Klaus Cort @Klaus-Cort

Erythropoietin (EPO) levels were significantly lower in critical and deceased Covid-19 patients:

Article The relationship between serum erythropoietin, hepcidin, and...

Article Low Serum Erythropoietin Levels are Associated with Fatal CO...

Suggested treatment for both Covid-19 and LongCovid: rhEPO :

https://brieflands.com/articles/jkums-126623.html

https://pubmed.ncbi.nlm.nih.gov/?term=erythropoietin+covid

https://www.researchgate.net/post/Covid-19_Erythropoietin_EPO_deficiency_syndrome2

https://www.researchgate.net/post/EPO_treatment_of_Covid-194

Signs, symptoms and co-morbidities in PostCovid indicate continued EPO deficiency:

Pathogenesis : the immune response to the virus is so strong (with inflammatory cytokines), that it damages the kidneys EPO production.

Inflammatory cytokines

TNF-alpha, IFN-gamma, IL1B, IL6, IL17A ... (etc.) all suppress EPO:

Article Inhibition of erythropoietin production by cytokines: Implic...

Article Cytokine Profiles Associated With Acute COVID-19 and Long CO...

Article Effect of TNF-α on EPO- and EPOR-Induced Erythroid Progenito...

Article The Role of Interferons in Long Covid Infection

Article IFN-γ directly inhibits the activity of erythropoietin in hu...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805325/

https://journals.lww.com/jasn/Fulltext/2003/07000/Increased_Expression_of_Erythropoiesis_Inhibiting.8.aspx

Article CIS3/SOCS3 suppresses erythropoietin signaling by binding th...

Article Role of Erythropoietin in Inflammatory Pathologies of the CNS

Figure 1:

https://drive.google.com/file/d/1oPSw3MSpMkjW74HLoT2gXV1oWUNecSuO/view?usp=sharing

arrow direction = "increase of". EPO treatment would move "Covid-19" to the right in the figure. It follows that too much EPO can be harmful - at the far right in the figure.

There could be further causes of EPO deficiency:

Article Addressing the ‘hypoxia paradox’ in severe COVID-19: literat...

Obesity, diabetes and pain in the joints

https://nature.com/articles/ncomms1526

Article Erythropoietin (EPO) ameliorates obesity and glucose homeost...

Article Erythropoietin Non-hematopoietic Tissue Response and Regulat...

https://pubmed.ncbi.nlm.nih.gov/?term=diabetes+covid

https://pubmed.ncbi.nlm.nih.gov/?term=diabetes+erythropoietin

Article Erythropoietin Reduces Insulin Resistance via Regulation of ...

Article Erythropoietin improves insulin resistance via the regulatio...

https://www.jpeds.com/article/S0022-3476(96)70195-6/fulltext

Article Erythropoietin Non-hematopoietic Tissue Response and Regulat...

Article Erythropoietin and obesity-induced white adipose tissue infl...

Article Adipose tissue is a critical regulator of osteoarthritis

https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(22)00227-2/fulltext

Article Blunted erythropoietin to anemia in rheumatoid arthritis

Article Hypoxia and its implications in rheumatoid arthritis

Article R-h-erythropoietin counteracts the inhibition of in vitro er...

Article What is the role of erythropoietin prolotherapy on pain reli...

https://www.jrheum.org/content/jrheum/28/11/2430.full.pdf

Article The links of hepcidin and erythropoietin in the interplay of...

Article Decreased serum erythropoietin and its relation to anti-eryt...

Muscle pain, exercise intolerance, lack of energy and mitochondria

Article Clinical Characteristics and Mechanisms of Musculoskeletal P...

Article The erythropoietin receptor expressed in skeletal muscle is ...

https://pubmed.ncbi.nlm.nih.gov/?term=erythropoietin+Muscle

Article The erythropoietin receptor expressed in skeletal muscle is ...

Article Effect of Erythropoietin on Exercise Capacity in Patients Wi...

Article Skeletal muscle alterations and exercise performance decreas...

Article Erythropoietin, a Novel Versatile Player Regulating Energy M...

Article The erythropoietin receptor expressed in skeletal muscle is ...

Article Acute erythropoietin injection increases muscle mitochondria...

https://www.nature.com/articles/s41467-023-44432-3

Article Erythropoietin Treatment Enhances Muscle Mitochondrial Capac...

Article Erythropoietin improves functional and histological recovery...

Article Exogenous ketosis elevates circulating erythropoietin and st...

Aging

Accelerated biological aging in COVID-19 patients:

https://www.nature.com/articles/s41467-022-29801-8

Article Accelerated ageing is associated with increased COVID-19 sev...

Accelerated ageing is associated with increased COVID-19 severity and differences across ethnic groups may exist:

https://www.nature.com/articles/s43587-022-00321-w

https://pubmed.ncbi.nlm.nih.gov/?term=Erythropoietin+aging

Lack of energy - red blood cells

EPO regulates the lives and deaths of red blood cells.

The primary effect of EPO is increased number of red blood cells and thereby increased oxygen uptake, which is much needed in severe cases of Covid-19 - and in LongCovid.

Article Hematological alterations associated with long COVID-19

Article Changes in Hematological and Hemorheological Parameters Foll...

https://pubmed.ncbi.nlm.nih.gov/32825629/

https://pubmed.ncbi.nlm.nih.gov/33171297/

Article Anemia of inflammation

Article IFN-γ directly inhibits the activity of erythropoietin in hu...

https://pubmed.ncbi.nlm.nih.gov/32983414/

http://researchgate.net/publication/357172246_Activation_of_Sphingomyelinase-Ceramide-Pathway_in_COVID-19_Purposes_Its_Inhibition_for_Therapeutic_Strategies/comments

EPO is the natural inhibitor of the Sphingomyelinase-Ceramide-Pathway :

Article Oxidative Stress and Suicidal Erythrocyte Death

Article Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role a...

Article Cholesterol Deficiency Causes Impaired Osmotic Stability of ...

Article Fine‐Tuning of Cholesterol Homeostasis Controls Erythroid Di...

(Hemoglobin is measured in gram per liter or deciliter blood. It says nothing about blood volume, how many liter of blood the patient has. There is a reason for, that LongCovid patients look pale and are tired).

Blood volume perturbations in the postural tachycardia syndrome

https://www.amjmedsci.org/article/S0002-9629(15)32537-4/abstract

HDL-Cholesterol deficiency, lipids and thrombosis

Article High-density lipoprotein cholesterol: A marker of COVID-19 i...

https://www.frontiersin.org/articles/10.3389/fpubh.2021.705916/full

https://www.ajkd.org/article/S0272-6386(06)00763-3/fulltext

https://www.hilarispublisher.com/open-access/effect-of-erythropoietin-therapy-on-the-lipid-profile-in-patients-with-chronic-kidney-disease-a-single-center-study-2161-0959.1000140.pdf

Article COVID-19 and lipids. The role of lipid disorders and statin ...

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00389-8/full

Article Kidney-secreted erythropoietin lowers lipidemia via activati...

Article High-density lipoprotein as a modulator of platelet and coag...

Article Post–COVID-19 Arterial Thrombosis: A Systematic Review

Article Thrombo-inflammation in Long COVID – the elusive key to post...

Article Treatment of Stroke With Erythropoietin Enhances Neurogenesi...

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1257988/full

EPO inhibits (/regulates) NF-kappaB and thereby reduce TNF-alpha:

Article Suppression of NLRP3 Inflammasome by Erythropoietin via the ...

Article TNF-alpha driven inflammation and mitochondrial dysfunction ...

https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0043-1775965.pdf

Co-aministration of thrombolytic therapy and rhEPO should be avoided:

Article Recombinant Human Erythropoietin in the Treatment of Acute I...

Complement system and Micro-amyloid-fibrinogen-clots

Article Persistent complement dysregulation with signs of thromboinf...

EPO regulates the Complement system:

https://www.ajkd.org/article/S0272-6386(03)50023-3/fulltext

Article Plasmapheresis to remove amyloid fibrin(ogen) particles for ...

The micro amyloid fibrinogen clots are yet another sign of erythropoietin deficiency in LongCovid :

Article Inflammation, serum C-reactive protein, and erythropoietin resistance

(press DOI link to see full text)

And EPO treatment is how to get rid of them :

https://karger.com/hrp/article-abstract/44/4/189/370642/Total-Fibrin-and-Fibrinogen-Degradation-Products?redirectedFrom=fulltext

Decreased platelet activation through glycoprotein VI

Preprint Dysregulated Platelet Function and Thrombosis in Patients wi...

Article Dysregulated platelet function in patients with postacute se...

Article Erythropoietin induces association of the JAK2 protein tyros...

Article Protein tyrosine kinase, mitogen-activated protein kinase an...

Article Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in ...

https://www.sciencedirect.com/science/article/pii/S0006497120543085

Article TNF-α (Tumor Necrosis Factor-α)

Endothelial dysfunction and heart disease

Article Persistent Endothelial Dysfunction in Post-Acute COVID-19 Sy...

Article Diabetes, Heart Failure, and COVID-19: An Update

Article Evidence of Pulmonary Hypertension after SARS-CoV-2 Infectio...

https://www.kidney-international.org/article/S0085-2538(15)45998-8/fulltext

https://academic.oup.com/eurheartj/article/28/16/2018/492834?login=false

Article Erythropoietin therapy improves endothelial function in pati...

Article Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by...

Article Important Role of Endogenous Erythropoietin System in Recrui...

https://www.sciencedirect.com/science/article/abs/pii/S0196978119301597

Article Erythropoietin Activates Mitochondrial Biogenesis and Couple...

Article Erythropoietin Attenuates Cardiac Dysfunction in Rats by Inh...

Article Cardiomyocyte Specific Knock‐out of Erythropoietin Has Adapt...

Article Regulation of TLR4 expression mediates the attenuating effec...

Article Erythropoietin and Its Angiogenic Activity

Chronic stress, hypocortisolemia

... caused by EPO-deficiency, inflammatory stress and maybe corticosteroid treatment.

Erythropoietin negatively regulates pituitary ACTH secretion :

https://www.sciencedirect.com/science/article/abs/pii/S000689931500181X?via%3Dihub

"Prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain." :

Article Chronic Stress, Cortisol Dysfunction, and Pain: A Psychoneur...

Article Cortisol Exerts Bi-Phasic Regulation of Inflammation in Humans

Article Protracted stress-induced hypocortisolemia may account for t...

Article Erythropoietin attenuates locomotor and cognitive impairment...

Article Erythropoietin prevents the effect of chronic restraint stre...

Hair Loss

Article Prevalence of telogen effluvium hair loss in COVID-19 patien...

Article Erythropoietin promotes hair shaft growth in cultured human ...

Article Human hair follicles are an extrarenal source and a nonhemat...

Brain fog and demyelinaton

As mentioned above ("Lack og energy - red bloodcells") is EPO essential for sphingomyelin, and the same goes for myelin:

Article Association of CNS demyelination and COVID-19 infection: an ...

https://pubmed.ncbi.nlm.nih.gov/?term=Erythropoietin+myelin

Article Erythropoietin Increases Myelination in Oligodendrocytes: Ge...

https://www.eneuro.org/content/6/4/ENEURO.0421-18.2019

https://pubmed.ncbi.nlm.nih.gov/?term=amyloid+beta+erythropoietin

https://pubmed.ncbi.nlm.nih.gov/?term=Erythropoietin+dementia

Article Therapeutic Effect of Erythropoietin on Alzheimer’s Disease ...

Article The Impact of Low Hemoglobin Levels on Cognitive Brain Functions

Article Erythropoietin attenuates locomotor and cognitive impairment...

Article Erythropoietin improves memory function with reducing endoth...

Article Erythropoietin promotes hippocampal mitochondrial function a...

Article Erythropoietin Regulates the In Vitro and In Vivo Production...

Erythropoietin re-wires cognition-associated transcriptional networks:

https://www.nature.com/articles/s41467-023-40332-8

https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark4408.pdf

Article Serum Brain-Derived Neurotrophic Factor (BDNF) in COVID-19 P...

Article Erythropoietin protects primary hippocampal neurons increasi...

Article Intranasal injection of recombinant human erythropoietin imp...

Introducing the brain erythropoietin circle to explain adaptive brain hardware upgrade and improved performance :

https://www.nature.com/articles/s41380-022-01551-5

Microglia activation and neuroinflammation

Article Microglial Inflammatory Responses to SARS‐CoV‐2 Infection: A...

Article Neuroprotective erythropoietin attenuates microglial activat...

Article Erythropoietin as a new therapeutic opportunity in brain inf...

Brain erythropoietin fine-tunes a counterbalance between neurodifferentiation and microglia in the adult hippocampus:

https://www.sciencedirect.com/science/article/pii/S2211124721009827

Article The neurobiology of long COVID

Article Evidence That Erythropoietin Modulates Neuroinflammation thr...

An effective erythropoietin dose regimen protects against severe nerve injury-induced pathophysiological changes with improved neural gene expression and enhances functional recovery:

https://www.sciencedirect.com/science/article/abs/pii/S1567576919326633

EPO prevents neuroinflammation and relieves depression via JAK/STAT signaling :

https://www.sciencedirect.com/science/article/abs/pii/S0024320523007373

Depression and other mental disorders

https://www.nature.com/articles/1301439

Article Antidepressant-Like Effects of Erythropoietin: A Focus on Be...

Article Erythropoietin Pathway: A Potential Target for the Treatment...

Article Effects of erythropoietin on emotional processing biases in ...

https://www.iomcworld.org/open-access/a-possible-mechanism-of-antidepressant-like-effect-of-recombinant-human-erythropoietin-46047.html

https://www.nature.com/articles/s41537-022-00213-3

https://pubmed.ncbi.nlm.nih.gov/?term=Schizophrenia+erythropoietin

Article The Relationships Between Stress, Mental Disorders, and Epig...

Article Erythropoietin protects primary hippocampal neurons increasi...

Cognitive impairment in children

Article Cognition and Mental Health in Pediatric Patients Following COVID-19

EPO is essential for brain development:

Article Erythropoietin Regulates the In Vitro and In Vivo Production...

Article Erythropoietin in Brain Development and Beyond

https://nature.com/articles/s41380-022-01551-5

https://sciencedirect.com/science/article/pii/S1878747923004452

https://www.hindawi.com/journals/ari/2012/953264/

https://nature.com/articles/s41598-023-46783-9

Article Erythropoietin in Human Milk: Physiology and Role in Infant Health

Blood-brain-barrier

Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment:

https://www.nature.com/articles/s41593-024-01576-9

Article Erythropoietin protects the in vitro blood-brain barrier aga...

The relationship between erythropoietin pretreatment with blood–brain barrier and lipid peroxidation after ischemia/reperfusion in rats

https://www.sciencedirect.com/science/article/abs/pii/S0024320506009684

Erythropoietin protects against hemorrhagic blood–brain barrier disruption through the effects of aquaporin-4

https://www.nature.com/articles/labinvest201484

Loss of or distorted taste

EPO is vital for the maintenance of both myelin and sphingomyelin.

Article Taste Dysfunction in Multiple Sclerosis

Article Differential effects of membrane sphingomyelin and cholester...

Article Sphingolipid/cholesterol regulation of neurotransmitter rece...

Article No Smell, No Taste—Dealing With a “Senseless” Phase of the P...

https://www.sciencedirect.com/science/article/pii/S2211124721009827

Blindness

Article Abrupt bilateral blindness as a rare post-acute demyelinatin...

Article Vision Loss and COVID-19 Infection A Systematic Review and M...

https://pubmed.ncbi.nlm.nih.gov/?term=erythropoietin%20blindness&page=2

Inhibiting Ceramide synthesis preserves photoreceptor viability and functionality :

Article Sphingolipids as Emerging Mediators in Retina Degeneration

Article Erythropoietin in Optic Neuropathies: Current Future Strateg...

Article Erythropoietin in ophthalmology: A literature review

Article The effect of systemic erythropoietin and oral prednisolone ...

Article Erythropoietin protects the inner blood–retinal barrier by i...

Article Intranasal injection of recombinant human erythropoietin imp...

Hearing loss

Article One year on: an updated systematic review of SARS-CoV-2, COV...

https://www.everydayhealth.com/coronavirus/hearing-loss-and-tinnitus-are-lesser-known-symptoms-of-covid-19/

https://pubmed.ncbi.nlm.nih.gov/?term=hearing+eryhthropoietin

Article Sudden Sensorineural Hearing Loss Associated with Nutritiona...

EPO ↔ Melatonin ↔ Serotonin ↔ EPO --> dopamine

and insomnia

(they mutually increase one another)

Article Circadian rhythm of human serum erythropoietin

Article Impairment of endogenous melatonin rhythm is related to the ...

https://pubmed.ncbi.nlm.nih.gov/19767630/

https://pubmed.ncbi.nlm.nih.gov/31132978/

https://www.researchgate.net/publication/365592639_Efficacy_and_safety_of_oral_melatonin_in_patients_with_severe_COVID-19_a_randomized_controlled_trial

https://www.researchgate.net/publication/359178853_Melatonin_increased_hypoxia-inducible_factor_HIF_by_inhibiting_prolyl_hydroxylase_A_hypothesis_for_treating_anemia_ischemia_and_covid-19

https://www.researchgate.net/publication/373771449_The_global_challenges_of_the_long_COVID-19_Journal_of_Clinical_Images_and_Medical_Case_Reports

https://www.pnas.org/doi/10.1073/pnas.2113852118

https://www.cell.com/cell/fulltext/S0092-8674(23)01034-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867423010346%3Fshowall%3Dtrue

Article Therapeutic Effect of Erythropoietin on Alzheimer’s Disease ...

https://www.nature.com/articles/1301439

https://www.pnas.org/doi/10.1073/pnas.1103964108

https://www.mdpi.com/1422-0067/23/15/8144

Article Erythropoietin improves neurobehavior by reducing dopaminerg...

Article Stimulating effect of erythropoietin on the release of dopam...

Article Erythropoietin Regulates the In Vitro and In Vivo Production...

Article International Journal of Molecular Sciences Dopamine Transmi...

Fatty liver

Article Metabolic-Associated Fatty Liver Disease Is Highly Prevalent...

https://besps.journals.ekb.eg/article_210608.html

Article Erythropoietin suppresses hepatic steatosis and obesity by i...

Article The Potential Role of Erythropoietin on Fatty Liver Induced ...

https://www.nature.com/articles/srep17878

Article COVID-19 and hepatic injury: Diversity and risk assessment

Article Liver Function in Patients with Long-Term Coronavirus Diseas...

Article Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thi...

Alcohol intolerance

Article New Alcohol Sensitivity in Patients With Post-acute Sequelae...

Article Intranasal erythropoietin ameliorates neurological function ...

Article Erythropoietin as an adjunctive treatment for methanol-induc...

https://www.archivesofmedicalscience.com/pdf-93892-67779?filename=The%20influence%20of.pdf

Kidney damage

Article Long-term interplay between COVID-19 and chronic kidney disease

Article Kidney Damage in Long COVID: Studies in Experimental Mice

Article Erythropoietin ameliorates renal interstitial fibrosis via t...

https://journals.lww.com/jasn/fulltext/2021/11000/kidney_outcomes_in_long_covid.19.aspx

Article Erythropoietin Protects the Kidney by Regulating the Effect ...

Article Renal Cell Protection of Erythropoietin beyond Correcting Th...

https://www.frontiersin.org/articles/10.3389/fmed.2020.00047/full

Article Erythropoietin and renal protection

https://www.frontiersin.org/articles/10.3389/fmed.2020.00047/full

https://journals.lww.com/jasn/fulltext/2021/10000/erythropoietin_reduces_auto__and_alloantibodies_by.21.aspx

Recombinant human erythropoietin reduces rhabdomyolysis-induced acute renal failure in rats

https://www.sciencedirect.com/science/article/abs/pii/S0020138311005602

Erythropoietin protects against rhabdomyolysis-induced acute kidney injury by modulating macrophage polarization

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477572/

https://journals.lww.com/kidney360/fulltext/2022/11000/heme_proteins_and_kidney_injury__beyond.25.aspx

Inflammation and lung tissue damage

(Not meaning that inflammation is only in lungs)

Article Novel Coronavirus-Induced NLRP3 Inflammasome Activation: A P...

Article Suppression of NLRP3 Inflammasome by Erythropoietin via the ...

Article Post-COVID-19 Pulmonary Fibrosis: Facts-Challenges and Futur...

https://erj.ersjournals.com/content/54/suppl_63/PA2425

Preprint Multimodal Molecular Imaging Reveals Tissue-Based T Cell Act...

https://www.nature.com/articles/nrneph.2014.73

Article Neutrophil extracellular traps and long COVID

Article Erythropoietin inhibits neutrophil extracellular traps forma...

https://www.nature.com/articles/s41590-023-01724-6

Article Immunosuppressive Effects of Erythropoietin on Human Allorea...

Article Mitochondrial Metabolism Regulation of T Cell-Mediated Immunity

Article Differential Roles of SOCS Family Members in EpoR Signal Transduction

Article SOCS Proteins: Negative Regulators of Cytokine Signaling

Article Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be ...

Article Erythropoietin acts as an anti-inflammatory signal on murine...

Article Erythropoietin Receptor Is Expressed on Human Peripheral Blo...

https://www.nature.com/articles/s41590-023-01724-6

https://researchgate.net/publication/51902180_The_Receptor_That_Tames_the_Innate_Immune_Response

https://www.nature.com/articles/s41419-020-2276-8

https://researchgate.net/publication/331975246_Erythropoietin_a_multifaceted_protein_with_innate_and_adaptive_immune_modulatory_activit

Article EPO ameliorates lung injury by accelerating pulmonary endoth...

Article Cytoprotective effects of erythropoietin: What about the lung?

Article Erythropoietin Attenuates Pulmonary Vascular Remodeling in E...

Article Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role a...

Article Erythropoietin: A Potent Inducer of Peripheral Immuno/Inflam...

Article Erythropoietin as a new therapeutic opportunity in brain inf...

Article Erythropoietin and its derivatives: from tissue protection t...

Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury:

https://erj.ersjournals.com/content/33/6/1403

Article Erythropoietin Protects against Diffuse Alveolar Hemorrhage ...

Erythropoietin inhalation enhances adult canine alveolar-capillary formation following pneumonectomy:

https://pubmed.ncbi.nlm.nih.gov/30785346/

Autoimmunity

Article Autoimmunity is a hallmark of post-COVID syndrome

https://www.frontiersin.org/articles/10.3389/fimmu.2021.639370/full

Article Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines ML...

Article Erythropoietin and autoimmune neuroinflammation: lessons fro...

https://www.sciencedirect.com/science/article/abs/pii/S0896841121000378

Article Erythropoietin reduces experimental autoimmune encephalomyel...

Article Erythropoietin inhibits SGK1-dependent TH17 induction and TH...

Article Erythropoietin: A Potent Inducer of Peripheral Immuno/Inflam...

Article Erythropoietin Reduces Auto- and Allo-Antibodies By Inhibiti...

IgG antibodies and EPO resistance

Preprint Transfer of IgG from Long COVID patients induces symptomology in mice

Restrained memory CD8+ T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID:

https://www.medrxiv.org/content/10.1101/2024.02.11.24302636v1

STAT5 Is Critical To Maintain Effector CD8+ T Cell Responses:

https://journals.aai.org/jimmunol/article/185/4/2116/103277/STAT5-Is-Critical-To-Maintain-Effector-CD8-T-Cell

Article Molecular Sciences STAT5 as a Key Protein of Erythropoietin ...

(article only selected for the headline)

Article Erythropoietin Receptors and IgG Autoantibody Expression on ...

Article Successful Treatment of Aplastic Anemia with G-CSF and High ...

Article Pancytopenia and Profound Neutropenia as a Sequela of Severe...

Article Association between Anti-Erythropoietin Receptor Antibodies ...

Antibodies to Erythropoietin Are Associated with Erythropoietin Resistance in Hemodialysis Patients in KwaZulu-Natal (South Africa): https://journals.lww.com/sjkd/fulltext/2020/31050/antibodies_to_erythropoietin_are_associated_with.4.aspx

CD8+ T cells and activation of T-cell receptor heterodimers

https://www.nature.com/articles/s41590-023-01724-6

”NIH-funded study suggests need to boost CD8+ T cell response after infection.”:

https://www.nih.gov/news-events/news-releases/sars-cov-2-infection-weakens-immune-cell-response-vaccination

https://www.cell.com/immunity/fulltext/S1074-7613(23)00125-5#%20

Article STAT5 is critical to maintain effector CD8+T cell responses

Article Molecular Sciences STAT5 as a Key Protein of Erythropoietin ...

Article STAT5 and CD4+ T Cell Immunity

https://www.sciencedirect.com/science/article/pii/S0006497120622261

https://www.sciencedirect.com/science/article/abs/pii/0011393X95851283

Article The Role of Tissue-resident T Cells in Stress Surveillance a...

Mitochondrial dysfunction, viral persistence and deficient phagocytosis

With "exhausted" CD8+ T cells, it is worth remembering that immune cells also have mitochondria, and they need energy to do their job:

https://www.nature.com/articles/s41590-023-01724-6

Article Acute erythropoietin injection increases muscle mitochondria...

https://www.nature.com/articles/s41467-023-44432-3

Article The Role of Taurine in Mitochondria Health: More Than Just a...

Article Erythropoietin stimulates tyrosine phosphorylation and tauri...

Article Taurine and inflammatory diseases

Article The Innate Immune Response to Infection Induces Erythropoiet...

SARS-CoV-2 fragments may cause problems after infection:

https://www.nih.gov/news-events/nih-research-matters/sars-cov-2-fragments-may-cause-problems-after-infection

Article Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic ...

Correction of Deficient Phagocytosis During Erythropoietin Treatment in Maintenance Hemodialysis Patients:

https://www.sciencedirect.com/science/article/abs/pii/S0272638612804549

Erythropoietin enhances Kupffer cell number and activity in the challenged liver:

https://www.nature.com/articles/s41419-018-1274-6

Gut microbiota dysbiosis

https://www.sepsis.org/news/the-connection-between-covid-19-sepsis-and-sepsis-survivors/

Article Detection of Intestinal Dysbiosis in Post-COVID-19 Patients ...

https://www.sciencedirect.com/science/article/pii/S0753332223008636

https://diabetesjournals.org/diabetes/article/72/Supplement_1/239-LB/149885/239-LB-Erythropoietin-Alters-Fat-Mass-and-Gut

Article Gut Microbiota and Mitochondria: Health and Pathophysiologic...

Article Gut Microbiota Correlates With Clinical Responsiveness to Er...

Iron dysregulation

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19:

https://www.nature.com/articles/s41590-024-01754-8

Fatal COVID-19 pulmonary disease involves ferroptosis:

https://www.nature.com/articles/s41467-024-48055-0

Article Erythropoietin inhibits ferroptosis and ameliorates neurolog...

Article Erythropoietin ameliorates cognitive dysfunction in mice wit...

Chapter Iron Deficiency and Anemia Associated with Infectious and In...

Article Pantohematogen Efficacy Evaluation in Complex Sanatorium Reh...

Article The role of hypoxia and inflammation in the regulation of ir...

Article SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeo...

Article Anemia and iron metabolism in COVID-19: a systematic review ...

https://www.nature.com/articles/labinvest201711

Article Association of Endogenous Erythropoietin Levels and Iron Sta...

Dysautonomia and POTS

The causes of these conditions are not fully known/understood/agreed upon. But many very likely explanatory factors have been mentioned in the above.

Blood volume perturbations in the postural tachycardia syndrome :

https://www.amjmedsci.org/article/S0002-9629(15)32537-4/abstract

Article Treatment of Orthostatic Hypotension with Erythropoietin

Erythropoietin in Autonomic Failure:

https://www.sciencedirect.com/science/article/abs/pii/B978012589762450116X

"These patients also have a significant reduction in plasma erythropoietin":

Article Diabetic Cardiovascular Autonomic Neuropathy

Sexual and reproductive function

Men

Article Changes of sperm parameters in men recovered from coronaviru...

Article Erythropoitein Increases In Vitro Motility and Vitality of H...

Article Sphingomyelin Modulates Capacitation of Human Sperm In Vitro

https://www.cureus.com/articles/199842-post-covid-19-demyelinating-disease-and-its-effect-on-the-lower-urinary-tract-a-rare-case-of-a-14-year-old-man#!/

Article Erythropoietin stimulates testosterone production in man

https://pubmed.ncbi.nlm.nih.gov/?term=Erythropoietin+erectile+function

Endothelial Dysfunction in Erectile Dysfunction:

https://onlinelibrary.wiley.com/doi/10.1002/j.1939-4640.2003.tb02743.x

In male patients sexual desire, frequency of sexual intercourse was strengthened after rhEPO therapy:

Article Effect of erythropoietin on gonadotropic hormones and sexual...

Women

Article Female reproductive health impacts of Long COVID and associa...

Article Early outlined interdisciplinary theoretical explanation of ...

Improvement of sexual function was remarkable in female patients:

Article Effect of erythropoietin on gonadotropic hormones and sexual...

Why women more often suffer from LongCovid ?

Adult females mount stronger innate and adaptive immune responses than males: https://www.nature.com/articles/nri.2016.90

This means a stronger EPO-TNFalpha imbalance.

Estrogen suppresses and testosterone increases the production of EPO in the kidneys:

https://pubmed.ncbi.nlm.nih.gov/15784734/

Article Gender Differences in Dose of Erythropoietin to Maintain Hem...

Article The Effect of Testosterone on Erythropoietin Levels in Anemic Patients

This makes a threshold for younger to middle age female patients to recover their own EPO-production, while in particular younger men quickly recover from or don't get Covid-19 and rarely suffer from LongCovid.

Insights into early recovery from Long COVID—results from the German DigiHero Cohort:

https://www.nature.com/articles/s41598-024-59122-3

This may thus also explain the age-distribution in LongCovid.

Racial/ethnic differences

Article Racial/Ethnic Disparities in Post-acute Sequelae of SARS-CoV...

Article The Association of Race With Erythropoietin Dose in Patients...

Article Ethnic differences in anemia among patients with diabetes me...

Conclusion

EPO deficiency is "the common denominator" in both LongCovid and in Covid-19.

Pathogenesis : the immune response to the virus is so strong (with inflammatory cytokines), that it damages the kidneys EPO production.

Covid-19 and LongCovid are immunologic, hematologic, metabolic, neurologic and endocrinologic diseases.

That sounds complicated, but it is all due to deficiency of a single substance, that stands ready in our common medicine cabinet.