February 2024 in Covidlandia - jabs, brains, and zombies
Studies of interest to primary care. Curated with commentary.
I wrote a similar post at the end of January, and it seemed quite popular - so here we go for February! The science of Covid continues to evolve, and I think we have never seen such a sustained, massive research focus on one infectious disease in my lifetime. It is too much for any one clinician to keep up with… but here are the highlights that caught my attention last month as a primary care doc, curated and presented succinctly with sources for those who want a deeper dive.
Updated vaccines keep working
The updated XBB Covid vaccine, which only 22% of American adults received this fall/winter, provided approximately 54% protection against symptomatic SARS-CoV-2 infection when compared with not getting the updated vaccine.
This updated vaccine was specifically found to provide good protection against the JN.1 variant which has dominated for months, and has also worked well against other circulating lineages.
What’s more, the new updated vaccine continued to provide 49% protection out to 119 days studied after the shot (about 4 months and counting).
So I’m sticking with this CDC conclusion: All persons aged ≥6 months should receive the updated 2023–2024 COVID-19 vaccine. CDC will continue monitoring COVID-19 vaccine effectiveness, including against severe disease and for expected waning.
Many of my patients who had not received the updated vaccine did so during their regularly scheduled appointments with me this fall and winter. I am grateful for that kind of trust. This kind of study helps our conversation big time. Who doesn’t want a 50% lower risk of getting Covid for a while?
A Canadian study found a similar conclusion - updated vaccines increase protection
The updated, currently available XBB.1.5 vaccine afforded a level of protection comparable to the seasonal influenza vaccine, reducing the risk of outpatient medical visits for COVID-19 by about 50% overall.
Among people reporting a prior history of confirmed Covid illness, the XBB booster provided even higher protection, reducing the COVID-19 risk by around 70%. Who doesn’t want a 70% lower risk of getting Covid for a while?
CDC/ACIP state that people over age 65 should get another boost this spring.
Building on the data above, and lots more studies and discussion, the CDC announced this week a sort of real world compromise:
Recommended isolation periods with Covid are now officially minimal. I’m not going to even memorize them, because they are based on capitulation to real world behaviors, and not on the science which still shows most people are infectious for a week plus.
Hospitalizations and deaths are mostly occurring in older age groups, hence the “should get a booster this spring.” Don’t forget that ventilation and masks still work to varying degrees, and a booster can only do so much if you’re in a room for an hour with someone who has Covid.
Seniors should get the new booster four months after their last vaccine dose if they got one, or at least three months after a Covid infection. I think it’s ok to time this individually and try to game it out within the context of your own life and plans.
Between October and November of this year the VAST majority - 95% of hospitalized adults - were not up-to-date on their annual Covid-19 vaccines.
More evidence that Covid can affect the brain and our cognition in bad ways
There were additional studies out this month, including two just published in the NEJM which I will highlight next. But this first one, published in The Lancet, caught my eye first.
In this study out of the UK and Germany, researchers tested the cognitive performance speeds of three groups of people between 2021 and 2023:
People with no history of Covid illness
People with a history of Covid, but no reported long Covid (No post covid condition/PCC)
People with a history of Covid, but suffering from long Covid (PCC)
I cropped the most important part out of a pretty intense graphic to show the crux of the study results - relatively severe impairment of reaction times and cognitive performance speeds was seen in the majority of people reporting long Covid (PCC):
To me, studies like this indicate that the game has still changed. While it is very difficult to never get Covid, and almost all of us have or will, it is still worth trying not to get Covid gratuitously. Staying up to date with vaccines, treating Covid when we are sick, and staying home/wearing a mask to protect others from infection when we are sick are evergreen, prudent ideas.
I previously wrote about my own aggressive treatment plan for when I get Covid. I am still more cautious than most people, and continue to wear an N95 in little examining rooms.
Two additional studies keep building on the evidence of cognitive problems after Covid infections
Here are those two that were just published a few days ago in the NEJM (1, 2, 3). The estimated effect of Covid illness upon IQ is something that most of us can relate to and better understand conceptually. We all know what IQ is. The researchers extrapolated their findings to this kind of horrifying conclusion - when compared with uninfected controls, people with the following Covid illness patterns lost IQ points at a rate of:
Mild Covid with resolved symptoms = 3 IQ points lost
Unresolved symptoms = 6 points
Covid requiring ICU admission = 9 points
Reinfection = additional 2 points
Dr.
, in his post on these studies, concluded:The 2 new studies are the largest to date to prospectively assess Covid impact on cognitive function, and both are consistent in showing declines as compared with controls without Covid. The assessment of cognition in the cohort from England was more in-depth, but of shorter duration, and demonstrated the favorable effect of symptom resolution. The extrapolation to a loss of 3 to 9 IQ points is difficult contextualize, and the risk of long-term sequelae is unknown. It is worthwhile noting that these IQ score losses represent averages, and there is considerable variability in cognitive deficit. In contrast, the Norwegian study only got into memory but had much longer, serial assessment up to 3 years. None of this is good news for Long Covid and the brain, folks.
I sleep slightly better at night when I consider that these studies were potentially biased. In a note I posted on Substack this week I stated:
A lot of potential for bias here. In the first study, those people motivated to stay in the survey might have been suffering from long Covid and problems that compelled them to respond. In the second study we are talking about self-reported memory problems via questionnaire, and so once again there is the same potential for response bias and recall bias for those people knowing they had Covid. Hard to "blind control" for that.
So bottom line, for me the same conclusions I noted above apply: stay in the Covid game, protect yourself as much as you reasonably can while still living your life, stay up to date with vaccines, and treat Covid when you get it. There are multiple proven pathways by which Covid illness can damage the brain and lead to repetitive, cumulative cognitive problems. I see this in my practice.
The more vaccine doses, the more protection against long Covid, cardiovascular disease, and mortality
A new study published in Nature Communications of almost 1.2 million people in Hong Kong demonstrates the protective effect of Covid-19 vaccination against long Covid, and suggests that the more doses people have had the less likely they will experience long-term symptoms related to the virus.
Unvaccinated participants with Covid had the greatest risk of all observed clinical sequelae, including major cardiovascular diseases (>4 times the risk).
Participants with 1 dose prior to infection had 3X the risk of subsequent cardiovascular disease
Those receiving 2 doses had a 2.5X the risk of CV disease
Those receiving 3 or more doses had “only” 2X the risk of CV disease
The risk of all-cause mortality was most significant between the unvaccinated and vaccinated, with almost a fivefold reduction in risk of all-cause mortality between unvaccinated patients and patients with complete vaccination during the acute phase of infection. The risk of all-cause mortality dropped even further among patients with a booster dose of vaccine.
After the first 30 days following infection, risk of death continued to be significantly lower for those fully vaccinated and boosted against COVID-19, with participants who received three or more doses of vaccines not incurring any significant risk of clinical sequelae from 91 days onward from their initial infection.
Vaccines continue to work well for kids
For any parents who are still considering whether or not to vaccinate their kids, these numbers are hard to argue with:
Among adolescent 12 to 15 year-olds during the Delta period, vaccine effectiveness (VE) was 98.4% against SARS-CoV-2 infections —> 99.0% (mild disease), 98.7% (moderate-to-severe disease) and 99.0% (ICU admissions).
Corresponding VEs during Omicron in adolescents were 85.5% —> 87.0%, 84.8%, and 91.5%.
Among children 5 to 11 year-olds during Omicron, VE was 74.3% —>
73.5%, 75.5%, and 84.9%.
What about myocarditis? In this study, published in Annals of Internal Medicine, risk for myocarditis was similar in the vaccinated versus unvaccinated groups during Delta, and lower in the vaccinated groups during Omicron.
Kids that received the bivalent booster last year did great
They had a 54% reduction in Covid illnesses.
Good for them, their families, their schools, and their communities. Published in JAMA.
Kids can get banged up by Covid, too.
It is estimated that 5.8 million children in the U.S. may be impacted by long Covid symptoms and ongoing problems. From the lead author of the review paper published in Pediatrics, Dr. Melissa Stockwell:
A lot of what we know about Long Covid really does come from adults, there’s much less that’s known about kids. And I think that pediatricians, for many of them, Long Covid isn’t really on their radar. That’s been hard for families who have talked to us in RECOVER: they know something’s wrong with their child, they go to the doctor, and at best, the doctor doesn’t know what they’re looking at and doesn’t know how to manage it. And at worst, the doctor doesn’t believe the family and the child…
This is another reason why I keep my child up to date with Covid vaccinations. They have been shown to keep adding benefit, though most studies are in adults.
I don’t listen to doctors and others who trivialize Covid, even in kids.
There has been a 10% rise in Type 1 diabetes in children since the pandemic started
As to mechanisms, this study revealed factors such as direct viral damage, metabolic dysfunction, and immune responses contributing to higher rates.
The global number of children experiencing the life threatening complication of diabetic ketoacidosis (DKA) and severe DKA increased 25%, and 19.5%, respectively, when compared to pre-COVID-19 years.
Covid can leave behind zombie particles
We keep learning more about viral infections since the pandemic forced us to reconsider everything - from the false dichotomy of airborne versus droplet spread, to the notion that the body wins an uncontested victory after infection.
In this case “zombie” molecules can persist after Covid illness and the actual SARS CoV-2 viruses have been kicked out:
The research team found SARS-CoV-2 fragments can imitate innate immune peptides, a class of immune molecules that amplify signals to activate the body’s natural defenses. Peptides are chains of amino acids like proteins, only shorter. These immune peptides can spontaneously assemble into new structures (“zombies”) with double-stranded RNA, a special form of a molecule essential for building proteins from DNA, typically found in viral infections or released by dying cells.
The resultant hybrid complex of the immune peptides and double-stranded RNA kicks off a chain reaction that triggers an immune response.
Pregnant women can develop long Covid at relatively high rates
Up to 10% of women infected with Covid during pregnancy go on to develop long Covid, with post-exertional malaise and fatigue being the two most common symptoms persisting at 6 months.
This study was published in AJOG. Covid vaccines are approved for pregnant women, benefits outweigh rare risks, and fetuses benefit from additional protection thus gained, too.
Rebound after antivirals? This study says yes.
The CDC has concluded that Paxlovid rebound is not a thing. And yet there are some studies which do contradict this. This recent one, published in Clinical Infectious Diseases, recently found:
Symptomatic rebound occurred in 32% of 130 patients who received nirmatrelvir/ritonavir as compared with 20% of 241 untreated patients
Virologic rebound occurred in 27% of treated vs. 7% of untreated patients
Patients with more severe COVID-19 were more likely to experience rebound.
The average daily number of symptoms was similar in the treated and untreated groups, but the average viral load was lower in treated patients.
One individual study does not change the overall consensus, but in my mind I think Paxlovid rebound is probably a limited thing - but does not in any way change my prescribing habits or recommendations. Rebound or not, antivirals reduce the risk for severe outcomes and the risk for long COVID. Doctors are not using it enough, and patients are not asking for it enough. Maybe a 5-day course is too short.
And finally: Yes! You can still give blood if you are vaccinated. Please do.
I had not heard of this conspiracy theory until this week when one of my patients told me that he had stopped donating blood after receiving his mandatory two Covid vaccines back when they first came out.
I’m sure he is being informed by the wrong parties.
So yes, you can still donate blood if you’ve been vaccinated, boosted, or are totally up to date. If I ever need a transfusion I would absolutely prefer to receive blood from someone up to date with vaccinations.
The Red Cross asks people to wait at least 10 days after Covid infections to donate blood. The need for blood and platelets is constant. And yet I would wait longer than 10 days after infection to allow for more complete recovery by the potential donor.
Concluding lightning round for February articles that caught my eye
Updated vaccines available since this fall worked quite well to prevent infection, with over 50% effectiveness.
95% of people hospitalized this fall and winter were not up to date with Covid vaccinations.
CDC and ACIP therefore state that people over age 65 years should get a booster this spring.
Most people aren’t staying home or masking when they are sick anyway, so the CDC capitulated to the popular will over the unchanged science of infectiousness.
Covid can affect the brain, and potentially chip away at our IQ. It’s worth playing the game if you can, and try not to get infected. Even resolving to wear a respirator on planes and paying attention to poorly ventilated indoor public spaces can make a difference in your personal risk.
Vaccines work well for kids, who can also get banged up by long Covid and other complications.
Pregnant women are at risk of long Covid, too.
Zombie particles can be left behind by Covid infections, and are a new topic of research.
Paxlovid rebound? Maybe. But the CDC consensus is nah. But regardless of the 100% true answer, it’s better to treat and reduce viral loads.
We can (and should!) donate blood, regardless of vaccination status.
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I hope you appreciate this month’s highlight show, with ideas relevant to primary care. Please let me know your thoughts, positive or negative, and a thumbs up or thumbs down on future installments :)
Take good care.
Thx. Great summary and commentary wish you were my PCP.
Thanks, Ryan. The hospitalization numbers (unvaxxed vs vaxxed) are staggering. How can some people put such a low value on their own life? You mentioned “playing the game” wisely - being unvaxxed is like going all in at poker with a really crappy hand. I’m getting my spring Covid vax this afternoon, already got my RSV & others, so I’ll be vaxxed to the max.