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• Another RCT on 338 hospitalized adult patients with severe COVID-19 pneumonia from Argentina did not find any difference in clinical status or overall mortality or in prespecified subgroups (Simonovich 2020). • So it may depend on the patients – and on the level of antibody titers. Among 3082 patients hospitalized with COVID-19, the efficacy was moderated by mechanical ventilation status (Joyner 2020). In patients who were not receiving mechanical ventilation, transfusion of plasma with higher antibody levels was associated with a lower risk of death than transfusion of CP with lower antibody levels. • In an RCT on early administration of high titer CP to 160 mildly ill older adults, severe respiratory disease developed in 16% who received CP and in 31% who received placebo (Lipster 2020). • CP may be also very helpful in patients with humoral deficiency induced by anti-CD20 monoclonal antibodies such as rituximab. In 17 consecutive patients with profound B cell lymphopenia and prolonged COVID-19 symptoms, all but one patient experienced an improvement of clinical symptoms within 2 days.
4. Immunomodulators While antiviral drugs are most likely to prevent mild COVID-19 cases from becoming severe, adjuvant strategies will be needed, particularly in severe cases. Coronavirus infections may induce excessive and aberrant, ultimately ineffective host immune responses that are associated with severe lung damage (Channappanavar 2017). Similar to SARS and MERS, some patients with COVID-19 develop acute respiratory distress syndrome (ARDS), often associated with a cytokine storm. This is characterized by increased plasma concentrations of various interleukins, chemokines and inflammatory proteins. Various host-specific therapies aim to limit the immense damage caused by the dysregulation of pro-inflammatory cytokine and chemokine reactions (Zumla 2020). Immunosuppressants, interleukin blocking agents such as anakinra or JAK-2 inhibitors are also an option (Mehta 2020). These therapies may potentially act synergistically when combined with antivirals. Numerous drugs are discussed, including those for lowering cholesterol, for diabetes, arthritis, epilepsy and cancer, but also antibiotics. They are said to modulate autophagy, promote other immune effector mechanisms and the production of antimicrobial peptides. Other immunomodulatory and other approaches in clinical testing include bevacizumab, brilacidin, cyclosporin, fedratinib, fingolimod, lenadilomide and thalidomide, sildenafil, teicoplanin and many more. However, convincing clinical data is pending for most strategies. COVID Reference ENG 006.9
