LAUSR

There is no absolutely proven treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The infection continues to spread rapidly worldwide and causes many people deaths. Patients with rheumatic disease can become easily and severely infected with SARS-CoV-2 because their immune system is suppressed [1]. Patients with rheumatic diseases use many immunosuppressants such as disease-modifying antirheumatic drugs. It has been shown in many studies that hydroxychloroquine is effective for SARS-CoV-2 infection [2]. Tocilizumab is used for patients with severe SARS-CoV-2 infection [2]. Steroids use is not recommended during SARS-CoV-2 infection since the drugs may increase the tendency to pneumonia [1]. Cyclosporine is a potent immunosuppressive agent and often uses for immunosuppression after organ transplantation. It is widely used in the treatment of vasculitis by rheumatologists [3]. Cyclosporine can be used in the treatments of Behçet’s disease, psoriatic arthritis, and lupus nephritis [3]. Nowadays, it is not used for the treatment of rheumatoid arthritis [3]. Serious side effects of cyclosporine have limited its use. Administration of immunosuppressive agents inhibits the activation of T cells and render patients with rheumatic diseases susceptible to infections [1]. Therefore, it should be clarified whether cyclosporine can be used in SARS-CoV-2 infection. Cyclosporine is a calcineurin inhibitor that inhibits calcium-dependent interleukin (IL)-2 production. It blocks the calcineurin activity by complexing with cyclophilin in the cell and suppresses gene transcription of IL-2. Cyclosporine has been shown to inhibit SARSCOV viral replication at very low and non-toxic doses [4–6]. Similarly, it inhibits the replication of other coronaviruses and human immune deficiency virus [5, 6]. Cyclosporine can inhibit cyclophilin functions of the SARS-COV virus by inhibiting the peptidyl-prolyl isomerase activity or may act by directly inhibiting the nsp12 RNA-dependent RNA polymerase activity of the virus [6]. There is a resemblance between SARS-CoV-2 and SARS-CoV based on the fulllength genome phylogenetic. Therefore, cyclosporine can be successful in SARS-CoV-2 treatment. It is known that the virus binds to the angiotensin-converting enzyme 2 (ACE2) and enters the cell. The virus binds to ACE2 at low cytosolic pH [7]. The upregulation of ACE2 is thought to increase the viral load and exacerbate the disease [7]. Three important structures maintain cell pH. These ion regulators are lactate/H+ ion symporter (also called monocarboxylate transporters), Na+/H+ exchanger (NHE), and Cl/HCO3 exchangers. Hydroxychloroquine does not affect any of these channels. It increases intracellular pH through hemi-gap junctional channels [8]. The SARSCoV-2 infection creates a hypoxic environment by increase lactate. In anaerobic conditions, lactate formation increases by lactate dehydrogenase. MCT pumps lactate and H+ ion simultaneously from the extracellular area to the cytosol to lower the elevated lactate level. NHE becomes active as a reflex due to the increase of H+ ion in the cell [7]. After the activation of NHE, Na+ and Ca+2 are introduced into the cell, while H+ ion is pumped out of the cell. As this reaction continues, the cell continues to swell and lose its functions and eventually dies [7]. It seems that both MCT and NHE are active at the maximum level in SARS-CoV-2 infection. Rheumatology INTERNATIONAL