Overview of Therapy
COVID-19 treatment is essentially supportive and, in fact, specific vaccines or therapies are not yet available. The COVID-19 vaccine is considered to be an effective prophylactic strategy. About 90 institutions around the world are working on identifying a specific and safe vaccine [148]. As of 8 April 2020, the global research and development landscape for COVID-19 vaccines has included 115 vaccine candidates. Most of these are currently in the preclinical phase and only some of these (mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio and LV-SMENP-DC and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute) have recently moved into clinical development [149].
The therapeutic protocols used for the general population have also been adopted in patients with chronic renal failure, regardless of the stage of the disease [150].
Antiviral drugs (Lopinavir/ritonavir (200/50 mg 2 cp × 2/day), Darunavir (800 mg/day), Ritonavir (100 mg/day), Darunavir/cobicistat (800/150 mg/day)) have been effective for the management of SARS-CoV-2 infection, in asymptomatic/paucisymptomatic patients and in patients with more severe manifestations [150,151].
Hydroxychloroquine (known as an antimalarial drug) was successfully used in the early stages of the pandemic until May 26th, 2020, when AIFA suspended authorization for its use for the treatment of SARS-CoV-2 infection [152,153].
Tocilizumab (anti-IL-6 monoclonal antibody) has been used in association with steroids and/or antiviral drugs, for the treatment of more severe clinical cases and patients with rapidly and significantly increasing levels of D-dimer. The dosage is 8 mg/kg body weight with a maximum infusion dose of 800 mg for a maximum of three administrations [154,155].
Unlike hydroxychloroquine, both antiviral drugs and tocilizumab do not require dosage adjustments in relation to the values of the glomerular filtrate [150].
Given the state of hypercoagulability and the high incidence of thromboembolic complications in COVID-19 patients, high doses of low molecular weight heparin have been added to the therapeutic protocols [156].
For kidney transplant patients, immunosuppressive therapy must be reshaped, in particular, mycophenolate, azathioprine and calcineurin inhibitors must be suspended during the active phases of the disease [150]. Tocilizumab, on the other hand, may be effective in these patients, but randomized trials are needed [157].
For COVID-19 patients undergoing intermittent dialysis, the methods that obtain the greatest clearance of the pro-inflammatory molecules are preferred; in patients with AKI, hemodynamically unstable and requiring dialysis, continuous dialysis treatments are preferred (CVVH with pre and post-dilution at a dose > 25 mL/Kg/h), using citrate as the first choice anticoagulant (after serial assessments of serum calcium and lactic acid) and, alternatively, unfractionated heparin (constantly monitoring the patient’s APPT) [150].
Interferons have also been proposed as a possible therapy, although the timing of their use is critical since their benefit is realized if given before or early on in infection and may actually be harmful if given in the later stages. Clinical studies are underway to test their efficacy [158].
A recent phosphoproteomics analysis of SARS-CoV-2 infected Vero E6 cells (a cell line derived from monkey kidney epithelial cells) showed dramatic changes in phosphorylation of both host and viral proteins. Furthermore, viral infection induced the formation of casein kinase II (CK2)-containing filopodia containing budding viral particles. The authors have stated that pharmacologic inhibition of several kinases including CK2 and p38 MAP (mitogen-activated protein) kinases may be potential future COVID-19 therapies [159].
A summary of the main contents of this paper is depicted in Table 1.