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Comment by microtherion | Hacker News Reader

The emergence of a second wave of infections in Manaus, Brazil, despite an estimated 76% of the population having acquired antibodies in the first wave, would seem to pretty conclusively demonstrate that a natural immunity strategy (or an emergence of natural immunity in the absence of a coherent strategy) (a) did not work well for the people and (b) provided an incubator for new, more dangerous strains to evolve.

https://www.thelancet.com/article/S0140-6736(21)00183-5/full...

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Every time this has come up I’ve seen people point out that there were methodological problems with the study that found such high seroprevalence, and that plus the fact that there’s still few actual concrete documented reinfections - even as the P1 variant has spread around the world - or the fact that there’s no evidence P1 escapes any of the vaccines designed for wildtype (of course, the immune system is complicated!), at least points in the direction that there never was a 76% infection rate in Manaus.

You can always quibble with the exact percentage (and the article I posted discusses some of the objections), but there is considerable evidence that there must have been a fairly high infection rate — given the minimal measures taken, there hardly is another explanation for why the first wave petered out and case numbers stayed low for several months. Excess deaths in the first wave were .15% of the population of the city, which is relatively young, which also points to a high infection rate.

And all of that didn't help one bit in the second wave.

A year ago, many people took seriously Swedish claims that Stockholm was close to herd immunity. Now Manaus is never supposed to have reached herd immunity levels. It seems to be a bit of a "No True Scotsman" type of situation.

Take a look at this: https://web.archive.org/web/20210204143915/https://www.novav...

Go to slide 28.

This is Novavax's presentation of clinical trial results. As part of their phase 2 trial in South Africa at the end of 2020, they gave everyone antibody tests. In the placebo arm, 30% of that arm was seropositive (had antibodies from a prior infection). Of the seronegative group, 2.9% contracted COVID during the study. Of the seropositive group, 2.9% contracted COVID during the study.

At the time, most infections in SA were the B.1.351 variant (referred to in the presentation as 501Y.V2). This variant has many of the same mutations as P.1 and is believed to have a similar ability to evade immunity.

I'm sorry - a preliminary trial for a vaccine that's not currently in widespread use being ineffective against a different variant makes a pretty flimsy case for the danger of reinfection with P1.

And actually, Novavax later announced that actually, natural immunity does provide protection against the SA variant [1]:

> A previously reported initial analysis from the study through 60 days indicated that prior infection with the original COVID-19 strain might not completely protect against subsequent infection by the variant predominantly circulating in South Africa. However, the complete analysis of the South Africa trial indicates that there may be a late protective effect of prior exposure with the original COVID-19 strain. In placebo recipients, at 90 days the illness rate was 7.9% in baseline seronegative individuals, with a rate of 4.4% in baseline seropositive participants.

Moreover: the SA variant and P.1 aren't necessarily similar in terms of immunity evasion. For instance: SA isn't using the AZ vaccine at all because of how ineffective it is against their variant, but it works just fine against P.1. Or look at this paper [2]:

> Neutralization titres against P.1 were similar to those against B.1.1.7 and only a minority of samples failed to reach 100% neutralization at 1:20 dilution of serum, considerably better than neutralization of B.1.351, where titres were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer and ChAdOx1 nCoV-19 AstraZeneca vaccines respectively.

[1] https://ir.novavax.com/news-releases/news-release-details/no...

[2] https://www.biorxiv.org/content/10.1101/2021.03.12.435194v1

I'm not talking about the vaccine aspect of the trial, just the placebo arm where they did the antibody tests. I hadn't seen their 90 day update, so thanks for that.

Your original statement that there were few documented reinfections. They found 30 of them here under controlled study conditions, and prior infection provided less than 50% protection against B.1.351.

To my knowledge, there hasn't been a controlled study like this in Brazil. The in vitro results you cited suggest that while the immune escape of P.1 is not as great as B.1.351, it still is very substantial, and reinfection will occur in a substantial number of patients.

Per the Washington Post just two days ago [1], there have been just 71 confirmed reinfections worldwide, which is why I made that claim. Unless half of those came from that study, I’m not really sure how to square this.

I disagree with your assessment of P.1 immune escape being “very substantial” based on those in vitro results. It’s on par with the UK variant, which has no evidence - real world or otherwise - or reputation at all for widespread reinfection or vaccine escape. Never mind that in vitro results don’t even tell the whole story of an in vivo immune response. To be perfectly honest, I’m struggling to see how you’re making that claim.

[1] https://www.washingtonpost.com/business/can-you-get-covid-tw...

Washington Post cited BNO news, which is just one guy I believe. I don't know if he's just sourcing these from news stories or what. If they're seeing 30 reinfections over 3 months in 650 study participants, you can be quite sure that there are a lot more than 71 reinfections in the world.

There is no evidence of widespread reinfection in Manaus.

There's some evidence, as explained in that article. It's just equivocal, as is the evidence in most COVID-19 studies, even the strong studies. Unlike most studies, though, neither the above nor the original study showing Manaus seroprevalence seem easy to dismiss. For example, the reinfection study notes that the elapsed time before the first wave and second wave was greater than the period of immunity established by other studies.

Definitely something to keep an eye on.

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