COVID-19: a Science Primer and How the HealthTech Ecosystem is Addressing the Crisis

In the four months since it broke as an issue on global media, the coronavirus crisis has fundamentally changed society. We now realize we are more connected — and more vulnerable — as a global society than ever before.

Technology and science are at the epicenter of the effort to fight this pandemic — and we wanted to offer Pitango HealthTech’s perspective on the science behind COVID-19 responses, and to share examples of innovative companies on the front lines (several of which we are proud to say are in our portfolio).

We view 4 major areas where innovation is playing a fundamental role in shaping the trajectory of the pandemic:

1. Diagnostics — PCR tests being moved to the point-of-care to expedite results and serological tests being deployed at scale to determine population immunity
2. Therapeutics — rapid mobilization around developing a vaccine (including with novel RNA-based methods) and testing various repurposed antiviral drugs against COVID-19
3. Care management — remote monitoring, EMR analytics, symptom triage and decision support startups allowing medical providers to better care for patients
4. Population health and prevention — geolocation-based technologies that track and manage large patient pools to prevent the spread of the virus

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1. Diagnostics

Diagnosis of coronavirus is done in one of two primary methods:

a) RT-PCR (Real-Time Polymerase Chain Reaction) — the most accurate and common method, based on a technique that uses heating and cooling to amplify a virus’ RNA in a collected specimen and then determines infection based on the concentration of that RNA.

RT-PCR testing has many steps, but essentially requires preparation kits (which include ‘recipes’ — protocols of how to extract the RNA from a specimen and reagents used in the biochemical extraction process), as well as RT-PCR machines (physical centrifuges and machines that perform the heating and cooling, use fluorescent lighting to read-out amplified RNA and deliver the readout on the concentration of the RNA).

In practice, PCR testing bottlenecks exist for many reasons. Not all places that have PCR machines (commercial, medical or academic laboratories) are authorized to make valid clinical readouts. This creates the need to transport samples to a few central authorized labs — which is time-consuming and inefficient. In addition, the assay-preparation ‘recipes’ by technicians can be complex and take multiple hours, making labs’ throughput rate too slow to keep up with demand.

b) IgG and IgM — immunoglobulins tests (also known as serological tests) — detect the presence of antibodies to a specific virus in blood. After it contracts a virus, the body’s immune system develops antibodies that were meant to help in fighting off the virus. IgG and IgM tests use a biochemical reaction of the specific antibody to determine its concentration in blood — and therefore the likelihood that an individual was infected. IgM is the first antibody to be developed by the body in reaction to a foreign ‘particle’ — and therefore the quickest to be possibly detected — while IgG is the most abundant — and therefore easiest to find.

Because it takes time for the body to develop antibodies, IgG and IgM tests are not effective at determining whether an individual is currently infected. Instead, they are a good method for measuring a population’s exposure to a disease, as even those that didn’t display symptoms will typically develop antibodies.

The healthcare ecosystem is innovating on these two methods to improve COVID-19 diagnostics in several ways.

a) In the PCR field, the main emphasis is on moving the testing process from central labs to the point of care by developing smaller versions of the traditional PCR machine that can be used in medical centers or in the field. Several companies have done this, including Cepheid — a provider of existing clinical diagnostic hardware, Mesa Biotech and Abbott, among others. These machines and tests differ in several parameters, such as the viral genetic sequence that each amplifies or the amplification method (e.g. Abbott uses a set of proteins and chemical reactions to replicate the viral genetic material instead of temperature changes(.

Other companies are trying to innovate by creating better, faster protocols or reagents for the in-lab testing process — which is how the majority of tests will continue being done in the near future. Roche and Thermo Fisher had their tests approved by the FDA, and smaller companies like Qiagen and DiaSorin are also in the process.

Click Dx (now Visby Medical) — a Pitango portfolio company — took this concept even further. While most new devices or tests require professional handling, calibration and cleaning, Click Dx developed not only a miniaturized version of the PCR machine but also a way to automate the sample-prep ‘recipe’ so that it can be used by anyone, anywhere with a simple one-time disposable kit that takes minutes to prepare. Much like in computing, where shifts occurred from mainframes to PCs and laptops to mobile phones, Click Dx is developing the mobile phone of PCRs — putting the diagnostic capability in a mobile palm-sized single-use device. Click is currently in the process of scaling production and distribution of coronavirus tests that will allow medical professionals of all levels to quickly test patients — reducing the burden on critical staff and resources.

Finally, several consumer health startups are trying to address the sample collection bottleneck by shifting it to the home — allowing patients to avoid coming to medical centers. EverlyWell, Nurx and Carbon Health have claimed to launch at-home sample collection products (which patients then send directly to company labs). However, the FDA has currently halted these tests and prohibited makers from marketing them given concerns of reliability.

b) On the serological side, many are saying that mass-testing is the only way to truly fight the pandemic. By identifying those that have been exposed to the virus, we would be able to allow them to return to normal economic activity, leverage their plasma antibodies to treat currently infected individuals and understand how close we are to ‘herd immunity’ — where a large enough share of a society is immune to the disease.

Several companies have risen to this challenge. Biomerica, BM and BioMedomics, for instance, have all developed tests that can use blood from a small finger prick and get results in 10–15 minutes. The main challenge with serological testing is the sensitivity — the true positive rate — and bringing it up to a sufficiently high level, but this is being actively worked on to make sure that no prior carries are left undetected, with the hope of increasing it significantly in the coming weeks.

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2. Therapeutics

The race for a COVID-19 vaccine started almost immediately after the virus emerged in Wuhan, China. Therapeutic strategies can be divided into two main categories:

a) Vaccines: several large biopharma companies — including Gilead and Pfizer — as well as smaller ones — like Novavax and Regeneron — are racing to develop a vaccine through multiple mechanisms.

An interesting, highly innovative development in this space is the introduction of mRNA-based vaccines. Traditionally, vaccines use weakened but real forms of the virus. Now, innovative companies like Moderna are working on a method to inject people with an mRNA-based “information molecule” that will contain the genetic RNA code of the virus rather than the virus itself. This will invoke a similar physical reaction — i.e. the body’s developing antibodies to the virus before it contracts it — but offers advantages in terms of speed to get clinical results and speed-to-market in production and scaling.

Though the FDA and other regulatory bodies are working to expedite the approval process of vaccines, it will likely take a minimum of 18 months to get to market given the need to test safety and efficacy in large populations.

b) Antiviral drugs: while a vaccine is being developed, the healthcare community is mobilizing around many efforts to find treatments for the disease, evidenced by the 300+ trials currently taking place globally.

Many of the treatments use existing drugs that are being repurposed to fight coronavirus. High hopes centered around Gilead’s Ebola drug Remdesivir and on Kaletra, a combination of HIV antiviral medication Lipinavir and Ritonavir from Abbvie, but these are still experimental and potentially ineffective — as are others like Avigan and Favilair. Chloroquine, a quinine-based antimalarial drug that is now a generic is also being examined in various formulations — but also has high toxicity levels that make it dangerous and potentially lethal due to cardiac complications.

In tandem, new novel treatments are also being explored — for instance EIDD-2801, a broad spectrum anti RNA nucleoside, which was licensed to Ridgeback Pharmaceuticals by Emory’s drug development institute. The drug has a filed IND and human testing is imminent. It is active preclinically against SARS, MERS, influenza and RSV in addition to COVID-19, and is promising given that it is highly orally available by capsule and liquid.

The global healthcare ecosystem and the biotech community are working tirelessly to test these various treatment options in order to understand what treatments work and for whom — and to do so at record speed. _____________________________________________________________

3. Care management

As we have witnessed over recent weeks, the main challenge with coronavirus is the sudden influx and overwhelming demand it creates on health systems. Hospitals and physicians desperately need immediate help in managing care for their patients and, on this front, Israeli innovation is at the forefront.

a) Remote monitoring and telemedicine — the ability to help patients without requiring physical contact is finally truly coming to the limelight. EarlySense, a Pitango portfolio company, is a leader in this space through its contact-less device placed under the patient’s bed that can detect vital signs, including heart rate, respiratory rate and motion — and it is currently deployed in multiple hospitals in Israel and in the US. Many other Israeli companies have products relevant for this space, including Tyto Care, which provides the ability to measure various biomarkers remotely, and Datos, which provides integration solutions to feed collected medical information to physicians.

b) Symptom triage — the ability to quickly provide initial answers to people concerned as to whether they are infected allows physicians to focus on those truly in need of treatment. Israeli company K Health quickly tweaked its AI-powered triage algorithm for coronavirus symptoms. Other companies around the world, including Babylon Health are doing the same. This will help keep people who do not need it out of the hospital and away from infection centers.

c) Analytics and patient management — resource allocation in hospitals — and specifically in ICUs — is potentially the most challenging part of the COVID-19 fight. Clew Medical, another portfolio company of ours, is the forefront of this fight. Clew connects to ICU EMRs to produce real-time actionable alerts based on the countless monitored markers. In addition, Clew offers a complete patient management system and remote tele-ICU control tower that allows physicians to observe and track patients — and issue critical treatment teams — from afar. Clew’s system has been deployed in Israel’s leading hospitals, and rapid efforts to integrate into the Italian hospital system are underway, with other countries quickly being added to the pipeline.

d) Equipment and protective gear — shortages in hospital supplies are, by now, a global phenomenon. Here, too, innovation can help. Companies like Sonovia — an Israel startup developing textiles that are resistant to bacteria and fungus — can help in quickly answering demand for medical protection

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4. Population health and prevention

The ability to know where infected individuals traveled, to monitor hospital capacity, to distribute patients and to communicate across parts of the healthcare system — and with citizens — is paramount in this crisis.

Both healthcare and technology companies are trying to assist in this fight. For instance, healthcare analytics company Definitive Healthcare and geo-spacial and mapping company Esri established a partnership to share data on hospital beds, ICU resources and patient movements. This is part of Esri’s COVID-19 GIS Hub, a broader effort to establish maps, datasets and applications on coronavirus for global use.

In Israel, the Weizman Institute established a project to create a live predictive model on the virus’ spread using a customized medical questionnaire that asked citizens to report on any potential symptoms. The project’s team analyzes the information as well as people’s whereabouts to create statistical models that can guide policymakers.

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The above review includes just a select list of the many ways in which the healthtech ecosystem is helping to drive solutions for this crisis. We are humbled to be able to support some of the groundbreaking entrepreneurs on the front lines, and to be part of this incredibly agile and impactful ecosystem. We wish all responders, medical providers and others luck as they attempt to address this crisis.

Note: this article is current as of April 1, 2020. Since then, many developments have occurred that are not reflected in the above.