COVID-19: Prevention & Investigational Treatments

Updated - December 1, 2022. M Puckey BPharm

• What is COVID-19
• COVID-19 Vaccines
• Treatments
• Investigational Vaccines

What is COVID-19?

COVID-19 is the disease caused by an infection of the SARS-CoV-2 virus, first identified in the city of Wuhan, in China's Hubei province in December 2019. COVID-19 was previously known as 2019 Novel Coronavirus (2019-nCoV) respiratory disease before the World Health Organization (WHO) declared the official name as COVID-19 in February 2020.

The SARS-CoV-2 virus belongs to the family of viruses called coronaviruses, which also includes the viruses that cause the common cold, and the viruses that cause more serious infections such as severe acute respiratory syndrome (SARS), which was caused by SARS-CoV in 2002, and Middle East respiratory syndrome (MERS), which was caused by MERS-CoV in 2012. Like the other coronaviruses, the SARS-CoV-2 virus primarily causes respiratory tract infections, and the severity of the COVID-19 disease can range from mild to fatal.

For more information on COVID-19 Symptoms, Prevention and Risks

• COVID-19: Symptoms, Prevention and Risks

Stay up to date on COVID-19 News

• COVID-19 News (Newsfeed from Drugs.com)

FDA approved COVID-19 Vaccines

• Comirnaty (BNT162b2, COVID-19 Vaccine, mRNA) last updated September 14, 2022.
  Vaccine platform: mRNA vaccine
  FDA approval date:  August 23, 2021.
  Company: Pfizer Inc. and BioNTech.
  Comirnaty is a nucleoside-modified messenger RNA (modRNA) that encodes the viral spike (S) glycoprotein of SARS-CoV-2.vaccine
  FDA approved as a 2-dose series to prevent coronavirus disease 2019 (COVID-19) in patients 12 years and older.
  Emergency Authorizatation:
  Primary series: third in primary series dose to individuals 12 years of age and older with certain kinds of immunocompromise.
  Comirnaty contains the same vaccine as Pfizer-BioNTech COVID-19 Vaccine (monovalent). They contain one messenger RNA (mRNA) component of the original strain of SARS-CoV-2 virus. The FDA approved vaccine has the brand name Comirnaty, and when it is used under an Emergency Use Authorization (EUA) approval it has the name Pfizer-BioNTech COVID-19 (monovalent). See below for more information on Pfizer-BioNTech COVID-19.
   

• Spikevax (mRNA-1273) last updated September 14,2022
  Vaccine platform: mRNA vaccine
  FDA approval date:  January 31, 2022.
  Company: Moderna Us, Inc.
  Spikevax vaccine is FDA approved vaccine to prevent coronavirus disease 2019 (COVID-19) in patients 18 years and older.
  It also has Emergency Use Authorisation for:
  A two-dose primary series to individuals 12 years through 17 years of age.
  A third primary series dose to individuals 12 years of age and older with certain kinds of immunocompromise, given at least 4 weeks after second dose.
  Spikevax contains the same vaccine as Moderna COVID-19 Vaccine (monovalent).
  The FDA approved vaccine has the brand name Spikevax, and when it is used under an Emergency Use Authorization (EUA) approval it has the name Moderna COVID-19 Vaccine (monovalent).
  Moderna COVID-19 Vaccine, Bivalent is different from Spikevax and Moderna COVID-19 Vaccine (monovalent).  Spikevax and Moderna COVID-19 Vaccine (monovalent) contain one messenger RNA (mRNA) component of the original strain of SARS-CoV-2.  Moderna COVID-19 Vaccine, Bivalent contains two mRNA components of SARS-CoV-2 virus, one of the original strain of SARS-CoV-2 and the other one in common between the BA.4 and BA.5 lineages of the omicron variant of SARS-CoV-2.

COVID-19 Vaccines Available Under FDA Emergency Use Authorization (EUA)

• Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) (updated September 8, 2022)
  Vaccine platform: mRNA vaccine
  Pfizer-BioNTech COVID-19 Vaccine (monovalent) is a nucleoside-modified messenger RNA (modRNA) that encodes the viral spike (S) glycoprotein of SARS-CoV-2.
  Pfizer-BioNTech COVID-19 Vaccine, Bivalent, contains two messenger RNA (mRNA) components of SARS-CoV-2 virus, one of the original strain of SARS-CoV-2 and the other one in common between the BA.4 and BA.5 lineages of the omicron variant of SARS-CoV-2.
  Pfizer-BioNTech COVID-19 Vaccines are available under Emergency Use Authorization to protect against COVID-19.
  Company: Pfizer Inc. and BioNTech.
  Pfizer-BioNTech COVID-19 Vaccine (monovalent)
  Has emergency use authorization for:
  Three-dose primary series for individuals 6 months through 4 years of age.
  Two-dose primary series for individuals 5 years of age and older.
  Third primary series dose for individuals 5 years of age and older who have been determined to have certain kinds of immunocompromise.
  Booster dose of Pfizer-BioNTech COVID-19 Vaccine (monovalent) is no longer authorized for individuals 5 years of age and older. Instead Pfizer-BioNTech COVID-19 Vaccine, Bivalent now has EUA as a booster dose. See below for more information.
  Pfizer-BioNTech COVID-19 Vaccine, Bivalent
  Pfizer-BioNTech COVID-19 Vaccine, Bivalent has emergency use authorization for use in individuals 5 years of age and older as a single booster dose administered at least 2 months after either:
  -Completion of primary vaccination with any authorized or approved monovalent COVID-19 vaccine.
  -Or receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.

  Pfizer-BioNTech COVID-19 (monovalent) contains the same vaccine as Comirnaty.
  Under an EUA approval the original vaccine has the name Pfizer-BioNTech COVID-19 (monovalent) and when it is used as a FDA approved medicine it has the brand name Comirnaty.

• Moderna COVID-19 Vaccine (mRNA-1273) last updated September 14, 2022.
  Vaccine platform: mRNA vaccine
  There are two different types of Moderna COVID-19 Vaccines, the original Moderna COVID-19 Vaccine which is monovalent and Moderna COVID-19 Vaccine, Bivalent.
  Moderna COVID-19 Vaccine (monovalent) contains one messenger RNA (mRNA) component of the original strain of SARS-CoV-2 and has emergency use authorization to prevent COVID-19 for:
  -Two-dose primary series for individuals 6 months of age and older.
  -Third primary series dose for individuals 6 months of age and older who have been determined to have certain kinds of immunocompromise.
  Moderna COVID-19 Vaccine, Bivalent contains two messenger RNA (mRNA) components of SARS-CoV-2 virus, one of the original strain of SARS-CoV-2 and the other one in common between the BA.4 and BA.5 lineages of the omicron variant of SARS-CoV-2.
  Moderna COVID-19 Vaccine, Bivalent has emergency use authorization for use in individuals 6 years of age and older as a single booster dose when given at least 2 months after either:
  -Completion of primary vaccination with any authorized or approved monovalent COVID-19 vaccine, or
  -Receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine.
  Moderna COVID-19 Vaccine (monovalent) contains the same vaccine as Spikevax.
  When the original Moderna COVID-19 Vaccine is used as a FDA approved vaccine it has the brand name Spikevax, and when it is used under an Emergency Use Authorization (EUA) approval it has the name Moderna COVID-19 Vaccine (monovalent).
• Novavax COVID-19 Vaccine (NVX-CoV2373, Nuvaxovid, Covovax) (last updated October 20, 2022)
  Vaccine platform: Protein Subunit
  Novavax COVID-19 Vaccine, Adjuvanted contains the SARS-CoV-2 spike protein and Matrix-M adjuvant.
  Novavax COVID-19 Vaccine, Adjuvanted received Emergency Use Authorization to protect against COVID-19 for individuals 12 years and older for the primary series. It has EUA as a booster dose for 18 years and older.
  Primary series:
  Two-dose primary series given three weeks apart for individuals 12 years and older.
  Booster dose: for individuals 18 years of age and older, at least 6 months after completion of primary vaccination with an authorized or approved COVID-19 vaccine:
  -for individuals that a FDA-authorized mRNA bivalent COVID-19 booster vaccine is not accessible or clinically appropriate, and
  -for individuals 18 years of age and older who elect to receive the Novavax COVID-19 Vaccine, Adjuvanted because they would otherwise not receive a booster dose of a COVID-19 vaccine.
• Janssen - Johnson & Johnson COVID-19 Vaccine (Janssen COVID-19 Vaccine, Ad26.COV2-S)
  Vaccine platform: Non-Replicating Viral Vector
  Janssen COVID-19 Vaccine is composed of a recombinant, replication-incompetent human adenovirus type 26 vector that expresses the SARS-CoV-2 spike (S) antigen to elicit an immune response and protect against COVID-19. The FDA originally granted Emergency Use Authorization (EUA) for Janssen COVID-19 Vaccine on February 27, 2021 for active immunization to prevent COVID-19 caused by SARS-CoV-2. On May 5, 2022,  the FDA limited the use of Janssen COVID-19 vaccine to individuals 18 years of age and older for whom other authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, or individuals who elect to receive the Janssen COVID-19 Vaccine because they would otherwise not receive a COVID-19 vaccine. Janssen COVID-19 Vaccine is given to patients who fit the criteria above, as a single-dose primary regime with a single booster dose which is given at least 2 months after other primary dose.

Treatments

• Remdesivir (Veklury) The original  FDA approval has now been expanded for treatment for COVID-19 patients who are 28 days of age and older, who weigh at least 3 kilograms (about 7 pounds). Patients must have a positive SARS-CoV-2 viral test, be hospitalized, or non hospitalized patients must have mild-to-moderate COVID-19 and be at high risk for progression to severe COVID-19, including hospitalization or death.
  Remdesivir is a SARS-CoV-2 nucleotide analog RNA polymerase inhibitor (an antiviral drug with broad-spectrum antiviral activity).
• Bamlanivimab (LY-CoV555) is a recombinant, neutralizing human IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2.
  Bamlanivimab is no longer authorized to be used as a monotherapy, to treat recently diagnosed COVID-19, after the FDA Emergency Use Authorization (EUA) was revoked on April 16, 2021.
  A combination therapy consisting of bamlanivimab and etesevimab (see below) is now available. Bamlanivimab and etesevimab has two separate Emergency Use Authorizations, one for the treatment of COVID-19 and another for post-exposure prophylaxis.
• Baricitinib (Olumiant) was FDA approved on May 10, 2022, to treat COVID-19 in patients 18 years and older who are hospitalized and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
  Baricitinib has an Emergency Use Authorization (EUA) received from the FDA on July 28, 2021 to treat COVID-19 in hospitalized pediatric patients 2 years to less than 18 years of age, who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO.
  Previously the EUA required that Baricitinib had to be used with remdesivir (Veklury), but this requirement has been revoked and it can now be used without remdesivir.
  Baricitinib is Janus kinase (JAK) inhibitor
  Baricitinib is marketed under the brand name Olumiant and is also an FDA approved medicine for the treatment of rheumatoid arthritis and adult patients with severe alopecia areata.
• Bebtelovimab has had the EUA revoked on November 30, 2022 because it is not expected to neutralize Omicron subvariants BQ.1 and BQ.1.1. Bebtelovimab is a monoclonal antibody that was used for the treatment of specific patients who have COVID-19. It binds to the spike protein of the virus that causes COVID-19 and works against the omicron variant and the BA.2 omicron subvariant. The FDA originally granted Emergency Use Authorisation on February 11, 2022 for mild to moderate COVID-19 patients, who are 12 years of age and older, weighing at least 40 kilograms (88 pounds). They must have a positive COVID-19 test, and be at high risk of progression to severe COVID-19, including hospitalization or death, and unable to use alternative COVID-19 treatment options that are approved or authorized by the FDA, as they are not accessible or clinically appropriate.
  Bebtelovimab is not currently authorized for emergency use in any U.S. region at this time.
• Casirivimab and Imdevimab (REGEN-COV, Ronapreve) is unlikely to be effective against the omicron COVID-19 variant. For this reason the EUA has been amended to state that it can only be used for patients who are infected with a COVID-19 variant that is susceptible to carsirivimab and imdevimab. It was originally granted Emergency Use Authorization by the FDA on November 21, 2020 for the treatment of mild to moderate COVID-19 in patients.  They must be at high risk for progression to severe COVID-19 and must be 12 years or older and weigh at least 40kg. The EUA was expanded  so that REGEN-COV could be used as post-exposure prophylaxis in patients who are at high risk of severe COVID-19.
• Bamlanivimab and Etesevimab is a combination of two monoclonal antibodies that work to block the infectivity of the SARS-CoV-2 virus. It is unlikely to be effective against the omicron COVID-19 variant. For this reason the EUA has been amended to state that it can be used only for patients who are infected with a COVID-19 variant that is susceptible to Bamlanivimab and Etesevimab. It was originally authorized to be used for COVID-19 by an Emergency Use Authorization (EUA) on 9 February 2021. An amendment to the EUA means that Bamlanivimab and Etesevimab can be used by neonates, pediatric patients and adults.
  It can be used as treatment of mild to moderate COVID-19 in patients who have a positive SARS-CoV-2 viral test and are at high risk of progressing to severe COVID-19, including hospitalization or death.
  Another amendment to the EUA means it can also be used as post-exposure prophylaxis (prevention) for people who have close contact with an someone who infected with SARS-CoV-2, or who are at high risk of exposure to a SARS-CoV-2 infected individual in an institutional settings such as a nursing homes, prisons etc. It can only be used as post-exposure prophylaxis by people who are at high risk of progression to severe COVID-19, including hospitalization or death, and are not fully vaccinated, or who are not expected to develop an adequate immune response to a complete SARS-CoV-2 vaccination series.
• Evusheld (AZD7442, tixagevimab with cilgavimab) has been issued an Emergency Use Authorization (EUA) for pre-exposure prevention of COVID-19 in a specific group of patients.  Tixagevimab and cilgavimab are long-acting monoclonal antibodies that block the virus’ attachment and entry into human cells by binding to different but overlapping sites on the virus’ spike protein.
  Evusheld can be used by patients who are 12 years and older and weigh at least 40 kg (approximately 88 pounds).  Patients must not currently be infected with SARS-CoV-2 virus and not recently be exposed to the virus. They must also have a moderate to severely compromised immune system or be unable to be vaccinated against COVID-19 due to severe adverse reaction to available vaccines and/or the components of the vaccine. Evusheld may be effective for pre-exposure prevention of COVID-19 for six months and after this time a repeat dose may be given.
• Kineret (Anakinra ) is an interleukin-1 (IL-1) receptor antagonist that works to reduce acute severe lung inflammation. Kineret received Emergency Use Authorization (EUA) on November 8, 2022  to treat COVID-19 in hospitalized adults with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR).  Kineret is also FDA approved to treat  severe rheumatoid arthritis in adults, neonatal onset multisystem inflammatory disease (NOMID) in newborn babies, and deficiency of interleukin-1 receptor antagonist (DIRA) in adults and children.
• Molnupiravir (Lagevrio®, MK-4482) is Merck's oral antiviral capsule that is a potent ribonucleoside analog that inhibits the replication of SARS-CoV-2, the virus that causes COVID-19.
  On December 23, 2021 the FDA issued an Emergency Use Authorization (EUA) for molnupiravir as a treatment of COVID-19 for patients 18 years and older, who are at risk developing severe illness, including hospitalization or death. Patients must have have a current diagnosis of mild-to-moderate COVID-19, and they must also be unable to use alternative COVID-19 treatment options, due to being inaccessible or being clinically inappropriate. Molnupiravir should be started within 5 days of first COVID-19 symptoms.
• Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged) previously called PF-07321332: Nirmatrelvir is an oral SARS-CoV2-3CL protease inhibitor and ritonavir slows the metabolism of nirmatrelvir making nirmatrelvir more effective. 
  On December 22, 2021 the FDA issued an Emergency Use Authorization for Paxlovid for the treatment of mild-to-moderate coronavirus disease (COVID-19).  Paxlovid can be taken by patients 12 years and older who weigh at least 40kg (88lb), have a current diagnosis of mild-to-moderate COVID-19 and are at a high risk of progressing to severe COVID-19, including hospitalization or death. Paxlovid should be started with 5 days of first COVID-19 symptoms.
  Paxlovid may be prescribed for an individual patient by physicians, advanced practice registered nurses, and physician assistants that are licensed or authorized under state law to prescribe drugs. It may also be prescribed for an individual patient by a state-licensed pharmacist under specific conditions.
• Tocilizumab (Actemra) was granted FDA approval  on December 21, 2022 for the treatment for adult patients that are hospitalized with COVID-19 and who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
  Tocilizumab is also available under Emergency Use Authorisation for pediatric patients (2 years old to less than 18 years of age) with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO.

Investigational Treatments

• Bemcentinib: An AXL kinase inhibitor called bemcentinib has been fast-tracked in a UK Phase II clinical trial to study its effectiveness in the treatment of hospitalized patients with COVID-19. Bemcentinib has previously been studied in cancer patients and has been shown to be safe and well-tolerated. It has also been reported to exhibit potent antiviral activity in preclinical models against several enveloped viruses, including Ebola and Zika virus, and recent data have expanded this to include SARS-CoV-2.
• Bevacizumab: A VEGF inhibitor called bevacizumab (marketed under the brand name Avastin for certain types of cancer) being studied as a treatment for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in critically ill patients with COVID-19. Early studies show an improvement of oxygenation and shortening of duration of oxygen-support, but more randomized controlled trials are warranted.
• Chloroquine phosphate: The older anti-malaria drug chloroquine was studied for effectiveness for COVID-19 but scientific data showed that chloroquine was unlikely to be effective for COVID-19 and also caused serious adverse effects. For these reasons on June 15, 2020 the FDA revoked the emergency use authorization (EUA) that had allowed chloroquine phosphate to be used for covid-19 patients.
• Colchicine: An older anti-inflammatory drug called colchicine is being studied to prevent complications of COVID-19 in high risk patients. Colchicine has long been used in the treatment of gout.
• Convalescent Plasma: On 6 December, 2021, The World Health Organisation (WHO) updated the Therapeutics and COVID-19: living guidelines to recommend against the use of convalescent plasma for treatment of non-severe COVID-19 patients. It also recommended against using convalescent plasma for treatment of severe or critical COVID-19 patients, unless it is part of a clinical trial.">updated the Therapeutics and COVID-19: living guidelines to recommend against the use of convalescent plasma for treatment of non-severe COVID-19 patients.  It also recommended against using convalescent plasma for treatment of severe or critical COVID-19 patients, unless it is part of a clinical trial.
  On August 23, 2020, the FDA issued an emergency use authorization (EUA) for investigational convalescent plasma for the treatment of COVID-19. Studies have been completed with varying results, including the clinical trial SIREN-C3PO  (NCT04355767) which showed convalescent plasma did not prevent disease progression of COVID-19. Another clinical trial NCT04338360 for hospitalized COVID-19 patients who were not receiving mechanical ventilation showed convalescent plasma transfusion with higher anti–SARS-CoV-2 IgG antibody levels lowered the risk of death compared to patients given convalescent plasma with lower levels of anti–SARS-CoV-2 IgG antibody levels. 
• Dexamethasone: Results of the RECOVERY clinical trial (NCT04381936) showed that the cheap and widely available steroid dexamethasone reduced the 28-day mortality in hospitalized COVID-19 patients who were receiving respiratory support. The NIH COVID-19 treatment guideline lists dexamethasone as a treatment for hospitalized adult COVID-19 on oxygen support. The trial also showed that there was no benefit and in fact may possibly cause harm to COVID-19 patients who did not require oxygen. 
• Favipiravir: (FabiFlu®) An antiviral drug called favipiravir which was reported February 17, 2020 to have received marketing approval in China for the treatment of influenza, was also approved for use in clinical trials as a treatment for novel coronavirus pneumonia. On March 31, 2020, Fujifilm announced the start of a Phase 3 clinical trial of Avigan (favipiravir) on COVID-19 patients in Japan. Avigan is approved in Japan for use as an antiviral in the treatment of influenza. On April 9, 2020 -- Fujifilm announced the start of a Phase 2 clinical trial of favipiravir in approximately 50 COVID-19 patients in the U.S. On June 19, 2020, Glenmark Pharmaceuticals Limited announced the marketing approval of favipiravir (FabiFlu®) for the treatment of mild to moderate COVID-19 patients in India.
• Fluvoxamine: The selective serotonin reuptake inhibitor (SSRI) antidepressant fluvoxamine may work to prevent serious illness in COVID-19 patients who aren't yet hospitalized according to a small study. The current National Institutes of Health (NIH) COVID-19 treatment guidelines report that there is still insufficient evidence either for or against the use of fluvoxamine for the treatment of COVID-19.
• Hydroxychloroquine and azithromycin: The results of large, randomized controlled trials have failed to show a benefit using a combination of the anti-malaria drug hydroxychloroquine and the macrolide antibacterial drug azithromycin (Zithromax) to treat COVID-19.
  The National Institutes of Health (NIH) recommends against the use of hydroxychloroquine and azithromycin for COVID-19.
• Hydroxychloroquine sulfate: Early in the COVID-19 pandemic, clinical trials studied the effect of the malaria drug hydroxychloroquine on COVID-19. The RECOVERY Trial (NCT04381936) was a large, randomized, controlled, open-label, platform trial comparing hydroxychloroquine treatment with usual standard care for COVID-19. The results indicated that patients treated with hydroxychloroquine did not have a lower level of deaths, and hydroxychloroquine did not provide other benefits in patients hospitalized with COVID-19.
  The emergency use authorization (EUA) that had been issued by the US FDA  in March 2020 to allow the emergency use of hydroxychloroquine sulfate for the treatment of COVID-19 in certain hospitalized patients, was revoked on June 15, 2020.
  The National Institutes of Health (NIH) recommends against the use of hydroxychloroquine for COVID-19.
  Hydroxychloroquine was first approved by the FDA in 1995 under the brand name Plaquenil, and it is used in the treatment of patients with lupus and arthritis.
• Ivermectin: An anti-parasitic drug called ivermectin is currently being investigated as a treatment for coronavirus SARS-CoV-2, which is the virus that causes COVID-19. The FDA has not approved ivermectin for use in treating or preventing COVID-19 in humans. The World Health Organization (WHO) recommend not to use ivermectin in patients with COVID-19, except in clinical trials.
• Lenzilumab is a GM-CSF (Granulocyte-macrophage colony-stimulating factor) neutralizing monoclonal antibody that has been studied to reduce the excessive  inflammatory response that may occur in COVID-19.
  The phase 3 randomized, double-blind, placebo-controlled clinical trial called LIVE-AIR showed that early use of lenzilumab improved the chance of survival without the need for mechanical ventilation. Patients included in the study were hospitalized with COVID-19, required supplemental oxygen but had not yet progressed to invasive mechanical ventilation.
• Leronlimab: A CCR5 antagonist called leronlimab has shown promise in calming the 'cytokine storm' in a small number of critically ill COVID-19 patients hospitalized in the New York area.
• Lopinavir and ritonavir: A drug combination of lopinavir with ritonavir has been studied as a treatment for COVID-19 in a number of large, randomized controlled trials, with the results showing a lack of clinical benefit. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial using lopinavir with ritonavir was discontinued after the data showed no decrease in mortality and similar lengths of hospital stay times.  The NIH recommends against using lopinavir with ritonavir for hospitalized or non hospitalized patients.
• Methylprednisolone: A widely used glucocorticoid called methylprednisolone is being studied for safety and effectiveness in the treatment of hospitalized COVID-19 patients. Methylprednisolone is used in severe COVID-10 for its anti-inflammatory effect as it reduces the systemic inflammatory response that leads to lung injury and multisystem organ dysfunction.  The NIH COVID-19 treatment guidelines  indicate methylprednisolone can be used if dexamethasone is unavailable. Clinical trial results comparing treatment with dexamethasone to methylprednisolone in hospitalized patients with severe SARS-CoV2 Pneumonia showed both statistically significantly reduced recovery time and the need for transfer to intensive care.
• MK-7110 (formerly CD24Fc): is a potentially first-in-class investigational recombinant fusion protein. In April 2021, Merck announced the discontinuation of the development of MK-7110 and instead focus its pandemic efforts on advancing molnupiravir and on producing Johnson & Johnson’s COVID-19 vaccine. MK-7110 works by modulating the inflammatory response to SARS-CoV-2, principally by targeting a novel immune pathway checkpoint. Interim results from a Phase 3 study showed a greater than 50 percent reduction in the risk of death or respiratory failure in patients hospitalized with moderate to severe COVID-19.
• Peginterferon Lambda: Clinical trials using Peginterferon Lambda to treat COVID-19 have been completed with varying results. In one trial on non hospitalized COVID-19 patients Peginterferon Lambda increased the proportion of patients with viral clearance by day 7, which could potentially prevent clinical deterioration. In another trial non hospitalized patients with uncomplicated COVID-19 did not have a significant reduction time in viral clearance or resolution of symptoms when compared with placebo.
• Zyesami (RLF-100: aviptadil) is a formulation of vasoactive intestinal polypeptide (VIP) which binds to alveolar type 2 cells in the lungs inhibiting pro-inflammatory cytokines. Zyesami is currently enrolling patients for Phase 3 trials for hospitalized patients with life-threatening cases of COVID-19 and is part of the  NIH Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) public-private partnership.  It is a randomized, blinded, placebo-controlled clinical trial using Zyesami and the antiviral remdesivir (Veklury) both alone and in combination, to treat hospitalized COVID-19 patients who are experiencing Acute Respiratory Distress Syndrome (ARDS).
• Sarilumab: An interleukin-6 (IL-6) receptor antagonist called sarilumab (marketed under the brand name Kevzara for the treatment of rheumatoid arthritis) has been studied in critically ill COVID-19 patients who were in an intensive care unit (ICU).  Results showed sarilumab improved patient outcomes including survival.  The NIH COVID-19 treatment guidelines have sarilumab as an alternative if tofacitinib is not available, for treatment of hospitalized patients who require oxygen delivery through high-flow device or non invasive ventilation, or invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). 
• Sotrovimab (Xevudy) is no longer authorized to treat COVID-19 in the United States from 5 April 2022.  The authorization was canceled as it is unlikely to be effective against Omicron BA.2, the most common variant of COVID-19 at this time.
  It is a monoclonal antibody designed to block SARS-CoV-2 viral entry into healthy cells and clear infected cells.
• Statins: Statins (HMG CoA reductase inhibitors): The family of cholesterol lowering medications are studied to determine whether they can reduce severity of COVID-19.  Statins are thought to have an anti-inflammatory and immunomodulatory effect. Currently the recommendations for NIH is that if you are already taking a statin prescribed for your health condition, and then get COVID-19 you should continue taking your statin as prescribed.  NIH does not recommend starting statins when you get COVID-19 if you have not been prescribed it for a health condition previously.
• STC3141: An investigational drug called STC3141 has been approved to commence phase II clinical research in Australia for the treatment of acute respiratory distress syndrome (ARDS) suffered by COVID-19 patients.
• Umifenovir: An antiviral drug called umifenovir (marketed in Russia under the brand name Arbidol, and also available in China for the treatment of influenza) is being studied in China and other countries as a treatment for COVID-19.

Investigational Vaccines

Several pharmaceutical companies and research organizations worldwide are involved in the development of potential vaccines.

• BBIBP-CorV (Vero cells)  (Also known as Sinopharm BIBP COVID-19 vaccine) Vaccine platform: Inactivated
  On May 26, 2021 JAMA  published a prespecified interim analysis of the Phase 3 trial which showed that the vaccine was 78.1% effective against symptomatic cases and 100% against severe cases.
• Convidecia (Ad5-nCoV, Pakvac) Vaccine platform: Non Replicating Viral Vector
  CanSino Biologics Inc. has announced that its recombinant novel coronavirus vaccine (Adenovirus Type 5 Vector) candidate (Ad5-nCoV), co-developed with Beijing Institute of Biotechnology (BIB), has been approved to enter into a Phase 1 clinical trial in China. The company announced on February 25, 2021 interim analysis data of the phase III clinical trial of Convidecia shows it has overall efficacy of 65.28% at preventing all symptomatic COVID-19 disease 28 days after single-dose vaccination.
• CoronaVac Vaccine Platform: Inactivated
  Sinovac Biotech Ltd. interim results of double-blind, randomised, placebo-controlled Phase 3 trials  (NCT04582344) showed high efficacy for preventing symptomatic COVID-19 (83·5% relative to placebo) and COVID-19-related hospitalisation (100%) at least 14 days after the second dose.
• COVAC1 (LNP-nCoVsaRNA) Vaccine platform: RNA Vaccine
  COVAC1 is a self-amplifying RNA (saRNA) that is lipid nanoparticle (LNP) encapsulated.
  Imperial College London announced in a Preprint with THE LANCET that Phase 1 dose-ranging trial that 87% of the 192 people had a strong antibody response to COVAC1.
• CVnCoV Vaccine platform: mRNA vaccine
  CureVac AG announced October 12, 2021 that CVnCoV will be withdrawn from regulatory review as CureVac will shift their focus of COVID-19 vaccine development to second-generation mRNA technology.   Phase 2b/3 randomized, observer-blind, placebo-controlled studies had been initiated in December 2020 to assess the dose and efficacy of CVnCoV.
• GX-19 Vaccine platform: DNA vaccine
  Genexine announced the approval of a clinical phase 1/2a trial of DNA vaccine GX-19 in Korea.
• INO-4800 Vaccine platform: DNA vaccine
  Inovio Pharmaceuticals, Inc. announced on April 6, 2020 FDA acceptance of the Investigational New Drug (IND) application for its DNA vaccine candidate INO-4800, paving the way for a Phase 1 clinical trial. On June 30, 2020, the company announced positive interim clinical data from the Phase 1 trial, with plans to initiate a Phase 2/3 efficacy trial upon regulatory concurrence. On September 28, 2020, Inovio announced that the planned Phase 2/3 trial of INO-4800 has been put on partial clinical hold at the request of the FDA.  On November 09, 2021 the FDA lifted the partial clinical hold and therefore provided authorization to proceed for Phase 3 trial for its COVID-19 Vaccine Candidate, INO-4800.
• MRT5500 Vaccine platform: mRNA vaccine
  On September 28, 2021 Sanofi announced it will not pursue the development of MRT5500 and will instead focus on the final development stages of its recombinant COVID-19 vaccine in conjunction with GSK.  Initial data from a Phase 1/2 study showed positive interim results with neutralizing antibody seroconversion in 91% to 100% of study participants, two weeks after the second injection.
• SCB-2019 (CpG 1018/Alum) Vaccine platform: Protein Subunit
  On Sep 22, 2021 Clover Pharmaceuticals announced that the randomized, double-blinded, placebo-controlled Phase2/3 SPECTRA Trial had met its primary and secondary endpoints. Efficacy against severe COVID-19 and hospitalization was 100%, and efficacy against moderate-to-severe COVID-19 was 84%.  Efficacy against any severity of the Delta variant of COVID-19 was 79%.  The SCB-2019 antigen is combined with CpG 1018 advanced adjuvant and aluminum hydroxide (alum).
• Sputnik V (Gam-COVID-Vac) Vaccine platform: Non-Replicating Viral Vector
  On February 2, 2021 interim analysis of results of randomised controlled Phase 3 trial showed Gam-COVID-Vac had a 91.6% efficacy against COVID-19. It is a combined vector vaccine based on recombinant adenovirus type 26 (rAd26)  and recombinant adenovirus type 5 (rAd5)  which are administered intramuscularly separately with a 21-day interval.
• V590 and V591 Vaccine platform: Replicating Viral Vector
  Merck announced a collaboration with IAVI (International AIDS Vaccine Initiative) to develop an investigational vaccine against SARS-CoV-2, using the recombinant vesicular stomatitis virus (rVSV) technology that is the basis for its Ebola Zaire virus vaccine (Ervebo). On January 25, 2021, the company announced that it was discontinuing the development of its SARS-CoV-2/COVID-19 vaccine candidates (V590 and V591) and confirmed plans to switch focus instead to advancing its therapeutic candidates.
• Vaxzevria (formerly AZD1222, ChAdOx1 nCoV-19) Vaccine platform: Non-Replicating Viral Vector
  Vaxzevria was developed by Oxford University’s Jenner Institute, with AstraZeneca responsible for development and worldwide manufacturing and distribution.  A randomised, double-blinded, placebo-controlled phase III study  (D8110C00001) of Vaxzevria in the United States, Peru and Chile showed vaccine efficacy was 62.6%  in patients who had had two doses within the recommended dosing interval.  Vaxzevria is authorised for use in the European Union.
• VXA-CoV2-1 Vaccine platform: Non-Replicating Viral Vector
  On May 3, 2021 Vaxart announced VXA-CoV2-1 would move into Phase 2 studies. It is an oral tablet COVID-19 vaccine which targets both the spike protein (S) and nucleoprotein (N).

More information

• Information for Clinicians on Therapeutic Options for COVID-19 Patients (CDC)
• COVID-19 Treatment Guidelines (NIH)
• Assessment of Evidence for COVID-19-Related Treatments (ASHP)
• "Solidarity" Clinical Trial for COVID-19 Treatments (WHO)
• Convalescent plasma therapy
• DRAFT Landscape of COVID-19 Candidate Vaccines (WHO)
• Fact Sheet: Explaining Operation Warp Speed (U.S. Department of Health & Human Services)