**3. Results**

Ten studies were included. Calcineurin inhibitor therapy has been documented to be effective in various coronaviral diseases both in vitro as well as in vivo. So far, no data in immunocompetent patients on effects of CNI in human SARS-CoV-2 infections have been published. The results are shown in Table 1.


**Table 1.** Coronaviral serotypes and treatment with calcineurin inhibitors.

ALV = alisporivir, CNI = calcineurin inhibitor, CoV = coronavirus, CsA = cyclosporin A, CsAd = cyclosporine A derivatives, IFN-α = interferon alpha, MERS = Middle East respiratory syndrome, Tac = tacrolimus.

The available studies with in vivo data on SARS-CoV, MERS-CoV and SARS-CoV2 include studies performed on animal models of coronavirus-related diseases. SARS-CoV replication has been studied in mice, Syrian golden and Chinese hamsters, civet cats, and non-human primates [21], and MERS-CoV in mice, camelidae and non-human primates [21]. These animal studies investigated protease inhibitors, monoclonal and polyclonal antibodies, convalescent plasma, interferons, ribavirin, lopinavir/ritonavir in both SARS-CoV and MERS-CoV [21], but to our knowledge there are no animal data on SARS-CoV and SARS-CoV-2 addressing CNI therapy. Exceptions are the feline and turkey CoV, which do not have the possibility of spillover into human hosts [13,14]. The other exception is alisporivir, a nonimmunosuppressive cyclophillin inhibitor (CsA analog) in SARS-CoV, with strong in vitro dose-dependent antiviral properties against SARS-CoV-2 [16].

## **4. Discussion**

So far, the COVID-19 pandemic has led to more than 17 million SARS-CoV-2 infected patients and over 700000 deaths [7]. The number of cases is still, or again, on the rise in many countries and there currently is no geographic region where the pandemic seems totally under control.
