The World Health Organization is looking into the surge capacity needed for acute and intensive care, as data from China suggest that 15–20% of COVID-19 cases require hospitalization, while data from Italy show that 10–25% of patients will require ventilation. Once a mechanical ventilator is needed, the survival rates do not favor patients in ICUs.
A mechanical ventilator is a relatively unsophisticated (though incredibly important) machine. The first mechanical ventilator was invented by American George Poe (cousin of Edgar Allan Poe) in 1908. Using two brass piston cylinders operating by a simple handle, he employed the device to revive rabbits and other small animals. Eventually his device was used to save a human life in 1909.
For the pioneers of mechanical ventilation who evolved their medical devices over the past century, one first needed basic physiological knowledge of how humans breathe.
From a mechanical point of view, breathing is a simple exchange in pressures.
Breathing from a Physiological Point of View
When you inhale, your diaphragm and the muscles between your ribs contract. This creates negative pressure like a vacuum, pulling air through your mouth and nose, down your throat, and into your windpipe, commonly known as your trachea. The trachea splits into the left and right bronchus on either side of your lungs. The air fills bronchioles to their ends, which have tiny pockets called alveoli, where diffusion of oxygen and carbon dioxide takes place.
When you exhale, your diaphragm relaxes and expands, bringing positive pressure back to your lungs as air leaves your lungs and passes through your voice box and trachea, and out of your mouth and lungs. As you exhale, airflow is measured by the difference between the positive and negative pressures created by the elastic recoil of your lungs and chest wall.
COVID-19 symptoms include fever, dry cough and shortness of breath. All over the news, we’ve heard about the urgent scramble of nations trying to secure the medical equipment their medical communities and citizens most need to successfully treat and help patients recover from coronavirus infections.
A medical ventilator works for a patient when they are struggling to breathe on their own. A plastic tube is inserted in the patient’s mouth and down their throat. A humidifier connected to the tube warms and moistens the air blown in from the ventilator, and the air is then blown out. The ventilator helps the patient receive oxygen and decrease carbon dioxide while they are in a weakened state and fighting the COVID-19 virus. The decision to use a mechanical ventilator depends on several critical patient-specific factors. To learn more about the physiology of breathing, click here.
Noninvasive Ventilation
There are several different types of ventilators that are used for varying degrees of breathing difficulties. At the first stage of ventilation care (performed in nonintensive care units) for COVID-19 patients, there is noninvasive ventilation (NIV) and high-flow nasal cannula (HFNC). Medical professionals treating patients with COVID-19 or those suspected of suffering from COVID-19 through noninvasive positive pressure ventilation (NIPPV) and HFNC must be aware that these methods result in a higher risk of aerosol generation than invasive mechanical ventilation. Therefore, airborne precautions must be taken, and medical personnel are required to wear a full face mask with filtered circuits. Noninvasive mechanical ventilation is not preferred for COVID-19 patients because it is more likely to spread COVID-19 by generating airborne particles containing the dangerous virus pathogens.
Since noninvasive ventilation releases more COVID-19 particles into the air, invasive ventilation is the preferred method for patients having severe breathing difficulties. For those suffering moderate breathing difficulties, patients are often given a noninvasive oxygen machine to use at home after learning how to use it properly. These patients are then monitored remotely by medical professionals as they use the machines at home for recovery. However, certain patients develop difficulty breathing despite oxygen supplementation provided by noninvasive ventilators.
Invasive COVID-19 Ventilation
Hospital specialists attach a non-rebreather mask, which is connected to a plastic reservoir bag that contains high concentration oxygen with a one-way valve. This allows patients to exhale air containing high amount of CO2 while inhaling oxygen-rich air. This is the first step in an emergency when a patient is deemed likely to need an invasive mechanical ventilator.
(Image courtesy of Khaleej Times.)
If a patient is still having extreme trouble breathing and has acute respiratory distress syndrome (ARDS), respiratory specialists will turn the patient on their stomachs and continue with oxygen therapy. This is known as prone positioning. Prone ventilation follows, where the patient receives volume-controlled, pressure-controlled or high-frequency ventilation types, depending on what is appropriate for the patient-specific situation. This may reduce the need for intubation, which is the first step of mechanical ventilation.
If prone positioning and ventilation methods are not enough, and the patient’s oxygen level is still not above 90 percent and the patient is still conscious, they will receive medications for sedation and muscle relaxation. Bag mask ventilation is then performed by hand while the patient’s body is supported by a specialist. Endotracheal intubation then begins. Using a laryngoscope, the patient’s tongue is pressed down, and a trained specialist (e.g., respiratory therapist, physician, hospitalists, intensivists (ICU), or paramedics) uses the tool to view the vocal cords in the trachea. An endotracheal tube is inserted and fastened in place. Now a mechanical ventilator can transmit oxygen directly into the patient’s lungs.
Mechanical Ventilator Manufacturers
Medtronic
The Puritan Bennett 980 Ventilator is an ICU mechanical ventilator. (Image courtesy of Medtronic.)
Medtronic manufactures the Puritan Bennett 980 (PB 980) and Puritan Bennett 840 (PB 840) high-performance ventilators for use in ICUs around the world. The company also manufacture a smaller, portable ventilator called the Puritan Bennet 560 (PB 560).
Responding to the global pandemic, Medtronic has not only ramped up production to nearly double its normal output, it has also posted design specifications for the portable PB 560 ventilator. The design files include hardware specs, manufacturing instructions, ventilator-design documents, PCB drawings, BOMs, 3D CAD files, source code files and other technical files. They are available for academics, inventors, startups and anyone who is willing to “leverage their own expertise and resources to evaluate options for rapid ventilator manufacturing.”
Other top ventilator manufacturers with COVID-19 response plans include Becton Dickinson, Philips, Hamilton Medical, Fisher & Paykel Healthcare, Draeger and GE Healthcare.
How Are Vaccines Manufactured?
There are three production technologies available for making vaccines: egg based, cell based and recombinant technology based.
Egg-based flu vaccines are the most common production technology for creating candidate vaccine viruses (CVVs). There are two types of vaccines: inactivated and live attenuated. Inactive means killed. Active means weakened and is commonly referred to as a “nasal spray flu vaccine.”
The CVVs are grown in fertilized chicken eggs and are incubated for a few days. After the virus replicates, fluid with the virus is extracted from the eggs. The viruses are killed, and the virus antigen is purified for use in flu shots. Manufacturing continues with quality testing, filling and distribution. Nasal spray vaccines are not killed but weakened. Vaccines then continue through a different FDA-approved production method. The egg-based production method takes longer than cell-based flu vaccines, which were approved in 2016.
Cell-based flu vaccines are used only to make inactivated (killed) flu shots and only one company named Seqirus is FDA approved to manufacture vaccines in this way.
Lab workers at Seqirus take a candidate virus vaccine (egg based in origin) from the Centers for Disease Control and Prevention (CDC) or an approved partner. Then the CVVs are injected into mammalian cells, which function as a xerox machine for viruses. The CVVs replicate, fluid containing the viruses is extracted, and virus antigen purification process begins. This is again followed by quality control, purification and testing methodology. The results are shipped to the FDA for approval and then distributed for use as vaccinations. A third type of production of vaccines does not require a candidate vaccine virus for production. It is produced by recombinant technology.
To produce vaccines with recombinant technology, scientists use DNA for hemagglutinin (HA), which is a surface protein found in flu viruses. This method was approved by the FDA in 2013, and only one vaccine is produced this way in the United States.
A flu virus has something called an antigen, which acts as a catalyst in human immune systems. The HA is a flu virus antigen, and when human immune systems detect HA, they start creating antibodies for the virus that the surface protein (the antigen HA in this case) represents. In labs, DNA for HA is combined with a baculovirus. A baculovirus is a virus that infects only invertebrates. Geneticists use the baculovirus as a courier to bring the genetic instructions of HA to an FDA-approved host cell. Once it is there, the cell quickly produces HA antigen, which is then collected. After the antigen is collected, it goes through quality control, purification and testing by both internal geneticists and FDA lab specialists prior to distribution.
What Makes the Coronavirus Different?
It’s important to remember that “coronavirus” as it’s known means COVID-19. Coronaviruses are in fact a group of related viruses that cause everything from respiratory tract infections and the common cold (less commonly than rhinoviruses), while more lethal versions cause MERS (Middle East Respiratory Syndrome), SARS (Severe Acute Respiratory Syndrome) and COVID-19. COVID-19 is caused by a SARS-CoV-2 pathogen, the “novel” part of the COVID-19 pandemic. It is called SARS-CoV-2 because of its similarity to SARS. Both wield spike proteins that allow these coronaviruses to attack human cells. Both have zoonotic origins, though SARS-CoV-2 (COVID-19) seems to have come from the most-trafficked animal in the world, pangolins.
SARS-CoV-2 is a stealthier form of SARS. SARS could be quarantined and contained more easily because the virus would go straight into a human’s lungs and caused symptoms. This is not how the COVID-19 pathogen works. It hides in throats without the host showing any symptoms. This allows the virus to spread far and wide before causing terrific damage en masse.
Supercomputers and AI Are Helping Researchers Produce Vaccines and Treatments
Creating a vaccine for COVID-19 is the most urgent task for medical researchers and vaccine manufacturers around the world, and given the novel SARS-CoV-2 pathogens’ trickery, everyone involved in the race to eliminate COVID-19 needs all the help they can get. Tech giants, government organizations and academic institutions never hesitate to demonstrate the amazing capabilities of their supercomputers and AI, and thankfully these technologies are in the hands of researchers looking to expedite the creation of a vaccine, which generally takes 12-18 months.
High Performance Computing Consortium
In March, the creation of the COVID-19 High Performance Computing Consortium was announced by the White House in the United States. The consortium is made of academic institutions, federal agencies and computing industry entities. The goal of the group is to provide researchers who are working to create a vaccine for COVID-19 with access to supercomputers in the hopes of eradicating the global pandemic.
There are 16 supercomputers available for researchers, and the hardware list is astonishing. There are 34,000 GPUs, 775,000 CPU cores and 330 petaflops of storage. Researchers apply for access to the supercomputers and can then run simulations of specific molecules against the effects of COVID-19, predicting its mutations and different evolutions along the way.
COVID-19 Open Research Dataset (CORD-19)
The Allen Institute for AI partnered with different research groups to distribute the COVID-19 Open Research Dataset (CORD-19). This free resource contains 51,000 articles about COVID-19 and the coronavirus family of viruses for researchers using natural language processing to gain insights into new ways to attack and defeat COVID-19.
There is a full-text search engine called the CORD-19 Explorer to help researchers sift through the huge volume of academic papers. There is also a tool called CoViz, which allows researchers to quickly find associations between concepts in the dataset.
Distributed Computers Help Search for COVID-19 Spike Protein Variations
Stanford researchers created an interesting project called “Folding@Home” (FAH) that calls on people all over the world with an Internet connection to donate their local computing power to create, run and maintain a virtual supercomputer. The distributed supercomputer is being used to help researchers find a vaccine for COVID-19.
The Stanford researchers are asking for your unused processing power to research a part of COVID-19’s spike protein. The spike protein allows the coronavirus to catch itself on cells in humans, which triggers the infection that has killed more than 130,000 people out of 2 million infected (more than 500,000 have recovered) so far. The spike protein is a shapeshifter. It’s shape changes as proteins unfold and fold repeatedly. For researchers, this means studying every possible shape that COVID-19’s spike protein takes. The number of differently shaped spike proteins is massive.
Bottom Line
The credit and praise for helping the world community face COVID-19 belongs to medical professionals all over the world. Computing has changed the way hospitals manage their facilities. Hospitals use servers and networked workstations, laptops and electronic devices with micro-motherboards to keep track of patient care while protecting privacy and centralizing important information. AI and supercomputers are helping researchers fast track a vaccine using every possible bit of information available. And among the most vital machines for giving patients stricken with COVID-19 a fighting chance is the mechanical ventilator. But even these amazing machines are just hunks of computing electronics if they are not operated by highly trained personnel. The world needs humans to pull together (metaphorically speaking as social distancing is crucial to minimizing casualties) and unite in defeating COVID-19 once and for all.