-infected with the flu and I had the flu twice. But it is highly misleading; almost to the point of lying with the truth, as each strain was unique and represents a different pathogen.

    Each individual has their own immune systems; with unique strengths and weaknesses. We have a model with Tinea versicolor (a fungal infection of the skin). Many people eliminate the virus A significant number do not. You see them on the beach; their skin has a mottling effect due to the fungus.

    To imply that one has been reinfected with COVID-19, without first demonstrating that the viral strains are identical, is at the best, lying with the truth.

    In some cases the size of the inoculation is sufficient to mount a weak immune response but insufficient to mount an enduring immune response. We see this all the time and that is why some vaccinations require a two step process; or require re-immunization after a number of years.

    Even if these reports are accurate, it doesn’t matter. The vast majority develop a robust and enduring immune response. As in Tinea versicolor, there will be a minute segment of the population that cannot eliminate the virus.

    • Yes, SARS-CoV-2 mutates, but, having two distinct viral RNA sequences are vital to prove that this was a reinfection and not a persistent one. You brought up the flu. We have seasonal flu shots because of antigenic drift. These influenza viruses are still recognizably influenza A and influenza B to the body, which is why, even if the shot constituents do not match the circulating virus at the time of vaccine, the shot still reduces both chance and severity of infection. Before we travelled widely by air, our choice of flu shot was based on prevalent strains in Asia and Oceania the season before. Thousands of active duty military members participated in this seasonal antigen testing through “Project Gargle”, including the thousands of tech training students that rotated through Sheppard AFB when I served there as an AD USAF doc. Since the advent of widespread travel, our guesses are more guess than surveillance. Our shots have been “misses” many years of the last decade, yet the shot still provides protection. As for your T. versicolor analogy, that fungus is part of the normal skin flora. The question is not “why don’t people clear it?”, the question is why does it cause a skin manifestation in some people at all. So, in short, your 20 minute Google search should have been expanded a bit

  • Thought the most telling line in the article came at the beginning. But somehow seems to be missing from regular reporting of the overall Covid impact (first time infection).

    “There are millions and millions of cases,” said Michael Mina, an epidemiologist at Harvard’s T.H. Chan School of Public Health. The real question that should get the most focus, Mina said, is, “What happens to most people?”

    What, in fact, does happen to most people facing covid? And is it realistic that we can avoid getting it…especially if reinfection is a thing?

    Protect those at risk as best we can…but hiding from it seems impossible.

  • Do you all know how exhausting this is.
    1. Who is this random Nevada man? People could hardly get testing in March and April yet they had time sequence the rna from his infection, save it in some database and when he got sick again compare it?

    2. Every single time they come up with a treatment option they say , “there arent enough trials to give this a go” Yet you have 4 counts of reinfection and we definitively say that ppl get reinfected. Is it not possible that they just still have fragments of viral rna in their system?

    Is this never going to be over ? Why is it taking so long to find a treatment yet they have time to sequence and do comparative studies on one mans illness.

    • Tasha, no. The virus sequencing from both infections revealed differences in the virus’s genetic makeup, serving as evidence that they were separate infections with two different COVID virus mutations rather than leftover virus fragments from one infection. In other words, reinfection.

    • How did they have time to sequence and the insight to save this specific mans viral sequence to compare a 2nd time ?

    • Tasha, I went to the article (Lancet preprint), and it seems the first test was performed at a ‘community-based testing event’. It’s possible they were saving samples and possibly doing some research on them.

      As for disparities in testing availability – it’s been insane. My mom got an antigen test and was diagnosed in 30 minutes. A friend’s son who was exposed at college was put in quarantined and told he had to wait 4 days for a test and then at least 48 hours for another. My son failed a screening test at his college (he reported a sore throat on the symptom app – probably slept with his mouth open or something 🙂 ) He had a test within hours and results back in 24. His school is surveillance testing, and he is tested *every week* with results back in 24-48. How? Resources. My kid is at a private school that is all-in on making this semester work. My friend’s kid is at a state school that didn’t have a plan, and absolutely does not have the resources to do what my kid’s school is doing. This is why we need a *NATIONAL* response – to distribute resources where they are needed most! We also need a surveillance testing program of asymptomatic people, but the CDC just completely nixed anything like that in their new guidelines.

      The people doing the re-sequencing are not the same people working on treatments, rest assured. There are lots of us out here working on all aspects of the virus. The timeline for treatments and a vaccine is *incredibly fast*! I know it doesn’t seem that way, but science on this thing is actually moving at an unprecedented pace. It takes time to set up studies, enroll people, there’s all kinds of privacy stuff and safety considerations when doing human trials. Here’s hoping they don’t rush the vaccine at the cost of safety. We want a safe, effective vaccine. We’ll get one. And we will have treatments too. Even better, there are people working right now to make sure those treatments are accessible and affordable, even though they don’t exist yet.

      Hope I answered some of your questions?

  • A quote from above describing the Reno case:

    “Eventually, he became so sick that he had to be hospitalized and was found to have pneumonia.

    “Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first.”

    Well, that makes sense — pneumonia is not Covid-19.
    But then later, the author writes:

    “‘The fact that somebody may get reinfected is not surprising,’” Malik Peiris, a virologist at the University of Hong Kong, told STAT earlier this week about the first reinfection. “’But the reinfection didn’t cause disease, so that’s the first point.’”

    The Nevada case, then, provides a counterexample to that.

    Well, actually, no it doesn’t, because the author has already told us, and I quote from above:

    “Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first.”

    Unless I’m missing something here, it does not serve as a counterexample and should be corrected: simply delete that incorrect statement.

    • Hi Kevin,

      Understandable confusion. If I get you right, you’re saying that “pneumonia“ is not “Covid19” and therefore we are not seeing the same disease, especially since the researchers noted they saw two different DNA sequences here. So there are two issues to address.

      First: “Pneumonia” isn’t the name of a specific infection. It’s a descriptor for acute lung parenchyma (the oxygen-transferring part) infection by any number of viruses or bacteria. So we can and do say COVID19 causes a viral pneumonia.

      Second: the reason the DNA sequencing was different the second time is not because it was no longer Covid but because viruses (like the cold and flu) mutate through reproduction all the time. A new Covid infection SHOULD have a different sequence just as a woman should have different DNA from her grandmother, while still being recognizable as human.

      In this case, this is important because it indicates that the body may not always be able to develop antibodies that can fight off new generations of Covid. We were hoping that “reinfection” might be nominal and be largely asymptomatic due to immune response, but this new case raises doubts.

      Hope that helps.

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