An article hypothesizes that acetazolamide could benefit symptomatic COVID-19 patients due to the parallelism with high altitude pulmonary edema (HAPE), a condition that benefits from acetazolamide therapy. In short, the authors notes that COVID-19 and HAPE patients can potentially display decreased ratio of arterial oxygen partial pressure to fractional inspired oxygen (Pao2:FiO2), low oxygenation (hypoxia), abnormal breathing (tachypnea), reduced CO2 in the blood (hypocapnea), and patchy infiltrates with ground glass-like changes from radiologic findings within the lungs which may indicate hydrostatic pulmonary edema. Autopsies of COVID-19 patients also found episodes of pulmonary edema, pro-inflammatory concentrates, and early stages of acute respiratory distress syndrome (ARDS) leading to alveolar damage. HAPE patients may experience alveolar damage due to pressure changes and have exhibited pulmonary edema, potentially leading to ARDS. In light of these similarities, acetazolamide's positive effects seen by a reduction in hypoxic pulmonary vasoconstriction and lactate dehydrogenase levels along with improved minute ventilation and expired vital capacity in HAPE patients have been hypothesized to benefit COVID-19 patients. [1]

Another speculatory preprint article explores focuses on the drug itself. Acetazolamide is a potent inhibitor of carbonic anhydrase, the enzyme responsible for catalyzing the reversible reaction involving the hydration of carbon dioxide and dehydration of carbonic acid. While it's mechanism explains its benefit in reducing aqueous humor and intraocular pressure, its effect in acute mountain sickness (AMS) and HAPE is uncertain. The authors speculate acetazolamide may inhibit renal carbonic anhydrase which leads to bicarbonaturia and metabolic acidosis, thereby dampening the hyperventilation-induced respiratory alkalosis seen in HAPE and AMS patients. Acetazolamide has also been studied in patients with mild to moderate COPD which showed improved arterial oxygenation when administered at low and cautious doses. However, the drug may become harmful in those who cannot respond to stimulated ventilation (such as severe COPD or ARDS symptoms). Excessive accumulation of CO2 in blood may also lead to acid-base disorders. [2], [3]

AcetaZOLAMIDE is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (e.g., some types of glaucoma), in the treatment of certain convulsive disorders (e.g., epilepsy), and in the promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema).

AcetaZOLAMIDE is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.

AcetaZOLAMIDE is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of acetaZOLAMIDE decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that acetaZOLAMIDE has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of acetaZOLAMIDE is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result of renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.

Placebo-controlled clinical trials have shown that prophylactic administration of acetaZOLAMIDE at a dose of 250 mg every eight to 12 hours (or a 500 mg controlled-release capsule once daily) before and during rapid ascent to altitude results in fewer and/or less severe symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute mountain sickness (AMS). Pulmonary function (e.g., minute ventilation, expired vital capacity and peak flow) is greater in the acetaZOLAMIDE treated group, both in subjects with AMS and asymptomatic subjects. The acetaZOLAMIDE treated climbers also had less difficulty in sleeping.