While COVID-19 community transmission, mortality, and hospitalization rates have come down across the country in recent months, the efforts to understand more about SARS-CoV-2, the virus responsible for COVID-19, continue at full speed. “The energy is still robust,” says Judith Aberg, MD, Chief of Infectious Diseases for the Mount Sinai Health System and Dr. George Baehr Professor of Clinical Medicine at the Icahn School of Medicine at Mount Sinai.
Judith Aberg, MD
Much research progress has been made since COVID-19 was declared a pandemic by the World Health Organization on March 11, 2020, but more work remains to be done.
“At all levels, from academic institutions to federal agencies, resources are still being poured into studying COVID-19 and this level of dedication is unlikely to go away anytime soon.”
Judith Aberg, MD
“It is precisely because, as a community, we have put so much effort into studying COVID-19 that we were able to learn so much about the virus and come up with vaccines and therapeutics at an unprecedented pace,” says Miriam Merad, MD, PhD, Director of the Marc and Jennifer Lipschultz Precision Immunology Institute, and Mount Sinai Professor in Cancer Immunology.
How has COVID-19 knowledge grown over the years?
A recent breakthrough was learning why COVID-19 affects older people more severely than children, says Dr. Merad. In many other respiratory diseases, such as influenza, typically both very young and very old people are most susceptible to complications.
“One of the biggest factors we’ve discovered is that age affects innate immune response,” she says. Older individuals are more likely to have a defective response in which their type I interferon activity is less likely to mount an antiviral or anti-inflammatory response, she adds.
Understanding the links of age to inflammatory response had also been a big piece in solving the COVID-19 puzzle, Dr. Merad says.
“It appears that SARS-CoV-2 might not be directly destroying organs. Rather, pathogenic-led inflammation might be doing so instead.”
Miriam Merad, MD, PhD
While SARS-CoV-2 is in the class of coronaviruses, very little was known about its specific pathophysiology, how it infects cells and induces injury, and how the host can control the virus. The scientific community has made inroads into these fields over the past year, especially in recent months, Dr. Merad notes.
Miriam Merad, MD, PhD
At the start of the pandemic, there were also no objective biomarkers to characterize the disease. Today, researchers have identified various measures, including platelet hyperactivations, microclots, and immune and microbiome dysfunction, as ways to analyze the impacts of COVID-19 on the body, especially for post-acute sequelae of COVID-19, the condition colloquially known “long COVID.”
“It’s really bleeding-edge,” says David Putrino, PhD, Director of Rehabilitation Innovation at the Mount Sinai Health System. “It has really coalesced over time, and has taken two years before impressive articles were coming out about meaningful biomarkers.”
How had COVID-19 research been challenging?
“It is really difficult to do research in the middle of a pandemic,” recalls Dr. Merad. With measures in place to keep staff safe from infection, as well as prevent lab leaks, it became challenging to develop animal models. Additionally, given that COVID-19 was a new disease, there were few good models to start with, she adds.
Barriers to knowledge, tools, or resources also made studying COVID-19 an uphill task. As the disease has symptoms that span multiple specialties, including neurology, immunology, pulmonology, cardiology, and more, an effective effort into studying the pathogen required broad capabilities.
David Putrino, PhD
“I’m a neuroscientist, focusing on electrophysiology of the brain, and had a set of tools I was comfortable using,” says Dr. Putrino. “But along came COVID-19 and suddenly I had to become an expert on immune physiology, on drawing blood, and running a wet lab.”
“Collaboration became necessary, especially with people outside our usual fields.”
David Putrino, PhD
“While I feel fortunate that I’m in a position from a funding and career standpoint that can support my needs for long COVID research, many others aren’t as fortunate to develop those skill sets,” Dr. Putrino says. The reality of many scientists needing to keep their labs running and applying for grants could mean it was easier to relegate COVID-19 research to someone else, he adds.
The nascent field of COVID-19 research, especially for long COVID, means the scientific community is still divided on various definitions. But with the pandemic dying down, researchers are able to communicate and collaborate more effectively across the country on standards and definitions when it comes to conducting research or collecting data, especially as scientific conferences return in full force, Dr. Merad says.
What are some things we still don’t know about COVID-19?
On the clinical side, it is not clear for hospitalized patients what are the best immune modulating therapies or strategies. “When should we start combination immune modulating therapies? Are antivirals effective in patients on high flow oxygen if they still are shedding virus?” says Dr. Aberg. “We are still trying to optimize modalities.”
New treatments for COVID-19, including antiviral drugs such as Paxlovid, are now available to help reduce the likeliness of developing severe disease. But some shortfalls remain.
“For example, Paxlovid has significant drug-to-drug interactions and not everyone can take that,” notes Dr. Aberg. “We’re still learning how to be able to manage those who are immunocompromised and are experiencing persistent viral shedding.”
Some of the monoclonal antibody treatments that had been developed for COVID-19 and had shown efficacy earlier in the pandemic have since become less effective against current circulating variants. “We need to develop tools for rapid sequencing of virus to detect which variant is causing disease while simultaneously having available active antibody therapies. We hope that future anti-SARS-CoV-2 monoclonal antibodies will be effective to treat and prevent COVID-19, especially for those who are immunocompromised,” Dr. Aberg says.
In basic science, many questions about viral pathophysiology remain unanswered, especially with regards to how it affects coagulation, thrombosis, and inflammation, says Dr. Merad. Even with the success of COVID-19 vaccines at reducing infection incidence and severity, people still can still be infected, and it is not clear why that is so, she adds.
What is the current state of COVID-19 research and where is it headed?
Clinicians are looking at whether they can combine different treatment modalities, especially for immunocompromised patients, says Dr. Aberg.
The National Institutes of Health is still conducting its efforts through the networks the agency has formed during the pandemic, and is conducting multicenter clinical trials, Dr. Aberg points out. It has preserved its expedited pipeline for testing novel therapeutics, including the use of “adaptive platform studies,” where new investigative agents could use an adapted template without the need for developing a new protocol from scratch.
Long COVID clinical trials are coming down the pipeline, says Dr. Putrino. A trial to test the use of Paxlovid for treating long COVID has received an Institutional Review Board approval from the Food and Drug Administration, making it one of the first of its kind for a targeted treatment of the condition, he notes.
The discovery of objective biomarkers will also pave the way for new drugs to be developed for long COVID, or for existing treatments to be explored, says Dr. Putrino.
These biomarkers could also be leveraged for uses beyond COVID-19. “The pandemic made us realize how we have few assays to measure our immune fitness to tell us whether someone can be susceptible to disease,” says Dr. Merad. Immune biomarkers could be used to develop assays to measure whether an individual could mount a good immune response, perhaps to vaccination, or just in general. “Can we build novel tools to measure our immune fitness, in the same way we can measure our blood sugar?” she questions.
It is undeniable that clinicians and researchers are committed to COVID-19 research, says Dr. Merad. “That’s what we’re fighting for,” she says. “We’re talking to everyone—industry partners, government entities—on the need for continued effort, and everyone is on board.”
Here are Some COVID-19 Research Milestones at Mount Sinai
2022
- Dec 8: Mount Sinai researchers published one of the first studies about changes in blood gene expression during COVID-19 being linked to long COVID
- Aug 9: Mount Sinai launched CastleVax, a clinical-stage vaccine research and development company, whose capabilities can be leveraged to tackle SARS-CoV-2
- June 28: Mount Sinai-led team showed immune particles derived from the blood of a llama could provide strong protection against every COVID-19 variant
- June 14: Mount Sinai researchers have developed a rapid blood assay that measures the magnitude and duration of someone’s immunity to SARS-CoV-2
- Mar 31: Faculty from the Icahn School of Medicine at Mount Sinai play key roles in the SAVE program, established by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH)
- Mar 21: Clinical investigators at the Icahn Mount Sinai launched a Phase 1, open-label, placebo-controlled study to evaluate the safety and immunogenicity of an egg-based COVID-19 vaccine in healthy, vaccinated adults who have never been infected with COVID-19
2021
- Nov 29: Icahn Mount Sinai served as a hub site for two cohort studies as part of nationwide health consortium study by NIH on the long-term effects of SARS-CoV-2
- May 25: Mount Sinai and the Pershing Square Foundation expanded a saliva-based COVID-19 testing program
- April 5: Mount Sinai launched the Mount Sinai COVID-19 PCR Saliva Testing program for businesses and leisure activities in New York
- Jan 27: Mount Sinai researchers demonstrated using a machine learning technique called “federated learning” to examine electronic health records to better predict how COVID-19 patients will progress
- Jan 27: Scientists at University of California, San Francisco, and the Department of Microbiology at Icahn Mount Sinai reported data showing the promise and potential of Aplidin® (plitidepsin), a drug approved by the Australian Regulatory Agency for the treatment of multiple myeloma, against SARS-CoV-2
2020
- Dec 29: Emergent BioSolutions and Mount Sinai initiated a clinical program to evaluate COVID-19 Human Hyperimmune Globulin product candidate in the first of two Phase 1 studies for potential post-exposure prophylaxis in individuals at high risk of exposure to SARS-CoV-2
- Sept 17: The Clinical Laboratories of The Mount Sinai Hospital has received emergency use authorization from the New York State Department of Health for quantitative use of Mount Sinai’s COVID-19 antibody test
- June 17: Mount Sinai submitted a request to the U.S. Food and Drug Administration (FDA) for issuance of an emergency use authorization for quantitative use of its serologic test
- May 14: Mount Sinai established the Institute for Health Equity Research to understand the effects of health issues including COVID-19
- April 15: Mount Sinai Laboratory, Center for Clinical Laboratories received emergency use authorization from the UFDA for an antibody test
- April 3: Mount Sinai developed a new remote monitoring platform to help health care providers care for COVID-19 patients who are recovering at home
- April 1: Scientists, physicians, and engineers at Mount Sinai launched STOP COVID NYC, a web-based app to capture the symptoms and spread of COVID-19 in New York City