Table 2.
The most important drugs used and/or tested in treating COVID-19[35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99]
| Drug | Rationale use for COVID-19 | Dosage | Conclusions |
|---|---|---|---|
| Antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ).[35,36,37,38,39] Used for treatment of malaria and autoimmune diseases (e.g., systemic lupus erythematosus and rheumatoid arthritis). No evidence of the efficacy in the prevention of COVID-19. They might block the production of pro-inflammatory cytokines (such as interleukin-6), thereby prevent ARDS. HCQ showed three times more potent than CQ in cytotoxic response and HCQ showed more efficacies in reducing viral nasopharyngeal carriage of SARS-CoV-2 in patients with COVID-19. | Have antiviral properties against various viruses, including coronaviruses. They intracellularly protonated and increase the pH of the cell, pH changes inhibit viral infusion with the cell membrane. They can also inhibit nucleic acid replication and appear to interfere with the terminal glycosylation of ACE2 receptor expression which prevents SARS-CoV-2 receptor binding and spread of infection. CQ has a potent cytotoxic response and inhibits viral replication. Used as a prophylactic as in-vivo models show high inhibition of viral spread before viral exposure | Oral; 500mg of QC phosphate (300mg QC) each time, 2 times/day; no more than 10 days and with a different regimen in several countries. Oral HCQ sulfate dosage used or being investigated in clinical trials: 400mg once or twice daily for 5-10 days. Oral HCQ sulfate with azithromycin (France): 200mg 3 times daily for 10 days with or without azithromycin (500mg on day 1, then 250mg once daily on days 2-5), FDA states that the dosage regimens of CQ and HCQ unlikely to have an antiviral effect in pts with COVID-19 based on a reassessment of in vitro EC50/EC90 data and calculated lung concentrations. | Efficacy and safety of CQ and HCQ for treatment or prevention of COVID-19 not established. No data to date indicating that in vitro activity against SARS-CoV-2 corresponds with clinical efficacy for treatment or prevention of COVID-19. QC suggested as a possible option and included in Chinese guidelines for the treatment of COVID-19. NIH COVID-19 Treatment Guidelines Panel recommends against the use of HCQ & CQ for the treatment of COVID-19. Emergency use authorization (EUA) for HCQ & CQ now revoked. Azithromycin has been recommended to use with HCQ to give a synergistic effect in treating COVID-19. |
| Data from a large, randomized, controlled trial showed no evidence of benefit in mortality or other outcomes such as hospital length of stay or need for mechanical ventilation for HCQ treatment in hospitalized patients with COVID-19. Only limited clinical trial data available to date to evaluate the use of HCQ & CQ for treatment or prevention of COVID-19. The majority of data to date involves use in pts with mild or moderate COVID-19; only limited clinical data on use in pts with the severe and critical disease. A small, randomized study in hospitalized adults in China compared CQ with lopinavir /ritonavir (Huang et al). Double-blind randomized phase 2b study in Brazil, (Borba et al). Many clinical trials of HQC were conducted in different countries as a single drug or combination and/or comparison of the other drugs. | |||
| Antiviral drugs: remdesivir[35,36,40,41,42]: Broad-spectrum antiviral (nucleotide analog prodrug) with activity against various viruses, including coronaviruses. Metabolize the cell and tissue to activate the nucleoside triphosphate (GS-443902) which inhibits the viral RNA-dependent RNA polymerases in the viral infectious cycle cascade. May also involve lethal mutagenesis and chain termination of the virus. Initially, it is developed for the treatment of Ebola hemorrhagic fever, but it has no approval until now for any indications. Many viruses have resistance to these agents to result in exo-ribonuclease proofreading and removal; Remdesivir has the potential to avoid this. Pharmacokinetic data were available from evaluations for Ebola. Multiple international clinical trials were conducted and ongoing, the safety and efficacy of remdesivir for the treatment of COVID-19 are not yet established | In vitro evidence of activity against SARS-CoV-2 in Vero E6 cells. In Rhesus macaques infected with SARS-CoV-2, treatment with a 6-day regimen of IV remdesivir initiated 12 hours after virus inoculation was associated with some benefits (lower disease severity scores, fewer pulmonary infiltrates, lower virus titers in bronchoalveolar lavage samples) compared with vehicle control; remdesivir. Treatment did not reduce viral loads or infectious virus titers in nose, throat, or rectal swabs compared with vehicle control. In vitro activity against SARS-CoV and MERS-CoV; active in animal models of SARS and MERS; prevented MERS in Rhesus macaques when given before infection and provided benefits when given after animal already infected. NIH panel states that data are insufficient to recommend for or against the use of remdesivir for the treatment of mild or moderate COVID-19. | Optimal dosage and duration of treatment not known. EUA recommended loading dose of 200mg by IV infusion on day 1, followed by maintenance doses of 100mg by IV infusion once daily from day 2 for adults and children weighing 40kg or more.; for children weighing 3.5 to less than 40kg; loading dose of 5 mg/kg by IV infusion on day 1, followed by maintenance doses of 2.5 mg/kg by IV infusion once daily from day 2. Optimal duration of treatment not known; but for pts requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days and for those not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days recommended. The recommended dose for another phase 3 clinical trials was 200mg IV on day 1, then 100mg IV daily on days 2-5 or 200mg IV on day 1, then 100mg IV daily on days 2-10. | Not commercially available; the most promising direct-acting antiviral (DAA) currently being investigated for COVID-19. Efficacy and safety of remdesivir for treatment of COVID-19 not established. FDA warns that concomitant use of remdesivir and CQ or HCQ is not recommended; there is in vitro evidence that CQ antagonizes intracellular metabolic activation and antiviral activity of remdesivir. In situations where remdesivir supplies are limited, the NIH COVID-19 Treatment Guidelines Panel recommends that remdesivir be prioritized for use in hospitalized patients with COVID-19 who require supplemental oxygen, but are not mechanically ventilated or on ECMO. NIH COVID-19 Treatment Guidelines Panel recommends the use of remdesivir for the treatment of severe COVID-19 in hospitalized patients who have oxygen saturation (SpO2) of 94% or lower on room air. |
| FDA issued a EUA on May 1, 2020, that permits the use of the drug for the treatment of COVID-19 only in hospitalized adults and children with suspected or laboratory-confirmed COVID19 who have severe disease. | |||
| HIV protease inhibitors [Lopinavir (LPV), Atazanavir (ATV), Darunavir (DRV), Nelfinavir (NFV), Saquinavir (SQV), and Tipranavir (TPV),[43,44,45,46,47,48,49]]. NIH COVID-19 Treatment Guidelines Panel and Infectious Diseases Society of America (IDSA) recommends against the use of LPV/RTV or other HIV protease inhibitors for the treatment of COVID-19, except in the context of a clinical trial. clinical trials to date using LPV/RTV have not shown a clinical benefit in patients with COVID-19. Multiple international clinical trials were conducted and ongoing for the use of Lopinavir and Ritonavir, LPV/RTV with ribavirin and interferon β1b vs LPV/RTV alone, LPV/ RTV with or without Umifenovir (Arbidol®) and LPV/RTV vs chloroquine, LPV/RTV vs hydroxychloroquine vs placebo, and DRV/ RTV in conjunction with chloroquine or oseltamivir) in treating the disease | LPV, NFV, SQV, and TPV: Some evidence of in vitro activity against SARS-CoV-2 in Vero E6 cells. LPV evidence also of in vitro activity against SARS-CoV-1 and MERS-CoV and some evidence of benefit in animal studies for the treatment of MERS-CoV. ATV: Some evidence that ATV alone or with ritonavir (ATV/RTV) has in vitro activity against SARS-CoV-2 in Vero E6 cells, human epithelial pulmonary cells (A549), and human monocyte. DRV: In one study, DRV with cobicistat had no in vitro activity against SARS-CoV-2 at clinically relevant concentrations in Caco-2 cells; in another study, high DRV concentrations were required for in vitro inhibition of SARS-CoV-2 in Vero E6 cells. LPV/RTV Clinical Experience (SARS and MERS): Evidence of some clinical benefit when used in conjunction with ribavirin and/or interferon. | Lopinavir/Ritonavir (LPV/RTV) oral; 200mg/50mg/capsule, 2 capsules each time, 2 times/day; no more than 10 days. Or LPV/RTV (COVID-19): LPV 400mg/ RTV 100mg orally twice daily for 10- 14 days. LPV 400mg/ RTV 100mg orally twice daily with or without Umifenovir (Arbidol® 200mg every 8 hours). LPV/RTV (COVID-19): LPV 400mg/ RTV 100mg orally twice daily for no longer than 10 days 13 with or without interferon (5 million units of interferon-α or equivalent twice daily given in 2 mL of sterile water by nebulization) and with or without ribavirin for up to 10 days. LPV/RTV (SARS): LPV 400mg/RTV 100mg orally twice daily for 14 days with ribavirin. LPV/RTV (MERS): LPV 400mg/RTV 100mg orally twice daily with ribavirin (various regimens) and/or interferon-α; LPV 400mg/RTV 100mg orally twice daily with interferon β1 b (0.25mg/mL sub-Q on alternate days) for 14 days | LPV/RTV: Efficacy for the treatment of COVID-19, with or without other antivirals, not established. Darunavir: Manufacturer states they have no clinical or pharmacologic evidence to support the use of DRV/cobicistat for treatment of COVID-19 and there are no published clinical studies that have evaluated efficacy and safety of DRV, DRV/cobicistat, or the fixed combination of DRV, cobicistat, emtricitabine, and tenofovir alafenamide for treatment of COVID-19. Besides, initial unpublished results from an open-label, controlled study in China indicated that a 5-day regimen of DRV/cobicistat was not effective for the treatment of COVID-19. Atazanavir, Nelfinavir, Saquinavir, Tipranavir: No data to date to support use in the treatment of COVID-19. Only limited data on LPV/RTV used with or without interferon in pts with COVID-19 outside of clinical trials. |
| Ribavirin[50,51,52]: a prodrug of purine nucleoside analog (mimic the purine analog guanosine in RNA); broad-spectrum antiviral. Inhibit RNA synthesis of viruses. associated with hemolytic anemia, especially after taking a high dose (1-2 gm), which is needed for coronaviruses treatment. Ribavirin is a teratogen; contraindicated in women who are pregnant and in male partners of those pregnant women. In combination with other immunosuppressive therapies; azathioprine or IFN can lead to severe side effects. | Structural elements prohibit the subsequent addition of nucleoside analogs, effectively stop the synthesis of RNA. Used to treat HCV, RSV, hepatitis C, B, and respiratory viruses. Usually used in combination therapy to treat MERS-CoV and HCoV-OC43. Ribavirin and INF-α combination therapy are efficient in treating MERS-CoV. Patients treated with lopinavir/ritonavir had a lower risk of SARS and death. More studies about. | Intravenous infusion; 500mg each time, 2 to 3 times/day in combination with IFN-α or lopinavir/ritonavir; no more than 10 days. Oral ribavirin has been dosed as a 4-gram loading dose followed by 1.2 grams every eight hours in two small studies for SARS. In the management of COVID-19, data is limited to ongoing studies using a dosing strategy of 400mg by mouth twice daily for 14 days as a part of a combination regimen. However, Ribavirin side effects like anemia and myelosuppression, myelotoxicity, and pancytopenia limited its use | No effect to use Ribavirin as monotherapy, but it gives potential activity when combined with other anti-viral agents such as Lopinavir/Ritonavir or chloroquine analogs. Patients SARS treated with lopinavir/ritonavir had better outcomes as compared to those given ribavirin alone; because Lopinavir works by inhibiting the decomposition of gag-pol protein, while ritonavir works by inhibiting the decomposition of gag-pol protein precursor and inhibiting lopinavir metabolism, thus increasing its concentration. |
| Neuraminidase inhibitors[53,54,55,56]: Oseltamivir; Antivirals active against influenza viruses. | Neither oseltamivir nor zanamivir has shown inhibition of cytopathic effect against SARS-CoV in vitro cell culture. | The dosage of oseltamivir was 75mg orally once or twice daily. Oseltamivir did not inhibit the replication of SARS-CoV-2 in infected Vero E6 cells in vitro. | Several clinical trials are currently looking at Oseltamivir in combination with other medications for coronavirus. |
| No data to date support use in the treatment of COVID-19. | |||
| Favipiravir[57,58,59,60,61]: RNA-dependent RNA polymerase (RdRP)] has anti-SARS-CoV-2 activity. Favipiravir found to help to clear the virus faster than lopinavir/ritonavir (4 days vs. 11 days, respectively). Favipiravir may be effective against SARS-CoV-2. Multiple clinical trials initiated in pts with COVID-19 in China, Japan, USA, and other countries to evaluate favipiravir alone or in conjunction with other antivirals or other agents. Only very limited clinical trial data available to date to evaluate the use of favipiravir in the treatment of COVID-19. Data needed to substantiate initial reports of efficacy for treatment of COVID-19 and identify optimal dosage and treatment duration. | Broad-spectrum antiviral with in vitro activity against various viruses, including coronaviruses. In vitro evidence of activity against SARS-CoV-2 in infected Vero E6 cells reported with high concentrations of the drug. Licensed in Japan and China for the treatment of influenza. Not commercially available in the US. Efficacy and safety of Favipiravir for treatment of COVID-19 not established. Favipiravir is contraindicated in women with known or suspected pregnancy and precautions should be taken to avoid pregnancy during treatment with the drug. If Favipiravir is used in pts receiving acetaminophen, the maximum recommended daily dosage of acetaminophen is 3 g. | Some of one ongoing trial dosage: 1600mg twice daily on day 1, then 600mg twice daily thereafter for 7–10 or 14 days was used in several open-label COVID-19 studies in adults and adolescents ≥16 years of age in China. Or 1600mg twice daily on day 1, then 600mg twice daily for 6 –13 days or 1800mg twice daily on day 1, then 800mg twice daily for 9 –13 days for treatment of COVID-19 in adults. Or of 1800mg twice daily on day 1, followed by 800mg twice daily on days 2–10 for early treatment of suspected or confirmed COVID-19 in adults. Specifies a Favipiravir dosage of 1800mg twice daily on day 1, then 1000mg twice daily on days 2–14 for treatment of COVID-19 in adults. | Given the lack of pharmacokinetic and safety data for the high Favipiravir dosages proposed for the treatment of COVID19, the drug should be used with caution at such dosages. Favipiravir is associated with QT prolongation. Some have suggested close cardiac and hepatic monitoring during treatment, as well as monitoring of plasma and tissue concentrations of the drug and, if possible, the active metabolite. Some data suggest that favipiravir exposure may be greater in Asian populations. Early embryonic deaths and teratogenicity observed in animal studies. There are different dosage regimens in other trials. |
| Umifenovir (Arbidol®)[53,54,55,56]: Used to treat influenza. Broad-spectrum antiviral with in vitro activity against various viruses, including coronaviruses. inhibit SARS-CoV-2 in vitro | Although data limited, in vitro activity against SARS-CoV-1 and SARS-CoV-2 reported. Licensed in China, Russia, Ukraine, and possibly other countries for prophylaxis and treatment of influenza | Dosage recommended for treatment of COVID-19 in China: Adults, 200mg orally 3 times daily for no more than 10 days | Not commercially available in the US. Included in some guidelines for the treatment of COVID-19. Efficacy for the treatment of COVID-19 not established. |
| Baloxavir[62,63,64], only limited clinical trial data available to date to evaluate the use of Baloxavir for treatment of COVID-19 | Antiviral active against influenza viruses In vitro antiviral activity against SARS-CoV-2 shown in one trial. | Chinese trials specify an oral dosage of 80mg on day 1 and day 4, and another dose of 80mg on day 7 (as needed); not to exceed 3 total doses | No data to date support use in the treatment of COVID-19. Favipiravir was not good in helping patients recover, but, was better than Lopinavir/Ritonavir in clear the virus. |
| Galidesivir[53,54,55,56] : Used to treat influenza. | the new drug that is currently being developed for a variety of viral infections | Optimal dosage and duration of treatment not known | Not yet been approved for human use. Clinical trials are starting in Brazil |
| More evidence is needed before these drugs are recommended according to the National Health Commission (NHC) of China for provisional treatment of COVID-19 | |||
| Immunosuppressive Drugs Tocilizumab[34,65,66]: Used for the treatment of rheumatoid arthritis. Tocilizumab added to Lopinavir, methylprednisolone, and oxygen therapy in 20 patients with severe COVID-19 resulted in rapid reductions in fever in all patients, improvement in oxygenation for 75%, and facilitated discharged from the hospital in 95% of patients. | Recombinant humanized monoclonal antibody specific for the interleukin-6 (IL6) receptor; IL-6 is a proinflammatory cytokine. Tocilizumab may potentially combat cytokine release syndrome (CRS) and pulmonary symptoms in severely ill patients with COVID-19. The dosing of tocilizumab for COVID-19 is still not well established. intravenous tocilizumab 400mg. | Tocilizumab is typically given IV to treat cytokine release syndrome (CRS) and in patients with COVID-19; however, the drug has been given subcutaneously in some patients. China recommends an initial dose of 4–8 mg/kg IV infused over more than 60 minutes. If the initial dose not effective may administer the second dose (in the same dosage as the initial dose) after 12 hours. No more than 2 doses should be given; the maximum single dose is 800mg, maximum dose of 800mg. | In China, tocilizumab can be used to treat severely or critically ill patients with COVID-19 with extensive lung lesions and high IL-6 levels 2 NIH COVID-19. Treatment Guidelines Panel states that there are insufficient clinical data to recommend either for or against the use of tocilizumab in the treatment of COVID-1. The role of routine cytokine measurements (e.g., IL-6, CRP) in determining the severity of and treating COVID-19 requires further study. |
| Ruxolitinib[67,68,69,70]: Antineoplastic Agents; Janus kinase (JAK) 1 and 2 inhibitor; may potentially combat cytokine release syndrome (CRS) in severely ill patients. Limited published clinical trial evidence regarding efficacy and safety in patients with COVID-19. | Ability to inhibit a variety of proinflammatory cytokines, including interferon, has been raised as a possible concern with the use of JAK inhibitors in the management of hyper inflammation resulting from viral infections such as COVID19. Compassionate use of Ruxolitinib in combination with Eculizumab | Various dosages are being evaluated.; for example, 5 mg twice daily for 14 days with possible extension to 28 days and 5 or 15mg twice daily (approximately every 12 hours). Severe reactions observed in some patients with COVID-19 following initiation of ruxolitinib. Multiple international clinical trials were conducted and ongoing, for the treatment of COVID-19 | NIH COVID-19 Treatment Guidelines Panel recommends against the use of JAK inhibitors for the treatment of COVID19 except in the context of a clinical trial; the panel states that at present the broad immunosuppressive effect of JAK inhibitors outweighs the potential for benefit. |
| Baricitinib[71,72,73]: Antirheumatic Drug; Janus kinase (JAK) 1 and 2 inhibitors; disrupts regulators of endocytosis (AP2- associated protein kinase 1 [AAK1] and cyclin G associated kinase [GAK]), which may help reduce viral entry and inflammation; also may interfere with intracellular virus particle assembly. Currently, no known published controlled clinical trial evidence supporting efficacy or safety in patients with COVID-19 | Inhibits JAK1 and JAK2- mediated cytokine release; may combat cytokine release syndrome (CRS) in severely ill patients. Ability to inhibit a variety of proinflammatory cytokines, including interferon, has been raised as a possible concern with the use of JAK inhibitors in the management of hyper inflammation resulting from viral infections such as COVID-19. | Therapeutic dosages of Baricitinib (2 or 4 mg orally once daily) are sufficient to inhibit AAK1. Dosage information is not yet available. NIH COVID-19 Treatment Guidelines Panel recommends dosage adjustment if Baricitinib is administered concurrently with a strong OAT3 inhibitor. Not recommended in patients with severe hepatic or renal impairment | Minimal interaction with CYP enzymes and drug transporters and low protein binding of Baricitinib allow for combined use with antiviral agents and many other drugs. NIH COVID-19 Treatment Guidelines Panel recommends against the use of JAK inhibitors for the treatment of COVID19 except in the context of a clinical trial. |
| Anakinra[74,75,76,77,78]; Antirheumatic Drug; Recombinant human interleukin-1 (IL-1) receptor antagonist. IL-1 levels are elevated in patients with COVID-19; anakinra may potentially combat cytokine release syndrome (CRS) symptoms in severely ill patients with COVID-19. Currently, no known published prospective clinical trial evidence supporting the efficacy or safety of anakinra for the treatment of COVID19. Encouraging preliminary results reported in China with another disease-modifying antirheumatic drug, tocilizumab. | Anakinra has been used off -label for severe chimeric antigen receptor T cell (CAR T-cell)-mediated cytokine release syndrome (CRS) and macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis. IL-1 levels are elevated in patients with these conditions. Case reports and series describe a favorable response to anakinra in these syndromes, including survival benefit in sepsis and reversing cytokine storm in adults with MAS after tocilizumab failure. | Various dosage regimens are being studied. Trial protocol in Italy (COVID-19 with hyper inflammation and respiratory distress): 100mg by IV infusion every 6 hours (total of 400mg daily) for 15 days. Some studies underway in Europe are evaluating 100mg given subcutaneously once daily for 10 or 28 days, respectively, or until hospital discharge. Anakinra is approved only for subcutaneous administration in the U.S. Numerous other clinical trials evaluating anakinra in the treatment of COVID-19 are planned or underway, mainly in Europe | NIH COVID-19 Treatment Guidelines Panel states that there are insufficient clinical data to recommend either for or against the use of anakinra in the treatment of COVID-19. Safety profile: Well established in adults with sepsis and has been studied extensively in severely ill pediatric patients with complications of rheumatologic conditions; pediatric data on use in acute respiratory distress syndrome/ sepsis are limited. Pregnancy: Limited evidence to date: unintentional first-trimester exposure considered unlikely to be harmful. |
| Sarilumab[78,79,80]: Antirheumatic Drug; based on encouraging results in China with a similar drug, tocilizumab, a large, U.S.-based, phase 2/3, randomized, double-blind, placebo-controlled, and adaptively designed study evaluating efficacy and safety of sarilumab in patients hospitalized with severe COVID-19 | Recombinant humanized monoclonal antibody specific for the interleukin-6 (IL-6) receptor; IL-6 is a proinflammatory cytokine. Sarilumab may potentially combat cytokine release syndrome (CRS) and pulmonary symptoms in severely ill patients. | Dosage of 400mg IV as a single dose or multiple doses (based on protocol criteria); the lower-dose (200-mg) treatment arm was discontinued following a preliminary analysis of study results. Multiple clinical trials to evaluate sarilumab for treatment of COVID-19 are registered at clinicaltrials.gov. | Currently, no known published clinical trial evidence supporting efficacy or safety in the treatment of COVID-19. NIH COVID-19 Treatment Guidelines Panel states that there are insufficient clinical data to recommend either for or against the use of sarilumab in the treatment of COVID-19. No new safety findings observed with use in patients with COVID-19. |
| Interferons (IFNs)[81,82,83,84]; Antineoplastic Agents and Immunomodulatory Agents. An endogenous protein released by the host cell in action of inflammation and infection. It stimulates the immune response against viral replication. INF-α broad-spectrum antiviral that is used in many viral infections. IFN-α and IFN-β are active in vitro against SARS -C0V-2 in Vero cells at clinically relevant concentrations; 1 in vitro study suggests SARS-CoV-2 is more sensitive than SARS-CoV-1 to IFN-α. lack of clinical benefit observed with the use of type 1 IFNs, generally in combination with ribavirin, for treatment of SARS and MERS. | In vitro studies indicate only weak induction of IFN following SARS-CoV-2 infection, and a possible role for IFNs in prophylaxis or early treatment of COVID19 has been suggested to compensate for possibly insufficient endogenous IFN production. IFN-α and IFN-β are active in vitro against MERS-CoV in Vero and LLCMK2 cells and rhesus macaque model of MERS-CoV infection; type I IFNs also active in vitro against SARS-CoV-1 in Vero, fRhK-4, and human cell lines; IFN-β is more active than IFN- α in vitro against SARS-CoV-1 and MERS-CoV. Efficacy and safety of IFNs for treatment or prevention of COVID-19 not established. | Various sub-Q dosages of IFN beta-1a and IFN beta-1b are being evaluated for the treatment of COVID -19. Chinese guidelines suggest IFN alfa dosage of 5 million units (or equivalent) twice daily via atomization inhalation for the treatment of COVID-19. IV IFN beta-1a did not reduce ventilator dependence or mortality in a placebo-controlled trial in patients with ARDS. IFN lambda is thought to provide important immunologic defense against respiratory viral infections. and may have less potential than type 1 IFNs to produce a systemic inflammatory response, including inflammatory effects on the respiratory tract; | NIH COVID-19 Treatment Guidelines Panel recommends against the use of IFNs for treatment of COVID-19, except in the context of a clinical trial, because no benefit was observed with the use of IFNs for treatment of other coronavirus infections (SARS, MERS), clinical trial results for treatment of COVID-19 are lacking, and toxicity of IFNs outweighs the potential for benefit. Interferon alfa via atomization inhalation is included in Chinese guidelines as a possible option for the treatment of COVID-19. Surviving Sepsis Campaign COVID-19 subcommittee states that there is insufficient evidence to issue a recommendation on the use of interferons, alone or in combination with antivirals, in critically ill adults with COVID-19. |
| COVID-19 Convalescent Plasma[85,86,87,88,89,90,91]; Plasma obtained from patients who have recovered from COVID-19 (i.e., COVID-19 convalescent plasma) that contains antibodies against SARS-CoV-2 may provide short-term passive immunity to the virus; theoretically, such immunity may prevent or contribute to recovery from the infection, possibly as the result of viral neutralization and/or other mechanisms. Efficacy and safety of COVID-19 convalescent plasma for the treatment of COVID-19 not established. Theoretically, convalescent plasma should be more effective if given during the early course of the disease. Logistics of obtaining, processing, storing, and distributing COVID-19 convalescent plasma evolving. FDA does not collect COVID-19 convalescent plasma and does not provide such plasma; healthcare providers and acute care facilities obtain COVID-19 convalescent plasma from FDA-registered establishments. | Convalescent plasma therapy has been used in the treatment of other viral diseases with various degrees of success. In patients with SARS-CoV1 infection, the use of convalescent plasma was reported to shorten the duration of hospitalization and decrease mortality. SARS patients who received convalescent plasma less than 14 days after onset of symptoms had better outcomes than those who received such plasma later in the course of the disease. Appropriate criteria for selection of patients to receive investigational convalescent plasma, an optimal time during the disease to receive such therapy, and appropriate dosage (e.g., volume, number of doses) not determined. Convalescent plasma is regulated as an investigational product. FDA guidance suggests that convalescent plasma be collected from individuals with laboratory-confirmed COVID-19 infection and complete resolution of symptoms for at least 14 days before donation. | Analysis of key safety indicators in 5000 adults who participated in a US FDA Expanded Access Program suggests that IV transfusion of COVID-19 convalescent plasma is safe in hospitalized patients with COVID -19; 31 however, potential risks associated with COVID-19 convalescent plasma therapy (e.g., the inadvertent transmission of other infectious agents, allergic reactions, thrombotic complications, transfusion-associated circulatory overload, transfusion-related acute lung injury [TRALI], antibody-dependent enhancement of infection) and steps to mitigate such risks not fully determined and require further evaluation. Although there is some evidence suggesting possible benefits of convalescent plasma in patients with COVID-19, available data to date are largely from case reports or series; confirmation from additional randomized controlled studies is required. There are no convalescent blood products currently licensed by the FDA. | NIH COVID-19 Treatment Guidelines Panel states that there are insufficient data to recommend for or against the use of convalescent plasma in pts with COVID-19. The Surviving Sepsis Campaign COVID19 subcommittee suggests that convalescent plasma not be used routinely in critically ill adults with COVID-19 because efficacy and safety not established and uncertainty surrounding optimal preparation of convalescent plasma. Optimal timing of donor plasma collection with recovery from COVID19, most appropriate methods of antibody testing, and minimum titers of SARS-CoV-2 antibody in convalescent plasma that may be associated with clinical benefits in pts with COVID-19 not determined. FDA issued a guidance for industry to provide recommendations to healthcare providers and investigators regarding administration and study of investigational COVID-19 convalescent plasma. Donation of the convalescent plasma guidelines and protocols should be followed. |
| Corticosteroids[26,92,93,94,95,96,97,98]; Patients with severe COVID-19 develop a systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction. It has been proposed that the potent anti-inflammatory effects of corticosteroids might prevent or mitigate these harmful effects. different factors to consider in giving dexamethasone to patients with COVID-19 which include; review the patient’s medical history and assess the potential risks and benefits of administering corticosteroids, monitor patients with COVID-19 for adverse effects (e.g., hyperglycemia, secondary infections) after administration dexamethasone, and review a patient’s medication regimens to assess potential interactions as dexamethasone is a CYP3A4 inducer. When stopping corticosteroids taper down the dose, and monitor the recurrence of inflammation and the signs of adrenal insufficiency. | Inhaled corticosteroids may mitigate local inflammation and inhibit virus proliferation. There are currently no published studies specifically evaluating the use of inhaled corticosteroids in patients with COVID-19. A small case series from Japan observed possible clinical benefit in 3 patients with mild to moderate COVID-19 pneumonia following oral inhalation of ciclesonide; however, without a control group, it is not known whether the patients would have improved spontaneously. Adjunctive therapies for COVID-19, in the case of asthma exacerbation or COPD and septic shock, otherwise, it should be avoided due to the lack of effectiveness and possible harm including avascular necrosis, psychosis, diabetes, and delayed viral clearance; in addition to, higher risk of mortality and secondary infections. It isn’t recommended using dexamethasone in patients with COVID-19 who do not require supplemental oxygen (AI). | The initial dosage of orally inhaled ciclesonide used in the published case series from Japan of 3 patients with COVID-19 pneumonia was 200 mcg 2 times daily. If necessary, the dosage was increased to 400 mcg 3 times daily. The authors suggested continued use of ciclesonide oral inhalation for about 14 days or longer. Clinical trials evaluating the use of inhaled corticosteroids (e.g., budesonide, ciclesonide) in patients with COVID-19 are being planned or underway, including the following trials registered at clinicaltrials.gov. recommended of dexamethasone is 6 mg per day for up to 10 days; in patients with COVID-19 who are mechanically ventilated (AI) and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated (BI). | NIH COVID-19 Treatment Guidelines Panel recommends that inhaled corticosteroids used daily for the management of asthma and COPD to control airway inflammation should not be discontinued in patients with COVID-19. The panel also states that no studies to date have investigated the relationship between inhaled corticosteroids in these clinical settings and virus acquisition, the severity of illness, or viral transmission. Currently, there is no clinical evidence supporting adverse or beneficial effects of premorbid use or continued administration of inhaled corticosteroids in patients with acute respiratory infections due to coronaviruses. Randomized controlled clinical studies are needed to assess the benefits of inhaled corticosteroids for the treatment of COVID-19 in patients with and without chronic respiratory conditions. |
| Miscellaneous Drugs[99,100,101]; In vitro study found that ivermectin can stop SARS-CoV-2 from replicating. Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum antiviral activity in vitro. It inhibited the causative virus (SARS-CoV-2), as the single addition of the drug to Vero-hSLAM cells 2 h post-infection with SARS-CoV-2 reduces the virus by about 5000-fold within 48h. Ivermectin, therefore, warrants further investigation for possible benefits in humans, and a lot more research is needed to see if the doses studied would be safe and effective against the virus in humans.[63] Researchers think that colchicine could work similarly to tocilizumab in patients with COVID-19 in that it might be helpful if the immune system becomes too activated and a cytokine storm occurs. A large clinical trial is currently running to see if colchicine; when given soon after a COVID-19 diagnosis, can lower the chances of hospitalization and death. One research investigated azithromycin in combination with hydroxychloroquine for COVID-19. They reported that 93% of patients cleared the virus after 8 days, but there was no control group; so we don’t know if people would have cleared the virus on their own or due to the medications. There are also concerns about potentially serious side effects; when using azithromycin and HCQ. | |||
The optimal management of COVID-19 is evolving and updated quickly. However, many drugs are being under clinical trials to find drugs that are effective against the virus.