Potential Treatments

There are no specific therapies yet approved by the United States Food and Drug Administration (FDA), the World Health Organization (WHO), or the Centers for Disease Control and Prevention (CDC) for the treatment of the virus Severe Acute Respiratory Syndrome 2 (SARS-CoV-2), which causes the disease COVID-19. At least 25 drugs are under the process of investigation, with 10 in clinical trials.

Listed below are some of the treatment options being considered and clinical trials are underway to evaluate them:

Vaccines 

The first vaccine was developed only 4 weeks after the genetic sequence of SARS-CoV-2 was provided by China. Ultimate development of a successful vaccine may prove challenging, as there is new data showing that different strains of SARS-CoV-2 may exist. 

  • Vaccine “mRNA1273” was implemented in a phase 1 trial which began on 3/26/20 in Washington State. If deemed successful and safe, it may take 9-12 months to become available for the public. 

  • Vaccine Adenovirus Type 5 Vector 

  • 52 other vaccine candidates are currently within the pre-testing stage.

Antimicrobial Therapy (Antimalarials)

Chloroquine & Hydroxychloroquine

  • Hydroxychloroquine
    5X more potent than Chloroquine.
    Both have lab proven activity against SARS-CoV-2. Clinical trials are underway for both of these medications. Both have been used in China and South Korea with favorable results. In some situations, azithromycin has been used in combination with hydroxychloroquine. On 3/28/20, the Food and Drug Administration (FDA), used the Emergency Use Authorization (EUA) order to allow the use of hydroxychloroquine / chloroquine to treat COVID-19 patients (not equivalent to the FDA officially approving the drug for this indication).

    • In a United States veteran hospital-based study of 368 patients with COVID-19, hydroxychloroquine, either with or without Azithromycin, did not reduce the risk for mechanical ventilation and actually increased mortality rates in those given hydroxychloroquine alone.

    • Though yet uncertain, these medications may work by disruption at various levels of viral replication, assembly, and release. Both agents inhibit virus receptor binding by having effects on the ACE2 receptor and increasing the pH within cells, therefore having a negative effect on viral release from a host cell. It may inhibit pro-inflammatory cytokine production, therefore reducing the inflammatory cascade.

    • Side Effects: Cardiac rhythm disturbances and retinal damage (if used long term)

  • Azithromycin (Antibacterial)
    Has been shown to suggest potential benefit as an adjunct therapy in conjunction with hydroxychloroquine in a small open-label, non-randomized clinical trial.

    • Side Effects: Cardiac rhythm disturbances

AntiViral Therapy

Lopinavir - Ritonavir
FDA approved treatment of Human Immunodeficiency Virus (HIV) infection. It has been used in the past for SARS and is currently being evaluated as a treatment for Middle East Respiratory Syndrome (MERS). It has in lab and animal model activity for SARS-CoV and MERS-CoV and used in China in conjunction with interferon alpha to treat certain COVID-19 patients. 

  • Though it is uncertain, these medications may inhibit viral replication. Clinical trials are underway.

  • Side Effects - Cardiac rhythm disturbances, increased liver toxicity, and drug interactions

Remdesivir
An experimental anti-viral with significant activity against multiple coronaviruses, including animal models of MERS, was granted “expanded access” (for severely ill COVID-19 patients) by the FDA. Results of the first ever COVID-19 focused placebo control trial run by the National Institute of Allergy and Infectious Diseases (NIAID) showed that Remdesivir treated patients recovered quicker (11 days / 28% faster) compared to placebo (15 days). It has been given to several hundred patients with severe cases of COVID-19 in the United States, Europe, and Japan (outside of clinical trials).

  • Though not certain, this medication works by inhibiting viral replication. In lab data suggests antiviral activity against SARS-CoV-2. Multiple clinical trials are already underway.

Immunomodulating Therapy

A normal response to a viral infection involves multiple different cell types of the immune system. Ultimately these cells work by triggering the production of various proteins (cytokines), which make up the inflammatory cascade, playing different roles against viral infection.

In some patients, however, the viral infection triggers an exaggerated, overwhelming immune response in the form of overproduction of certain inflammatory cytokines (“cytokine storm”), leading to further tissue damage. This is seen in some severe cases of COVID-19 that progress to having ARDS.

Some evidence supports that the degree of severity of COVID-19 illness is related to the amount of pro-inflammatory cytokines produced.

Severe COVID-19 disease is associated with the production of a different subset of cytokines compared to non-severe disease.

  • Severe Lung Disease
    Interleukin-1 (IL-1), IL-2, IL-6, IL-7, IL-10, IL-17, Tumor Necrosis Factor Alpha (TNF-Alpha), and Interferon-Gamma (INF-Gamma).

  • Tocilizumab
    Interleukin-6 (IL-6) Receptor-Inhibiting Monoclonal Antibody

    • Since the Systemic Inflammatory Response Syndrome (Cytokine release syndrome / “cytokine storm”) is proposed to be a significant aspect of severe COVID-19 disease, this medication blocks one of the inflammatory proteins (IL-6) and therefore inhibits further immune mediated inflammatory damage throughout the body.

    • It is an adjunct to antiviral therapy and initial data suggests that it may have clinical benefit 

    • Side Effects:

      • Gastrointestinal perforation

      • Liver damage

      • Infusion-related reactions

      • Low white blood cell count and low platelet count

  • COVID-19 Immune Globulin
    Plasma collected from those patients who have fully recovered from COVID-19 disease

    • Contains antibodies to SARS-CoV-2

    • Currently in clinical trials with rationale only to treat severe or life threatening cases of COVID-19

  • Intravenous Immune Globulin (IVIG)
    Immunoglobulin G from multiple healthy donors

    • Unknown mechanism of action and has showed efficacy in treating SARS and MERS.

  • Human Recombinant Soluble ACE2 (hrs ACE2)

    • Elevates the levels of ACE2 in the body, therefore increasing protection to tissues.

    • In phase I / II trials, it has shown to decrease SARS-CoV-2 infection in certain cell lines and prevented SARS-CoV-2 infection in human engineered blood vessels and kidney cell lines.

Corticosteroids

Though not recommended for the direct treatment of viral pneumonia, their use is focused on those individuals that suffer from secondary shock or acute respiratory distress syndrome (ARDS).

Other potential Modalities of Care

Diminazene aceturate, resorcinolnaphthalein, xanthenone
ACE2 activators can therefore increase protection against lung injury, including ARDS.

Apheresis System
EUA given by the FDA

  • Separates plasma from whole blood and filters out inflammatory cytokines.

  • Only to be used in ICU patients with confirmed or imminent respiratory failure.

Tofacitinib, Baricitinib, Ruxolitinib
(All in clinical Trials): Janus Kinase (JAK) Inhibitors

  • Block one or more JAK enzymes (JAK 1, JAK 2, JAK 3, TYK2), ultimately resulting in the reduction of other pro-inflammatory cytokines downstream including, but not limited to, IL-6.

  • Anakinra: IL-1 Inhibitor (studies in clinical trials)

  • Colchicine (Anti-inflammatory): May reduce production of TNF - alpha and IL-6 (Trials underway)