Etiopathogenic theories about long COVID

Table 1 Diagnosis and treatment based on the theories of long coronavirus disease

Pathological condition to study	Clinic	Basic diagnostic method	Extension studies	Treatments
Neuropsychiatric manifestations	Anxiety depression headache; brain fog; early dementia fatigue/weakness/myasthenia mitochondriopathy suspected	Psychological tests; clinical questioning neurological examination	Cranial CT head MRI brain PET scan CSF analysis; electroencephalogram EMG/CNV; serum lactate-pyruvate/CSF	Psychological therapy psychiatric treatment pacing; brain electrostimulation; speech therapy; behavioral therapy
Viral persistence	Leukopenia, lymphopenia virus reactivation (herpes, EBV); persistently positive COVID tests	Nasal COVID antigen (or PCR-RT); IgM-IgG serology for herpes, CMV, EBV	Total body PET to viral reservoirs, RT-PCR for Sars Cov2: Serum; urinary; stool	Antivirals: Paxlovid (Yale trial); oral remdesivir; acyclovir, ganciclovir
Immunothrombosis	Clinical data of inflammation or thrombosis: Arthralgias/arthritis; myalgias; arterial/venous thrombosis	D-dimer ferritin; C reactive protein reactive thrombocytosis DHL; creatine phosphokinase myoglobin	Intentional search for amyloid microthrombi: Immunofluorescence microscopy; flow cytometry; alpha 2 antiplasmin; serum amyloid A platelet hyperactivation; platelet aggregometry	Triple therapy: Oral anticoagulants; dual antiplatelet; gastric protection. Fibrinolytics chelators vitamins
Immune dysregulation	Frequent infections; de novo appearance of autoimmune diseases	Leukopenia, lymphopenia reactive lymphocytosis	Lymphocyte subpopulation; CD4/CD8/natural killers; miscellaneous and specific antibodies	Immunomodulators immunostimulants biological therapy; monoclonal antibodies (temelimab)
Vagus nerve injury	Brain fog dysautonomias	Electrocardiogram holter; ambulatory blood pressure monitoring	Vagus nerve ultrasound tilted table test	Electrostimulation of the vagus nerve; Cardiac rehabilitation Pyridostigmine
Dysbiosis	Brain fog depression/anxiety irritable colon chronic diarrhea	Coprological stool culture	Intestinal dysbiosis test stool calprotectin dysbiosis specific kits: Gastrotest; GI effects; healthy gut	Nutritional treatment Prebiotics; antibiotics (doxycycline, amoxicillin/clavulanate); probiotics: Lactobacillus PS128 fecal transplant
Miscellany	Hepatic steatosis chronic kidney failure dysthyroidisms; chronic lung disease		Kidney, liver, thyroid function female hormonal profile spirometry, chest X-ray, chest CT	Specific treatments
Commercial kits for persistent COVID diagnosis			CheqUp; IncellKINE

CT: Computed tomography; CMV: Cytomegalovirus; EMG: Electromyography; EBV: Epstein-Barr virus; GI: Gastrointestinal; MRI: Magnetic resonance imaging; PET: Positron emission tomography; PCR-RT: polymerase chain reaction reverse transcriptase; IgM: Immunoglobulin M; IgG: Immunoglobulin G; COVID: Coronavirus disease.