An ongoing dialogue on HIV/AIDS, infectious diseases,
August 30th, 2020
Cases of SARS-CoV-2 Reinfection Highlight the Limitations — and the Mysteries — of Our Immune System
In case you didn’t notice, or perhaps were “off the grid” taking some well-earned time away from COVID-19 news, this past week we heard about several cases of SARS-CoV-2 reinfection.
We’ll come back to them in a moment, but first, some questions:
- Why does one parent never get sick when their kids start coughing and sneezing and dripping with colds, while the other gets a cold every single time?
- Why do some tourists happily dine on delicious street food in Mexico City, while this same cuisine will put others in their hotel bathrooms for the whole trip?
- Why are some people repeatedly plagued with strep throat, while others never get it in their lifetimes?
- Why is infection with Epstein Barr virus (nearly 100% in humans by adulthood) most of the time asymptomatic, while a certain unlucky few will be laid up with severe mononucleosis for weeks?
- Why did some gay men in U.S. cities contract HIV in the early 1980s after relatively few exposures, while some others with multiple known HIV-positive contacts never did? How did some commercial sex workers in Africa in the early 1980s escape HIV?
- Or, perhaps most relevant to the COVID-19 re-infection cases, why do some people get the flu twice within the same flu season? Or some (rare) people get chicken pox twice? (The second case is usually quite mild, fortunately.) Or even measles!
I start with these examples (and I could have chosen dozens more) to highlight that there’s a ton we don’t know about infection, immunity, and how they interact to protect us — or not to protect us — from disease.
So after hearing anecdotes about SARS-CoV-2 reinfection for months (many of them false-calls based on persistent low-level PCR positivity, not reinfection), now we have actual cases, and it’s worth considering some of the details.
The first occurred in a 33-year-old man 142 days after his initial symptomatic infection. Authorities picked up the infection on a screening test when he went through the Hong Kong airport, as he had no symptoms. In fact, he remained asymptomatic throughout. A brisk antibody response developed shortly after, a response not detected the first time.
Sequencing the virus from the two infections showed sufficient differences to prove reinfection, rather than relapse.
As noted wisely by immunology professor Dr. Akiko Iwasaki, “This is no cause for alarm – this is a textbook example of how immunity should work.”
News then broke with additional cases in Europe and Ecuador, about which we have limited details.
But this U.S. case in a 25-year-old immunocompetent man from Nevada deserves attention, and likely some worry.
Here are the clinical details of the history, summarized from the available pre-print (it has not yet been peer reviewed):
March 25: Onset of sore throat, cough, headache, nausea, diarrhea.
April 18: Tested positive for SARS-CoV-2 by PCR.
April 27: Symptoms resolved.
May 9 and 26: Tested negative for virus by two methods.
May 28: Onset of fevers, headache, dizziness, cough, nausea, and diarrhea. Chest x-ray negative.
June 5: Symptoms worsened, and now with hypoxia; admitted to the hospital and found to have new infiltrates on chest x-ray. PCR positive for SARS-CoV-2.
June 6: SARS-CoV-2 IgM and IgG antibody positive.
The authors state that the viruses isolated from the first and the second illness show sufficient genetic differences to support reinfection, rather than relapse. The likely source of the second infection was a parent, suggesting household transmission, though the sequences from the parent are not available.
These important case reports raise many questions, about which today we can only speculate, which is why many of the sentences following have question marks.
- How often does reinfection happen, and why? It doesn’t appear common, but we must conclude from these cases that it does occur. Perhaps with similar frequency to other coronavirus infections in humans?
- Will cases be as severe as the first infection? Based solely on the Nevada case’s household contact, it’s possible that severity may be related to intensity of exposure. Maybe he was not taking precautions in the household, believing himself immune? Some believe inoculum is an overlooked aspect of COVID-19 disease severity.
- When reinfection happens, will these new cases carry the same risk of transmission as the first infection? We will have to assume so, but it is plausible that an immune response will render people less infectious to others.
- How do these cases factor into policies about screening people who have already recovered from COVID-19? Given the long duration of PCR positivity in some people, some infection control specialists have advocated not retesting people who are admitted with prior disease if they are asymptomatic. Same for preprocedural screening. Seems we may need to put this policy change on hold until we have further data on reinfection, and how often it occurs.
- What are the implications for vaccine efficacy? Will a vaccine even work? If so, for how long? The cases suggest that a vaccine may need to be repeated periodically, but optimists can point to the HPV vaccine as a model of how vaccine immunity can be stronger than natural immunity, so we’ll see.
So remember, there’s a lot 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.