COVID-19

📆 There have been a huge number of “it’s been five years since the start of the pandemic” articles. (For example, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here, here.)

What have we learned? How have we changed? What is still broken? How are we still hurting? (A significant subset talk about five years of Long COVID.) What didn’t we do that we should have done? Who is to blame?

While obviously I see more English-language articles than non-English articles, I was surprised by the sheer number of articles from the UK about COVID-19 remembrance events and how people were still grieving. 😢 The UK had really strict lockdowns, and this article (2025-03-08) says that they spent a huge amount of money on the pandemic and had worse results.

Most of the articles talk about all the things that got broken, are still broken, and are probably going to stay broken. A lot talk about how, actually, the pandemic is not over.

💰 I mention this article from USA (2025-03-10) in the Recommended Reading section also, but it actually has a very worthwhile observation: COVID-19 led to more privatization of public health.

I have seen a fair number of articles which say that we are in worse shape for the next pandemic. There are some things which are obviously true: we have more vaccine skepticism and less trust in government. Absolutely. However, I think that there are some things that we learned that will be valuable in the next pandemic:

We have learned how to work remotely.
We Some of us have learned that masks work.
We Some of us have learned that airborne spread is really a thing.
We are starting to see patient-led studies, like the Remission Biome study.
We have demonstrated that we can run clinical trials, manufacture drugs, and approve them very quickly. (If you haven’t read about the UK’s amazing RECOVERY project for speedy drug trials, I encourage you to do so.)
We have a big infrastructure now which will get stuff delivered to our doors.

Long COVID

🎉🎉🎉 This cases study paper from USA (2024-11-08) reports that three Long COVID patients had complete recovery within a week of a casirivimab/imdevimab (Regeneron™) monoclonal antibody infusion. During this podcast interview (2024-12-07) with Dr. Nancy Kilmas, she said that the clinician who wrote the cases study paper actually treated eighteen more and sixteen got better.

Dr. Kilmas said they were all set to do a clinical trial of Long COVID patients with Regeneron, but then Regeneron got its authorization yanked (because the mutating variants made it ineffective) and so they couldn’t go ahead with the trial.

Dr. Kilmas said they expected FDA approval of a trial with Evusheld (replacing Regeneron) and planned to start trials in January 2025. (I couldn’t find that study on the clinical trials website, but maybe I’m just not good at searching their site. Also, the researcher interviewed is from USA, and things are such a shitshow in the US right now that who knows what is going to happen. The good news is that the study is being funded by the State of Florida (!!) and the Schmidt Family Initiative for Long COVID — not the US government, so maybe it will happen.)

This press release says that Evusheld is not authorized in the USA as of 2024-11-21. That was before the podcast, but trials can use unapproved drugs (and the virus that might be in long hauler’s bodies could be much older than what is circulating now).

There is also a trial at UCSF going on of a monoclonal antibody (AER002 (2024-01-14)) for Long COVID. The trial is supposed to finish in July 2025. So stuff is happening!

😢 Related: This paper from USA (2024-08-16) reports that non-hospitalized high-risk patients with COVID-19 who were given amubarvimab/romlusevimab (a Chinese-developed monoclongal antibody cocktail (2022-08-23)) were just as likely to get Long COVID as people who weren’t given amubarvimab/romlusevimab.

This paper from Japan (2025-03-05) reports that 35.5% of patients who were seen at clinics with COVID-19 but not admitted to hospital had at least one Long COVID symptom 12 weeks after onset. (NB: The survey did not have a control arm, so it’s possible that they asked questions like “did you ever have a headache” which healthy controls might have also said yes to.)

They found that people over 40 years old had a 280% higher risk than under-40s for respiratory symptoms and a 353% higher risk for neurologic symptoms. Antivirals (which I presume is Paxlovid and maybe Xocova) lowered the risk of respiratory symptoms by 68%. (It’s not clear from the non-paywalled portion if it was 68% lower than people who didn’t get the antivirals for people under 40 or people over 40.)

🎉⁉️🤯 Okay, this is kind of a WTF. This paper from Japan (2022-04-07) found that “abrading” the nasopharynx (that thing that PCR swabs touch) with a cotton swab and zinc chloride (once a week for three months) helps/cures Long COVID! Digging into this a bit, there’s established evidence that I Kid You Not, the ear/nose/throat areas are “well connected” to the autonomic nervous system. They found this because overstimulating it can cause lesions in the f kidney! (You can look at this reference from Japan (1978) if you want, but it’s in Japanese, thank you Google Translate!)

That might help to explain a little bit last week’s WTF where nasal surgery to correct deviated septums improved some people’s Long COVID.

This paper from Japan (2025-03-12) goes into a bit of detail about what happens — at both a macro and micro level — when you abrade a nasopharynx, but they admitted that they don’t know why it works. Maybe there’s a reservoir of virus in the nasopharynx? Maybe there’s cytokine release which is close enough to the brain that it gets into the brain and causes neuroinflammation? Whatever the cause, it’s kind of spooky weird.

🤐 This paper (2025-02-13) lists things medical professionals should never say to people with complex, poorly-understood disorders, and provides alternatives. I think it’s not just medical personnel who should avoid the words, but everybody, so I am going to reproduce the advice in full here:

Never-Words	Explanation and Impact	Alternative
“You don’t look sick”.	Many patients may appear healthy, but feel very sick with various symptoms, including fatigue and pain.	Please refrain from commenting on their appearance.
“You need to stay positive”.	Saying this to patients with debilitating symptoms with limited treatment implies that the patient did not stay positive or that the patient’s attitude is to blame for feeling or staying sick.	“I know it can feel discouraging to feel so sick, and especially for so long. We will work on this together”.
“At least it’s not cancer”.	Minimizing symptoms and disabilities is not well-received by patients who are suffering with non-terminal, but debilitating, and disabling conditions.	Comparing diseases to make a patient feel better is a strategy that is best avoided, since it usually has the opposite impact.
“Learn to live with this”.	While this may be practical advice, many patients have already adjusted to living with their illness, but they want to live better and be more functional.	“I know this illness can really disrupt your life. What did you do in order to adjust to this?”
“Good news: Your tests are all normal”.	This is good news for medical professionals, but patients may not care about the numbers or test results if they feel sick. This may also imply to patients that because their tests are normal, they have no reason to feel sick.	The tests we have run so far are not showing any abnormalities, and the good news is that we have excluded certain conditions based on the results of these tests.
“Many people have it worse”.	Deflecting the patient’s suffering can be perceived as gaslighting by the sufferer.	Please refrain from comparing patient’s diseases and experiences.
“Have you tried___(lifestyle measures: yoga, going for a walk, diet, etc.?)”	Many patients have already tried various lifestyle measures without benefits and are seeking further treatment from healthcare professionals, not recommendations of the same lifestyle measures.	What are the things you have tried that have or have not helped you?
“You feel sick because you are____(psychological label: anxious, depressed, stressed)	Many patients with chronic illness do have comorbid depression, anxiety, PTSD, and other psychiatric disorders, but in many patients, it is not an explanation nor a justification for why they feel ill. Further, it is important to note that people living with a chronic complex condition experience many losses due to having that condition.	If you are suspecting significant psychological or psychiatric comorbidities, please refer your patient to a mental health professional to address these issues.
“You feel sick because you are____(fitness label: deconditioned, overweight, underweight, out of shape)	Many patients have been previously healthy and active, and many patients want to restart exercising and lead an active lifestyle but cannot due to fatigue, pain, and post-exertional malaise.	Please refrain from commenting on the patient’s fitness level or body habits. A referral to a physical therapist with expertise in chronic fatigue may be helpful.
“You feel sick because you are____(hormonal status: perimenopausal, menopausal, postmenopausal, postpartum, pregnant, menstruating, ovulating)	Many patients with Long COVID, MECFS, and other chronic disorders are women who can often differentiate between hormonal symptoms and symptoms of chronic disease. Additionally, hormonal influence on symptoms is well-documented but is not an explanation or the cause of the underlying disease.	Please refrain from commenting on the patient’s hormonal status. A referral to a gynecologist or endocrinologist might be appropriate if there are concerns of hormonal abnormalities or need for hormonal supplementation.
“You need to____(instruction as cures: lose/gain weight, start exercising, get fresh air, get out of the house/bed, get a job, get a hobby, start dating etc.)”	While a healthy lifestyle is important, the patient did not choose to stop it: the lifestyle changed as a result of the illness. Additionally, while lifestyle measures are important, they are unlikely to cure or effectively treat the underlying medical condition.	“When you feel better, we will work together toward a common goal of improved quality of life and a healthier lifestyle”.
“You look too___(appearances: good, young, skinny, pretty)__to be sick”.	Comments on appearances are inappropriate because patients with chronic illness may not look sick like patients with acute illness. Many actually hide their ill-appearing looks, especially when seeing a healthcare professional.	Please refrain from commenting on patient’s appearance.
“We don’t have any treatment for your illness”.	While this may be true for some illnesses, given no FDA-approved therapies, symptomatic treatment is available, and the patient should not be made to feel like they are being abandoned by the medical team.	“We will talk about the available treatments we have that can make you feel better”.
“You need to stop thinking about your symptoms so much”.	In our experience, improved symptom control results in many patients improving their function and decreasing the negative thoughts and feelings about their symptoms. In those patients who continue to perseverate about their symptoms, psychological support, and cognitive-behavioral therapy may be appropriate.	“You have good awareness of your symptoms. I’m wondering if we can come up with a way for you to easily track them, so we that we can see the small changes when you begin to feel better”.
“You have to find something productive to do with your time”.	This statement assumes that patients are bored or have too much time on their hands, whereas, for most patients, having complex chronic illnesses is time- and energy-consuming and may be equivalent to having a full-time job managing disease and medical care. Additionally, many patients are not physically and/or cognitively well enough to be productive.	“Try to distract yourself with doing pleasurable and meaningful things that you can still do for short periods of time”.
“Don’t confuse your Google search with my medical degree”.	This statement has become popular among healthcare professionals, given various online information platforms and social media groups that patients use to obtain medical information. However, we find that many patients with complex chronic illnesses had to become educated in their disorder out of necessity, given limited help from medical professionals.	“I am glad you’re reading about your illness and educating yourself on possible tests and treatments. Thank you for bringing this information to me. I will look through it and let you know my thoughts”.

COVID-Related Excess Death and Sickness

👦 This report from Ireland (2025-03-03) (discussed in this article (2025-03-03)) says that teachers of children aged four to six are less ready for school along a number of axes: from poorer language and personal grooming skills to greater separation anxiety to poorer emotional regulation, etc. Interestingly, when they theorized about causes, they never mentioned that, y’know, the kids might be showing evidence of getting COVID-19 a bunch of times!

Pathology

🎉🎉🎉🎉 This study from Germany (2025-03-12) looks like they have figured out what causes multisystem inflammatory syndrome in children (MIS-C)! It’s not completely proven, but it sure looks like it is caused by COVID-19 reactivating Epstein-Barr Virus (EBV). EBV also causes/triggers/increases the risk of Multiple Sclerosis, a bunch of different cancers, and a number of autoimmune disorders. Oh, and EBV causes mononucleosis. EBV is nasty. (This article (2024-05-27) mentions that Moderna is working on a vaccine; I sure hope it works.)

Note that kids get MIS-C four to eight weeks after they recover from COVID-19, and can happen even if the COVID-19 was asymptomatic. In this press release about the paper (2025-03-12), one of the authors says, “Put simply, [EBV] wakes up from a dormant state because the COVID infection has thrown the child’s immune system in such disarray that it becomes unable to keep the dormant infection in check” (emphasis mine). COVID-19 f’s with your immune system, y’all!

🏥 This paper from Canada (2025-03-10) reports that homeless people are admitted to hospital from the ED at the same rate, but they are admitted to critical care 36% less often than housed people. I figured that the lower admittance rate to critical care meant that the unhoused weren’t being taken as seriously, but the mortality rate was basically the same. So I don’t know what it means.

🛌 This paper from Canada (2025-03-12) reports that a bunch of chronic conditions make the risk of a severe COVID-19 infection higher. However, osteoporosis 🦴 actually decreases the risk of severe COVID-19. !!!

Compared to people without the condition, the risks are:

64% higher for chronic lung disease;
35% higher for high blood pressure;
46% higher for a weakened immune system;
120% higher for ME/CFS or fibromyalgia;
42% lower for osteoporosis.

Vaccines and Other Preventatives

🎉💊 This press release (2025-03-12) reports that Ensitrelvir, when given after exposure to a household member testing positive for COVID-19, reduced the risk of developing an infection by 57%.

😢💉This article from Canada (2025-03-11) reports that the federal government has cancelled a contract with Novavax for Novavax to manufacture its vaccine at the federally-funded Biologics Manufacturing Centre in Montreal. Novavax was supposed to be an anchor tenant, but they didn’t manufacturing for their vax done in time, and got eclipsed by Pfizer and Moderna. I think that meant that they just didn’t have the money to do an expansion or the demand for what a new factory would produce.

(I was thinking it would be great to get Moderna in there — the USA is getting kind of hostile to mRNA vaccines, and Canada would welcome them warmly. Well, this press release (2024-02-23) says that Moderna is now manufacturing in Laval, Quebec, so it’s unlikely to join the Biologics Manufacturing Centre.)

🎉💉 This paper (2025-03-05) reports that they’ve developed a treatment which can be used as a prophylactic as well in test tubes and mice. It is basically two monoclonal antibodies linked together (a biclonal antibody?) One antibody latches hard onto a a spot on the Non-Terminal Domain (NTD) — a piece of the spike protein which is just below the tip, i.e. slightly farther away from the host cell — which doesn’t change very much from variant to variant. The other antibody targets the Receptor Binding Domain (RBD), the part which is the “key” to “unlock” the host’s cell wall so that the virus can slip inside and take over.

The combination of the NTD antibody and the RBD antibody work better joined together than the separate NTD and RBD monoclonal antibodies do together. I couldn’t figure out from the paper why that is — I’m not convinced they know — but I have a metaphor which I use. Imagine you are trying to prevent dolphins (the SARS-CoV-2 viruses in this metaphor) from pushing a big button with their noses. The NTD antibody is like a big sea snake trained to grab onto dolphins; the RBD is a blind octopus with a nose bumper and harness it has been trained to put over the dolphins’ head and nose. If you just have sea snakes, they might grab on to the dolphins, but that doesn’t stop the dolphins from swimming around. The octopi by themselves would have a hard time finding dolphins to put the harness on, and maybe the dolphins would move away while they were trying. Even if you have octopi and sea snakes running around at the same time, they still aren’t going to be working that well without coordination. However, if you leash the sea snake and the octopus together, then the octopus has a good shot at finding the dolphin’s nose when the snake grabs on to the dolphin. Similarly, latching onto the NTD gives the RBD antibody time to find and jam up the RBD.

It might even be simpler. It might be that the RBD antibody has all the subtlety of a refrigerator, but that it’s large enough that it just flat gets in the way of the RBD part of the spike, keeping the RBD from getting close enough to the ACE2 receptor to “unlock” the cell wall. In the snake/octopus example, imagine that the octopus doesn’t ever manage to get the harness over the dolphin’s head/nose (because it’s the wrong shape for this variant of dolphin, work with me here), but if the octopus is just in front of the dolphin’s nose, the dolphin won’t be able to push the button.

There was also some stuff in the paper which I didn’t completely understand which seemed to say that the NTD antibody could latch onto one spike and the RBD antibody could latch on to a different spike, and that was good somehow that I didn’t follow. Maybe that gets the two viruses to interfere with each other, making it harder for the spikes near the attachment point to grab on to cells? Maybe glomming viruses together makes them too big to fit through the opening in the cell wall? I’m not sure.

Transmission

👍💉This preprint from USA (2025-03-05) is mostly about using computer modelling to figure out what the likely transmission chains were from incomplete information. One of the things that came out of the preprint, however, was that the model run on some real-world data thinks that vaccinated, boosted, and infected people transmit COVID-19 at a 34.1% lower rate than unvaccinated infected people. People who had a vaccination without a booster transmitted 9.81% less than people who were unvaccinated. 34.1% is not sterilizing immunity, but it’s sure more than nothing!

Mitigation Measures

👍🚫💲😷 Want some free N95 duckbill masks? This Government of Canada site lets you get 100 at once. A catch is that you have to pick them up in Langley. (Disclaimer: I am not affiliated and don’t know if they are any good.)

😷 This older paper from USA (2021-05-18) compares different mask types for bearded men. N95s respirators are significantly better than KF94 or KN95, but be careful: the big difference between the respirators is actually whether the masks have earloops or headbands; when this study was done, there weren’t KF94 or KN95s with headbands.

Filtering efficiency over time for multiple different beard lengths

This article also found that filtering efficiency went way up if the men wrapped their beard in an exercise band before putting on the mask, like shown in this photo:

Note: My bearded spouse wears a FloMask, which has a silicone seal over his face/beard (and a headband), and he passed a home fit test with the FloMask. Home fit tests aren’t perfect by any means, but he has been using that mask for three or four years (including when singing with a chorus!) and neither of us have gotten COVID-19 that we know of. (Yes, we do take other precautions, like being ultra careful about never unmasking in indoor places outside of our apartment, doing nasal saline irrigation, etc., but I have the impression that masks are more important. Yes, it’s possible that we both had asymptomatic infections at the same time, but that seems unlikely, especially since I have a history of catching respiratory viruses easily.)

H5N1

Transmission

This article (2025-03-13) reports that there have now been 985 herds in the USA with known H5N1 infections, with 754 in California.

Treatments

‼️🧀🐦‍⬛🤧‼️This preprint (2025-03-14) reports that cheese made from raw milk at pHs of 6.6 and 5.8 still had detectable H5N1 after 60 days of aging. Milk made at a pH of 5.0 did not have any detectable H5N1.

Soft cheeses generally aren’t aged for very long. Here’s what I found out about different harder cheeses:

Parmesean (usually unpasteurized): this page says the pH is 5.3 to 5.9. This page says that Parmesean is usually aged for at least 12 months.
Swiss (sometimes unpasteurized): this page says the pH is 5.3 to 5.5. This page says it is “typically aged for anywhere between 3 to 4 months”, and “Some varieties, like Emmental and Gruyere, may be aged for longer periods of time, ranging from 4 months to over a year.”
Cheddar (sometimes unpasteurized): this page says the pH is 5.1 to 5.4. This page says it is usually aged “from several months to several years”.

💊🐦‍⬛🤧 This report from the US CDC (2025-03-07) says that all of the flu medications work, at least partially, against avian flu. Oseltamivir (Tamiflu) worked four times better in test tubes on the Cambodian clade (2.3.2.1c) than on the flu in the Americas (clade 2.3.4.4b), but baloxavir, tivoxavir, zanamivir, peramivir, laninamivir, AV5080, and pimodivir were all at least 50% effective in test tubes — even when low doses were used.

Economics

🥚💸 I mentioned recently that the increase in the price of eggs in the USA was not because of bird flu, it was profiteering. This article (2025-03-08) seems to corroborate that: apparently the USA’s largest egg producer reported their profits went up by 342%.

🐄🤧💸 This case study preprint from USA (2025-03-03) of one herd reports that the economic loss from H5N1-infected cows producing less milk and/or dying is about USD$950 per cow with symptoms. About 20.0% of the herd showed symptoms, while blood tests showed that 89.4% of the cows had been infected. Cows with symptoms were six times as likely to die as unsymptomatic cows.

Marburg

🎉🎉🎉🎉 This article (2025-02-13) reports that Tanzania’s Marburg outbreak is over. Good job, Tanzania!