Four Approaches To Treat Covid-19 

Antivirals

How it works

An antiviral works by chemically disrupting a specific point in the replication cycle of a virus. It thus slows down the infection by limiting the multiplication of viral particles, and effectively “helping” the immune response if taken soon enough.

• Antivirals rarely achieve stopping a viral infection, but are an effective method of virus control, and help gain time pending the development of a vaccine.
• Antivirals are often coupled to drugs stimulating the immune system's response.

Impact

Given similarities between viruses’ mechanisms, antivirals already developed for other diseases are being tested. We expect multiple options to be available and fasttracked approved in the next few months.

• Most already proved their efficacy in other diseases (Ebola, H1N1, influenza).
• Chloroquine (already approved on malaria and arthritis, and off-patent) has so far shown promising results in a small study and is experimentally already being used.

Key technologies and players

There are four types of antivirals: RNA polymerase inhibitors, RNA interference, protease inhibitors, and lysosomal enzyme inhibitors. They act at different stages of the replication cycle of the virus.

• Gilead is leading the race on RNA polymerase inhibitors.
• Chloroquine and Hydroxychloroquine are part of the Lysosomal enzyme inhibitors.
• Zhejiang Hisun / Fujifilm are the closest to a possible approval with Favilavir, a drug initially used for influenza, and that has been experimentally used in China.

An Overview: Antivirals

Anti-Inflammatory Drugs 

How it works

An infection of the upper and lower respiratory tract causes a respiratory syndrome, inducing the release of pro-inflammatory cytokines. Anti-inflammatory drugs control cytokines release and avoid an immune hyper reaction.

• Cytokines release is a necessary step to fight off the viral infection. But their excessive production may lead to autoimmune damages, potentially lethal.

Impact

These drugs could be useful to treat severely ill patients for the underlying consequence of COVID-19, pneumonia. Anti-inflammatory drugs could receive an emergency approval by the FDA and other drugs agencies in the world in the coming months.

• Most advanced trials are in Phase 2/3, and more top-line data are expected in the next few weeks.
• China has already approved Roche’s Actemra in China for the treatment of severe complications related to COVID-19.

Key technologies and players

IL-6 is a pro-inflammatory cytokine that may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19 infection.

• The role of IL-6 is supported by preliminary data from a single-arm study in China using another IL-6 receptor antibody.
• The two leaders on this field (Sanofi/Regeneron and Roche/Chugai) are in Phase 2/3.

Passive Immunization

How it works

Passive immunization provides exogenous, pre-formed antibodies that can prevent or treat infectious diseases. A person receives antibodies or lymphocytes that have been produced by another individual’s immune system.

• Production is usually constrained by the need of donor blood (healed patients).
• This approach was already used in several infections such as Ebola, or H1N1.

Impact

Passive immunization approach has the potential to enhance our immune system to fight against the virus. Compared to a classical vaccine that stimulates the body to produce its own antibodies, passive immunization would be quicker to deploy and effective also on already infected patients.

• A novel approach, but most treatments for COVID-19 are still in preclinical trials.

Key technologies and players

Regeneron is the technological leader, having developed a proprietary platform that is able to produce antibodies using mice, thus avoiding the need for donor blood that constrains most other players.

• Regeneron has already demonstrated the effectiveness of its antibody platform during the Ebola epidemic in Congo. A comparative study of its treatment was stopped ahead of schedule as the results were extremely positive.
• The technology also allows for a quick ramp-up of capacities for large-scale production.

An Overview: Passive immunization

Active Immunization (Vaccines)

How it works

A vaccine works by training the immune system to recognize and combat pathogens, using weakened (or killed) versions. The body reacts to the vaccine by making antibodies, thus ensuring immunization.

• Only specific molecules called antigens (present on all viruses and bacteria) must be introduced into the body to trigger an immune response without risking illness.

Impact

Over the medium term, in order to prevent future COVID-19 outbreaks a vaccine is the only solution. But the real breakthrough would be the development of a universal coronavirus vaccine, which works for every member of the virus family, even when the virus mutates.

• Despite this seeming far-fetched, according to Icosovax (a synthetic biology start-up) it should be feasible and the company is moving its vaccine towards clinical trials.

Key technologies and players

Beyond classical vaccine technologies, novel approaches such as mRNA- and DNAbased are being developed. The main benefits compared to conventional vaccines are lower cost and faster production, allowing a rapid response to epidemics, and they may also have fewer side effects.

• Moderna is leading the race of the vaccine development and is already in Phase 1, using a mRNA- based approach.
• If a mRNA vaccine gets approved for COVID-19, this would be a first for this innovative technology, opening the way for it to be applied to every other type of infection (and even disease).

An Overview: Active Immunization (Vaccines)

Diagnostic Testing 

How it works

Diagnostic testing is based on three possible approaches: detect viral RNA, detect antibodies, detect the presence of pulmonary pathology.

• Currently the most used tests are those detecting the viral RNA: tests could have high specificity, but will only detect an « active infection ».
• Detecting antibodies involves exposing a blood sample to proteins that mimic the coronavirus’ spiky casing; if antibodies in the blood attack the protein, the sample changes color. The risk is missing early-stage infections.
• CT scans help identify and characterize pneumonia. However, the technique is not able to differentiate among different types of pneumonia.

Impact

Diagnostic testing is one of the critical factors in the fight against the spread of COVID-19: patients and suspected people are identified and isolated more quickly. Early diagnosis allows adequate public safety measures to be put in place and to decongest hospitals.

• In countries where tests have been conducted at massive scale (notably in South Korea), a flatter spread curve has been observed.

Key technologies and players

The main technological race is in the detection of viral RNA, where RT-PCR tests are the current « golden standard », but Next Generation Sequencing (NGS) and CRISPR-Cas are quickly becoming valid alternatives.

• RT-PCR suffers from a number of shortcomings, notably in terms of time to result and false negatives rate, impacted by elements exogenous to the test itself.
• NGS allows to detect presence of an infectious agent even without knowing which one it is, and read its full genome sequence, which allows also to track mutations.
• CRISPR-Cas machinery provides an accurate response in 10-15 minutes, but the technology is still in its testing phase, and is not yet widely available.

An Overview: Diagnostic Testing

Focus On RT-PCR diagnostics: Market Overview

Respiratory Machines

How it works

Ventilators are machines that support breathing. These machines are mainly used in hospitals, and are of different types: noninvasive ventilation (NIV), invasive ventilation (IV), bilevel devices (BLDs).

• NIVs deliver air to the patients through a mask or a mouthpiece.
• IVs deliver air through a tube inserted in the trachea by either intubation or tracheotomy.
• BLDs (non-invasive) deliver two distinct air pressures for inhaling and exhaling.

Impact

Ventilators get oxygen into the lungs, remove carbon dioxide from the body, and basically support patients with respiratory insufficiency and failure. They are essential for critical cases, where the COVID-19 infection has caused damage to the lungs’ tissues and pneumonia is worsening.

• Hospitals have a limited number of machines and if they get overwhelmed during massive outbreaks, it becomes impossible to provide adequate care to all patients.

Key technologies and players

Technology is fairly standardised, and the race is to both produce the ventilators in volumes, and « multiply » the number of patients that can be served by an existing machine.

• Major medical devices producers have these machines in their catalogs.
• Automotive manufacturer are being pushed to provide manufacturing capacity by converting existing plants.
• Prisma Health announced a breakthrough system allowing the use of a single ventilator machine on four patients at the same time.

Catalysts

• Improving COVID-19 data from Italy. Passing the peak and showing that confinement measures work will reboost hope and confidence.
• New treatment. Any drug that shows reliable positive results from advanced trials will help reduce fears in the population.
• China. Continued control of the epidemic and resuming « normal » life will provide a useful benchmark to start anticipating how the future will shape

Risks

• Italy setback. A renewed deterioration in case numbers it Italy would undercut all current hopes that measures are working.
• Delay in flattening the curve after peak. Confinement measures lasting too long risks being worse than the ill they are attempting to cure.
• China. The materialization of the feared second outbreak would be a blow to all hopes of bringing the situation under control.