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Thanks for the book recommendation! Much appreciated! > I’m curious why you think any of this should be novel to the coronavirus COVID-19. We are affected by e

Thanks for the book recommendation! Much appreciated! > I’m curious why you think any of this should be novel to the coronavirus COVID-19. We are affected by every infection. This review paper might summarize my inclination to consider SARS-CoV-2 different in this regard: “The Neurobiology of Long COVID” — M. Monje, PhD, Neurology at Stanford & A. Iwasaki PhD, Immunobiology at Yale. Publication status: In Print, Journal Pre-Print Available Online October 7, 2022 — https://doi.org/10.1016/j.neuron.2022.10.006 https://doi.org/10.1016/j.neuron.2022.10.006 One paragraph mentions effects in children: “Similarly, a 2-year a retrospective cohort study using the TriNetX electronic health records network of 1,487, 712 individuals with COVID-19 and a similar number of matched controls with a different respiratory infection found continued risk of cognitive impairment at 2-years from diagnosis (Taquet et al., 2022). In contrast to risk of cognitive impairment, the risk of anxiety and mood disorders normalized within 2 months following SARS-CoV-2 infection (Taquet et al., 2022). This TriNetX study provides some of the only available data about cognitive deficits in children and found in this retrospective cohort study that children did not exhibit an increased risk of anxiety or mood disorder diagnoses, but did exhibit increased risk of cognitive deficits (HR 1.2) and insomnia (HR 1.29) compared to children with different respiratory infections (Taquet et al., 2022). Unlike the adult cohort in this study, the risk of cognitive deficits in children normalized to the level observed in controls with a different respiratory infection by 491 days after COVID-19 (Taquet et al., 2022).” There’s a lot more to the paper.

svnt 4y ago
The paragraph you referenced is wholly dependent on one paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385200 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385200 and in particular on the supplementary materials. Referencing table S9 (for children) in the appendix/supplementary there are only four categories of illness where the p values are still possibly meaningful after correction: cognitive deficits, epilepsy or seizures, intracranial hemorrhage, insomnia The two common conditions, cognitive deficits and insomnia, are only significant because of the arbitrary follow-up period selected of six months. If you examine the charts shown in Figure S1 in the same appendix, you can see that cognitive deficit has no long-term effect, and that actually COVID-19 seems to be protective in the longest term (as is the case with anxiety). This to me is suggestive of the fact that social aspects/expectations are dominating the reported symptoms for these common experiences. None of the symptoms, even insomnia, are quantified. I can't find if/where they break it out by sub-classification but they seem to lump together real measurements of cognitive deficit with self-reports of brain fog. Similarly anxiety is not well-quantified. For intracranial hemorrhage and seizures the effect is more pronounced, but as you can probably infer from the pixelation of the charts in S1 for these two, the sample sizes here (children with these symptoms), are tiny, and so the results are underpowered. If I wanted to keep looking this is the only avenue I'd consider. As far as effects in other populations, they compare e.g. sinusitis and laryngitis on equal footing with lung infections resulting in hospitalization and possibly ventilation for COVID-19. That to me suggests there is the problem of confounding based on the impacts of reduced perfusion and oxygenation of brain tissues due to actual major lung infections that is more present in the COVID-19 data than the control dataset. A respiratory infection for this purpose ought to be something that can seriously impact perfusion and brain oxygenation -- they don't seem to have realized that and instead used "respiratory infections" without further qualification. The Taquet et al study is the best study I've seen on it and I'm still totally unconvinced this is anything beyond hypoxic brain injury (and only minorly so -- in most survivors it seems to be primarily fear, hypochrondria or provider nudging).
- AnthonBerg 4y ago
  Thank you for taking a look. The passage on the effect in children is a tiny part of the whole work. From the introduction: COVID-19 may affect the central nervous system in (at least) six main ways (Figure 1). First, the immune response to SARS-CoV-2 in the respiratory system may cause neuroinflammation - increasing cytokines, chemokines and immune cell trafficking in the brain and inducing reactive states of resident microglia and other immune cells in the brain and brain borders. Second, SARS-CoV-2 rarely may directly infect the nervous system. Third, SARS-CoV-2 may evoke an autoimmune response against the nervous system. Fourth, reactivation of latent herpesviruses like Epstein-Barr virus may trigger neuropathology. Fifth, cerebrovascular and thrombotic disease may disrupt blood flow, disrupt blood-brain-barrier function, and contribute to further neuroinflammation and/or ischemia of neural cells. Lastly, pulmonary and multiorgan dysfunction occurring in severe COVID can cause hypoxemia, hypotension and metabolic disturbances that can negatively affect neural cells. It is important to recognize that these mechanisms of nervous system injury are not mutually exclusive, and a combination of mechanisms may occur in some individuals, with varying frequency and timing. It has been shown that there are many markers for Long COVID, many of which present as neurological and cognitive issues. Two markers have been shown to be reliable and consistent: Patient reports – and unusually low cortisol levels. The other markers are things such as elevated inflammatory cytokines. Fear and hypochondria and provider nudging do not manifest in those ways. Also: Provider nudging? I have heard of nothing but universal and unscientific dismissal of anything COVID-related when people go to health providers for long-term issues. I don’t think that’s it. I can’t see how this could be anything less than real, and how children could possibly be exempt from the effects. And we aren’t looking because we think we know it’s nothing.

svnt 4y ago

The paragraph you referenced is wholly dependent on one paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385200 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385200 and in particular on the supplementary materials. Referencing table S9 (for children) in the appendix/supplementary there are only four categories of illness where the p values are still possibly meaningful after correction: cognitive deficits, epilepsy or seizures, intracranial hemorrhage, insomnia The two common conditions, cognitive deficits and insomnia, are only significant because of the arbitrary follow-up period selected of six months. If you examine the charts shown in Figure S1 in the same appendix, you can see that cognitive deficit has no long-term effect, and that actually COVID-19 seems to be protective in the longest term (as is the case with anxiety). This to me is suggestive of the fact that social aspects/expectations are dominating the reported symptoms for these common experiences. None of the symptoms, even insomnia, are quantified. I can't find if/where they break it out by sub-classification but they seem to lump together real measurements of cognitive deficit with self-reports of brain fog. Similarly anxiety is not well-quantified. For intracranial hemorrhage and seizures the effect is more pronounced, but as you can probably infer from the pixelation of the charts in S1 for these two, the sample sizes here (children with these symptoms), are tiny, and so the results are underpowered. If I wanted to keep looking this is the only avenue I'd consider. As far as effects in other populations, they compare e.g. sinusitis and laryngitis on equal footing with lung infections resulting in hospitalization and possibly ventilation for COVID-19. That to me suggests there is the problem of confounding based on the impacts of reduced perfusion and oxygenation of brain tissues due to actual major lung infections that is more present in the COVID-19 data than the control dataset. A respiratory infection for this purpose ought to be something that can seriously impact perfusion and brain oxygenation -- they don't seem to have realized that and instead used "respiratory infections" without further qualification. The Taquet et al study is the best study I've seen on it and I'm still totally unconvinced this is anything beyond hypoxic brain injury (and only minorly so -- in most survivors it seems to be primarily fear, hypochrondria or provider nudging).

AnthonBerg 4y ago
Thank you for taking a look. The passage on the effect in children is a tiny part of the whole work. From the introduction: COVID-19 may affect the central nervous system in (at least) six main ways (Figure 1). First, the immune response to SARS-CoV-2 in the respiratory system may cause neuroinflammation - increasing cytokines, chemokines and immune cell trafficking in the brain and inducing reactive states of resident microglia and other immune cells in the brain and brain borders. Second, SARS-CoV-2 rarely may directly infect the nervous system. Third, SARS-CoV-2 may evoke an autoimmune response against the nervous system. Fourth, reactivation of latent herpesviruses like Epstein-Barr virus may trigger neuropathology. Fifth, cerebrovascular and thrombotic disease may disrupt blood flow, disrupt blood-brain-barrier function, and contribute to further neuroinflammation and/or ischemia of neural cells. Lastly, pulmonary and multiorgan dysfunction occurring in severe COVID can cause hypoxemia, hypotension and metabolic disturbances that can negatively affect neural cells. It is important to recognize that these mechanisms of nervous system injury are not mutually exclusive, and a combination of mechanisms may occur in some individuals, with varying frequency and timing. It has been shown that there are many markers for Long COVID, many of which present as neurological and cognitive issues. Two markers have been shown to be reliable and consistent: Patient reports – and unusually low cortisol levels. The other markers are things such as elevated inflammatory cytokines. Fear and hypochondria and provider nudging do not manifest in those ways. Also: Provider nudging? I have heard of nothing but universal and unscientific dismissal of anything COVID-related when people go to health providers for long-term issues. I don’t think that’s it. I can’t see how this could be anything less than real, and how children could possibly be exempt from the effects. And we aren’t looking because we think we know it’s nothing.