COVID-19 Research: A Look at the Past Two Years
In the two years since COVID-19 began its global assault, people around the world have responded in dramatically different ways.
The general population has scrambled to figure out what they should do, how to protect their families, and where they can find enough toilet paper and hand sanitizer. Politicians have angrily debated travel restrictions, emergency funding, and vaccine and mask mandates.
Behind all that noise, however, scientists and researchers toiled away, making historic scientific breakthroughs while developing the tests, vaccines, remedies, and research that have allowed humanity to get some control over the deadly virus.
From China to Germany to the labs at the University of Miami Miller School of Medicine, scientists have borrowed from old research and developed new technologies to slow down the deadly onslaught of COVID-19.
The combined efforts have not stopped the virus entirely but have slowed the rate of hospitalizations and, most importantly, deaths. Scientists themselves have become the targets of unprecedented public scrutiny and waves of disinformation campaigns. Still, they have forged ahead and collectively crafted one of the most remarkable scientific responses in history.
“The rapidity at which information was created and shared in the COVID-19 pandemic is unlike anything that has ever occurred in science,” said Carl Schulman, M.D., M.S.P.H., Ph.D., senior associate dean for research operations at the Miller School.
Here’s a look at some of the most significant scientific breakthroughs of the past two years:
As most Americans were ringing in the new year and preparing for Super Bowl LIV in Miami, they had no idea what was happening on the other side of the world. But scientists in China and Australia were already decoding the genetic sequence - or genome - of SARS-CoV-2, the scientific name for the COVID-19 coronavirus.
Genetic sequencing was pioneered in the 1970s, a process that was sped up in the 2000s thanks to improved computer processing and genetic-sequencing machines. That foundation allowed a consortium of researchers, led by the Shanghai Public Health Clinical Center, to decode the COVID-19 genome just ten days after the first reported pneumonia cases in Wuhan, China.
The team published its findings and released the genome publicly, allowing researchers worldwide to begin working on their responses. It didn’t take long for another group of researchers to take the next step: developing a test to identify whether a person was infected.
The polymerase chain reaction technique, most commonly known as a PCR test, was first developed by a scientist in California in the 1990s. Teams from the German Center for Infection Research (DZIF) soon began specializing in the technique and used it to develop diagnostic tests for the Zika virus, MERS (Middle East Respiratory Syndrome), and SARS (Severe Acute Respiratory Syndrome).
That history allowed the team at DZIF to quickly take the COVID-19 genome and develop a PCR test published by the World Health Organization (WHO) and replicated worldwide.
By March, the COVID-19 virus was tearing around the world, prompting the first wave of lockdowns, travel bans, and skyrocketing infection rates. In the U.S., where the virus appears to have first made landfall near Seattle, Washington, it raced around the country at staggering speeds, overwhelming hospitals, shuttering businesses, and forcing Americans to begin home-schooling and working from home.
At that point, it was clear that the nation’s ability to test for COVID-19 would be critical, so researchers at the Miller School partnered with biopharmaceutical company Heat Biologics, Inc., to develop a rapid test for the virus. At the time, the only tests available required intense lab work that took up to six hours to get a result.
Sylvia Daunert, Ph.D., PharmD, M.S., and chair of the Department of Biochemistry and Molecular Biology, said they were able to use their experience developing similar tests to create a COVID-19 test that could provide on-the-spot results on a paper strip in under 30 minutes.
“This should allow for much earlier detection — within a couple days of exposure — providing critical and time-sensitive information to help curb the spread of the disease,” Dr. Daunert said at the time.
In early April at Columbia University Irving Medical Center in New York City, eight COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) were waiting to be intubated and placed on a ventilator.
By that point, the damage caused by COVID-19 to victims’ lungs had become well-known, setting off a global scramble for ventilators as hospital staff raced to get their patients onto the breathing machines. At the New York City hospital, only one patient could be intubated at a time, so hospital staff flipped three of their waiting patients onto their stomachs, a practice known as “proning” that, in theory, distributes oxygen more evenly throughout the body.
Within an hour, the oxygenation levels of the three patients improved to the point that they no longer needed to be placed on a ventilator. Hospital staff were so astonished that they changed their procedures, added proning to their standard routine, and tried to spread the word to other hospitals.
Similar scenes played out in intensive care units around the world as doctors and nurses learned that their old ways of treating lung complications didn’t necessarily apply to COVID-19. Using the medical version of word of mouth, they fine-tuned a cocktail of steroids that helped patients survive and recover from the virus. They learned to resist the urge to place patients on ventilators and crafted ventilator settings specifically for COVID-19 victims.
Rather than waiting years for research institutions to do full studies, they mixed and matched, and tested procedures until they found treatments that worked. Now, studies are showing that proning helps increase oxygenation and reduces mortality.
“Now that we know that, we know to avoid trying to intubate them,” Dr. Schulman said. “We’re doing the exact opposite of what we were doing in the initial part of the pandemic, and it for sure has improved outcomes.”
Proning and tweaking ventilator settings were never going to be enough, so researchers kept digging for additional solutions. And they found one inside the human body: stem cells.
The powerful cells have been studied for over a century, but their true power has only been uncovered in recent decades. Because stem cells can be coaxed into developing into many kinds of cells found in the human body, they have been used as a repair system for many ailments.
That’s why Joshua M. Hare, M.D., Louis Lemberg Professor of Medicine and founding director of the Interdisciplinary Stem Cell Institute (ISCI) at the Miller School, teamed up with researchers from other institutions to perform a comprehensive analysis to determine if stem cells would help COVID-19 patients.
Dr. Hare and the team found that mesenchymal stem cells were not only safe for patients suffering from ARDS but that they could help reduce the severe inflammation in the lungs caused by the immune system’s reaction to the coronavirus infection.
Months later, another team at the Miller School put Dr. Hare’s idea into practice and verified his findings. The team used mesenchymal stem cells pulled from umbilical cords on 24 ARDS patients. The results were clear: 91% survived past a month, compared to 42% of patients who did not receive the treatments, and 80% of stem cell recipients fully recovered by day 30, compared to 37% of patients who did not receive the treatment.
“It’s like smart bomb technology in the lung to restore normal immune response and reverse life-threatening complications,” said the study’s lead author, Camillo Ricordi, M.D., director of the Diabetes Research Institute (DRI) and Cell Transplant Center at the Miller School.
Heading into the summer of 2020, medical professionals were still struggling to balance the needs of COVID-19 patients with the goal of freeing up beds and protecting healthcare workers. That led to a new wave of telehealth, where doctors started seeing patients virtually through video-conferencing platforms like FaceTime and Zoom. And it prompted the University of Miami Health System to develop a “Televigilance” program.
Discharged patients who still required monitors were sent home with TytoCare home health devices, which electronically transmit the patients’ core vital signs - temperature, blood pressure, heart rate, and oxygen saturation. The devices also could be outfitted with adaptors to examine the patient’s heart, lungs, skin, mouth, and ears.
All that information allowed doctors to quickly identify any troubling developments without risking exposure to the virus while freeing up more hospital space.
“Merging the benefits of telemedicine visits with the clinical accuracy obtained through recording patient vital signs and an extensive physical examination enhances the opportunity to closely monitor specific patients immediately after hospital discharge or ER release,” said Sabrina Taldone, M.D., M.B.A., medical director of the UHealth Televigilance program and associate program director of the Internal Medicine Residency Program at the Miller School of Medicine.
As COVID-19 continued to spread, researchers around the globe raced to produce a safe, effective vaccine. And in July, the Miller School announced its first major contribution to that effort.
Long before Moderna became a household name, the Miller School was chosen by the National Institutes of Health COVID-19 Prevention Trials Network (CoVPN) to test the vaccine candidate developed by the biotechnology company. The Miller School enrolled about 1,000 volunteers in South Florida in the clinical trial, which helped create the data necessary for Moderna’s vaccine to be approved by the federal government later in the year.
Led by infectious diseases expert Susanne Doblecki-Lewis, M.D., M.S.P.H., associate professor of clinical medicine, the trials were designed to ensure that volunteers represented the full range of South Florida’s diverse community, taking into account their gender, age, race, ethnicity, and those particularly at risk because of medical conditions.
“This is how we will help ensure that any vaccine that is developed will be relevant for those who could benefit most from it,” Dr. Doblecki-Lewis said at the time.
Researchers at the Miller School didn’t just help other companies test their vaccine candidates - they developed one of their own.
Working once again with Heat Biologics, the team unveiled a vaccine candidate that reprograms live T-cells to secrete antigens that activate a strong, long-term immune system response against SARS-CoV-2. T-cells are a type of white blood cell that plays an integral role in the body’s immune system.
Heat Biologics developed and patented the use of the protein glycoprotein 96 (gp96), and the Miller School validated its effectiveness through an intense study where it was injected into mice.
“This is crucial in protecting against COVID-19, since these T-cells in the respiratory system are the first to encounter the virus,” said Natasa Strbo, M.D., D.Sc., assistant professor of microbiology and immunology and the lead author of the study.
With the holiday season approaching and Americans debating whether to go home for Thanksgiving, people were desperate for a faster way to check whether they had COVID-19.
On Nov. 17, 2020, the U.S. Food and Drug Administration (FDA) granted Lucira Health, a California healthcare company, the first emergency use authorization for a diagnostic, at-home rapid test. The company had been developing disposable test kits to detect the DNA and RNA of infectious diseases for five years. That allowed the company to fast-track its development of the COVID-19 test.
“Now, more Americans who may have COVID-19 will be able to take immediate action, based on their results, to protect themselves and those around them,” Jeff Shuren, M.D., J.D., director of FDA’s Center for Devices and Radiological Health, said at the time.
In the 1960s, researchers set a new world record when they developed a vaccine for the mumps in only four years.
When the FDA granted emergency use authorization on Dec. 11, 2020, to a COVID-19 vaccine developed by Pfizer-BioNTech, the record was shattered. Just one year after the first COVID-19 victims fell ill in China and ten months after the virus was first detected in the United States, the road to global vaccination was possible.
Both Pfizer-BioNTech and Moderna, which developed its own vaccine, took advantage of advances in mRNA technology to establish their vaccines. Researchers had long been experimenting with mRNA, which teaches cells how to make a protein that will trigger an immune response. For COVID-19, the mRNA instructs cells in the body to create the so-called “spike protein,” training the immune system to fight it.
Dushyantha Jayaweera, M.D., a professor of medicine and former senior associate dean for research at the Miller School, said the staggering speed of the vaccine development could be attributed to the fact that those companies already had mRNA development processes in place. He likened it to an assembly line at a car manufacturing plant. If a war breaks out and a car manufacturer needs to stop production of their vehicle and start producing military jeeps, it doesn’t have to start from scratch, it simply swaps in new parts, and the assembly line roars on.
“All they had to do was substitute Ebola with the SARS-CoV-2 spike protein,” he said. “They plugged it into the platform, and within a month, it it was done. Moderna and the Janssen COVID vaccines were tested in Miami by the University of Miami researchers.” The team also did many large studies with COVID convalescent plasma over this period, although the studies suggested that convalescent plasma works only when used very early in the disease.
Ever since the vaccines were approved, nearly five billion people – 65% of the global population – have received at least one vaccine shot, according to data compiled by The New York Times.
As the pandemic entered its second year, scientists knew it was only a matter of time before the virus mutated. Since it is a RNA virus and lacks the ability to proof read when it replicates, it makes spontaneous errors, said Dr. Jayaweera. So, it was anticipated that another wave of death and destruction would occur. That’s why the Miller School led a pilot program to track COVID-19 variants.
Months before the delta and omicron variants swept across the globe, molecular microbiologists at UM had already established a system to genetically sequence the COVID-19 variants quickly and determine how prevalent they were in South Florida. By February 2021, the teams had tested more than 500 COVID-19 positive samples from patients at UHealth Tower and Jackson Health System’s three hospitals, as well as students, faculty, and staff.
At the time, the researchers identified the less-lethal U.K. and Brazilian variants. Their work would eventually help local health officials understand the risks of the deadly delta variant and the highly-contagious omicron variant.
“I’d like to think that by looking actively and early at genetic variants that we’ll be able to be proactive and catch things ahead of time,” said David Andrews, M.D., an associate professor in the Department of Pathology and Laboratory Medicine at the Miller School. “This will be a lot easier to handle with knowledge rather than backtracking.”
Throughout the pandemic, one of the lingering questions has been whether the COVID-19 vaccine affects fertility.
After much public debate, the U.S. Centers for Disease Control and Prevention concluded that the vaccine does not affect fertility in females or males. Contracting the virus, however, can.
Several studies had showed that women who are hit with a severe case of COVID-19 could struggle to have a baby. And then, a study from the Miller School showed that the virus could invade the testis tissue in men and impair sperm production.
By testing the testis tissue of six men who died from COVID-19 and analyzing the biopsy of a living male who had previously contracted the virus, the team at UM found clear evidence that the virus could and did affect their reproductive systems.
“The finding is novel, remarkable, and certainly worthy of further exploration,” said study lead author Ranjith Ramasamy, M.D., associate professor and director of reproductive urology at the Miller School.
Two years after COVID-19 first entered the U.S., scientists are just starting to understand the long-term effects of the virus.
Painful side effects will clearly linger in victims with post-acute COVID-19 syndrome (PACS), better known as “Long COVID.” Researchers at the Icahn School of Medicine at Mount Sinai, New York, concluded that victims will deal with physical impairments, loss of some cognitive functions, and the inability to conduct their usual level of physical exertion. Put together that means that some PACS victims “may have a reduced ability to participate in society.”
Just as they did at the start of the pandemic, scientists and researchers around the world will continue to pore over every bit of data to finally put a stop to the pandemic.
The pandemic showed how the global scientific community can work together when facing a global threat.
But Dr. Schulman said typically, worldwide collaborations are unlikely given that funding rarely flows so freely.
Dr. Jayaweera said scientists did an admirable job fast-tracking research throughout the pandemic but believes that process revealed some institutional flaws in the U.S.
For example, the National Institutes of Health handed out nearly $5 billion for COVID-19 research. Unfortunately, they spread it out amongst so many projects that few could study a large enough sample size to make their findings useful. In fact, only 5% of COVID-related clinical drug trials had an adequate sample size to show a difference between study arms, according to data from the U.S. Food and Drug Administration.
In contrast, in the United Kingdom, a national health service allowed researchers to quickly access as many patients as they needed for their studies with rapid implementation and analysis of data, Dr. Jayaweera said.
“Across the U.S., we were fragmented,” he said. “I wish we could reengineer the entire research system across the nation so that we are more effective, spend less money, and get better bang for the buck.”
Alan Gomez is a contributing writer for UMiami Health News.
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