All the COVID-19 vaccines and treatments currently in clinical trials – Digital Trends

The coronavirus pandemic is a serious health risk, which is why countries around the world are racing to find vaccines and treatments. Nearly 1,000,000 cases of COVID-19 have been confirmed globally, and by the time you read this, the death toll will have surpassed 50,000.

Some potential treatments listed here were previously in clinical testing for other diseases, such as cancer, allowing the trials for COVID-19 to be fast-tracked. Many arent aimed at the coronavirus itself but instead will hopefully reduce some of the severe side effects the disease causes, like hyperinflammation and respiratory distress.

Notably, many of the proposed treatments have gone through U.S. Food and Drug Administration (FDA) approval for other uses or are currently going through that process, meaning the route to getting approved for a clinical trial to study their effects on COVID-19 patients is shorter and faster than it would be for a new drug. Some of these are being utilized under compassionate use rules, meaning they arent part of clinical trials but are being administered to COVID-19 patients in life-threatening situations.

The path from trial to treatment is long and complex. As new treatments and vaccines make their way to new phases, well update this list. For now, weve excluded those in preclinical phases.

Note: These drugs are all in the early stages of testing for efficacy against COVID-19 and taking them without supervision can have tragic consequences. An Arizona man died after reportedly taking a form of chloroquine used to clean fish tanks. Youll see a long list of potential treatments below, but many of them wont progress to wider testing or use, because theyll prove either unsafe or ineffective.

A vaccine would prevent people from getting sick, instead of treatments to alleviate the system or kill the disease once it has already infected you. Often, vaccines either use an inactive (dead) or live attenuated (less potent) version of the pathogen to build up the bodys defenses. By introducing these weakened forms to the immune system, it can start making antibodies without having to battle the virus itself. Once the body has made antibodies once, it has been trained to recognize the pathogen and can start making them again if the actual virus finds its way inside. Immunity from an inactive vaccine may not last as long, while live-attenuated types have implications for immunocompromised people. In addition, such vaccines havent proven effective for some viruses, like HIV.

Currently, there is no approved vaccine for COVID-19. Coronaviruses caused SARS in the early 2000s and MERS in 2012. The two epidemics were contained before vaccines were created, but some work was started for both. Some companies are building on that research to find a vaccine for COVID-19, which is caused by a novel coronavirus. The Coalition for Epidemic Preparedness Innovations, or CEPI, is an organization helping to accelerate vaccine development. About 35 companies and academic institutions are searching for a COVID-19 vaccine; two in phase-1 clinical trials, and over 40 in preclinical development. A few have begun testing in animals, while biotech firm Modernas attempt has started human trials.

Despite how quickly the research is being developed, there are some aspects of the process that cant be sped up, like widespread testing for side-effects and dosing. Even then, there are logistical hurdles to scaling production and distributing vaccines to affected countries. Experts are predicting it will take 18 months for a vaccine to be widely available.

Non-replicating viral vector; Adenovirus Type 5 vector (Ad5-nCoV): Adenoviruses are common viruses that can lead to bronchitis or pneumonia. Theyve been heavily studied as potential vectors for vaccines, to deliver the antigens that stimulate the production of protective antibodies. These viral vectors can also bolster the immune response in ways traditional vaccines do not.

CanSino Biologics is testing a vaccine candidate in healthy adults, the first phase of clinical testing. In 2017, the company, collaborating with the Chinese Academy of Military Medical Sciences Bioengineering Institute, developed an ebola vaccine. The potential COVID-19 vaccine, AD5-nCoV, is based on the same technology. Its a non-replicating viral vector, so it can infect cells but has been rendered incapable of multiplying. Johnson & Johnson is working on a similar type of vaccine, which will be ready for phase one trials in September.

RNA; LNP-encapsulated mRNA (mRNA 1273): The National Institute of Allergy and Infectious Diseases (NIAID) and Modernas potential vaccine builds on research into the MERS virus. Its a messenger RNA or mRNA vaccine, where a bit of the viruss genetic material gets injected into your muscle. The role of mRNA is to carry genetic information from DNA needed to make proteins. The RNA is packaged in lipid nanoparticles (LNPs), to help effectively deliver it. The mRNA would deliver instructions to cells on how to make proteins to fight the virus. No RNA vaccines have even been approved for human use, but this effort is one of several backed by CEPI.

Monoclonal antibodies (mAb) are used in treatments for cancer and ebola. Made in a laboratory, these molecules work as substitute antibodies, according to the Mayo Clinic, boosting or mimicking the bodys immune system to attack the virus. They can do so in a variety of ways, including flagging cells for destruction and binding to different types of cells. The majority of those being researched for COVID-19 are in the pre-clinical phase, but several are in clinical trials right now.

Actemra (tocilizumab): Small proteins known as cytokines are part of the bodys immune response, released when theres an infection. Inflammation is a side effect, as blood and other fluids flow to the source of infection. A cytokine storm is when an abundance of the proteins cause hyperinflammation, which can lead to serious complications and death. It has been reported in SARS and MERS patients and could be causing some of the more severe symptoms in some people with COVID-19. Interleukins are one group of cytokines. Actemra is a rheumatoid arthritis drug that blocks interleukin-6 (IL-6) to keep it from attacking healthy tissue when the immune system overreacts. It helped several critical COVID-19 patients recover, but a controlled clinical study needs to be performed, according to The Wall Street Journal.

Avastin (bevacizumab): In healthy adults, vascular endothelial growth factor (VEGF) promotes the formation of new blood vessels and is important for healing wounds. Some COVID-19 patients have been shown to have elevated levels of VEGF, possibly due to hypoxia (low blood oxygen) and inflammation. Avastin is a VEGF blocker and has been used to treat several types of cancer for over 15 years. A clinical trial at the Qilu Hospital of Shandong University in Jinan, China will assess its effectiveness at treating shortness of breath.

Gimsilumab: Gimsilumab is a monoclonal antibody that targets a pro-inflammatory cytokine known as a granulocyte-macrophage colony-stimulating factor (GM-CSF). Its presence can elevate the expression of pro-inflammatory cytokines, causing a kind of feedback loop that increases inflammation. GM-CSF has been found in elevated levels of COVID-19 patients admitted to the ICU, according to pharmaceutical company Roivant. It wants to test Gimsilumab as a treatment for acute respiratory distress syndrome (ARDS). The condition is caused by fluid build-up in the lungs air sacs and the breakdown of surfactant, so that lungs cant fully inflate. Targeting GM-CSF represents a promising strategy for curbing lung damage while allowing time for the virus to clear, Dr. Elizabeth Volkmann, founder and co-director of the UCLA Connective Tissue Disease-Related Interstitial Lung Disease Program, said in Roviants press release.

Kevzara (sarilumab): Like Actemra, Kevzara is a rheumatoid arthritis drug that blocks IL-6. Dr. Naimish Patel told The Wall Street Journal why blocking that cytokine could help COVID-19 patients recover: Even though the virus is diminishing, its sending signals to the immune system to keep attacking. Hes head of global development for immunology and inflammation for Sanofi, which makes Kevzara, along with Regeneron.

Leronlimab (PRO 140): CCR5 is a protein on the surface of white blood cells that plays an important role in the way HIV develops in the human body. Leronlimab is a monoclonal antibody being studied as a potential treatment for HIV. It binds to the CCR5 receptor, which inhibits the release of inflammatory cytokines. Biotechnology company CytoDyn modified its clinical trial to evaluate Leronlimabs effect on severe cases of COVID-19.

PD-1 blocking antibody: There are two types of tolerance in your immune system. Central tolerance is the main way it distinguishes your own cells from outside threats, while peripheral tolerance keeps the body from over-reacting when it encounters allergens or microbes. Usually, the protein programmed cell death-1 (PD-1) helps limit T cell activity during infection to reduce inflammation. But if PD-1 binds to another protein, PD-L1, it prevents T cells from attacking cancerous cells. Monoclonal antibodies that block PD-1 are known as immune checkpoints inhibitors (ICIs). Theyve shown success in treating various types of tumors by preventing PD-1 from binding with PD-L1, freeing T cells to target the tumor. Thymosin, meanwhile, targets PD-L1. A clinical trial at Southeast University in China will study the efficacy of PD-1 and thymosin in COVID-19 patients with severe pneumonia caused by lymphocytopenia (low levels of lymphocytes, including T cells).

Sylvant (siltuximab): Another monoclonal antibody that blocks the action of IL-6, siltuximab is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat multicentric Castleman disease (MCD). This rare lymph node disease acts similarly to lymphoma, causing an overgrowth of cells. Doctors at Papa Giovanni XXIII Hospital in Italy will observe its effects on patients with COVID-19, in the hopes it will reduce inflammation in those with severe respiratory disorders.

TJM2 (TJ003234): TJM2, like Gimsilumab, is a monoclonal antibody that targets pro-inflammatory cytokine GM-CSF. In November 2019, the FDA approved it for clinical trials to treat rheumatoid arthritis. I-Mab Biopharma, which makes TJM2, is a U.S.- and China-based biopharmaceutical company. It will now explore the mAbs effectiveness in fighting cytokine storming in patients with serious reactions to COVID-19.

There are a variety of antiviral drugs for diseases like hepatitis, the flu, and herpes many of which could potentially be repurposed to fight coronavirus. They work in different ways to stop the replication of viruses. For example, some flu antivirals are neuraminidase inhibitors. Neuraminidases are enzymes that cut acids and proteins on the surface of virus envelopes, releasing the replicated virus to infect new cells. Neuraminidase inhibitors can help reduce the amount of new viruses that are released inside the human body. The hope is that some of these antivirals will also stop the replication of COVID-19 once a patient has contracted it, lessening the duration or severity of the disease.

Arbidol (umifenovir): This broad-spectrum antiviral blocks virus entry into healthy cells by inhibiting membrane fusion. Its not currently approved by either the EMA or FDA, though it is available in Russia and China. A study at the Guangzhou 8th Peoples Hospital in China will observe its effect on patients with COVID-19. Though people are selling Arbidol on eBay in the U.K., the Medicines and Healthcare Regulatory Agency told The New Statesman, Not only are they breaking the law, they are acting with total disregard of your health.

ASC09: HIV requires protease enzymes to reproduce. Protease inhibitors prevent newly replicated viruses from maturing and invading healthy white blood cells. To see if the same disruption works on COVID-19, China-based biotechnology company Ascletis Pharma will test ASC09 in clinical trials.

Azvudine: Azvudine is a nucleoside reverse transcriptase inhibitor (NRTI). HIV uses the enzyme reverse transcriptase in reverse transcription, converting RNA into DNA. Inhibitors block the enzyme, preventing the virus from replicating. The clinical trial for Azvudines efficacy against COVID-19 will take place at the Peoples Hospital in Guangshan County, China.

Favilavir/Favipiravir/T-705/Avigan: Favipiravir is a broad-spectrum antiviral thats been utilized in Japan to treat influenza. Inside cells, it mimics the organic compound purine and eventually becomes included in the viruss RNA strand as it grows. Exactly how Favipiravir inhibits viral RNA synthesis once its incorporated is unclear, but there is some indication it could be used in COVID-19 patients as well. In clinical trials in China, patients who received the medication tested negative for the virus after a median of four days; those who didnt receive it took 11 days to test negative, according to The Guardian.

Ganovo (danoprevir): Ascletis Pharma developed Ganovo as a direct-acting antiviral agent (DAA) to treat hepatitis C. The efficacy of DAAs in general has been called a monumental advance over previous hepatitis C therapies. Ganovo inhibits the viruss protease, which is necessary for its replication. The effectiveness of Ganovo, in combination with another protease inhibitor (ritonavir), will be tested at Chinas Ninth Hospital of Nanchang.

Kaletra/Aluvia (lopinavir/ritonavir): Kaletra is a combination of protease inhibitors ritonavir and lopinavir, used to treat HIV. Earlier this year, The New England Journal of Medicine published the results of a study of 199 patients with severe COVID-19 patients at Jin YinTan Hospital in China. Those that received the lopinavir-ritonavir treatment saw no difference in the mortality rate. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit, according to the authors of the study.

Prezcobix (darunavir): Like ASC09, Prezcobix is a protease inhibitor, used to treat HIV, in conjunction with a pharmacokinetic enhancer. Cobicistat is one such drug, which slows the breakdown of Prezcobix, allowing it to stay in the body for longer and at a higher concentration. Johnson & Johnson sent Prezcobix to Chinese health authorities in January to gauge its effectiveness in treating COVID-19. The companys chief scientific officer, Paul Stoffels, told The Wall Street Journal that studying the drugs effects in ill patients could help researchers find a treatment that works.

Remdesivir: This drug has gotten more press than many of the other potential treatments. Its a broad-spectrum antiviral, and has been studied as a treatment for Middle East respiratory syndrome (MERS), a respiratory illness that is caused by the same family of viruses as COVID-19. Gilead, the company that makes Remdesivir, hoped the drug would work against Ebola, but it wasnt nearly as effective as two other drugs at preventing death from the disease. Some experts are hopeful that it will have more luck with COVID-19, and there are several clinical trials underway.

Truvada (emtricitabine and tenofovir): You may have seen commercials for this drug for whats known as PrEP (pre-exposure prophylaxis). When taken properly, it can reduce the risk of HIV infection. Truvada is a combination of two antiretroviral medications: emtricitabine and tenofovir. Both prevent HIV from replicating, and while they work in different ways, each blocks the reverse transcriptase enzyme needed for reproduction. The Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital are conducting the clinical trial for Truvada against COVID-19.

Xofluza (baloxavir marboxil): Endonuclease is an enzyme that initiates flu virus replication. Polymerase acidic endonuclease inhibitors, like Xofluza, interfere with that replication. Xofluza received FDA approval in 2018 to treat the flu, and now the First Hospital Affiliated of Zhejiang Universitys Medical School wants to research the drug as a treatment option for COVID-19 patients with pneumonia.

Cellular therapy replaces or repairs damaged cells or tissues and is used in a range of diseases. Many types of cells have been studied for this purpose, including stem, progenitor, and primary cells. Cell therapy is being used and researched for everything from inflammatory bowel disease to cancer. CAR T-cell, for example, is a therapy in which doctors modify a patients T cells to identify and go after cancer cells.

Mesenchymal stem cells: Stem cells can self-renew through cell division and can also differentiate into different types of cells, like bone cells or liver cells. Mesenchymal stem cells (MSCs) are adult stem cells and can be taken from either humans or animals. Pneumonitis, or the inflammation of the walls in the air sacs of the lungs, is one potential side-effect of COVID-19. There has been some research on using MSCs to treat lung damage caused by radiation for cancer treatment. Chinas Institute of Basic Medicine is conducting clinical trials to see the cell therapys effect on COVID-19 patients with pneumonitis.

MultiStem: Biotech company Athersys created MultiStem, a stem cell product made from multipotent adult progenitor cells (MAPCs) derived from bone marrow. MPACs can self-renew and differentiate into several cell types. Acute respiratory distress syndrome (ARDS) is similar to pneumonia; it makes it difficult for the lungs to fully inflate and can lead to serious complications and death. MultiStem already underwent an early-stage clinical trial for treating ARDS, and the results showed the patients had lower mortality rates and were off ventilators more quickly than those who didnt receive the treatment. The company is working with the FDA to fast-track a clinical trial testing for COVID-19, according to WKSU.

RNA therapies are a fairly recent development and are being studied to treat several diseases, including macular degeneration and Zika. The therapies work in a few different ways, either by targeting nucleic acids (DNA or RNA), targeting proteins, or encoding proteins. A therapy might prevent messenger RNA from being translated into protein or it might encode a normal version of a protein instead of a mutated one. Right now, the potential RNA therapies for COVID-19 are all in preclinical phases.

There are a number of other treatments scientists are researching to see if they can help alleviate some of the severe symptoms of COVID-19. They dont necessarily fit into the categories above.

APN01: Scientists have found that during infection, COVID-19s viral trimeric spike protein binds to human receptor angiotensin-converting enzyme 2 (ACE2). One study showed that deactivating ACE2 caused severe lung injury in mice infected with a strain of avian influenza while administering recombinant human ACE2 was effective at lessening the damage. APN01 is a recombinant human angiotensin-converting enzyme 2 (rhACE2) created by Aperion Biologics to treat acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). The company began a clinical trial with APN01 on COVID-19 patients in February. A similar trial is underway at the First Affiliated Hospital of Guangzhou Medical University.

Chloroquine/Hydroxychloroquine: These two antimalarial drugs have been getting a lot of attention, though their efficacy as a treatment for COVID-19 is still unknown. Malaria is caused by a parasite, while COVID-19 is caused by a virus. The reason some researchers are looking at these drugs as potential coronavirus treatments is that chloroquine and other drugs were able to block coronaviruses from infecting cells in laboratory testing. These drugs were researched as possible treatments for MERS during the 2012 outbreak. The mechanism by which these malarial drugs would work against COVID-19 is uncertain, but one hypothesis is they change cells surface acidity, so the virus cant infect them. Or chloroquines might activate the immune system. Chloroquine and hydroxychloroquine have not been appropriately evaluated in controlled studies, not to mention that they have numerous and, in some cases, very deadly side effects, Katherine Seley-Radtke, professor of chemistry and biochemistry at the University of Maryland, wrote at The Conversation. There are a few clinical trials underway looking into their efficacy.

Gilenya (fingolimod): Multiple sclerosis causes the bodys own immune system to attacknerves insulating layer, or myelin. The presence of pro-inflammatory white blood cells in the central nervous system can also damage the myelin sheath. A sphingosine 1-phosphate receptor modulator is believed to keep certain white blood cells (lymphocytes) from leaving the lymph nodes and crossing the blood-brain barrier, where they would further damage nerve cells. Pneumonia is an acute inflammatory response that develops in some people with COVID-19, and the First Affiliated Hospital of Fujian Medical University wants to test this MS drugs effectiveness on reducing its severity.

Jakafi/Jakavi (ruxolitinib): Myelofibrosis is a somewhat rare blood cancer in which fibrous scar tissue replaces spongy bone marrow. Many patients with this and a couple of other types of blood cancer have an acquired mutation in the Janus Kinase 2 gene. It causes bone marrow to produce too many abnormal blood cells. Janus kinase inhibitors, or JAK inhibitors, block the function of these enzymes. Because of their role in cytokine production, JAK inhibitors are also used to treat inflammatory diseases, including rheumatoid arthritis. (Cytokines are a normal part of the bodys response to infection, but an overabundance can lead to hyperinflammation.) Patients with severe reactions to COVID-19 could have an excess of cytokines causing lung inflammation. A clinical trial at Tongji Medical College of Huazhong University of Science and Technology will study the effect of Jakafi and mesenchymal stem cells on COVID-19 patients with pneumonia.

Losartan: Angiotensin is a peptide hormone that constricts blood vessels and raises blood pressure. Angiotensin II receptor antagonists or blockers are prescribed for hypertension because they block the hormone. Losartan is one such drug, and the University of Minnesota is conducting clinical trials to see its effect on lung inflammation in COVID-19 patients.

Methylprednisolone/corticosteroids: Methylprednisolone is a synthetic corticosteroid, which mimics how the bodys hormones work to reduce inflammation. Corticosteroids are used to treat a plethora of conditions, from asthma to lupus to arthritis. Though they were used during severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks, the World Health Organization doesnt currently advise the use of corticosteroids for COVID-19, according to a February article from The Lancet. Clinical trials for glucocorticoid therapy are going forward at Peking Union Medical College Hospital and Tongji Hospital.

Novaferon: Interferons are cytokine mediators that alert the immune system when theres a viral infection. Lab-made interferons are used to treat several diseases, including hepatitis B. Exactly how interferons affect the virus is unclear, but its thought to interfere with its life cycle, while also boosting cell-mediated immunity. Novaferon is one man-made interferon used to treat hepatitis B, and the First Affiliated Hospital of Zhejiang University Medical School will study whether its effective against COVID-19.

Rebif (interferon beta-1a): Interferon beta-1a is an interferon used to treat multiple sclerosis. Exactly how Rebif, an interferon made by Merck KGaA, works in MS patients isnt known, but it does lessen inflammation and reduce the bodys immune response that damages the myelin sheath. The French Institut National de la Sant et de la Recherche Mdicale (INSERM) will use Rebif in a clinical trial, to see if it similarly reduces inflammation in COVID-19 patients.

Washed microbiota transplantation: Some people who take antibiotics end up wiping out their colon of the healthy bacteria that help stave off clostridium difficile (C. difficile), which can lead to a serious infection. Fecal microbiota transplantation (FMT) reintroduces healthy bacteria via a donors stool, transferred by colonoscopy or another procedure. The washed microbiota process is a way of purifying the sample beforehand. A clinical trial at the Second Affiliated Hospital of Nanjing Medical University is doing a clinical trial on the procedure to examine its effect on COVID-19 patients with antibiotic-associated diarrhea.

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All the COVID-19 vaccines and treatments currently in clinical trials - Digital Trends