7  Corticosteroids

7.1  Hypothesis: Corticosteroids can modulate inflammation
Corticosteroids are commonly used for modulation of a variety of inflammatory conditions. In addition to a daily regimen, they can be used in the form of pulse therapy to treat flares of autoimmune diseases. However, caution in the use of corticosteroids is needed due to the potential serious side effects associated with corticosteroid drugs and that corticosteroids generally suppress the immune system. The latter means that corticosteroids modulate hyper inflammation and, on the other hand, inhibit immune responses that are vital for the host defense against the virus [29].

7.2  Rationale: Corticosteroids might help accelerate recovery from COVID-19
The study [30] investigated the effect of inhaled corticosteroids ciclesonide, cortisone, prednisolone, dexamethasone, and fluticasone on the replication of the MERS-CoV. Among the four compounds, the only ciclesonide was capable of inhibiting viral replication. Also, ciclesonide induced a significant inhibition of viral replication of other human coronaviruses, such as HCoV-229E and SARS-CoV, and another positive-strand RNA virus, rubella virus, while not affect the viral replication of negative-strand RNA viruses, e.g., influenza and respiratory syncytial virus. For the MERS-CoV, a nonstructural protein 15 (NSP15) appeared to act as the target of ciclesonide. An amino acid substitution in the NSP15 conferred resistance of the mutated MERS-CoV to ciclesonide. Mometasone could help deal effectively with the mutated MERS-CoV. For the SARS-CoV2, all three ciclesonide, mometasone, and lopinavir were able to inhibit viral replication to a similar degree. Interestingly, their effect was more noticeable than serine protease inhibitors, e.g., nafamostat and camostat in cells that Vero cells that express TMPRSS2. It indicates the tendency of the SARS-CoV2 to enter the cell through the cathepsin/endosomal pathway rather than through the TMPRSS2/cell surface pathway.
The study [31] included 46 patients with severe COVID-19, of these 26 patients received methylprednisolone (1–2 mg/kg/d for 5–7 days), and 20 patients received standard therapy without methylprednisolone. The first group achieved faster improvement in clinical symptoms (fever and peripheral oxygen saturation) and lung lesions detected by CT imaging. However, two deaths occurred in the first group and one death in the second group. Moreover, the two groups did not differ in laboratory parameters, including WBC, lymphocyte count, monocyte count, and cytokines (IL-2, IL-4, IL-6, and IL-10) six days after treatment.
There is a report of the patient with COVID-19 treated with methylprednisolone since day 8 of the disease course. However, his situation worsened and developed respiratory failure and died on day 14 [32].