Treatments of Interest for COVID-19

The chart below provides information or resources on pharmacotherapy of interest for COVID-19, the disease caused by the SARS-CoV-2 virus. Additional resources on pharmacotherapy, which are frequently updated, include:

At this point, no pharmacotherapy has been proven effective for COVID-19, so treatment is largely supportive. Resources pertinent to supportive therapy include:

Our chart, COVID Pharmacotherapy FAQs: Addressing Patient Questions, provides information to help answer and correct misconceptions about pharmacotherapy as it relates to COVID-19.

**Search for the latest information on COVID-19 clinical trials.**



Pertinent Information or Resources

Note that DOSES provided are examples only for ADULTS; the optimal dose has not been determined for any treatment.

Anakinra (Kineret)

Anakinra is an IL-1 antagonist. IL-1 may have a role in ARDS.65

Anakinra 5 mg/kg twice daily intravenously in moderate to severe ARDS (non-ventilator) and inflammation (elevated C-reactive protein and/or ferritin) (n=29) was associated with improved survival compared to a similar historical cohort (90% vs 56%, p = 0.009).65 These patients also received hydroxychloroquine and lopinavir/ritonavir.65 A lower dose of anakinra (100 mg twice daily subcutaneously) did not seem to provide benefit.65

Preliminary evidence from case reports suggest benefit in patients with severe COVID-19 and secondary hemophagocytic lymphohistiocytosis.19

See for ongoing studies.


Macrolides have in vitro antiviral (e.g., Zika, Ebola), anti-inflammatory, and immunomodulatory activity.2,7

Insufficient evidence to support widespread use [Evidence level C].2,28

Was used in a small, widely publicized study with hydroxychloroquine in six patients to prevent bacterial superinfection in COVID-19 patients (see hydroxychloroquine, below).2 Subsequent observational data including 74 additional patients suggests that the combination can reduce viral load and perhaps improve the clinical course, but there was no comparator group.28 Also see the hydroxychloroquine section below for information on its use in a U.S. cohort study.75

NIH guidelines recommend against the use of azithromycin plus hydroxychloroquine outside of a clinical trial.50 See for the latest information on these studies.

When used with hydroxychloroquine or chloroquine (and other QT prolonging medications), QT prolongation is of increased concern.2,6


Investigational synthetic form of vasoactive intestinal polypeptide hypothesized to protect alveolar type 2 cells from viral injury.85

In an unpublished case-control study (n=51), treated patients had better survival and clinical improvement. Side effects include hypotension and diarrhea. Based on data from this study, the manufacturer has applied for an EUA for aviptadil.

Aviptadil is currently being studied for COVID-19 respiratory failure (Intravenous Aviptadil for Critical COVID-19 with Respiratory Failure [COVID-AIV)], NCT04311697). See

Aviptadil is also available through an Expanded Access protocol. For more information, see

Baloxavir (Xofluza)

No COVID-19 data.

Chloroquine phosphate*

*Chloroquine phosphate
500 mg = chloroquine base 300 mg6

Inhibits SARS-CoV-2 in vitro, but clinical trials have not shown benefit against other viruses.5 Also has immunomodulating effects.26 Early reports suggested that for COVID-19 pneumonia, it could speed clinical improvement and viral clearance.3

The FDA has revoked its EUA for chloroquine because it is unlikely to be effective, based on data from the EUA and elsewhere.73 In addition to efficacy concerns, the FDA’s revocation of its EUA for chloroquine was based on adverse effects; its known and potential benefits no longer outweigh the known and potential side effects (e.g., serious cardiac events and other serious side effects).33

The FDA recommends against chloroquine use for COVID-19 outside of a clinical trial.33 NIH guidance recommends against use of chloroquine for treatment of COVID-19 in hospitalized patients.50 It also recommends against use in nonhospitalized patients, except in a clinical trial.50

Clinical trials are planned on the use of chloroquine to prevent COVID-19 in healthcare workers. See

A Brazilian study of chloroquine phosphate 600 mg twice daily vs 450 mg twice daily stopped the high-dose arm due to higher instance of QT prolongation >500 milliseconds (18.9% vs 11.1%) and mortality (39% vs 15%).41 All patients received azithromycin.41 NIH guidance recommends against using high-dose chloroquine (600 mg twice daily for 10 days) for treatment of COVID-19.50

When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.2,4,6


Based on its anti-inflammatory effect, there is interest in using colchicine to alter the clinical course of COVID-19 in both inpatients and higher-risk outpatients.

The open-label GRECCO-19 study randomized patients to colchicine plus standard care or standard care (n = 105). The clinical primary endpoint, which included measurements of inflammation and clinical deterioration, occurred in 14% of the control group vs 1.8% in the colchicine group (p=0.02).9 This study’s findings are considered “hypothesis-generating” only.9

Additional clinical trials are underway. See for more information.

Keep in mind colchicine’s toxicities and drug interactions. See our chart, Colchicine Dosing and Interactions, for details.

Convalescent Plasma (COVID-19)

Small case series in patients hospitalized with severe COVID-19 show promise (e.g., defervescence, radiographic improvement, improved oxygen support requirements, viral clearance, improved clinical condition).62-64 It appears well-tolerated.62-64 Concerns include allergic reactions, fluid overload, transfusion-related lung injury, and viral infections.70 Risks do not appear different from other types of plasma.83,86

Unpublished data from the Mayo Clinic-led expanded access program (n=35,322) found a seven-day mortality rate of 8.7% in patients who received convalescent plasma within three days of diagnosis vs 11.9% in those who received it later (p<0.001). Thirty-day mortality was 21.6% vs 26.7% (p<0.0001). There seemed to be a dose-response relationship between the antibody levels in the transfused plasma and mortality reduction. Unadjusted seven-day mortality was 8.9% in the high titer group and 13.7% in the low titer group (p =0.048; relative reduction 35%). After adjusting for confounding, mortality benefit approached non-significance. About half of the 35,322 patients were in critical care units and 27.5% were receiving mechanical ventilation at the time of transfusion.69 In non-ventilator patients <80 years of age (n=1,018) who received high-titer plasma within three days, relative mortality reduction was 37% (p=0.03).18 It is important to note that this study was not designed to compare efficacy of convalescent plasma to that of standard therapy; goals were to assess safety and to identify signals of efficacy.69 Differences in outcome could be due to harm from low-titer plasma rather than benefit from high-titer plasma, or confounding by different management strategies.84

There is very limited published data on convalescent plasma for pediatric patients.23

The FDA has issued an EUA for use of convalescent plasma for all hospitalized patients, in part based on data from the expanded access program.70

The EUA does not replace clinical trials.70 The NIH states that convalescent plasma should not be considered the standard of care and encourages enrollment in prospective clinical trials.50 See and for more information.

The FDA has a fact sheet for healthcare professionals on convalescent plasma, including criteria for use, adverse effects, dosing, and more ( A fact sheet for patients and parents/caregivers is available at

A fact sheet explaining how the EUA differs from the discontinued expanded access program is available at

In Canada, convalescent plasma is only being supplied to physicians for use in the context of clinical trials under the authorization of Health Canada.71

Recovered patients interested in donating their plasma can do so through the American Red Cross (, or they can locate a donation center at Mobile blood drives in their area may be another option. In Canada, see


There is concern that corticosteroids have the potential to delay viral clearance, as observed in MERS-CoV and SARS.10 However, they are being studied for COVID-19.

In one institution in China, methylprednisolone use in patients with COVID-19 ARDS was associated with reduced mortality.16 This and other cohort studies were limited by confounding, and inclusion of patients with various disease severities and concomitant treatments.46

Data from the open-label RECOVERY trial, in which 2,104 patients were randomized to oral or intravenous dexamethasone 6 mg/day for 10 days, suggests a mortality benefit for COVID-19 patients requiring oxygen, especially for those requiring ventilation, over usual care (n = 4,321).31 NNT = 8 to prevent one death in ventilated patients, or 34 in patients requiring oxygen but not ventilation. It did not provide a mortality benefit (and may harm) patients not requiring oxygen. It also did not provide a mortality benefit for early disease (symptoms for a week or less). This suggests that dexamethasone’s mechanism involves an anti-inflammatory effect rather than an antiviral effect, because inflammation is more common in advanced disease, while viral replication is at maximum in early disease.

The open-label REMAP-CAP study (n=403) randomized COVID-19 patients admitted to intensive care for respiratory or cardiovascular support to hydrocortisone 50 to 100 mg every six hours for seven days, hydrocortisone started only if shock was clinically evident, or no hydrocortisone.68 Analysis suggests hydrocortisone was probably superior to no hydrocortisone in regard to organ support-free days at 21 days, but the study was stopped early.

The open-label CoDEX study (n=299) randomized COVID-19 patients with moderate to severe ARDS to dexamethasone 20 mg once daily for five days, then 10 mg once daily for five days.56 Ventilator-free survival days through day 28 were greater with dexamethasone (6.6 vs 4, p=0.04). However, 35% of the usual care patients received at least one dose of corticosteroids. Mortality was not affected, but this may be because the study was stopped early after the results of RECOVERY were released.

In a placebo-controlled study of corticosteroids for COVID-19 (CAPE COVID) (n=149), a hydrocortisone infusion was not superior to placebo in regard to death or need for respiratory support (mechanical ventilation or high-flow oxygen) at day 21.52 However, the study was likely underpowered to show a difference, and was stopped early pending RECOVERY publication.

The Brazilian MetCOVID study (n=416) did not find a mortality benefit for a five-day course of methylprednisolone over placebo.78 However, in a subgroup analysis, 28-day mortality was lower in the methylprednisolone group in patients <60 years of age (46.6% vs 61.9%). Most patients received mechanical ventilation or noninvasive oxygen, but patients not on oxygen with low oxygen saturation were not included. Mortality was relatively high in this study compared to the RECOVERY study. Patients with septic shock were allowed to receive hydrocortisone, which could have affected results.

In a WHO meta-analysis that included data from RECOVERY, CAPE COVID, CoDEX, REMAP-CAP, and three other studies (n=1,703), mortality at 28 days was lower in critically ill patients who received corticosteroids vs those who did not receive them (32% vs 40%)(OR 0.66, 95% CI 0.53 to 0.82, p<0.001).45 Including data from ventilator patients from MetCOVID did not affect results. Neither choice of corticosteroid (dexamethasone or hydrocortisone) nor days from symptom onset (>7 days vs ≤7 days) seems to affect efficacy. Benefit might be greater in patients not receiving mechanical ventilation. Based on these results, WHO strongly recommends systemic corticosteroids (dexamethasone 6 mg once daily or equivalent, via oral or intravenous route) for seven to ten days for severe/critical COVID-19, with glucose monitoring.51

The IDSA suggests dexamethasone 6 mg/day x 10 days (or until discharge, if earlier), for patients hospitalized with severe COVID-19 (oxygen saturation ≤94% on room air; need for supplementation oxygen, mechanical ventilation, or extracorporeal membrane oxygenation). If dexamethasone is not available, methylprednisolone 32 mg or prednisone 40 mg daily can be used.46 NIH guidelines similarly recommend dexamethasone 6 mg/day for up to 10 days in COVID-19 patients who require oxygen or mechanical ventilation.50 Corticosteroids are not recommended for COVID-19 patients not requiring treatment with supplemental oxygen.46,50

Harms of corticosteroids include hyperglycemia, agitation, confusion, and infection risk.46

Inhaled corticosteroids should be continued in asthma or COPD patients with COVID-19.50 The effect of inhaled corticosteroids on COVID-19 risk, severity, or transmission is unknown.50

Ciclesonide (Alvesco) and inhaled budesonide are being studied for treatment of COVID-19, but there is no data on efficacy yet. See for more information.


No data.

Dapagliflozin is being studied in COVID-19 patients with respiratory failure and with hypertension, diabetes, heart disease, or advanced renal disease to prevent organ failure, based on its known renal and cardiac benefit (DARE-19 study).

See for more information.


Interest in famotidine as a COVID-19 treatment stems from observations in China that patients who were taking famotidine who were infected with COVID-19 had better outcomes.55

In a retrospective U.S. study (n = 1,620), famotidine use (10 to 40 mg/day; n = 84) within 24 hours of admission was associated with reduced risk of death or intubation in hospitalized COVID-19 patients.67

The IDSA suggests against use of famotidine for COVID-19 outside of a clinical trial.46 See for more information.


Is a more potent inhibitor of SARS-CoV-2 than chloroquine in vitro.2 Also has immunomodulating effects.27

Early enthusiasm for hydroxychloroquine was based on a widely publicized open-label, randomized study in hospitalized patients testing positive for SARS-CoV-2.2 Six of 26 hydroxychloroquine patients were lost to follow-up: one due to death, three due to intensive care admission, one due to side effects (nausea), and one who left the hospital. Viral clearance at day six was 70% in the 20 remaining hydroxychloroquine patients vs 12.5% of the control patients (n = 16).2 Six treated patients also received azithromycin to prevent bacterial infection.2 In the combination group, viral clearance was 100% at day six vs 57.1% in the hydroxychloroquine-alone group.2 Also see subsequent observational data under “Azithromycin,” above.

In larger, open-label and cohort studies, despite some small, inconsistent benefit on clinical signs and symptoms, there was no benefit on viral clearance, length of stay, need for intensive care or mechanical ventilation, or mortality.29,39,42,43,49,60,66 In one study, thirty percent of hydroxychloroquine patients had adverse effects.42 In another study, the combination of hydroxychloroquine and azithromycin was associated with cardiac arrest.66 When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.2,6 Information on managing QT prolongation risk in these patients is available at

One large (n = 2,541) retrospective U.S. cohort study found reduced mortality with hydroxychloroquine +/- azithromycin vs usual care.75 Some patients with high cardiac risk were excluded. Select patients with severe COVID-19 and minimal cardiac risk also received azithromycin. Hydroxychloroquine was started within 48 hours of hospital admission in almost all patients. This study had several limitations. For example, the outcomes of almost 300 patients were not included in the analysis, and there were differences between treatment groups that could not be adequately adjusted for (e.g., baseline disease severity, other treatments received).

In a placebo-controlled study in outpatients, hydroxychloroquine did not improve symptoms.11 Forty-three percent of hydroxychloroquine patients had side effects vs 22% of placebo patients. Four hydroxychloroquine patients were hospitalized, and there was one outpatient death in this group. In the placebo group, ten placebo patients were hospitalized, one of which died (p=0.29).

The hydroxychloroquine arm of the large RECORD study was stopped due to lack of efficacy.31

The FDA has revoked its EUA for hydroxychloroquine because it is unlikely to be effective, based on data from the EUA and elsewhere.73 In addition to efficacy concerns, the FDA’s revocation of its EUA for hydroxychloroquine was based on adverse effects; its known and potential benefits no longer outweigh the known and potential side effects (e.g., serious cardiac events and other serious side effects).33 Due to the risk of arrhythmias, the FDA recommends against hydroxychloroquine use for COVID-19 outside of a clinical trial.33

The WHO has discontinued the hydroxychloroquine arm of the Solidarity Trial because interim results suggest there is little mortality benefit for hospitalized patients.74

Clinical trials are ongoing on the use of hydroxychloroquine to prevent COVID-19 in healthcare workers. See for regimens being studied.

Icatibant (Firazyr, generics [U.S])

SARS-CoV-2 uses ACE2 to enter cells. Because the resulting loss of ACE2 function might lead to bradykinin accumulation, there is interest in use of icatibant (a bradykinin antagonist) for severe COVID-19.

In a small case-control study, icatibant 30 mg every six hours x 3 was associated with improved oxygenation in hypoxic patients.81

See for ongoing studies.

IL-6 antagonist

Tocilizumab (Actemra);
sarilumab (Kevzara); siltuximab (Sylvant)

High IL-6 levels are associated with higher COVID-19 disease severity, especially in nonsurvivors.13

Some randomized studies suggest benefit for tocilizumab (Actemra) (e.g., mortality, need for mechanical ventilation, intensive care admission).13

The manufacturer of Kevzara (sarilumab) has discontinued its U.S. clinical trial in COVID-19 patients requiring mechanical ventilation (n = 194) because it did not meet its primary endpoint (improvement on a disease severity scale) or key secondary endpoints. The results of this study are not yet published.77

May cause increased infections, neutropenia, thrombocytopenia, and elevated liver enzymes.1,34-38 There are several cases of tocilizumab-associated worsening of COVID-19, perhaps due to immunosuppression, despite an associated reduction in inflammatory markers.80

NIH guidance recommends against use except in a clinical trial.50 See Could be considered on an individual basis (e.g., patients with cytokine storm, increased IL-6 levels, etc) with expert consultation.44


Ivermectin has several mechanisms that make it an attractive option for study for prevention and treatment of COVID-19. However, it has not demonstrated clinically significant antiviral efficacy for any virus in humans. Clinical trials are underway.32 See

Janus Kinase Inhibitors (Baricitinib [Olumiant], etc)

Interest based on potential to block IL-6 effects, reduce cytotoxic T cells, and increase regulatory T cells.

Baricitinib in combination with remdesivir reduced recovery time in hospitalized patients vs remdesivir alone in an unpublished NIH-sponsored study. Based on these results, the manufacturer plans to approach the FDA about EUA for the 4 mg dose for COVID-19.14

Baricitinib is being compared to placebo in the phase III COV-BARRIER study in hospitalized patients.14

NIH guidance recommends against use except in a clinical trial.50 See

ritonavir (Kaletra)

Lopinavir/ritonavir has not demonstrated anti-SARS-CoV-2 activity in humans.15 A small study suggested benefit (reduced composite endpoint of ARDS or death) for 2003 SARS vs historical control.17

Results from a randomized, open-label study (n=199) suggest it might reduce complications such as acute kidney injury, secondary infections, or need for mechanical ventilation in patients with COVID-19 pneumonia.15 However, time to clinical improvement was not reduced (main outcome measure).15 Gastrointestinal adverse effects may limit use.15,30

There is interest in studying lopinavir/ritonavir earlier in the disease course, or in combination with other medications.15 Use with ribavirin and interferon beta-1b early in the disease course (mean five days from symptom onset) was compared to lopinavir/ritonavir alone in hospitalized patients (n=127).58 In this open-label study, median time to viral clearance was seven days with combination therapy vs 12 days for lopinavir/ritonavir alone.58 Alleviation of symptoms occurred in four days vs eight days, respectively (p<0.0001).58

The WHO has discontinued the lopinavir/ritonavir arm of the Solidarity Trial because interim results suggest no mortality benefit for hospitalized patients.74

Additional clinical trials are planned or underway. See for more information.

Losartan, Telmisartan

Studies in mice suggest that ARBs can reduce lung damage caused by SARS-CoV.22

Clinical trials are underway for treatment of COVID-19. See for more information.


Not expected to be effective against SARS-CoV-2 because SARS-CoV-2 does not use neuraminidase.26

Has been used for COVID-19 pneumonia, but there is no efficacy data.12


Remdesivir has in vitro activity against SARS-CoV-2.40

In a cohort of 53 evaluable patients receiving oxygen support, or with oxygen saturation ≤94% on room air, remdesivir was associated with clinical improvement in regard to oxygen support requirements in 68% of patients.40 Mortality was 13%, which is less than in other case series and cohorts.40 Most of the patients (65%) were receiving mechanical ventilation or ECMO at baseline.40 The most common adverse events were liver enzyme elevation (23%), diarrhea (9%), rash, renal impairment, hypotension (8%), acute kidney injury, atrial fibrillation, multiorgan dysfunction, hypernatremia, and venous thrombosis (6%).40 Causality could not be assessed due to the effects of COVID-19 itself.40 Based on previous data, mild to moderate transaminase elevations are expected with remdesivir.40 Viral load was not evaluated,40 but in a previous case report, virologic improvement was seen.8

Preliminary analysis of a double-blind, placebo-controlled trial (ACTT-1) (n = 1,059), remdesivir seemed to shorten time to recovery (11 days vs 15 days; p <0.001), but mortality was not statistically different (8% vs 11.6%; p = 0.059).54,72 Similarly, a Chinese study found a nonsignificant trend toward faster recovery.61

  • In ACTT-1, most patients had severe disease at enrollment, defined as oxygen saturation ≤94% on room air, need for invasive or noninvasive oxygen supplementation, or respirations ≥24 breaths/minute.72 Most patients were receiving oxygen. Remdesivir did not show statistically significant benefit in patients not on supplemental oxygen, although there was an encouraging trend.72 Patients receiving mechanical ventilation or ECMO also did not seem to benefit.72

Unpublished data from the open-label SIMPLE-Severe study compared remdesivir-treated patients (n=312) to a matched cohort of patients receiving standard care (n=818).79 Included patients had oxygen saturation ≤94% on room air and radiologic evidence of pneumonia.82 Most patients were receiving some kind of supplemental oxygen (mostly low-flow).82 About 74% of remdesivir patients recovered (i.e., showed improvement in clinical status on a 7-point ordinal scale) by day 14 vs 59% of the standard-care patients. Mortality rate at day 14 was 7.6% in the remdesivir patients vs 12.5% in the standard-treatment group (OR 0.38, 95% CI 0.22 to 0.68, p = 0.001).79

A five-day course of remdesivir was associated with a statistically significant (but perhaps not clinically significant) improvement in clinical status on a seven-point ordinal scale in patients with moderate COVID-19 (radiographic evidence of pulmonary infiltrates and oxygen saturation >94% on room air) vs standard care in an open-label, randomized study (n=584). Most patients were not on any kind of supplemental oxygen. Viral load was not assessed. Patients randomized to a 10-day course (actual median treatment duration six days) did not benefit. The clinical status score used in this study could have underestimated benefit in this population with nonsevere disease.24

The FDA has issued an EUA for remdesivir for treatment of suspected or laboratory-confirmed COVID-19 in hospitalized adults and children based on data from the ACTT trial and Gilead’s SIMPLE studies.24,72.54,82 If remdesivir availability is limited at your hospital, the NIH recommends prioritizing use for patients requiring oxygen, but not high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO.50

The FDA has a fact sheet for healthcare professionals on remdesivir including criteria for use, adverse effects, dosing, and more ( A fact sheet for patients and parents/caregivers is available at

In the U.S., remdesivir (Veklury) has been distributed to hospitals by the government.57 When these supplies are exhausted, it will be available for purchase through Amerisource Bergan. This is a rapidly changing situation. For other potential opportunities for availability see,, or contact Gilead at 833-445-3230 (GILEAD-0) or

In Canada, remdesivir (Veklury) has received marketing authorization with conditions pending the results of additional clinical trials. Its approved indication is treatment of COVID-19 pneumonia requiring supplemental oxygen in patients ≥12 years of age who weigh ≥40 kg.59 Supplies are limited, but availability should improve in October.

Coadministration of remdesivir and chloroquine or hydroxychloroquine is not recommended based on in vitro data showing that these drugs might interfere with the metabolic activation and antiviral activity of remdesivir.53 In Simple-Severe, recovery rate at day 14 for patients who received hydroxychloroquine plus remdesivir was lower than in patients who received remdesivir alone (57% percent vs 69%, HR 0.61, 95% CI 0.45 to 0.83, p=0.002). Concomitant hydroxychloroquine use was not associated with increased mortality but was associated with a higher risk of adverse events.79

Another potential drug interaction involves inhibition of remdesivir elimination from hepatocytes by P-glycoprotein inhibitors. This interaction could result in hepatotoxicity.76


Not potent enough to be effective at safe doses; hematologic toxicity precludes use.26 See lopinavir/ritonavir section for information on combination use.


Statins might ameliorate COVID-19-mediated inflammation and prevent lung injury by affecting ACE2 expression.25

In a meta-analysis of almost 9,000 COVID-19 patients in studies looking at the risk of severe COVID-19 illness or mortality in statin users vs nonusers, statin use was associated with a reduced risk of severe or fatal COVID-19 (HR 0.7, 95% CI 0.53 to 0.94).25

NIH guidelines recommend against use specifically for COVID-19 treatment outside of a clinical trial.50

See for more information on planned or ongoing studies.

tPA (alteplase)

No data.

Interest based on reports of microvascular pulmonary thrombosis in COVID-19 patients.

Studies are underway to treat ARDS in COVID-19 patients. See


There is interest in using currently available vaccines to protect against SARS-COV-2 through nonspecific immune response (e.g., interferons, natural killer cells) or cross-reactive antibodies.21

Analysis of immunization records suggests that recent (within five years) vaccination with Hemophilus influenza type-B (HIB), measles/mumps/rubella (MMR), varicella, pneumococcal conjugate vaccine (Prevnar-13), high-dose influenza vaccine, and hepA/hepB vaccines is associated with a lower risk of testing positive for SARS-CoV-2.20

Oral polio, zoster, BCG, and MMR vaccines are being studied or studies are planned for prevention of COVID-19. See for more information.

Vitamin C

Intravenous vitamin C is being studied for treatment of severe COVID-19 disease based on previous data in sepsis and ARDS. However, there is no clear evidence of benefit even for these conditions.48

Oral vitamin C is being studied for treatment of COVID-19 disease in the outpatient setting, and as prophylaxis.

See for more information on these planned or ongoing studies.

Vitamin D

Interest in vitamin D stems from its effects on the immune system and pulmonary ACE2 expression. Studies are planned or underway using vitamin D for prevention or as a treatment adjunct. See for more information.


Zinc has in vitro activity against SARS-CoV.47

Studies of oral zinc, alone or in combination (e.g., with vitamin C, vitamin D, hydroxychloroquine [purported to help zinc get inside the cells47], azithromycin) to prevent COVID-19 disease are planned or ongoing.

See for more information.

Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; ARDS = acute respiratory distress syndrome; ECMO = extracorporeal membrane oxygenation; EUA = Emergency Use Authorization; IDSA = Infectious Diseases Society of America IL = interleukin; NIH = National Institutes of Health; NSAIDs = nonsteroidal anti-inflammatory drugs; SARS = severe acute respiratory syndrome; SARS-CoV-2 = the virus that causes COVID-19 disease; tPA = tissue plasminogen activator; TNF = tumor necrosis factor; WHO = World Health Organization

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.



Study Quality


Good-quality patient-oriented evidence.*

  1. High-quality RCT
  2. SR/Meta-analysis of RCTs with consistent findings
  3. All-or-none study


Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study


Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56.]

Prepared by the Editors of Therapeutic Research Center (361022).


  1. Product monograph for Kevzara. Sanofi Genzyme. Mississauga, ON L4W 4V9. August 2019.
  2. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56:105949.
  3. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020;14:72-3.
  4. FDA. Fact sheet for health care providers emergency use authorization (EUA) of chloroquine phosphate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients. Revoked. June 15, 2020. (Accessed September 15, 2020).
  5. Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res 2020;177:104762.
  6. Cortegiani A, Ippolito M, Ingoglia G, et al. Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for the treatment of COVID-19. J Crit Care 2020;59:176-90.
  7. Bermejo-Martin JF, Kelvin DJ, Eiros JM, et al. Macrolides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains. J Infect Dev Ctries 2009;3:159-61.
  8. Ko WC, Rolain JM, Lee NY, et al. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int J Antimicrob Agents 2020 Mar 6:105933. doi: 10.1016/j.ijantimicag.2020.105933.
  9. Deftereos SG, Giannopoulos G, Vrachatis DA, et al. Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial. JAMA Netw Open 2020;3:e2013136.
  10. World Health Organization. Clinical management of severe acute respiratory infection when COVID-19 is suspected. Interim guidance. May 27, 2020. (Accessed September 16, 2020).
  11. Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial. Ann Intern Med 2020 Jul 16.
  12. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13.
  13. Cortegiani A, Ippolito M, Greco M, et al. Rationale and evidence on the use if tocilizumab in COVID-19: a systematic review. Pulmonology 2020 Jul 20;S2531-0437(20)30153-9.
  14. Eli Lilly. Baricitinib in combination with remdesivir reduces time to recovery in hospitalized patients with COVID-19 in NIAID-sponsored ACTT-2 trial. September 14, 2020. (Accessed September 17, 2020).
  15. Cao B, Wang Y, Wen W, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020;382:1787-99.
  16. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180:934-43.
  17. Chu CM, Cheng VC, Hung IF, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252-6.
  18. FDA. FDA issues emergency use authorization for convalescent plasma as potential promising COVID-19 treatment, another achievement in administration’s fight against pandemic. August 23, 2020. (Accessed September 16, 2020).
  19. Dimopoulos G, de Mast Q, Markou N, et al. Favorable anakinra responses in severe COVID-19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host Microbe 2020;28:117-23.e1.
  20. Pawlowski C, Puranik A, Bandi H, et al. Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations. medRxiv. 2020.07.27.20161976. (Accessed September 18, 2020).
  21. Anbarasu A, Ramaiah S, Livingstone P. Vaccine repurposing approach for preventing COVID 19: can MMR vaccines reduce morbidity and mortality? Hum Vaccin Immunother 2020;5:1-2.
  22. Kuster G, Pfister O, Burkard T, et al. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19? Eur Heart J 2020;41:1801-3.
  23. Diorio C, Anderson EM, McNerney KO, et al. Convalescent plasma for pediatric patients with SARS-CoV-2-associated acute respiratory distress syndrome. Pediatr Blood Cancer 2020 Sep 4:e28693. doi:10.1002/pbc.28693.
  24. Spinner CD, Gottleib RL, Criner GJ, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA 2020;324:1048-57.
  25. Kow CS, Hasan SS. Meta-analysis of effect of statins in patients with COVID-19. Am J Cardiol Aug 12. doi: 10.1016/j.amjcard.2020.08.004.
  26. McCreary EK, Pogue JM. Coronavirus disease 2019 treatment: a review of early and emerging options. Open Forum Infect Dis 2020;7:ofaa105.
  27. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2020. (Accessed September 15, 2020).
  28. Gautret P, Lagier JC, Parola P et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow-up: a pilot observational study. Travel Med Infect Dis 2020;34:101663.
  29. Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zheijang Univ 2020;49:215-19.
  30. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 2020;323:1488-94.
  31. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19-preliminary report. N Engl J Med 2020 Jul 17. doi:10.1056/NEJMoa2021436.
  32. Banerjee K, Nandy M, Dalai CK, Ahmed SN. The battle against COVID 19 pandemic: what we need to know before we “test fire” ivermectin. Drug Res (Stuttg) 2020;70:337-40.
  33. FDA. Frequently asked questions on the revocation of the Emergency Use Authorization for hydroxychloroquine sulfate and chloroquine phosphate. June 19, 2020. (Accessed September 15, 2020).
  34. Product information for Kevzara. Sanofi-Aventis. Bridgewater, NJ 08807. April 2018.
  35. Product information for Actemra. Genentech. South San Francisco, CA 94080. May 2020.
  36. Product information for Sylvant. EUSA Pharma. Hertfordshire, U.K. HP2 4TZ. May 2020.
  37. Product monograph for Actemra. Mississauga, ON L5N 5M8. September 2019.
  38. Product monograph for Sylvant. Janssen. Toronto, ON M3C 1L9. March 2018.
  39. Chen Z, Hu JM, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv 2020.03.22.20040758. (Accessed September 17, 2020).
  40. Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med 2020;382:2327-36.
  41. Borba MG, Val FF, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open 2020;3(4.23):e208857.
  42. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open-label, randomized, controlled trial. BMJ 2020;369. doi: 10.1136/bmj.m1849.
  43. Mahevas M, Tran VT, Roumier M, et al. Clinical efficacy of hydroxychloroquine in patients with COVID-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ 2020;369. doi: 10.1136/bmj.m1844.
  44. British Columbia Ministry of Health. Unproven therapies for COVID-19. Updated August 21, 2020. (Accessed September 17, 2020).
  45. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JA, Murthy S, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 2020 Sep 2. doi: 10.1001/jama.2020.17023.
  46. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Last updated September 15, 2020. (Accessed September 16, 2020).
  47. te Velthuis AJ, van den Worm SH, Sims AC, et al. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc inonophores block the replication of these viruses in cell culture. PLoS Pathog 2010;6:e1001176.
  48. Surani S, Sharma M. Revisiting the role of vitamin C in sepsis. Is it a forlorn hope or is there still dearth of data? Open Respir Med J 2019;13:55-7.
  49. Magagnoli J, Narendran S, Pereira F, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. Med (NY) 2020 Jun 5. doi: 10.1016/j.medj.2020.06.001.
  50. NIH. Coronavirus disease 2019 (COVID-19). Treatment guidelines. Last updated September 1, 2020. (Accessed September 15, 2020).
  51. World Health Organization. Corticosteroids for COVID-19. Living guidance. September 2, 2020. (Accessed September 16, 2020).
  52. Dequin PF, Heming N, Meziani F, et al. Effect of hydrocortisone on 21-day mortality or respiratory support among critically ill patients with COVID-19: a randomized clinical trial. JAMA 2020 Sep 2. doi: 10.1001/jama.2020.16761.
  53. FDA. Fact sheet for health care providers emergency use authorization (EUA) of remdesivir (GS-5734). June 2020. (Accessed September 18, 2020).
  54. FDA. Fact sheet for health care providers. Emergency use authorization (EUA) for remdesivir (GS-5734). (Accessed September 18, 2020).
  55. Rogosnitzky M, Berkowitz E, Jadad AR. Delivering benefits at speed through real-world repurposing of off-patent drugs: the COVID-19 pandemic as a case point. JMIR Public Health Surveill 2020;6:e19199.
  56. Tomazini BM, Maia IS, Cavalcanti AB, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA 2020 Sep 2. doi: 10.1001/jama.2020.17021.
  57. Ison MG, Wolfe C, Boucher HW. Emergency use authorization of remdesivir: the need for a transparent distribution process. JAMA 2020;323:2365-6.
  58. Hung IF, Lung KC, Tso EY, et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomized, phase 2 trial. Lancet 2020;395:1695-704.
  59. Product monograph for Veklury. Gilead Sciences Canada. Mississauga, ON L5N 2W3. July 2020.
  60. Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2020;382:2411-8.
  61. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569-78.
  62. Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323:1582-9.
  63. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA 2020;117:9490-6.
  64. Ye M, Fu D, Ren Y, et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol 2020 Apr 15. doi: 10.1002/jmv.25882.
  65. Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol 2020;2:e325-31.
  66. Rosenberg ES, Dufort EM, Udo T, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA 2020;323:2493-502.
  67. Freedberg DE, Conigliaro J, Wang TC, et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study. Gastroenterology 2020;159:1129-31.e3.
  68. The Writing Committee for the REMAP-CAP Investigators, Angus DC, Derde L, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 corticosteroid domain randomized clinical trial. JAMA 2020 Sep 2. doi: 10.1001/jama.2020.17022.
  69. Joyner MJ, Senefeld JW, Klassen SA, et al. Effect of convalescent plasma on mortality among hospitalized patients with COVID-19: initial three-month experience. August 12. 2020. (Accessed September 16, 2020).
  70. FDA. Fact sheet for health care providers. Emergency use authorization (EUA) of COVID-19 convalescent plasma for treatment of COVID-19 in hospitalized patients. August 23, 2020. (Accessed September 16, 2020).
  71. Canadian Blood Services. COVID-19 and convalescent plasma, (Accessed September 16, 2020).
  72. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19-preliminary report. N Engl J Med 2020 May 22. doi: 10.1056/NEJMoa2007764.
  73. FDA. Letter to Gary L. Disbrow, Deputy Assistant Secretary, Director, Medical Countermeasures Programs, BARDA, in response to request for revocation of Emergency Use Authorization for chloroquine phosphate and hydroxychloroquine. June 15, 2020. (Accessed September 15, 2020).
  74. Bagozzi D. WHO discontinued hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19. News release. July 4, 2020. (Accessed September 18, 2020).
  75. Arshad S, Kilgore P, Chaudry ZS, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis 2020;97:396-403.
  76. Leegwater E, Strik A, Wilms EB, et al. Drug induced liver injury in a COVID-19 patient: potential interaction of remdesivir with P-glycoprotein inhibitors. Clin Infect Dis 2020 Jun 28. doi: 10.1093/cid/ciaa883.
  77. Anon. Sanofi and Regeneron provide update on Kevzara (sarilumab) phase 3 U.S. trial in COVID-19 patients. July 2, 2020. (Accessed September 17, 2020).
  78. Jeronimo CM, Farias ME, Val FF, et al. Methylprednisolone as adjunctive therapy for patients hospitalized with COVID-19 (Metcovid): a randomized, double-blind, phase IIa, placebo-controlled trial. Clin Infect Dis 2020 Aug 12. doi: 10.1093/cid/ciaa1177.
  79. Gilead press release. Gilead presents additional data on investigational antiviral remdesivir for the treatment of COVID-19. July 10, 2020. (Accessed September 18, 2020).
  80. Radbel J, Narayanan N, Bhatt PJ. Use of tocilizumab for COVID-19-induced cytokine release syndrome: a cautionary case report. Chest 2020;158:e15-9.
  81. van de Veerdonk FL, Kouijzer IJ, de Nooijer AH, et al. Outcomes associated with use of kinin B2 receptor antagonist among patients with COVID-19. JAMA Netw Open 2020 Aug;3(8):e2017708. doi: 10.1001/jamanetworkopen.2020.17708.
  82. Goldman JD, Lye DC. Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med 2020 May 27. doi: 10.1056/NEJMoa2015301.
  83. American Society of Hematology. COVID-19 and convalescent plasma: frequently asked questions. August 25, 2020. (Accessed September 23, 2020).
  84. Pau AK, Aberg J, Baker J, et al. Convalescent plasma for the treatment of COVID-19: perspectives of the National Institutes of Health COVID-19 treatment guidelines panel. Ann Intern Med 2020 Sep 25;doi: 10.7326/M20-6448.
  85. Anon. NeuroRx submits request for Emergency Use Authorization of RLF-100 (aviptadil) in the treatment of patients with critical COVID-19 and respiratory failure who have exhausted approved therapy. September 23, 2020. (Accessed September 28, 2020).
  86. FDA. Clinical memorandum re: EUA request. COVID-19 convalescent plasma. (Accessed September 24, 2020).

Cite this document as follows: Clinical Resource, Treatments of Interest for COVID-19. Pharmacist’s Letter/Prescriber’s Letter. October 2020.

Related Articles