The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national longitudinal study of cognition in 351 COVID-19 patients who had required hospitalisation, compared to 2,927 normative matched controls. Cognitive deficits were global and associated with elevated brain injury markers and reduced anterior cingulate cortex volume one year after admission. The severity of the initial infective insult, post-acute psychiatric symptoms, and a history of encephalopathy were associated with greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Treatment with corticosteroids during the acute phase appeared protective against cognitive deficits. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 is immune-mediated, and should guide the development of therapeutic strategies.
The paper doesn’t say much about which corticosteroids were considered. I haven’t looked at the supplementary files though.
The findings are both clinically significant and biologically plausible. Raised brain injury markers have been demonstrated in acute and post-acute COVID-19 and are associated with dysregulated innate and adaptive immune responses (14, 26). The pattern of acute inflammatory proteins can predict post-acute cognitive outcomes (27) and the finding, here, that acute treatment with corticosteroids may be protective for cognition is consistent with previous research (28), and further supports the hypothesis that brain injury in COVID-19 is immune-mediated. We have additionally shown that persistently raised serum GFAP was associated with post-acute cognitive impairment. GFAP is expressed by astrocytes, which participate in neuroimmune interactions within the brain. Its appearance in the plasma typically indicates injury of these cells and has been proposed as a prognostic biomarker for cognitive decline in the general population (29).
=> Could rapa help?
Would be consistent with the Kaeberlein survey: “Among all survey respondents, continuous rapamycin users were significantly less likely to have experienced a moderate or severe infection or long-COVID symptoms, compared to non-users (p < 0.005). […] We speculate that the anti-inflammatory effects of rapamycin may be helpful in reducing symptoms and restoring immune homeostasis in people suffering from long-COVID.”
I would want to avoid the tail risks so I am unsure whether it is a good idea to use an immunosupressive while having an infection. You might prevent the cognitive deficits, but you could die from sepsis. The cognitive deficits can be solved later.
Anecdotally I’ve seen people here from time to time say they kept taking rapamycin throughout an infection, and it persisted, and got worse. There’s also survivorship bias at play with anecdotes.
There was no difference in the proportion of patients who were alive and free from advanced respiratory support measures in the sirolimus group (n = 15, 83 %) compared with the placebo group (n = 8, 80 %). Although patients in the sirolimus group demonstrated faster improvement in oxygenation and spent less time in the hospital, these differences were not statistically significant. There was no between-group difference in the rate of change in serum biomarkers such as LDH, ferritin, d-dimer or lymphocyte count. There was a decreased risk of thromboembolic complications in patients on sirolimus compared with placebo.
The safety study is small and can’t detect rarer events afaik, only 1 in 15 if my thinking is correct, or the 15 people might’ve just been lucky, who knows.
Of course, we need more data, but that’s a good start: among 15 people HOSPITALISED with COVID-19 pneumonia, with an average age of 57 yo, most of them with at least another condition (diabetes, hypertension, obesity, CHF, or asthma/COPD), none died of sepsis. So, I assume that for healthy people with a mild infection, the risk would be even lower?
Here is a case of sirolimus levels increasing post-covid infection:
There are at least one case report of a 27-year old woman getting sepsis and dying from very high dose everolimus:
Also unless you are testing, you don’t know whether you got Covid or some other infection.
I prefer just taking the covid vaccines yearly along with influenza vaccine and vaccines that are associated with lower Alzheimer’s like it is for influenza: shingles, etc (though might be causal).
The first paper was on 0.5 mg daily and then switched to 0.5 mg every other day post-infection, so it’s not that much. Still, it was a 58-year-old male with a history of ischemic cardiomyopathy.
The second one (27yo woman) was on 10 mg/day, so it was definitely way higher than anyone here.