Hidden COVID-19 Virus Reservoirs in Bone Marrow May Raise Long-Term Blood Disease Risks
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 29, 2026 1 hour, 11 minutes ago
Medical News: For years, scientists have warned that infection with SARS-CoV-2 increases the risk of cardiovascular disease long after the initial illness has passed. Now, researchers are investigating an even more concerning possibility: the virus or its remnants may remain hidden deep inside the body's bone marrow, potentially driving chronic inflammation, immune dysfunction, abnormal blood cell production, and possibly increasing the long-term risk of blood disorders and even certain blood cancers in vulnerable individuals.
Scientists have found growing evidence that persistent SARS-CoV-2 in bone marrow may play a key role
in Long COVID and future blood-related health complications
The latest research, led by scientists from the Department of Medicine at the University of California, San Francisco (UCSF) as part of the Long-term Impact of Infection with Novel Coronavirus (LIINC) PASC Tissue Program, is providing compelling evidence that Long COVID may be fueled by persistent viral reservoirs located in tissues throughout the body rather than by damage left behind after the initial infection. The project is supported by the PolyBio Long COVID Research Consortium and involves collaborations with multiple research groups studying Long COVID.
The World's Most Comprehensive Tissue Investigation
Unlike previous studies that mainly relied on blood samples, the UCSF team has become the first in the world to systematically examine multiple tissues—including the gut wall, lymph nodes, cerebrospinal fluid, and bone marrow—to determine whether SARS-CoV-2 continues to persist months or even years after infection.
This
Medical News report highlights how researchers are using advanced Digital Spatial Omics technology capable of detecting viral RNA, viral proteins, immune cell activity, and gene expression at the level of individual cells. This allows scientists to determine precisely where viral material remains and how surrounding immune cells respond.
The program is co-led by Dr. Michael Peluso from UCSSF's Department of Medicine and builds upon the university's well-established LIINC cohort, one of the largest Long COVID research programs worldwide.
Bone Marrow Emerges as a Major Area of Concern
Among all tissues being investigated, bone marrow has become one of the most intriguing.
Bone marrow is responsible for producing virtually every blood cell in the body, including red blood cells, white blood cells, platelets, and numerous immune cells. If SARS-CoV-2 persists inside this critical organ, the consequences could extend throughout the entire body.
Earlier work by the research team has already demonstrated persistent immune activation within bone marrow. They have identified activated T cells in bone marrow alongside similar immune activity in the brainstem, spinal cord, gut wall, and lymph nodes.
Researchers also point to previous findings showing that childr
en suffering from Multisystem Inflammatory Syndrome in Children (MIS-C) had detectable SARS-CoV-2 RNA and viral proteins inside bone marrow, accompanied by excessive macrophage activation and increased numbers of megakaryocytes—the cells responsible for producing platelets.
These observations suggest that persistent viral material within bone marrow may continuously stimulate the immune system, contributing to chronic inflammation, abnormal clotting, immune exhaustion, and Long COVID symptoms.
Persistent Viral Reservoirs May Explain Long COVID
The UCSF investigators have previously demonstrated that SARS-CoV-2 RNA and spike protein can remain inside the gut wall for up to 2.5 years after infection. They also found that nearly one in ten people continues to have circulating spike protein in their blood months or years after recovering from COVID-19.
The researchers believe these persistent viral reservoirs may continually activate the immune system.
Bone marrow biopsies currently underway aim to determine whether viral material remains inside bone marrow immune cells such as myeloid cells and megakaryocytes. If confirmed, this could explain why many Long COVID patients continue experiencing fatigue, exercise intolerance, brain fog, clotting abnormalities, and systemic inflammation long after testing negative.
Brain and Nervous System May Also Be Affected
The project is also investigating how viral persistence affects the central nervous system.
Scientists believe spike protein may accumulate near the meninges surrounding the brain or enter through skull-associated lymphatic pathways. Earlier studies have shown spike protein can bind directly to fibrinogen, producing abnormal blood clots capable of activating inflammatory brain cells called microglia.
Analysis of cerebrospinal fluid from Long COVID patients has revealed inflammatory biomarkers, increased astrocyte turnover, immune activation, and evidence suggesting persistent viral material inside neural-derived exosomes.
Researchers are also searching for abnormal B cells and viral RNA within cerebrospinal fluid using ultrasensitive Simoa assays and metagenomic sequencing.
Gut, Blood Vessels and Physical Function
The gut remains another major viral reservoir under investigation. Researchers are expanding biopsy studies to determine whether SARS-CoV-2 persists alongside other viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), both of which may contribute to Long COVID.
The team is simultaneously measuring blood vessel health using EndoPAT technology and evaluating exercise performance through cardiopulmonary exercise testing. By comparing these physiological measurements with tissue viral burden, scientists hope to determine whether persistent viral antigens directly impair oxygen delivery, endothelial function, and physical performance.
Experimental Treatments Now Being Tested
The LIINC PASC Tissue Program is also evaluating whether antiviral therapies can eliminate tissue reservoirs.
Current clinical trials include investigational monoclonal antibody AER002 and Shionogi's antiviral drug ensitrelvir. Researchers are collecting blood, nasal swabs, gut biopsies, and lymph node samples before, during, and after treatment to determine whether reducing viral persistence improves Long COVID symptoms and restores normal tissue function.
Could Persistent Bone Marrow Infection Lead to Blood Disorders?
Although definitive proof is still lacking, scientists are increasingly concerned about the possible long-term consequences of persistent viral material within bone marrow.
Ongoing inflammation could interfere with normal blood cell production, leading to prolonged anemia, low platelet counts, impaired immune responses, or persistent bone marrow suppression. Infection of megakaryocytes may produce dysfunctional platelets that contribute to abnormal clotting or bleeding.
Some researchers also speculate that persistent inflammation may promote clonal hematopoiesis—a condition in which abnormal blood stem cell clones expand with age. Because clonal hematopoiesis is already associated with cardiovascular disease and blood cancers such as leukemia, persistent SARS-CoV-2 antigens could theoretically serve as an additional trigger in genetically susceptible individuals.
While isolated case reports have linked COVID-19 with later diagnoses of acute leukemia, current evidence remains observational but the possibility that SARS-CoV-2 directly or indirectly causes cancer is still being investigated. Large-scale studies are still needed before firm conclusions can be drawn.
Bone Health May Also Suffer
Researchers are also investigating whether chronic inflammation originating in bone marrow contributes to bone loss.
Persistent immune activation may stimulate bone-resorbing osteoclasts, lowering bone mineral density and increasing future risks of osteopenia, osteoporosis, vertebral fractures, and fragility fractures. Reduced mobility, chronic inflammation, vitamin D deficiency, and prolonged steroid treatment may further worsen these effects in some patients recovering from severe COVID-19.
Conclusion
The ongoing work from the University of California, San Francisco provides some of the strongest evidence yet that Long COVID may be driven by persistent viral reservoirs hidden inside critical tissues rather than representing simply the aftermath of an acute infection. The bone marrow findings are particularly important because this tissue governs blood formation, immune regulation, and inflammatory responses throughout the body. Although many of the bone marrow observations are still preliminary and await peer-reviewed publication, they raise important questions about whether persistent SARS-CoV-2 antigens could contribute to chronic inflammation, cardiovascular disease, immune dysfunction, clotting disorders, impaired blood cell production, and possibly increase the likelihood of blood disorders in susceptible individuals. Importantly, there is currently no conclusive evidence that SARS-CoV-2 directly causes leukemia or other blood cancers, but the biological mechanisms being explored deserve careful investigation. As additional bone marrow biopsies and tissue analyses become available, they may fundamentally reshape our understanding of Long COVID and help identify therapies capable of eliminating persistent viral reservoirs rather than merely treating symptoms.
The specific bone marrow findings described are preliminary and have not yet been published in a peer-reviewed journal. They were presented through the University of California San Francisco LIINC PASC Tissue Program and build upon the group's previously peer-reviewed publications on tissue viral persistence in Long COVID.
References:
https://polybio.org/projects/liinc-pasc-tissue-program-a-multimodal-assessment-of-the-tissue-based-virologic-drivers-of-long-covid/
https://www.sciencedirect.com/science/article/abs/pii/S2452318623000314
https://chi.scholasticahq.com/article/121430-sars-cov2-is-not-just-infection-but-a-culprit-of-donor-graft-failure-post-allogeneic-stem-cell-transplant
https://polybio.org/projects/sars-cov-2-persistence-and-impact-on-long-covid-megakaryocytes-platelets/
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(24)00438-4
https://link.springer.com/article/10.1007/s11914-023-00843-1
https://ashpublications.org/blood/article/136/25/2881/469789/Outcomes-of-patients-with-hematologic-malignancies
https://www.sciencedirect.com/science/article/pii/S2531137922000050
https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1651614/full
https://www.nature.com/articles/s41591-024-03278-y
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https://www.thailandmedical.news/articles/long-covid
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