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Persistent SARS-CoV-2 replication continually hijacks host folate and one-carbon metabolism to fuel de novo purine synthesis for viral RNA, depleting folate and stressing the methionine cycle (Zhang et al. Nat Commun 2021;12:1676). Chronic drain impairs methylation, elevates homocysteine, reduces glutathione, and drives Long COVID symptoms resembling B12 deficiency plus thrombosis risk; MTHFR variants plus metabolite profiles predict severity (Perła-Kaján Int J Mol Sci 2022;23:4181; Petrova et al. PNAS 2025).
In consideration of Black Maternal Health week coming to an end... Why is vitamin D deficiency not being actively targeted to improve both Maternal and Infant Health? High incidence of vitamin D deficiency, low cost to improve, potential large benefit...
🧐”Immunomodulatory Effects of Vitamin D in Pregnancy and Beyond” #vitaminD
frontiersin.org/articles/10.…
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Yes, the Hollis 2011 trial (NCT00292591) was a main one awaited around the 2011 statements.
Hollis JBMR 2011: RCT of 400/2000/4000 IU D3 from 12-16 wks. 4000 IU safest/most effective for maternal+neonatal 25(OH)D sufficiency (esp. darker skin); no related adverse events. pubmed.ncbi.nlm.nih.gov/2170…
Wagner AJOG 2013: 2000 vs 4000 IU community trial; both raised levels (higher cord blood with 4000); suggestive fewer infections/preterm issues. pubmed.ncbi.nlm.nih.gov/2313…
Combined JSBMB 2013: 4000 IU lowest hypovitaminosis + trend lower comorbidities; inverse 25(OH)D-comorbidity link. pmc.ncbi.nlm.nih.gov/article…
🤔 @grok the following is in the @acog recommendations regarding vitamin D and pregnancy.
“When vitamin D deficiency is identified during pregnancy, most experts agree that 1,000–2,000 international units per day of vitamin D is safe. Higher dose regimens used for treatment of vitamin D deficiency have not been studied during pregnancy. Recommendations concerning routine vitamin D supplementation during pregnancy beyond that contained in a prenatal vitamin should await the completion of ongoing randomized clinical trials.”…
Confirm that this was written in 2011 and keeps just getting reaffirmed. 🤔 What are these randomized clinical trials that they are waiting on since 2011? Give detailed citations.
🦵🥫📉🛣️?
🧐 “NET Biomarkers in COVID-19 and Post-COVID Syndrome: a Comprehensive Analysis”
pmc.ncbi.nlm.nih.gov/article…
⭐️ Following principles of Basic Science is following the Science…
(Though this is such a simple trial to do for a Long Covid clinic. Would likely be relevant to autoimmune diseases, such as Lupus / APS since have overlapping pathophysiology.)
Yes. Basic science on VDR signaling, MTHFR methylation, and micronutrient effects on inflammation, autoantibodies, NETs, and coagulation is core science. When specific trials are absent, applying those established mechanisms is following the evidence, not ignoring it. It supplies the rationale that clinical studies later test.
🧐 “Dynamic interaction between stress hormones and neutrophils promotes neutrophil extracellular trap formation with behavioral consequences”
sciencedirect.com/science/ar…
🧐 “Checking vitamin D is prudent for homebound ME/CFS (common deficiency risk). SARS-CoV-2 downregulates VDR signaling (Sci Rep 2021; PLOS One 2026) and hijacks folate/one-carbon metabolism involving MTHFR (Nat Commun 2021).”👀
Per @grok
No, the MCAM study (Regan et al. J Pediatr 2026) used only questionnaires on symptoms/function in 40 adolescents; no genetic, vitamin D/B, or homocysteine data.
Checking vitamin D is prudent for homebound ME/CFS (common deficiency risk). SARS-CoV-2 downregulates VDR signaling (Sci Rep 2021; PLOS One 2026) and hijacks folate/one-carbon metabolism involving MTHFR (Nat Commun 2021). Recent trials show correcting deficiency improves post-viral ME/CFS symptoms. B vitamins/homocysteine/genetics have weaker evidence but may identify modifiable factors.
🤔 A few statements that might be “good to know”…
Statements supported. Vit D deficiency linked to COVID thrombosis risk (e.g. OR 5.7) and higher long COVID odds in cohorts. NETs central to COVID immunothrombosis and general clotting. Homocysteine is modifiable thrombosis risk factor also tied to cognitive decline. aPL reported in COVID with proposed spike protein molecular mimicry.
These aid patient care via risk screening, Vit D/B-vitamin repletion to cut clots/long COVID/cognition issues, and refined coagulopathy management.
Cites: PMID 35834511; JCEM 2023; Front Immunol 2022 NETs; Hcy consensus reviews; Rheum Adv Pract 2021.
🤔 Seems likely of interest to the translational science type researchers?
Yes. Mouse studies on vitamin D antimicrobial induction (via CAMP/HBD2/NOD2) do not translate, as rodents lack the primate VDREs. See Gombart AF et al. FASEB J. 2005;19(9):1067-1077. doi:10.1096/fj.04-3284com. Metabolic: VDR-null mice resist obesity (opposite human links). Bouillon R et al. Nat Rev Endocrinol. 2014;10(2):79-87. doi:10.1038/nrendo.2013.226. Reviews: Dimitrov V, White JH. J Steroid Biochem Mol Biol. 2016;164:246-253; Marcinkowska E. Reports. 2020;3(1):1.
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Self-directed antibodies are found in people with #LongCovid. A key source of these was identified, and these autoantibodies and cell origin are also seen in lupus. @ImmunityCP
cell.com/immunity/fulltext/S…
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Scientists just found a reason for the exhaustion of long COVID — microscopic clots in the blood.
The study was published in the Journal of Medical Virology.
Researchers discovered that patients with the condition have nearly twenty times more microscopic blood clots than healthy individuals. Unlike typical clots, these 'microclots' are wrapped in sticky, web-like structures made of DNA and enzymes released by white blood cells.
These webs, known as neutrophil extracellular traps (NETs), act as structural armor, preventing the body from naturally breaking down the clots. This leads to a persistent blockage in the capillaries—the body's smallest blood vessels—which starves tissues of oxygen and drives chronic inflammation.
This discovery marks a massive shift in how post-viral illnesses are understood. Historically, many Long COVID patients struggled to find validation because standard blood tests routinely came back normal.
By showing that these microscopic clots are structurally bound to NETs, scientists are paving the way for targeted treatments, such as therapies designed to dissolve these persistent blocks. It also offers a glimmer of hope for millions suffering from other poorly understood chronic conditions, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), where similar microclotting patterns have been observed.
source: Thierry, A. R., Usher, T., Sanchez, C., Turner, S., Venter, C., Pastor, B., Waters, M., Thompson, A., Mirandola, A., Pisareva, E., Prevostel, C., Laubscher, G. J., Kell, D. B., & Pretorius, E. Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients. Journal of Medical Virology, 97(10), e70613.
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Vitamin D was classified as a vitamin by historical accident.
It’s actually a steroid hormone that crosses cell membranes and directly controls gene expression.
In chronic inflammatory and post-infectious conditions, the real issue can be resistance: the active hormone simply isn’t signaling efficiently.
Learn:
• What drives resistance
• How to actually test for it
• Why vitamin D acts more like a hormone
• Practical ways to improve your body’s response
Read more:
buff.ly/VIjX1UN
🧐 “Vitamin D ameliorates NETosis and Th17/Treg imbalance in experimental autoimmune thyroiditis”
sciencedirect.com/science/ar…
🧐 “Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility”
ajcn.nutrition.org/article/S…
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Evidence supports SARS-CoV-2 impairing VDR signaling (Valdés-López et al, PLOS One 2026) and hijacking folate/one-carbon metabolism, depleting folate (Zhang et al, Nat Commun 2021; Perła-Kaján et al, Int J Mol Sci 2022). Post-infection, vitamins D and B12 are often depleted (cohort HRs 1.56-1.79). In children this links to irritability, attention/cognitive issues, emotional problems and developmental delays via deficiency effects plus long-COVID neuro symptoms.
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Could vitamin D supplements help improve outcomes for people with inflammatory bowel disease (IBD)?
Using 20 years of real-world data from the U.S. Department of Veterans Affairs, NIH-supported researchers found that people with IBD who took vitamin D supplements had fewer IBD-related emergency room visits, hospitalizations, and steroid prescriptions.
The findings support current recommendations to screen patients with IBD for vitamin D deficiency and consider supplementation when appropriate: bit.ly/4xNiuqv
ALT Glass of water and vitamin D capsules on a table, with text stating, "RESEARCH NEWS: An analysis of real-world data finds that vitamin D supplements may improve IBD outcomes." NIH logo is present.
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SARS-CoV-2 impairs VDR signaling in monocytes/phagocytes, downregulating VDR and targets (CAMP, LYZ, IRF5) to drive IL-6 hyperinflammation (Valdés-López et al, PLoS One 2026;21(9):e0357030). Live Borrelia downregulates VDR ~60-fold in monocytes (Lemke et al, Front Immunol 2021;12:655739). Intracellular pathogens (Bartonella, Babesia, TBRF Borrelia) similarly block VDR, reducing antimicrobial peptides and enabling immune evasion; shared pathway links COVID exacerbation.
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Theoretically, optimizing vitamin D pathways may improve post-COVID symptoms via VDR-mediated immunomodulation (suppressing Th1/Th17, boosting Tregs and antimicrobial peptides), reduced inflammation/endothelial dysfunction, and neuroprotection/BBB support.
RCTs show benefits for fatigue, anxiety, and cognition (Charoenporn et al. Psychiatry Clin Neurosci 2024; Kodama et al. Nutrients 2026). Review: Chen et al. Nutrients 2023.
Optimizing one-carbon metabolism (folate/B12) could restore SAM methylation capacity hijacked by SARS-CoV-2 for viral RNA synthesis, lower homocysteine/oxidative stress, and aid neural recovery—symptoms overlap B12 deficiency.
Key: Zhang et al. Nat Commun 2021; McCaddon & Regland Med Hypotheses 2021; Petrova et al. PNAS 2025 (MTHFR link to long COVID).
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ANA and aPL (aCL, anti-β2GPI, aPS/PT) are most frequent in post-COVID. aPL link strongly to vascular/thrombotic injury via NETs/endothelial activation (Zuo Sci Transl Med 2020;12:eabd3876). Neural-targeted Abs associate with neurologic injury; IgG transfer recapitulates symptoms in mice (de Sá Cell 2026;189:3214). ID physicians refer to rheumatologists for post-infection autoimmunity with positive Abs or multisystem features; rheumatology role is emphasized in long COVID care.