By JJ Grandville
In case you haven't noticed, or perhaps you're "off the grid," taking some well-deserved time off from COVID-19 news, last week we learned of several cases of SARS-CoV-2 reinfection.
We'll come back to them in a moment, but first, a few questions:
- Why does one parent never get sick when their children start coughing, sneezing, and running a runny nose with colds, while the other parent catches a cold every time?
- Why do some tourists happily dine on delicious street food in Mexico City, while that same cuisine will leave others stuck in their hotel bathrooms for the entire trip?
- Why do some people suffer from strep throat repeatedly, while others never experience it in their lifetime?
- Why is it that infection with the Epstein-Barr virus (almost 100% in humans in adulthood) is asymptomatic most of the time, while some unfortunate individuals will suffer severe mononucleosis for weeks?
- Why did some gay men in US cities contract HIV in the early 1980s after relatively few exposures, while others with multiple known HIV-positive contacts never did? How did some sex workers in Africa escape HIV in the early 1980s?
- Or, perhaps more relevant to cases of COVID-19 reinfection, why do some people get the flu twice in the same flu season? Or why do some (rare) people get chickenpox twice? (The second case is usually quite mild, thankfully.) Or even measles!
I begin with these examples (and I could have chosen dozens more) to highlight that there are a lot of things we don't know about infections, immunity, and how they interact to protect us—or not—from disease.
So, after hearing anecdotes about SARS-CoV-2 reinfection for months (many of them called false based on persistent low-level PCR positivity, not reinfection), we now have real cases and it's worth considering some of the details.
The first case occurred in a 33-year-old man 142 days after his initial symptomatic infection. Authorities detected the infection through a screening test when he passed through Hong Kong airport, as he had no symptoms. In fact, he remained asymptomatic throughout. Shortly afterward, a robust antibody response developed, a response that went undetected the first time.
Sequencing the virus from the two infections showed sufficient differences to prove a reinfection, rather than a relapse.
As immunology professor Dr. Akiko Iwasaki wisely pointed out , "This is not cause for alarm; it's a textbook example of how immunity should work."
Phew.
Then news emerged of additional cases in Europe and Ecuador, about which we have limited details.
But this American case in a 25-year-old immunocompetent man from Nevada deserves attention and probably worries some.
Here are the clinical details of the story, summarized from the available preprint (not yet peer-reviewed):
March 25: Onset of sore throat, cough, headache, nausea, diarrhea.
April 18: Positive test for SARS-CoV-2 by PCR.
April 27: The symptoms resolved.
May 9 and 26: negative virus test by two methods.
May 28: Onset of fever, headache, dizziness, cough, nausea, and diarrhea. Chest x-ray negative.
June 5: Symptoms worsened and now included hypoxia; admitted to the hospital and new infiltrates were found on chest x-ray. PCR positive for SARS-CoV-2.
June 6: Positive SARS-CoV-2 IgM and IgG antibodies.
The authors state that the viruses isolated from the first and second illnesses show sufficient genetic differences to support reinfection, rather than relapse. The likely source of the second infection was one of the parents, suggesting household transmission, although the father's sequences are unavailable.
These important case reports raise many questions, about which we can only speculate today, which is why many of the following sentences have question marks.
- How often does reinfection occur, and why? It doesn't seem common, but we must conclude from these cases that it does occur. Perhaps with a frequency similar to other coronavirus infections in humans?
- Will the cases be as severe as the first infection? Based solely on household contact in the Nevada case, it's possible that severity is related to the intensity of exposure. Perhaps the infected person wasn't taking precautions at home, believing themselves to be immune? Some believe that the inoculum is an overlooked factor in the severity of COVID-19.
- When reinfection occurs, will these new cases carry the same risk of transmission as the first infection? We'll have to assume so, but it's plausible that an immune response will make people less infectious to others.
- How do these cases influence policies on screening people who have recovered from COVID-19? Given the long duration of PCR positivity in some individuals, some infection control specialists have advocated against retesting asymptomatic individuals admitted with a pre-existing condition. The same applies to pre-procedure screening. It appears we may need to suspend this policy change until we have more data on reinfection and how frequently it occurs.
- What are the implications for vaccine efficacy? Will a vaccine work? If so, for how long? Cases suggest that periodic vaccination may be necessary, but optimists can point to the HPV vaccine as a model of how vaccine immunity can be stronger than natural immunity, so we shall see.
So remember, there are many things we don't know about our immune system and how it works, and this is particularly true for a new infection and disease.
But one thing I do know?
"Immunity passports" are dead.