Table 1.

Summary of investigational treatments by COVD-19 effect.

Agent	Effect	Dosing	Stage	Mechanism	Commentary
Remdesivir	AV	•200 mg IV × 1, followed by 100 mg qd for 5–10 days	I–III	•RNA polymerase inhibitor (26)	•Adverse effects include elevated ALT and AST, phlebitis, constipation, headache, nausea. •Theoretical risk of renal injury. •Should not be used in pregnancy due to lack of data. •Has limited drug-drug interactions (no significant CYP effect) •Clinical trials underway in the US, UK, and China •Showed efficacy in COVID-19 treatment (27)
Lopinavir/Ritonavir	AV	•200 mg/50 mg/capsule, 2 capsules PO bid for no more than 10–14 days	I–III	•Protease inhibitor (28)	•Nearly 14% of patients cannot complete a course due to GI side effects (29). •Ritonavir is a potent CYP3A4 inhibitor (interacting with Rx such as apixaban, tacrolimus, and amiodarone). •In rare cases, Lopinavir/Ritonavir can cause liver injury, pancreatitis, and cardiac toxicity. •Treatment in mostly Stage II–III patients was not found to be superior to standard of care. Subgroup analysis suggestive that earlier treatment (Stage I) might be beneficial (28)
Favipiravir	AV	•1,600 mg PO bid x1d, then 600 mg PO bid for up to 14 days	I–III	•Broad spectrum inhibitor of RNA-dependent RNA polymerase (30, 31)	•Increases liver function parameters (AST, ALT, and total bilirubin) •Testis toxicity and has a risk for teratogenicity and embryotoxicity •Was found to be superior to Lopinavir/Ritonavir in a small controlled study (32)
Umifenovir	AV	•200 mg q8h for up to 14 days	I–III	•S protein/ACE-2 membrane fusion inhibitor (33)	•Metabolism by CYP3A4. Caution with strong inhibitors or inducers. •Hypersensitivity risk increases in children under 2 years of age •Limited clinical evidence shows promise in COVID-19 (34)
Hydroxychloroquine	AV A-IN	•Stage I–II −400 mg PO bid for first day followed by 200 mg bid daily for 5 days (35, 36) •Stage III—May consider extending treatment (200 mg bid) for up to 14 days (35)	I–III	•AV: replication-neutralization of the pH cellular organelles for gene replication •A-IN: inhibition of macrophage activation and reducing release of tissue TNF-a, IL-1, IL-6 (37–39) •A-IN: interfere with lysosomal activity and autophagy, disrupt membrane stability, alter signaling, and transcriptional activity, which can then inhibit immune activation and cytokine production (38)	•Adverse effects include: rash, nausea, and diarrhea. GI symptoms can be mitigated by taking with water; use with caution in diabetic patients may cause hypoglycemia (40) •Increased risk of retinopathy with a recommended maximal daily dose of 5.0 mg/kg. Avoid if history of retinal disease, macular degeneration, or previous treatment with tamoxifen (41) •Caution in patient at risk for QT prolongation. EKG at baseline and following initiation is generally advised, particularly in critically ill patients. •Contraindicated with Epilepsy, Porphyria, G6PD, and Myasthenia Gravis •Not proven effective for Pre-Exposure/Post-Exposure prophylaxis. IDS recommends for patients hospitalized with Pneumonia, as part of a clinical trial (29) •No definitive evidence from randomized controlled trials that it is effective (29)
Chloroquine	AV A-IN	•Stage I–II −500 mg bid for 5 days •Stage III—may consider extending treatment for up to 10 days	I–III	•A-IN: decrease secretion and/or receptor expression of cytokines such as TNF-a (39, 42) •Interfere with lysosomal activity and autophagy, similar to Hydroxychrloroquine (38)	•Has greater adverse event profile than Hydroxychloroquine and possibly less efficacy. Most common symptoms include abdominal cramps, nausea, anorexia. •Can increase QTc and result in hematologic effects (including hemolysis with G6PD deficiency). Can cause retinal toxicity and hypoglycemia. •As with Hydroxychloroquine, additional clinical trial data is necessary to determine efficacy and safety in COVID-19 patients (43). •No definitive evidence from randomized controlled trials that it is effective
Ivermectin	AV	•45–64 kg: 9 mg orally single dose •65–84 kg: 12 mg single dose •85 kg or more: 0.15 mg/kg orally single dose	I–II	•Broad-spectrum antiviral activity in vitro through inhibition of nuclear import of host and RNA viral proteins (44)	•May consider prophylactic use of Ivermectin in patients on corticosteroids who have high risk of Strongyloides hyperinfection •Possible considerations as adjunct therapy or replacement when other agents contraindicated •Contraindicated in Pregnancy
Ribavirin	AV	•IV 500 mg each time, bid or tid, no more than 10 days	II–III	•Inhibits viral RNA dependent RNA polymerase	•Can cause birth defects or death in an unborn baby (45) •Hematologic toxicity is observed in dose-dependent fashion. •Caution when used with azathioprine or HIV/AIDS medicines •Ribavirin is likely not effective when used alone and must be used in combination with IFN-α or lopinavir/ritonavir
Convalescent plasma donor containing SARS-CoV-2–specific antibody (IgG)	AV A-IN	•200–250 mL of ABO-compatible convalescent plasma × 2 (achieving 400 mL in total) on the same day it was obtained from the donor	I–III	•Neutralizing activity against SARS-CoV-2	•Allergic transfusion reactions •Likely most beneficial in early disease course (e.g., Stage I or Stage II), as its mechanism of action is to neutralize viral particles (46)
Azithromycin	A-IN	•500 mg qd × 1, then 250 mg bid for 4 days	II–III	•Inhibits RNA-dependent protein synthesis •Multiple immunomodulatory effects (47)	•Previous studies have shown some efficacy against viruses such as Influenza, Ebola, RSV, and Rhinovirus (48) •May confer benefit when added to Hydroxychloroquine (36, 49) •Should be used if superimposed bacterial Pneumonia. •Does increase QT interval, especially when added to Hydroxychloroquine. An EKG is recommended prior to start (and EKG or telemetry monitoring while on Tx is recommended) (50)
Doxycycline and other Tetracyclines	A-IN	•200 mg qd × 1, then 100 mg qd for 4 days. May consider extending treatment for up to 14 days	II–III	•Downregulation of NFkB pathway as well as TNFa, IL-1B and IL-6 •Possible inhibition of RNA replication (51)	•May confer benefit when added to Hydroxychloroquine. •Should be used if superimposed bacterial Pneumonia
Prednisone Methylprednisolone Dexamethasone Hydrocortisone	CS	•40–60 mg prednisone PO or 30–60 mg methylprednisolone IV, or 5–10 mg dexamethasone IV qd for up to 7 days •50 mg hydrocortisone IV q6H until improvement in shock	II–III	•Multiple immunomodulatory effects, including suppression of PMN migration and reversal of increased capillary permeability (52)	•Should not be used in Stage I (unless another indication) as it may increase viral load (53) •Indicated for asthma or COPD exacerbation or any shock with a history of chronic steroid use in excess of 10 mg prednisone daily. Also used for multipressor (>2 pressor) shock. •Use in patients with hypoxemia may confer a mortality benefit. If ARDS, higher doses may be required (54, 55)
Tocilizumab and other IL-6 inhibitors	A-IN	•4–8 mg/kg IV (usually 400 mg) × 1 dose. If inadequate response, may repeat one time after 12 h (56)	IIb–III	•Inhibits inflammatory cytokine storm •Inhibits IL-6 and signal transduction of RNA viruses but not of DNA viruses (57)	•Side effects include upper respiratory tract infections, mild stomach cramps. •Black box warning for a risk of serious infections, including tuberculosis and other opportunistic infections. Patients treated with this medication should be tested for latent tuberculosis prior to discharge from the hospital •Caution in neutropenia or thrombocytopenia •May interact with cholesterol-lowering medications, seizure medications, heart rhythm medications •May be beneficial for use in Cytokine Activation Syndrome (58)
IFN-α and other Type 1 Interferons	AV A-IN	•5 million U or equivalent dose each time, 2 times/day for Vapor inhalation	IIb–III	•Interfere with viral replication •Slowdown of cell metabolism and secretion of cytokines	•Inhalation pharmacodynamics and pharmacokinetics have never been assessed. •IV and SC modes of administration are well-described and proven safe in several clinical trials (under expert use), with similar pharmacodynamics and pharmacokinetics (59)
Prazosin and other alpha-1 adrenergic receptor (AR) antagonists	A-IN	•1 mg bid or tid, titrating up as tolerated	I–III	•Reduces catecholamine and cytokine response through alpha-1 AR antagonism	•Contraindicated if hypotension. •No current evidence for starting the Rx if patient is not already on it. A recent retrospective review found that patients previously treated with alpha-1AR antagonists had improved end points (60)
Atorvastatin and other Statins	A-IN	•Atorvastatin 40 mg qhs	I–III	Pleiotropic effects, anti-inflammatory	•If there is an indication for a statin, the statin should be started or continued (15)
Baricitinib	A-IN AV?	•Eli Lilly and National Institute for Allergies and Infectious Diseases (NIAID) announced that the drug will begin its first large randomized trial in COVID-19 patients, in late April in the U.S., and additional sites in Asia/Europe (61)	IIb–III	•JAK1/JAK2 inhibitor •Theoretic (but proven) antiviral properties	•FDA approved for treatment of rheumatoid arthritis. •Side effects include upper respiratory tract infection and reactive of herpes simplex and herpes zoster. •Black box warning for serious infections including TB. Patients must be tested for TB prior to starting treatment. •Increase risk of malignancy (including Lymphoma), and thromboembolism (61)
Colchicine	A-IN	•1.5 mg loading dose + 0.5 mg after 60 min, and then 0.5 mg bid for up to 3 weeks (62)	I–II	•Anti-inflammatory, through a variety of mechanisms including inhibition of neutrophil chemotaxis and IL-1 activation	•FDA approved for the treatment of gout and familial Mediterranean fever •Most common adverse effects are abdominal pain and diarrhea. •Adequate cardiovascular safety profile
Heparin, Enoxaparin, and other Anticoagulants	AC	•DVT Prophylaxis Dosing (e.g., Enoxaparin 40 mg SC qd, or Heparin 5000 SC tid) •Full anticoagulation—individualize to patient	II–III	Tissue factor pathway inhibition (54)	•Indicated as DVT prophylaxis for all hospitalized patients (Stage II) without contraindication for anticoagulation. •Full anticoagulation may be beneficial in Stage III, as it has shown benefit for those suffering from sepsis associated coagulopathy, ARDS, or D-Dimer levels >6-fold the upper limit of normal (54)

AV, Antiviral; A-IN, Anti-inflammatory; CS, Corticosteroid; AC, Anti-coagulant.

^*None of these Rx are considered standard of care for treatment of COVID-19, and ideally should be used as part of a clinical trial. Moreover, this table is not meant to be a comprehensive review of adverse effects and drug-drug interactions. Treatment must be individualized to the patient, considering the patient's age, comorbidities, clinical course, drug interactions, and hypersensitivities. Lastly, this table is meant to be updated as new evidence (and perhaps new agents or classes of agents) is presented.