LongCOVID machenism hypothesis _omochi_20231026

Mechanism hypothesis of LongCOVID Mechanism hypothesis Patients are NOT RECOGNIZING (Mild) diseases that cause acid-base imbalance e.g., Primary hyperaldosteronism, Gitelman syndrome, etc. Current Issues Patients are NOT RECOGNIZING ☞Not tested before COVID-19 infection Infected with COVID-19 Patients are NOT RECOGNIZING Significant increase in aldosterone levels Doctors CANNOT DIAGNOSE (Non-fatal) Hypokalemia Doctors say the blood test results are fine, but... Aldosterone rise is inevitable when infected with COVID-19 Laboratory Reference Ranges​ is POOR (Not optimized for Long COVID) e.g., Lower limit of Blood POTASSIUM level ☞ Many Cases that are worsen QOL are being overlooked Doctors CANNOT DIAGNOSE (Non-fatal) Acid-base imbalance (Mainly metabolic alkalosis) Occurrence of LongCOVID symptoms The theory has received little attention in long COVID. The solution I propose Are there any researchers who can conduct this? 1st Step The following correlation studies in longCOVID patients ・Aldosterone level ・Renin activity ・Blood electrolyte concentration, e.g. potassium, etc. ・Urinary electrolyte concentration ・patient symptoms ・patient performance level 2 nd Step Optimization of Laboratory Reference Range for Long COVID e.g., Raising Lower limit of Blood POTASSIUM level Only WHACK-A-MOLE treatments are available, which often miss the mark ☞ Symptons doesn't heal easily and comes back again and again 3 rd Step Diagnosis and treatment of underlying diseases using revised diagnostic criteria

Correlation between mechanism hypothesis and symptoms of LongCOVID Mechanism hypothesis Known Diseases (Mild) diseases that cause acid-base imbalance e.g., Primary hyperaldosteronism, Gitelman syndrome, etc. Possible Circumstances Possible Facts Infected with COVID-19 Known Mechanism Known Facts Significant increase in aldosterone levels Known Mechanism Known Facts (Non-fatal) Hypokalemia Doctors say the blood test results are fine, but... Known Mechanism Known Facts (Non-fatal) Acid-base imbalance (Mainly metabolic alkalosis) Corrirated Mechanism Corrirated Symptons with metabolic alkalosis Occurrence of LongCOVID symptoms Many symptoms can be explained by hypothesis and metabolic alkalosis LongCOVID symptons Possible cause ・fatigue ・joint pain ・muscle pain ・muscle weakness ・palpitations Typical symptoms of hypokalemia ・brain fog Mild consciousness disturbance due to hypokalemia ・Insomnia/midawakening ・Depression Parasympathetic inhibition due to hypokalemia ・Excessive gastric acid secretion (reflux) ・diarrhea Self-defense reaction against metabolic alkalosis (metabolic acidosis) ・Shortness of breath/ breathlessness Self-defense reaction against metabolic alkalosis (respiratory acidosis) ・hair removal ・Taste disorder ・Olfactory disorder Needs verification

Why LongCOVID is prolonged？ A hypothesis that is close to certainty Mechanism hypothesis Patients are NOT RECOGNIZING (Mild) diseases that cause acid-base imbalance Lack of potassium on daily basis e.g., Primary hyperaldosteronism, Gitelman syndrome, etc. Infected with COVID-19 Patients are NOT RECOGNIZING Significant increase in aldosterone levels Doctors CANNOT DIAGNOSE (Non-fatal) Hypokalemia Doctors say the blood test results are fine, but... Doctors CANNOT DIAGNOSE (Non-fatal) Acid-base imbalance (Mainly metabolic alkalosis) Occurrence of LongCOVID symptoms Acid-base balance abnormal state (Non-fatal but worsen QOL)

Issues in the medical field Should be defined by statistics targeting LongCOVID patients Not written in the textbook Current test standards don‘t allow access to appropriate treatment. × Enough QOL Necessary level for enough QOL Many doctors looks ONLY THIS Necessary for survival(less QOL) Potassium e.g., 3.5mmol/L Gray area Fatal LongCOVID patient’s typical level (hypothesis) Doctors say, “No problem” but patient's’ QOL is quite low Overlooked Acid-base balance abnormal state (Non-fatal) Not listening to the patient's complaints Normal State

Proposed Solution Mechanism hypothesis Patients are NOT RECOGNIZING (Mild) diseases that cause acid-base imbalance e.g., Primary hyperaldosteronism, Gitelman syndrome, etc. Current Issues Patients are NOT RECOGNIZING ☞Not tested before COVID-19 infection Infected with COVID-19 Patients are NOT RECOGNIZING Significant increase in aldosterone levels Doctors CANNOT DIAGNOSE (Non-fatal) Hypokalemia Doctors say the blood test results are fine, but... Aldosterone rise is inevitable when infected with COVID-19 Laboratory Reference Ranges​ is POOR (Not optimized for Long COVID) e.g., Lower limit of Blood POTASSIUM level ☞ Many Cases that are worsen QOL are being overlooked Doctors CANNOT DIAGNOSE (Non-fatal) Acid-base imbalance (Mainly metabolic alkalosis) Occurrence of LongCOVID symptoms The theory has received little attention in long COVID. The solution I propose Are there any researchers who can conduct this? 1st Step The following correlation studies in longCOVID patients ・Aldosterone level ・Renin activity ・Blood electrolyte concentration, e.g. potassium, etc. ・Urinary electrolyte concentration ・patient symptoms ・patient performance level 2 nd Step Optimization of Laboratory Reference Range for Long COVID e.g., Raising Lower limit of Blood POTASSIUM level Only WHACK-A-MOLE treatments are available, which often miss the mark ☞ Symptons doesn't heal easily and comes back again and again 3 rd Step Diagnosis and treatment of underlying diseases using revised diagnostic criteria

Comparison of diseases with LongCOVID-like symptoms Characteristic symptoms LongCOVID Gitelman syndrome POTS Fatigue ✅ ✅ ✅ Gets tired easily ✅ ✅ ✅ Muscle weakness ✅ ✅ ✅ Orthostatic hypotension ✅ ✅ ✅ Sodium deficiency dehydration ✅ ✅ Unknown Congenital renal abnormalities (impaired sodium reabsorption) Root Cause High correlation Unknown Mechanism of symptom occurrence Hypokalemia? Treatments that are said to work riffraff Established methods of treatment Unknown Explicit diagnostic methods High correlation ✅ Unknown Sodium deficiency dehydration ➡Elevated aldosterone levels ➡Hypokalemia Unnknown Sodium deficiency dehydration? Maybe ・Intravenous saline Effective ・Water and salt replenishment （Cure has been established） Effective ・ to K and Mg supplementation Effective to ・ Aldosterone antagonists LongCOVID? POTS? Unknnown Electrolyte concentrations in Unknown Applicable to serum and urine LongCOVID? Exclusion of similar diseases Applicable to POTS? Unknown

Revision History 日付 Ver. 改訂内容 2023/10/25 1.00 First Version 2023/10/30 1.01 Added p.6 “Comparison of diseases with LongCOVID-like symptoms” Added This page