COVID-19: Prevention & Investigational Treatments

Updated – July 2, 2020 J.Stewart BPharm

• What is COVID-19
• Symptoms
• Transmission
• Prevention
• If you are sick
• Risk factors
• Investigational treatments
• Off label drugs

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.

Serious illness from the infection is caused by the onset of pneumonia and acute respiratory distress syndrome (ARDS).

Stay up to date on COVID-19

Symptoms

The most common symptoms of COVID-19 include dry cough, fever, and shortness of breath. It is thought that symptoms can appear between 2-14 days after exposure although there have been isolated cases which suggest this may be longer. If you develop symptoms, you should stay at home to prevent the spread of the disease into the community. Wearing a face mask will help prevent the spread of the disease to others.
Update: March 10, 2020 — According to research published in the Annals of Internal Medicine, the median incubation period is estimated to be 5 days, and almost all (~98%) patients who have been infected will develop symptoms within 12 days. 
Update: April 14, 2020 — A new study suggests losing your sense of smell and taste is an early sign of COVID-19.
Update: April 27, 2020 — CDC adds six new symptoms to its list of COVID-19 symptoms to include: chills, repeated shaking with chills, muscle pain, headache, sore throat and new loss of taste or smell.

Transmission

The SARS-CoV-2 virus is thought to spread from person-to-person via: 

• droplet transmission (large respiratory droplets that people sneeze, cough or drip)
• aerosol transmission (when someone coughs or sneezes in the room, aerosolized droplets from talking and singing)
• contact transmission (touching a contaminated surface then touching your mouth, nose or eyes)
• direct transmission (kissing, shaking hands etc.)

Prevention

The best way to prevent infection is to avoid exposure to the virus.

The most important way to prevent COVID-19 is to WASH YOUR HANDS.

Wash your hands regularly and thoroughly with soap and water (lather for 20 seconds) OR use an alcohol based (at least 60%) hand sanitizer.

Other actions that help to prevent the spread of COVID-19:

• avoid contact with others who are sick
• avoid touching your mouth, nose, eyes or face
• cover coughs and sneezes (into a tissue or into your elbow)
• clean and disinfect surfaces (alcohol or bleach based cleaning solutions work best for coronaviruses)
• face masks will not protect you from COVID-19 directly, but can help reduce your risk of exposure to the virus, remind you to avoid touching your face, and will help prevent the spread of the disease to others
• social distancing
• self isolation.

Update: May 8, 2020 Healthy Vitamin D Levels Could Be Linked to COVID-19 Survival

What to do if you are sick

• Prevent the spread of COVID-19 if you are Sick (CDC)
• Environmental Cleaning and Disinfection Recommendations (CDC)

What to do if you come into contact with someone who is sick

Stay at home. If you have been exposed to someone who has tested positive for COVID-19, or someone who is showing symptoms of COVID-19, it may take up to two weeks for your symptoms to present. To keep yourself and others safe, you should isolate yourself from other people for 14 days. 

What is social distancing?

Social distancing means the physical separation of people. To practice social or physical distancing:

• Stay at least 6 feet (2 meters) from other people
• Do not gather in groups
• Stay out of crowded places and avoid mass gatherings

Risk Factors

Scientists are still researching risk factors for COVID-19 but data from China CDC suggest that the elderly, and people suffering from pre-existing medical conditions (such as heart disease, respiratory disease including asthma and COPD, or diabetes) have a higher risk of dying from the disease. There is research that suggests that smokers may be more susceptible to the SARS-CoV-2 virus. There is also evidence to suggest that people who use e-cigarettes (vaping) are at much higher risk of developing serious respiratory infections.
Update: March 16, 2020 — A Chinese study claims to have found that people with type A blood may be more susceptible to the novel Coronavirus (COVID-19).
Update: March 22, 2020 — CDC now includes people aged 65 years and older, people who live in a nursing home or long-term care facility, and people who are immunocompromised including those receiving cancer treatment as those who are at higher risk for severe illness. People with HIV may also be at higher risk of serious illness.
Update: June 25, 2020 — Who’s at Highest Risk From COVID-19? CDC Updates Its List

Investigational Treatments

Currently, there are no FDA approved treatments for COVID-19.

Update: Antiviral Trio Shows Mettle Against COVID-19 May 8, 2020
Update: Lots of Drugs Are Being Tested Against COVID-19 — But Will Any Work? April 23, 2020
Update: The Lowdown on COVID-19 Treatments April 21, 2020

• Baricitinib Phase 3 studies are in progress to determine the effectiveness of a Janus kinase (JAK) inhibitor called baricitinib (marketed under the brand name Olumiant for the treatment of rheumatoid arthritis) in the treatment of COVID-19 patients.
• 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 pneumonia at the Qilu Hospital of Shandong University in Jinan, China.
• Chloroquine phosphate The older anti-malaria drug chloroquine has been shown to have a wide range of antiviral effects, including anti-coronavirus. Studies in Guangdong Province in China suggest that chloroquine may help improve patient outcomes in people with novel coronavirus pneumonia.
• 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.
• Dexamethasone The cheap and widely available steroid dexamethasone reduced the risk for death among seriously ill COVID-19 patients by up to a third, according to researchers at the University of Oxford in England. The drug did not appear to help patients with less serious illness.
• EIDD-2801 A team of researchers at UNC-Chapel Hill is hopeful that a broad spectrum oral antiviral called EIDD-2801 could be used as a potential prophylactic or treatment for COVID-19 and other coronaviruses. Ridgeback Biotherapeutics has licensed EIDD-2801 and has received permission from the FDA to begin patient trials.
  Update: May 26, 2020 — Ridgeback Biotherapeutics and Merck enter collaboration agreement to develop EIDD-2801.
• Favipiravir 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.
• Fingolimod An approved drug called fingolimod (marketed under the brand name Gilenya for the treatment of relapsing forms of multiple sclerosis) is being studied as a treatment for COVID-19 at the First Affiliated Hospital of Fujian Medical University in Fuzhou, China.
• Hydroxychloroquine and azithromycin In a small study commissioned by the French government, 20 patients with COVID-19 were treated with a combination of the anti-malaria drug hydroxychloroquine and the macrolide antibacterial drug azithromycin (Zithromax). Results showed that all patients taking the combination were virologically cured within 6 days of treatment.
  Update: May 14, 2020 — NIH begins clinical trial of hydroxychloroquine and azithromycin to treat COVID-19 (NIH Press Release)
• Hydroxychloroquine sulfate It was reported in the journal Clinical Infectious Diseases on March 9 that the malaria drug hydroxychloroquine was effective in killing the coronavirus in laboratory experiments. Hydroxychloroquine was first approved by the FDA in 1995 under the brand name Plaquenil, and it is also used in the treatment of patients with lupus and arthritis. In March 2020, the US FDA issued an emergency use authorization (EUA) to allow the emergency use of hydroxychloroquine sulfate supplied from the Strategic National Stockpile (SNS) for the treatment of COVID-19 in certain hospitalized patients. On June 15, 2020, the FDA revoked the EUA.
• Ivermectin An anti-parasitic drug called ivermectin has been shown to be effective against the SARS-CoV-2 virus in an in-vitro laboratory study by researchers at Monash University in Melbourne, Australia. Further clinical trials need to be completed to confirm the effectiveness of the drug in humans with COVID-19.
• 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 called lopinavir/ritonavir approved to treat HIV under the brand name Kaletra is being studied in combination with the flu drug oseltamivir (Tamiflu) in Thailand. It was reported on February 18, 2020 that an elderly Chinese woman, the first patient to receive the “Thai cocktail” in Bangkok’s Rajvithi Hospital, had made a complete recovery after suffering from severe COVID-19-related pneumonia.
  Update: March 18, 2020 — According to a study in the New England Journal of Medicine, the lopinavir/ritonavir combination showed no benefit over standard care in hospitalized adult patients with severe COVID-19.
• Methylprednisolone A widely used glucocorticoid called methylprednisolone is being studied for safety and effectiveness in the treatment of novel coronavirus pneumonia in a number of hospitals in the Hubei province of China.
• Remdesivir An investigational antiviral drug called remdesivir is being studied in clinical trials in China, the United States, and the United Kingdom. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens that cause MERS and SARS, which are coronaviruses structurally similar to SARS-CoV-2.
• Sarilumab An interleukin-6 (IL-6) receptor antagonist called sarilumab (marketed under the brand name Kevzara for the treatment of rheumatoid arthritis) is being studied as a potential treatment for acute respiratory distress syndrome (ARDS) in patients critically ill from COVID-19.
• STC3141 An investigational drug called STC3141has been approved to commence phase II clinical research in Australia for the treatment of acute respiratory distress syndrome (ARDS) suffered by COVID-19 patients.
• Tocilizumab An interleukin-6 receptor antagonist called tocilizumab (marketed under the brand name Actemra for the treatment of rheumatoid arthritis and other inflammatory conditions) is being studied in a number of locations worldwide for the treatment of patients with COVID-19. 
• 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.

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

Investigational Vaccines

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

Update: Why Will It Take So Long for a COVID-19 Vaccine? April 6, 2020

• mRNA-1273 Moderna, Inc. has announced positive interim phase 1 data for an mRNA vaccine called mRNA-1273 from a study led by the National Institute of Allergy and Infectious Diseases (NIAID). The Company expects dosing in the Phase 3 study to begin in July 2020.
• AZD1222 (formerly ChAdOx1 nCoV-19) AZD1222 was developed by Oxford University’s Jenner Institute, with AstraZeneca responsible for development and worldwide manufacturing and distribution. A Phase I/II clinical trial of AZD1222 began in April 2020 to assess safety, immunogenicity and efficacy of the vaccine in over 1000 healthy volunteers across several trial centres in southern England.
• INO-4800 Inovio Pharmaceuticals, Inc. has announced 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.
• Ad5-nCoV 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. On June 29, 2020, the company announced the vaccine had received Military Specially-Needed Drug Approval in China.
• NVX-CoV2373 On May 25, 2020, Novavax, Inc. announced the commencement of a Phase 1/2 clinical trial of its coronavirus vaccine candidate, NVX‑CoV2373, a stable, prefusion protein made using its proprietary nanoparticle technology adjuvant (Matrix‑M™) to enhance immune responses and stimulate high levels of neutralizing antibodies. It is the first human trial to be conducted in the southern hemisphere, with approximately 130 participants across two sites in Australia. On July 7, 2020, the company announced that it had been selected to participate in Operation Warp Speed, with funding from the federal government to complete late-stage clinical development, including a pivotal Phase 3 clinical trial and the delivery of 100 million doses of NVX‑CoV2373 as early as late 2020.
• Sinovac Biotech Ltd. has announced the commencement of a Phase I clinical trial for its COVID-19 vaccine candidate to be conducted in Jiangsu Province, China.
• BNT162 Pfizer Inc. and BioNTech SE announced that the first participants have been dosed in the U.S. in the Phase 1/2 clinical trial for the BNT162 vaccine program to prevent COVID-19. The vaccine development program includes four candidates, each representing a different combination of mRNA format and target antigen. On July 1, 2020, it was announced that preliminary data from the Phase 1/2 trial for BNT162b1 demonstrated that the vaccine could be administered in a dose that was well tolerated and generated dose dependent immunogenicity. These results have not yet been peer-reviewed.
• Ad26.COV2-S Johnson & Johnson announced it has accelerated the initiation of the Phase 1/2a first-in-human clinical trial of its investigational SARS-CoV-2 vaccine, Ad26.COV2-S, recombinant.
• Merck has 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).
• SCB-2019 Clover Pharmaceuticals announced that the first participants have been dosed in the Phase 1 first-in-human study evaluating the company’s COVID-19 S-Trimer subunit vaccine candidate (SCB-2019) which is based on its proprietary Trimer-Tag© vaccine technology platform. The Phase I study will evaluate two adjuvant systems – GSK’s pandemic adjuvant system, and Dynavax’s CpG 1018 adjuvant combined with alum.
• COVAC1 Imperial College London announced that it has dosed the first healthy volunteer with its COVAC1 coronavirus vaccine candidate, which has been developed using the new self-amplifying RNA (saRNA) technology.
• GX-19 Genexine announced the approval of a clinical phase 1/2a trial of DNA vaccine GX-19 in Korea.
• CVnCoV CureVac AG announced the approval of a Phase 1 clinical trial for its mRNA vaccine to be conducted in Germany and Belgium.
• An oral COVID-19 vaccine candidate from Vaxart, Inc. has been selected to participate in a non-human primate (NHP) challenge study, organized and funded by Operation Warp Speed.
• In May 2020, the Trump Administration announced the framework and leadership for Operation Warp Speed, a public-private partnership to facilitate, at an unprecedented pace, the development, manufacturing, and distribution of COVID-19 countermeasures, between components of the Department of Health and Human Services (HHS), including CDC, FDA, NIH, and BARDA.
• According to an article in The New York Times on June 3, 2020, the Trump Administration has selected five companies (Moderna Inc, AstraZeneca Plc, Pfizer Inc., Johnson & Johnson, and Merck & Co Inc.) as the most likely candidates to produce a vaccine for the novel coronavirus. HHS did not confirm or deny the report.

More information

• DRAFT Landscape of COVID-19 Candidate Vaccines (WHO)
• Fact Sheet: Explaining Operation Warp Speed (U.S. Department of Health & Human Services)

References

• Centers for Disease Control and Prevention Coronavirus Disease 2019 (COVID-19) https://www.cdc.gov/coronavirus/2019-ncov/index.html Accessed February 18, 2020
• World Health Organization Coronavirus disease (COVID-19) outbreak https://www.who.int/emergencies/diseases/novel- coronavirus-2019 Accessed February 18, 2020
• Shanghai officials reveal novel coronavirus transmission modes https://www.chinadaily.com.cn/a/202002/08/WS5e3e7d97a310128217275fc3.html Accessed February 18, 2020
• Flu and HIV Drugs Show Efficacy Against Coronavirus https://www.the-scientist.com/news-opinion/flu-and-anti-hiv-drugs-show-efficacy-against-coronavirus-67052 Accessed February 18, 2020
• The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application https://annals.org/aim/fullarticle/2762808/incubation-period-coronavirus-disease-2019-covid-19-from-publicly-reported
• Symptoms of Coronavirus https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html Accessed April30, 2020
• Shanghai officials reveal novel coronavirus transmission modes www.chinadaily.com.cn/a/202002/08/WS5e3e7d97a310128217275fc3.html Accessed April30, 2020
• How to Protect Yourself & Others https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Fprevention.html
• Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov https://www.preprints.org/manuscript/202002.0051/v1 Accessed February 18, 2020
• Reduce your risk of serious lung disease caused by corona virus by quitting smoking and vaping https://tobacco.ucsf.edu/reduce-your-risk-serious-lung-disease-caused-corona-virus-quitting-smoking-and-vaping Accessed April 20, 2020
• Relationship between the ABO Blood Group and the COVID-19 Susceptibility https://www.medrxiv.org/content/10.1101/2020.03.11.20031096v2 Accessed March 16, 2020
• People Who Are at Higher Risk for Severe Illness – Older Adults https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/older-adults.html Accessed April 20, 2020
• Clinical trials for Baricitinib https://clinicaltrials.gov/ct2/results?cond=COVID&term=baricitinib&cntry=&state=&city=&dist=  Accessed April 30, 2020
• Clinical trials for Bevacizumab https://clinicaltrials.gov/ct2/show/NCT04275414 Accessed April 30, 2020
• Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia https://pubmed.ncbi.nlm.nih.gov/32075365/ Accessed April 30, 2020
• Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) (COVID-19) https://clinicaltrials.gov/ct2/show/NCT04322682 Accessed April 30, 2020
• Carolina researchers playing a key role in the development of new COVID-19 treatment https://www.unc.edu/posts/2020/04/06/carolina-researchers-key-role-in-the-development-of-new-covid-19-treatment/ Accessed April 30, 2020
• Favipiravir http://global.chinadaily.com.cn/a/202002/17/WS5e49efc2a310128217277fa3.html  Accessed April 30, 2020
• Fingolimod in COVID-19 https://clinicaltrials.gov/ct2/show/NCT04280588 Accessed April 30, 2020
• Hydroxychloroquine and Azitrhomy as a treatment for COVID-19 https://www.mediterranee-infection.com/hydroxychloroquine-and-azithromycin-as-a-treatment-of-covid-19/ Accessed April 30, 2020
• In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) https://pubmed.ncbi.nlm.nih.gov/32150618/  Accessed April 30, 2020
• Lab experiments show anti-parasitic drug, Ivermectin, eliminates SARS-CoV-2 in cells in 48 hours https://www.monash.edu/discovery-institute/news-and-events/news/2020-articles/Lab-experiments-show-anti-parasitic-drug,-Ivermectin,-eliminates-SARS-CoV-2-in-cells-in-48-hours Accessed April 30, 2020
• Bangkok Post https://www.bangkokpost.com/thailand/general/1860329/woman-74-recovers-from-virus-after-thai-cocktail Accessed April 30, 2020
• A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19 https://www.nejm.org/doi/full/10.1056/NEJMoa2001282   Accessed April 30, 2020
• Efficacy and Safety of Corticosteroids in COVID-19 https://clinicaltrials.gov/ct2/show/NCT04273321 Accessed April 30, 2020
• Clinical trials for tocilizumab in COVID-19 https://clinicaltrials.gov/ct2/results?cond=COVID&term=tocilizumab&cntry=&state=&city=&dist= Accessed April 30, 2020
• Clinical trials for umifenovir in COVID-19 https://clinicaltrials.gov/ct2/results?cond=COVID&term=umifenovir&cntry=&state=&city=&dist= Accessed April 30, 2020
• Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis SARS CoV-2 Infection (COVID-19) https://clinicaltrials.gov/ct2/show/NCT04283461  Accessed April 30, 2020
• CSIRO begins testing Covid-19 vaccineshttps://www.csiro.au/en/News/News-releases/2020/CSIRO-begins-testing-Covid-19-vaccines  Accessed April 30, 2020
• MIGAL’s Coronavirus Vaccine Project https://www.migal.org.il/en/node/7010   Accessed April 30, 2020

The following list of medications are in some way related to, or used in the treatment of this condition.

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