Pathology
Why do kids and old people have such different reactions to COVID-19? This paper from UK (2024-04-15) says that kid and adult epithelial cells (which line mucous membranes) are different. In particular, cells in elderly people had more of the receptors which SARS-CoV-2 uses to get into the cells, and kids’ cells generated more interferons.
Men, I have bad news for you. This paper from China (2024-04-07) found that various average sperm quality metrics dropped significantly after a COVID-19 infection, and stayed down for at least 30 days. The good news is that the metrics all seem to rebound to normal at 90 days.
They also said that men with only mild fevers did not see a quality drop, which makes me wonder if the sperm quality drop is due to the fever and not to COVID-19 per se. I found several papers which said the sperm quality drops temporarily after a fever.
This paper from Canada (2024-04-16) found that older people with diabetes were 28% more likely than older people without diabetes to develop at least one functional limitation in 2020 than pre-pandemic.
This paper from Denmark (2023-09-22) found that people over 50 who had a COVID-19 infection were not more susceptible to hospitalization for an infectious disease than those who did not have a COVID-19 infection.
This paper from USA (2024-04-16) found that people who tested positive for COVID-19 were more likely to report neurological/cognitive issues than people who did not. Their risks, compared to controls, were:
- depression: +44%;
- fatigue: +107%; (<- !!!)
- impaired cognitive function: +64%;
- impaired cognitive function abilities: +41%. (<- I don’t know what the difference between impaired cognitive function and impaired cognitive function abilities is, sorry.)
Transmission
This paper from USA (2024-04-10) found that yes, hamsters can be infected with COVID-19 via the eyeball. If they are infected via the eyes, the rodents do not have the classic respiratory signs. However, if they are infected through the respiratory tract, SARS-CoV-2 can still get into cells in the eye.
This paper from Germany (2024-04-15) found that 21% of the upper respiratory infections in winter 2022/2023 were from COVID-19, which I will remind you did not exist before 2019. This means that even without the retirements (and deaths!) of healthcare workers in the past few years, there is more of a burden on the German healthcare system than there was in 2019. There is little reason to think that the Canadian healthcare system is better off.
Vaccines
This paper from USA (2024-04-17) says they have made a new kind of vaccine. The vax in the paper is not for COVID-19, but it has interesting ideas. Apparently there are things called “small-interfering RNAs” (siRNA) which are short, non-coding RNA strands. (“Non-coding” means that they aren’t recipes that ribosomes use to make proteins.) In keeping with the body’s strategy of “use one thing to do seventy-six seemly unrelated things”, the body repurposes RNA to use short little sections of RNA (the siRNA) to do what is called RNA interference (RNAi). In RNAi, siRNA molecules glom on to the virus and chop it in two, which stops the virus cold. (NB: This is pretty new science: it got some people the Nobel Prize in 2006.)
However, viruses have evolved a defensive molecule to turn off RNAi: the virus-encoded suppressor of RNAi (VSR). But humans are also smart! This paper from USA (2024-04-17) says that they have made a version of a virus (Nodamura virus (NoV), not COVID-19) which they mucked up so that the NoV does not make the VSR that it normally does. This means that NoV is vulnerable to RNAi, which means it can’t replicate, which means that it is safe to inject as a vaccine! Basically, it’s a better live-attenuated virus (LAV) than the current state of the art.
(Quick refresher: LAV are viruses which “can’t” reproduce, but the things currently done to viruses to keep them from reproducing either make them “look” less like the “real” virus or they aren’t actually perfect at not reproducing. This means some people can get sick from LAVs. Current LAVs are particularly dangerous to give to people with compromised immune systems.)
Not only is the VSR-less virus less dangerous than traditional LAVs, it appears that the RNAi is not part of the adaptive immune system (which trains up B and T cells). The VSR-less virus was 100% effective in protecting knockout mice which did not have either B or T cells — even at 42 days post-immunization! The vax was even still 92% effective in B- and T-less mice at 90 days. Protected! Even with no B or T cells! This is great news!
Now, I don’t know if the siRNA learns to attacks the “real” virus itself or if it all it does is metaphorically hold the VSR-less virus down so that antibodies can learn to attack the “real” virus. Regardless, the immunity from the VSR-less vaccine pretty damn good.
I don’t know if using VSR-less viruses for vaccines would work for COVID-19, but I sure hope so!
This report from USA (2024-04-18) found that the effectiveness of the original monovalent mRNA vaccines given to children waned over time:
| Against | Time after vax | VE |
| hospitalization | <120 days | 52% |
| hospitalization | 120-364 days | 19% |
| critical care or death | <120 days | 57% |
| critical care or death | 120–364 days | 25% |
I had heard mutterings about Moderna’s next COVID-19 vax being better, but I couldn’t find hard info… until today! Here is a long slide deck on what Moderna’s got in the pipeline, with the COVID-19 section starting on p.67. The next vax version — called mRNA-1983 (vs. the current mRNA-1973) — has just the receptor binding domain (the “key” which attaches to the target cell receptor’s “lock” and opens the cell to the virus) and not the whole spike. The theory is that this will get the immune system to focus on making the most important antibodies. (It also occurs to me that then they won’t have the problem of needing to stabilize the spike.)
Indeed, in this case, theory and practice seem to be aligned. The BA.4/5 version of mRNA-1983 gave antibody titres 32% higher than mRNA-1973 did over all adults. It had an even greater advantage as age increased. Adolescents didn’t see much difference, but the over-75 cohort got 78% higher titres with mRNA-1983 than with mRNA-1973!
They had been hoping that using just the RBD and not the whole spike would mean they could give lower doses, which would cause fewer side effects. Unfortunately, while their charts show slightly lower side effects at the injection site (e.g. pain, swelling, etc.), it looks like the systemic effects (e.g. fatigue, headaches) look about the same or slightly worse. 🙁
One other piece of good news is that mRNA-1983 will be fridge-storable (instead of bone-chillingly cold freezer-stable) and it will come in pre-filled syringes. Both will make administering the shots logistically easier.
(NB: The Moderna slide deck also covers other vaccines Moderna is working on, including RSV, shingles, Epstein-Barr Virus, norovirus, cytomegalovirus, and genital herpes. If you are a vaccine nerd, it’s interesting reading.)
Treatments
This paper from USA (2024-04-16) found that patients hospitalized for COVID-19 who did not require supplemental oxygen on arrival were 17% less likely to die in the next 30 days if they got remdesivir than if they did not. The effectiveness was similar across strains: 17% for pre-Delta, 13% for Delta, and 24% for Omicron.
Long COVID
This opinion piece from USA (2024-04-16) says that “Catecholamine testing … is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.” That was news to me, but hey, it’s great to hear that they have something they can test.
This paper from USA (2024-01-23) found that Long COVID patients taking low-dose Naltrexone were ~5 times more likely to see reductions in fatigue and pain than those who did physical therapy alone.
This is anecdata, not science, but there’s not a lot of science for Long COVID patients, and this is a very cheap treatment so I will relay it: this post from a long hauler says that they are able to avoid post-exertional malaise by sitting in a Jacuzzi for 15 minutes after a workout.
This paper from Australia (2024-04-12) found that there were higher levels of various inflammatory proteins in long haulers than in people who had recovered from COVID-19 but did not have Long COVID. They said that the levels were so low that they had to use special nanotechnology to see them, but that these low levels caused a cascade of bad things whose understanding is above my pay grade. The researchers also said that those bad things didn’t happen when “in the presence of dexamethasone”. (NB: dexamethasone is a treatment for severe COVID.) Now, that sounded to me like dexamethasone should be a treatment for Long COVID, which would be huge, but they never mentioned that possibility. I maybe don’t understand the paper well enough.
This paper from Australia (2024-04-17) found that 62% of people with Long COVID did report having gotten better by two years from infection. (Another way of looking at it, however, is that 38% had not gotten better.)