Weekly coronavirus-related chat, questions, and minor updates - week of June 27

Freaking out about how many people I'm connected to have COVID or exposures. My spouse's grandmother and aunt, my aunt, my spouse's partner and their whole family, multiple coworkers at my remote job in the last few weeks, my best friend's coworker who was coughing at work yesterday, my mother's doctor who she was supposed to see this week but is in the hospital...

I'm worried for all of them and worried about newer variants and worried - no, angry - that this is the worst it's ever been in the small group of people I know and people who know them, and yet no one wears masks anymore. My county is at the highest level on both the new (weaker) CDC metric based on hospitalizations and the older metric based on actual transmission levels, and no one cares!

Cause of long-COVID symptoms revealed by lung-imaging research at Western University

Using a functional MRI where patients inhale xenon gas, researchers can see in real-time what it is happening inside the lungs. Preliminary results show symptoms are related to microscopic abnormalities that affect how oxygen is exchanged from the lungs to red blood cells. The research was published Tuesday in Radiology.

Having participants inhale the gas while being scanned by the MRI allowed researchers to see how the 500 million air sacs in the lungs deliver oxygen to the blood. In the case of long-COVID patients, the transition of the oxygen was depressed compared to healthy volunteers.

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"What we see in patients who have long-COVID, and they're symptomatic, is that they actually have normal pulmonary function. So their breathing tests that doctors would prescribe were normal, and their CT scans were normal. But the MRI told us a completely different story."

The BA.5 story (Eric Topol)

The Omicron sub-variant BA.5 is the worst version of the virus that we’ve seen. It takes immune escape, already extensive, to the next level, and, as a function of that, enhanced transmissibility, well beyond Omicron (BA.1) and other Omicron family variants that we’ve seen (including BA.1.1, BA.2, BA.2.12.1, and BA.4). You could say it’s not so bad because there hasn’t been a marked rise in hospitalizations and deaths as we saw with Omicron, but that’s only because we had such a striking adverse impact from Omicron, for which there is at least some cross-immunity (BA.1 to BA.5). Here I will review (1) what we know about its biology; (2) its current status around the world; and (3) the ways we can defend against it.

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While initially seen in South Africa soon thereafter in Portugal, BA.5 has been detected throughout the world. It led to a marked rise in hospitalizations in Portugal where it rapidly became dominant, and is now having such an effect, to a variable extent, in many European countries and Israel. It is frequently masked since the rise of BA.5 is occurring at the same time as the decline in BA.2 in several countries, and the magnitude of the BA.2 wave was different between countries.

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It will very soon be the dominant (>50%) variant in the United States. BA.5 was ~37% as of June 25th. The risk of reinfection with BA.5 has substantially increased because prior infections are far away (antigenically) from an aligned immune response.

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Boosters would help, and it is noteworthy that for people age 50+ there is a substantial (14-fold) reduction for mortality as recently documented by the CDC for a 4th shot (previously published by the Israel investigators in multiple observational studies). That is 99% reduction in mortality for 4-shots vs 86% for 3 shots. But only 1 in 4 Americans age 50+ have had a fourth shot!

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The issues that are being confronted at the FDA Advisory Committee center around whether an emergency authorization for a BA.1 booster is worthwhile now that the virus has moved onto a substantially different variant. The sad truth is that we can’t even get 75% of high-risk people to get a 4th shot (original vaccine) with a proven survival advantage. (Side note: million of these shots will soon expire, a profound waste, which should be made available to all people, age <50, who seek added protection).

Where’s the herd immunity? Our research shows why Covid is still wreaking havoc (The Guardian)

Last week a group of collaborators, including me and a professor of immunology and respiratory medicine, Rosemary Boyton, published a paper in Science, looking comprehensively at immunity to the Omicron family, both in triple-vaccinated people and also in those who then suffered breakthrough infections during the Omicron wave. This lets us examine whether Omicron was, as some hoped, a benign natural booster of our Covid immunity. It turns out that isn’t the case.

We considered many facets of immunity, including the antibodies most implicated in protection (“neutralising antibodies”), as well as protective “immune memory” in white blood cells. The results tell us it is unsurprising that breakthrough infections were so common. Most people – even when triple-vaccinated – had 20 times less neutralising antibody response against Omicron than against the initial “Wuhan” strain. Importantly, Omicron infection was a poor booster of immunity to further Omicron infections. It is a kind of stealth virus that gets in under the radar without doing too much to alert immune defences. Even having had Omicron, we’re not well protected from further infections.

Also, to be added to the now complex mix is “immune imprinting”. This is the finding that our immune response to Covid is shaped very differently, depending on our prior exposures – infection in one wave relative to another, plus vaccination. In our study, those who’d been infected in the first wave and then again with Omicron had particularly poor T-cell responses and no boosting of antibodies. That is, some combinations of exposures may leave us poorly protected relative to others.

Here is the paper.