Some 'lucky few' have 'resistance' or immunity to SARS-Cov-2 (Alpha?)

[Astronuc]

Back in June 2020, in São Paulo, Brazil, Thais Andrade has avoided infection with Covid-19 though her husband, Erik Soares de Araujo, fell seriously ill and had to be hospitalized.

https://www.statnews.com/2021/08/23/lucky-few-seem-resistant-to-covid19-scientists-want-to-know-why/

“When he hit 90% [on the oximeter], I said we can’t wait anymore,” Andrade recalled. “I called an ambulance.”

At the hospital that day in June 2020, a CT scan showed multiple lesions in her husband’s lungs — an indication of severe Covid-19 infection – which was later confirmed via a blood test. Erik, 44, had likely contracted the virus up to a week earlier, from a friend who had visited their home.

He spent the next several weeks on oxygen in the ICU, a stay that was complicated by blood clots before he was discharged. But it wasn’t his sudden decline and subsequent recovery that is notable: It’s that Andrade had been sharing the same close quarters with her husband while he was infected and able to transmit the virus. She never wore a mask in the home with him. They shared the same bed. They were physically intimate. Yet when tested for an active or past infection — twice — her bloodwork came up negative.

And that wasn’t the only time she was potentially exposed. As part of her research work as a veterinary neurologist, she went to a meeting at the University of São Paulo where an infected attendee set off a chain reaction of positivity – but Andrade dodged it. Her tests were again negative.

Both experiences suggest that Andrade may have won a sort of biological lottery — that she’s one of a lucky few “resistant” to the virus that has killed more than 4 million people. But how? That’s the mystery researchers around the world have set out to unravel.

Scientists want to know why. Her ACE2? Her B and T cells? Her age? Based on 2020, I'm guessing Alpha or an early variant.

 

[jack action]

With no more than 3% of the worldwide population who had Covid, and no more than 20% in localized areas (Seychelles on worldmeter), how did adjectives like "few" and "lucky" have been determined? How was it determined that this is a rare condition?

 

[Jarvis323]

I've always wondered about the rare cases you hear about where multiple people in the same household die from Covid. It would seem in some cases that such an exceptionally unlucky event, involving apparently healthy individuals, could reveal some hidden risk factors. But also, is it possible in some cases that mutations which make the virus more deadly but much less contagious occur in small clusters here and there and then go away?

 

[BillTre]

I've always wondered about the rare cases you hear about where multiple people in the same household die from Covid. It would seem in some cases that such an exceptionally unlucky event, involving apparently healthy individuals, could reveal some hidden risk factors. But also, is it possible in some cases that mutations which make the virus more deadly but much less contagious occur in small clusters here and there and then go away?

I hope these rare cases of seemingly unlikely occurances you speak of are well documented.
Otherwise, they could be suspect for a number of reasons.

 

[atyy]

The OP article is https://www.medrxiv.org/content/10.1101/2021.04.21.21255872v1. They did antibody tests (by collecting blood several weeks after their partners were infected), but as they didn't do PCR tests. From this review posted by @Ygggdrasil, there are other reports of people who test positive by PCR (consistent with being infected), who don't have detectable antibody levels 3 weeks or more later, but have detectable T cell responses. It seems the candidate genes they mention are related to NK cells. So it'd be interesting to do T cell tests or NK cell tests (as the authors suggest) in the people studied in the OP article.

https://www.nature.com/articles/s41590-020-00808-x
SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals.

https://www.nature.com/articles/s41591-020-01143-2
"Whether our observation that SARS-CoV-2-specific CD8+ T cells were detectable in individuals seronegative for anti-SARS-CoV-2 S or N IgG indicates a faster waning of the antibody response compared to the CD8+ T cell response in SARS-CoV-2 infection, as has been reported for SARS-CoV-1 infection13,14, needs to be investigated in further detail and in larger cohorts."

https://www.sciencedirect.com/science/article/pii/S0092867420310084
Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19.
[No PCR tests, maybe these "exposed" family members are like the subjects studied in the OP study?]

 

[morrobay]

And from the last paragraph/link above: Almost twice as many healthy individuals* who donated blood during the pandemic had memory T cell responses versus antibody responses. *Are these individuals those who may have been exposed to SARS 2 but not infected ? In any event it seems like the lucky are more than a few.

 

[atyy]

And from the last paragraph/link above: Almost twice as many healthy individuals* who donated blood during the pandemic had memory T cell responses versus antibody responses. *Are these individuals those who may have been exposed to SARS 2 but not infected ? In any event it seems like the lucky are more than a few.

Not sure what the correct terminology is, but in terms of true "resistance", I think so far I would only consider the RAB7A mutations mentioned in the OP.

For the rest, it seems it has to do with parts of the immune system being able to react (apart from antibody generation) even before the virus enters a cell and replicates. Here is a comment in another article about individuals who are exposed, not infected, but have T cell responses.

https://www.nature.com/articles/s41467-021-22036-z
"By contrast, the formation of CD4+ T memory does not rely on endogenous viral replication but involves endocytosis and/or phagocytosis of exogenous viral antigens, which are mostly derived from non-replicative viral particles or soluble viral proteins. Thus, CD4+ T cell memory may be more easily achieved in uninfected exposed individuals."

"Despite some subtle differences, most patients developed measurable amounts of SARS-CoV-2-specific CD4+ and CD8+ memory T cells which were stably maintained between 48–86 days after convalescence. Importantly, our discovery of the presence of significant levels of SARS-CoV-2-specific memory T-cell immunity in a group of individuals (close contacts) who were exposed to but not infected ... Although cross-reactive memory T cells were present in healthy donors who had never been exposed to SARS-CoV-2, their role in host protection needs to be thoroughly investigated as they were hardly able to proliferate."

 

[Kat-hi]

My husband's cousin was hospitalized for over a month with COVID and has quite a bit of lung damage (no smoker, 49 years old), her mother-in-law, who she took care of , was quite sick from it as well but not as sick as her, and her father-in-law died from it (he got it from a visiting nurse). Yet her husband did not get it. Her husband took care of his father prior to death when he found that he contracted COVID. She maintains that her husband did nothing special beyond what she did for protection. None were vaccinated at the time because vaccines were not yet available. This would seem to substantiate that some people have natural immunity.
Our next door neighbors ALL have COVID as I write this... EXCEPT for a male member who is the only non-biologically related person in that home. He works in a jail where multiple people have had COVID and his wife is an ER nurse who has COVID. All are vaccinated.