# SARS-CoV-2 Treatment: Current Therapeutic Options and the Pursuit of Tailored Therapy
## 15 Discussion
CQ/HCQ, lopinavir/ritonavir and azithromycin are associated with QTc prolongation and torsade de pointes (TdP) risk, alongside other cardiotoxic substances. Risk factors are represented by congenital long-QT syndromes, advanced age, female sex, structural heart disease, electrolyte disturbances (e.g., concomitant use of diuretics), hepatic/renal failure, concomitant QTc-prolonging medications, fever, sepsis, baseline QTc prolongation, and inflammatory state [12; 108]. Antiarrhythmics, calcineurin inhibitors, antidepressants, antipsychotics (exception aripiprazole and lurasidone), antiretroviral drugs, some antituberculosis drugs, antineoplastic agents, calcineurin inhibitors, M-TOR inhibitors, and salmeterol can all increase this effect, whereas bracicardizing drugs like \(\beta\)-blockers can aggravate clinical status [12; 65]. Corticosteroids are metabolized by CYP3A4 and are also able to induce it, leading to other potential interactions [42] (Tables 4 and 5). Notably, ARDS can increase pulmonary capillary permeability, increasing the volume of distribution of water-soluble drugs, reducing their systemic action and concentration [109; 110]. Pregnancy is an unexplored special condition: guidelines recommend to not withhold the treatment of COVID-19 in pregnancy even if there are not data about it. Children have some different indications compared to adults. Mild or moderate disease can be treated with supportive care alone, whereas remdesivir is approved in hospitalized children aged \(\geq\)12 years with COVID-19 who have risk factors for severe disease and have an emergent or increasing need for supplemental oxygen, or in hospitalized children aged \(\geq\)16 years with COVID-19 who have an emergent or increasing need for supplemental oxygen, regardless of whether they have risks factors for severe disease, even though it may be considered in all the cases where oxygen is needed by the patient [4]. Dexamethasone can be used for patients who need HFNC, NIV, IV, and ECMO. There are insufficient data to recommend baricitinib, tocilizumab or monoclonal antibodies, whereas convalescent plasma and sarilumab are contraindicated outside clinical trials. In a MIS-C setting, intravenous immunoglobulin, corticosteroids and anti-IL-1 antibodies are the main therapeutic option [4]. A low number of clinical trials have been reported, so these scenarios need further analysis in order to assess the safety of the newer drugs [111]. Treating immunocompromised patients is a challenging task, especially because many of the COVID-19 medications could aggravate the vulnerability related to basal and chronic conditions like HIV, transplants, and the assumption of other immunosuppressiveant drugs. These patients often suffer from opportunistic infections and reductions in immunosuppression are often advocated by many clinicians [4; 64; 112]. Hepatotoxicity is another key point in the therapeutic management: favipiravir, remdesivir, tocilizumab and lopinavir can induce it [23], and the clinician should be careful in cases where the patient has impaired liver function, in liver transplant settings or where concomitant treatments like paracetamol have been administered. Paracetamol is commonly used in COVID-19 symptomatic treatment, but clinicians should always avoid the coadministration with hepatotoxic compounds. Favipiravir produce a modest increase in paracetamol levels [65]. Lopinavir/ritonavir and remdesivir can damage renal function [79], and other drugs should be administered evaluating eGFR like HCQ or CQ (excreted in urine or in bile) [23]. Even in a cardiovascular setting, some difficulties may arise: antiplateletts can interact with COVID-19 therapy; P2Y12 inhibitor levels can be boosted by protease inhibitors; ticagrelor levels can be increased, whereas clopidogrel antiplatelet activity seems strangely to diminish. Prasugrel is considered to be the best option when the coadministration with lopinavir/ritonavir is needed [12; 65].