et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade LM22A-4 soluble human ACE2. Indeed, the risk for ENPP3 severe COVID-19 is usually 3-fold higher in CKD than in non-CKD patients; CKD is usually 12-fold more frequent in intensive care unit than in non-hospitalized COVID-19 patients, and this ratio is higher than for diabetes or cardiovascular LM22A-4 disease; and acute COVID-19 mortality is usually 15C25% for haemodialysis patients even when not developing pneumonia. data LM22A-4 showing inhibition of coronavirus replication, as this requires peptidyl-prolyl cis-trans isomerase activity of cyclophilin [70, 71], as well as evidence of its efficacy in haemophagocytic lymphohistiocytosis, which may be a complication of COVID-19 [72]. However, it remains an immunosuppressive and nephrotoxic agent and protocols for haemophagocytic lymphohistiocytosis suggest a delayed initiation of cyclosporine A not compatible with the time course of COVID-19. Drugs targeting complications Prophylactic low molecular excess weight heparin is the latest addition to the standard therapeutic bundle for COVID-19. Thus, beyond venous thrombosis due to inactivity, large vessel arterial thrombi and small vessel thrombi have been observed. Recently, anti-phospholipid antibodies were described [73]. Future therapeutic methods As discussed above, another interesting approach in COVID-19 is usually to block the early stages of SARS-CoV-2 contamination using human recombinant soluble ACE2, and clinical trials are ongoing [74, 75]. Very recently, LM22A-4 investigators from Sweden, Canada, Spain and Austria explained this new approach to the infection [76]. Infection of human blood vessels and kidney organoids by SARS-CoV-2 was significantly inhibited by recombinant soluble ACE2 (rACE2) at LM22A-4 the early stages of contamination. Soluble rACE2 competes with cell membrane ACE2 for computer virus binding. Currently a Phase 2 trial has started in 200 COVID-19 patients in Germany and Austria (“type”:”clinical-trial”,”attrs”:”text”:”NCT04287686″,”term_id”:”NCT04287686″NCT04287686). Additionally, a Chinese trial is evaluating NKG2D-ACE2 chimeric antigen receptorCNK cells (“type”:”clinical-trial”,”attrs”:”text”:”NCT04324996″,”term_id”:”NCT04324996″NCT04324996). NKG2D is an activating receptor of NK cells, which can identify and thus obvious virus-infected cells. Vitamin D has important functions beyond those of bone and mineral homeostasis that include modulation of the innate and adaptive immune responses. Vitamin D has pleiotropic effects in the immune system and documented benefits in chronic inflammatory says such as those observed in CKD patients [77]. To date, the benefit of vitamin D supplementation in COVID-19 patients has not been demonstrated; nevertheless, a clinical trial has been designed in Spain (“type”:”clinical-trial”,”attrs”:”text”:”NCT04334005″,”term_id”:”NCT04334005″NCT04334005). It was recently postulated that extracorporeal membrane oxygenation may help patients through non-specific removal of circulating pro-inflammatory cytokines that cause the cytokine storm [78]. Therefore, continuous renal replacement therapies may play an important role in patients with COVID-19 and sepsis syndrome. CONCLUSIONS In conclusion, CKD patients are at an increased risk of developing severe COVID-19. Moreover, the mortality rate appears to be higher than in the general population and not always directly related to the severity of pulmonary compromise. This is not surprising, given that viral (e.g. influenza) or severe infection is associated with an increased risk of cardiovascular events both in the general populace and in CKD patients [32, 33]. Additionally, CKD patients frequently have cardiovascular and diabetes comorbidities that may independently predispose to severe COVID-19. Given the absence of vaccine or approved therapy, nephrologists should advise CKD patients to follow interpersonal isolation recommendations directed at high-risk patients. These should be extended to dialysis models, where a high index of suspicion and screening for COVID-19 should be implemented. Additionally, if healthcare systems are overwhelmed by the pandemic, nephrologists should fight so that, despite the higher risk, CKD is not considered a comorbidity that weighs down the patient’s chances to access ICU care or a respirator. Discord OF INTEREST STATEMENT None declared. Recommendations 1. Sun P, Lu X, Xu C. et al. 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