Cyclosporine A plus low‐dose steroid treatment in COVID‐19 improves clinical outcomes in patients with moderate to severe disease: A pilot study

Abstract

Background COVID‐19 pandemic causes high global morbidity and mortality, and better medical treatments to reduce mortality are needed. Objective To determine the added benefit of Cyclosporine‐A (CsA), to low‐dose steroid treatment, in patients with COVID‐19. Methods Open‐label, non‐randomized pilot study of patients with confirmed infection of SARS‐CoV2, hospitalized from April to May 2020 at a single center in Puebla, Mexico. Comparative treatment with steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. Results 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ±13.3; 69% men), and 104 steroids alone (age 54.06 ±13.8; 61% men). All patients received clarithromycin, enoxaparin, and methylprednisolone or prednisone up to 10 days. Patient´s death was associated with hypertension (RR=3.5) and diabetes (RR=2.3). Mortality was 22 and 35% for CsA and control groups (p=0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (p=0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, p=0.001, log‐rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39‐3.34, 95%CI, p=0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35‐2.83, 95%CI, p=0.0003) for all patients. Conclusion CsA used as an adjuvant to steroid treatment for COVID‐19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider

“…A few small prospective studies at variable RoB evaluated mavrilimumab, 52 lenzilumab, 53 eculizumab, 54 sarilumab, 55 recombinant human IL-7 56 and the combination of ruxolitinib+eculizumab, 57 ruxolitinib+glucocorticoids 58 and cyclosporin+glucocorticoids. 59 However, none of them provided solid positive results.…”

Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial

“…Based on these two mechanisms, it has been suggested that CNIs could be used to treat COVID-19 (18). In fact, recent non-randomized studies suggest that cyclosporine could reduce mortality, mainly in patients with moderate to severe COVID-19 (19,20). Our study is the first RCT assessing the effect of corticosteroids plus a CNI (tacrolimus) in hospitalized patients with severe COVID-19.…”

“…In December 2019, a new type of human coronavirus (SARS-CoV-2), causing an emerging diseases (COVID- 19), was first recognized in China and spread globally (1,2). The COVID-19 was declared a pandemic by the WHO on March 12, 2020 (3), and it continues to spread worldwide, causing considerable morbimortality and economic damage.…”

Reply letter to: Inhibition of SARS‐CoV‐2 replication using calcineurin inhibitors: Are concentrations required clinically achievable?

“…J. L. G alvez-Romero 1 ; J. Deveaux-Homs 2 ; F. A. Real-Ram ırez 3 ; O. Palmeros-Rojas 4 & S. Pedraza-S anchez 5,6 From the 1…”

“…In response to the letter by Dr. Solanich and col., we acknowledge the authors for their comment about our recently published paper in Journal of Internal Medicine [1], on Cyclosporine plus steroids for COVID-19 treatment. Dr. Solanich and col. argue that it is unlikely that an in vivo antiviral effect of cyclosporine A (CsA) participates on the beneficial effects observed in our study on patients with COVID-19; their argument is based on a published paper showing that an in vitro concentration of 3.3 lM of CsA is necessary to reach LD50 of antiviral activity against SARS-CoV-2 tested on Vero cell cultures [2], which would be equivalent to 3968 ng/ml in plasma, representing 10 times the recommended clinical safe levels of CsA.…”