Long Covid Newsletter
Issue #16December 22, 20257 studies

Genetic blood clot risk tied to 21% higher long COVID odds

New genetic evidence reveals why some people develop long COVID while others don't—and it has to do with blood clots. Plus, researchers are mapping the brain changes behind persistent symptoms.

🧬 Genes predict long COVID risk through blood clotting pathways

  • Genetic analysis of 3,018 long COVID patients and 994,582 controls found that people with genetic variants increasing blood clot risk had 21% higher odds of developing long COVID

  • The association was independent of how severe their initial COVID infection was, suggesting blood clotting mechanisms drive long-term symptoms regardless of acute illness

  • Researchers identified protease-activated receptor 1 (PAR-1), a protein involved in blood clotting, as a potential molecular contributor to long COVID symptoms

Why it matters: This provides the first human genetic evidence that thromboembolism (blood clot formation) and long COVID share biological pathways, potentially explaining why some people develop persistent symptoms while others recover completely.

🥈 Top 2% journal 🔗 Nature cardiovascular research Journal Article 🗓️ Dec 16

Key Findings

🧠 Brain fog hits cognitive performance harder in long COVID than chemotherapy

  • Meta-analysis of 65 studies found people with long COVID brain fog scored significantly lower on cognitive tests compared to controls

  • Long COVID patients also reported 2.64 times higher fatigue levels and 1.48 times more depressive symptoms than those without brain fog

  • Montreal Cognitive Assessment was the most common test used, but researchers noted wide variation in how brain fog is measured across studies

💡 Standardized brain fog assessments could help doctors better diagnose and track cognitive improvements in long COVID patients.
🥉 Top 5% journal 🔗 BMJ Mental Health Systematic Review 🗓️ Dec 17

😴 Long COVID disrupts sleep for nearly 3 years after infection

  • Study of 2,406 Michigan adults found long COVID patients slept 0.35 hours less per night 1.5 years after infection

  • People with long COVID were 3.27 times more likely to sleep less than 6 hours nightly and 1.53 times more likely to experience moderate-to-severe sleep disturbance

  • Sleep problems persisted even 3 years post-infection, with long COVID patients nearly twice as likely to get inadequate sleep

💡 Long COVID's impact on sleep may contribute to other persistent symptoms like fatigue and cognitive problems.
🎖️ Top 10% journal 🔗 Sleep Journal Article 🗓️ Dec 18

🫁 COVID survivors develop unusual sleep apnea pattern

  • Study of 152 COVID survivors found 47.4% developed REM-predominant sleep apnea compared to just 17.8% of controls

  • People with this specific sleep apnea pattern were significantly more likely to report frequent fatigue (52.8% vs 35.7%)

  • COVID survivors actually had lower overall sleep apnea rates (50% vs 77.6%), but when they did develop it, it followed this unusual REM-heavy pattern

💡 This distinct sleep breathing pattern may help explain persistent fatigue in long COVID patients.
Top 20% journal 🔗 Sleep medicine Journal Article 🗓️ Dec 18

🔬 Ultrasound breaks down stubborn blood clots linked to long COVID

  • Low-frequency ultrasound at 150 kHz reduced amyloid microclot diameter by over 60% and eliminated more than 80% of large clots

  • These persistent microclots resist normal clot-dissolving enzymes and have been found in long COVID patients

  • Adding clot-dissolving drugs to ultrasound treatment provided only modest additional benefit, suggesting mechanical disruption is key

💡 Ultrasound therapy could offer a new approach for breaking down persistent clots that may contribute to long COVID symptoms.
Top 30% journal 🔗 Journal of Thrombosis and Thrombolysis Journal Article 🗓️ Dec 17

🧬 Genetic variant affects COVID severity through metabolism pathway

  • Patients with the C677T variant of the MTHFR gene who also had abnormal methionine metabolism levels experienced more severe COVID-19

  • One-carbon metabolism, a biochemical pathway critical for cellular function, was significantly disrupted in severe COVID patients

  • This genetic variant is relatively common and affects how the body processes certain vitamins and amino acids

💡 Genetic testing for MTHFR variants could help identify patients at higher risk for severe COVID outcomes.

🧠 Brain scans reveal physical changes in long COVID patients

  • MRI scans of 47 participants showed altered brain tissue signals in long COVID patients compared to both recovered COVID patients and healthy controls

  • Brain tissue microstructure changes correlated with physical and cognitive function scores

  • Long COVID patients also had different brain chemical levels compared to people who recovered from COVID without lasting symptoms

💡 Physical brain changes in long COVID patients provide biological evidence for their persistent cognitive and physical symptoms.
Top 20% journal 🔗 Brain, behavior, & immunity - health Journal Article 🗓️ Dec 17

Implications

These studies paint a clearer picture of long COVID as a multi-system disorder with measurable biological changes—from genetic blood clotting predisposition to altered brain structure and disrupted sleep patterns. The genetic findings particularly suggest that some people may be biologically predisposed to persistent symptoms, opening doors for personalized treatment approaches.

Studies in this issue

Primary sources used for this newsletter.

  1. Genetic Links Between Blood Clots and Long COVID in People of European Descent
    main storyNature cardiovascular research2025-12-16PMID 41402665
  2. REM-related obstructive sleep apnea in adults with past COVID-19 infection
    key findingSleep medicine2025-12-18PMID 41411839
  3. Combined Enzyme and Ultrasound Treatment May Break Down Amyloid Microclots
    key findingJournal of thrombosis and thrombolysis2025-12-17PMID 41405757
  4. Memory and thinking problems in long COVID and after chemotherapy: a review and combined analysis
    key findingBMJ mental health2025-12-17PMID 41407484
  5. Long COVID and Sleep Health Nearly 3 Years After COVID-19 Infection
    key findingSleep2025-12-18PMID 41408718
  6. MTHFR gene type and related metabolism predict how severe COVID-19 may be
    key findingProceedings of the National Academy of Sciences of the United States of America2025-12-18PMID 41410771
  7. Changes in brain tissue and chemical signals in people with long COVID and those recovered from COVID-19
    key findingBrain, behavior, & immunity - health2025-12-17PMID 41404601

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