As the Pandemic Recedes, COVID-19 Research Continues on Many Fronts

Updated on Mar 17, 2023 | COVID Response, COVID-19, Featured, Research

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.”

Read the latest on staying safe from COVID-19 in 2023
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

FREEDOM Trial Finds That High-Dose Anticoagulation Can Improve Survival for Hospitalized COVID-19 Patients

Mar 7, 2023 | Cardiology, COVID-19, Featured, Research

The FREEDOM trial was initiated and led by Valentin Fuster, MD, PhD, President of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital.

An international trial led by Mount Sinai found that high-dose anticoagulation can reduce deaths by 30 percent and intubations by 25 percent in hospitalized COVID-19 patients who are not critically ill, when compared to the standard treatment, which is low-dose anticoagulation. The innovative FREEDOM trial was initiated and led by Valentin Fuster, MD, PhD, President of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital.

The study results were announced Monday, March 6, in a late-breaking clinical trial presentation at the scientific sessions of the American College of Cardiology Together With World Congress of Cardiology (ACC.23/WCC) in New Orleans and simultaneously published in the Journal of the American College of Cardiology.

“What we learned from this trial is that many patients hospitalized with COVID-19 with pulmonary involvement, but not yet in the intensive care unit (ICU), will benefit from high-dose subcutaneous enoxaparin or oral apixaban to inhibit thrombosis and the progression of the disease,” Dr. Fuster says. “This is the first study to show that high-dose anticoagulation may improve survival in this patient population—a major finding since COVID-19 deaths are still prevalent.”

Clinical Insights, Early in the Pandemic

This work was prompted by the discovery early in the pandemic that many patients hospitalized with COVID-19 developed high levels of life-threatening blood clots. In March 2020, during the early days of the pandemic, Dr. Fuster observed patients with blood clots in their legs who had been admitted with COVID-19. After hearing from colleagues abroad of other cases of small, pervasive, and unusual clotting that had triggered myocardial infarctions, strokes, and pulmonary embolisms, he initiated decisive action.

“We became one of the first medical centers in the world to treat all COVID-19 patients with anticoagulant medications,” says Dr. Fuster, a pioneer in the study of atherothrombotic disease. “It was a decision that we believe saved many lives.”

This early protocol led to groundbreaking research and insights by Mount Sinai into the role of anticoagulation in the management of COVID-19-infected patients. Mount Sinai research showed that treatment with prophylactic (low-dose) anticoagulation was associated with improved outcomes both in and out of the intensive care unit among hospitalized COVID-19 patients. Researchers further observed that therapeutic (high-dose) anticoagulation might lead to better results. Then, they designed the FREEDOM COVID Anticoagulation Strategy Randomized Trial to look further into the most effective regimen and dosage for improving outcomes of hospitalized COVID-19 patients who are not critically ill.

Researchers enrolled 3,398 hospitalized adult patients with confirmed COVID-19 (median age 53) from 76 urban and rural hospitals across 10 countries—including hospitals within the Mount Sinai Health System—between August 26, 2020, and September 19, 2022. Patients were not in the ICU or intubated, and about half of them had signs of COVID-19 impacting their lungs with acute respiratory distress syndrome (ARDS). Patients were randomized to receive doses of three different types of anticoagulants within 24 to 48 hours of being admitted to the hospital and followed for 30 days. Equal numbers of patients were treated with one of three different drug regimens: low-dose injections of enoxaparin, high-dose injections of enoxaparin, and high-dose, oral doses of apixaban. They compared the combined therapeutic groups to the prophylactic group.

Informing Future Care

The primary endpoint was a combination of death, requirement for ICU care, systemic thromboembolism (blood clots traveling through the arteries), or ischemic stroke at 30 days. This endpoint was not significantly reduced among the groups. However, 30-day mortality was lower for those treated with high-dose anticoagulation compared with those on the low-dose regimen. Seven percent of patients treated with the low-dose anticoagulation died within 30 days, compared with 4.9 percent of patients treated with high-dose anticoagulation—an overall reduction of 30 percent. The need for intubations was also reduced in the high-dose group: 6.4 percent of patients on the high-dose regimen were intubated within 30 days compared with 8.4 percent in the low-dose group—a 25 percent reduction. The study showed high-dose anticoagulation to be especially beneficial for patients with ARDS, a condition where COVID-19 damages the lungs. Among patients with ARDS at the time of hospital admission, 12.3 percent in the low-dose anticoagulation group died within 30 days, compared with 7.9 in the high-dose group.

All groups had low bleeding rates, and there were no differences between the two therapeutic blood thinners for safety and efficacy.

“This is an important study for patients with COVID-19 who are sick enough to require hospitalization but not so ill as to require ICU management. In this group of patients with radiologic evidence of ARDS, therapeutic dose anticoagulation prevents disease progression, especially the need for intubation, and saves lives,” says co-Principal Investigator Gregg W. Stone, MD, Professor of Medicine (Cardiology), and Population Health Science and Policy, at the Icahn School of Medicine at Mount Sinai. “This is especially important as COVID-19 is not going away. Even in the United States, the current number of daily deaths, although much lower than at the peak of the pandemic, is twice that compared with just one year ago. And in other countries COVID-19 is raging”

The FREEDOM trial was coordinated by the Mount Sinai Heart Health System. Dr. Fuster raised all funding for the trial.

What You Need to Know About the Latest COVID-19 Variant

Jan 24, 2023 | COVID-19, Featured, Vaccines, Your Health

You may have noticed that more people you know have gotten COVID-19 recently. One reason is the virus that causes COVID-19 continues to evolve into variants that are more contagious.

The latest one is known as XBB.1.5, and since early December it has become the predominant variant in the New York metropolitan area, according to the Centers for Disease Control and Prevention (CDC).

This variant is thought to be highly transmissible due to its ability to partially evade antibodies produced through vaccines or past infections. However, the vaccines still offer excellent protection against severe illness and death.

New Guidance on COVID-19 Vaccines: In April 2023, the Food and Drug Administration and the Centers for Disease Control and Prevention announced some major changes for COVID-19 vaccines. Click here to read more about what you need to know.

In this Q&A, Bernard Camins, MD, MSc, Professor of Medicine (Infectious Diseases) at the Icahn School of Medicine at Mount Sinai and the Medical Director for Infection Prevention for the Mount Sinai Health System, explains more about the new variant and how to protect yourself.

No matter the variant, it is important to remember that COVID-19 is not going away. The key is to reduce transmission to those who are at risk of getting seriously ill:

  • If you feel sick, stay at home.
  • If you want to be more vigilant, wear a high-quality mask, avoid being unmasked at large indoor gatherings (such as eating at restaurants), especially when infection rates in your area are very high.
  • If you are at high-risk for a serious infection, talk with your medical provider so you are prepared should you get infected.
  • Don’t forget to get your flu shot; you can get that at the same time you get your COVID-19 booster shot.

How does this new variant differ from the earlier variants?

The nature of COVID-19 is that the new variants are likely going to be more contagious than the older ones. There is currently no evidence that this latest variant is more dangerous. The symptoms do not appear different.

 Does the newest, updated booster shot help protect me from this new variant?

According to the CDC, being up to date with the bivalent booster that became available in September 2022 offers the best protection against COVID-19. (It is the only booster now available.) The updated bivalent booster specifically targets both the BA.5 sub variant of Omicron, of which XBB.1.5 is a descendent, and the original SARS-CoV-2 virus. The original COVID-19 monovalent vaccines, and the monovalent booster that became available in the fall of 2021, only target the original virus, and therefore potentially offer less protection against the Omicron subvariants.

 I was recently infected with COVID-19. How long should I wait to get the latest bivalent booster?

You may consider waiting up to 90 days from your last infection before getting the bivalent booster. Reinfection is less likely in the weeks and months after infection. But you may want to talk with your provider if you are at increased risk of severe disease.

 I never got any vaccines. Can I skip the first and second monovalent vaccines and just get the bivalent booster?

No. Before you can get the bivalent booster, you still need to get two doses of the monovalent vaccine.

 I received my bivalent booster more than two months ago. Has my immunity started to wane?

Your immunity does begin to wane after three to four months, probably more so if you’re older, such as older than 50.

 Can I get another dose to bolster my immunity?

No. Currently, there are no more recommended doses after you have already gotten the bivalent booster, regardless of how long it has been.

 Will the bivalent booster and antiviral medications prevent me from developing long COVID?

We do not have definitive data yet to know how much protection the bivalent booster and antiviral medications such as Paxlovid™ offer against the development of long COVID. But we do know that being vaccinated certainly reduces your risk of developing it.

I am at high risk for complications from COVID-19. What should I do to protect myself from the latest subvariant?

Because COVID-19 is so widespread now, it’s hard to avoid getting infected or exposed. While it is reasonable to take precautions to avoid a COVID-19 infection, the goal should be to reduce the severity or prevent complications when you do get COVID-19. High-risk individuals should have a plan for how to get antiviral medications, which can prevent severe illness or death. For this to work, you must take the medications within the first five days of symptom onset. If you have not done so already, you should talk with your doctor or your care provider to create a plan for what antivirals you would need and how to get them. Having a plan is also important because you may be on medications that interact with certain antivirals, and you may need to stop taking those medications temporarily to prevent drug interactions. Those at high risk include older adults, those with chronic medical conditions, such as diabetes, and those with reduced ability to fight infections, such as those being treated for some cancers.

Read more from Mount Sinai experts about COVID-19

COVID-19 Travel Tips for This Holiday Season

Updated on Nov 10, 2022 | COVID-19, Featured

We are approaching the third holiday season during the COVID-19 pandemic, but this one is different from the others: Masking requirements and other social distancing guidelines are largely gone.

So what should you do if you are concerned about COVID-19 possibly interfering with your holiday plans? Just take some common-sense precautions, experts say. Here are some suggestions from Bernard Camins, MD, MSc, Professor of Medicine (Infectious Diseases) at the Icahn School of Medicine at Mount Sinai and the Medical Director for Infection Prevention for the Mount Sinai Health System.

Pay attention to all your vaccinations. Continue to stay up to date with your COVID-19 vaccinations. On September 1, the Centers for Disease Control and Prevention (CDC) recommended that those over age 12 get the newest COVID-19 boosters that also target the Omicron variant, and on October 12, the CDC extended that recommendation to those ages 5-11. You should get this vaccine if it has been at least two months since your last COVID-19 vaccine dose. Also, don’t forget your flu shot, as this season is expected to be worse than normal. And remember these shots may take up to two weeks for full protection to kick in.

It’s just as important to stay up to date even if you had COVID-19. The newest vaccine provides added protection, according to the CDC. If you recently had COVID-19, you may delay the next vaccine dose for three months from the onset of symptoms or from your first positive test.

When traveling, consider wearing a high-quality mask in crowded public areas. A surgical mask, which is more comfortable than a snug-fitting KN95 mask, provides some protection against viral infections. That might be prudent for a long plane ride. But to ensure better protection, wearing a clean cloth mask on top of the surgical mask, or wearing a KN95 mask or N95 mask is recommended. Also, onboard the plane, the most important time to consider wearing a mask is while the plane is still on the ground; once airborne, the plane’s sophisticated air filtration systems come on. (Two important footnotes on masks: Masking is still required in health care facilities in New York State, and health care facilities in areas where there is high COVID-19 transmission may require them. You are supposed to wear a mask in public if you are just getting over COVID-19.)

Be especially careful at gatherings and celebrations. If you have been dining at restaurants indoors or attending gatherings indoors without a mask on, then you have been exposed to respiratory viruses already. This holiday season, you are probably more likely to get infected during the many hours you are with friends and family around the dinner table or celebrating inside. That’s what happened a year ago when social distancing guidelines were relaxed. So general guidance on gatherings remains: Remember that some people may be more at risk, such as such as older adults, those with chronic medical conditions, such as diabetes, and those with reduced ability to fight infections, such as those being treated for some cancers. More fresh air is better. You may want to ask those gathering to consider taking an at-home test in advance.  Keep in mind these tests are not always sensitive enough to detect the onset of COVID-19 (home antigen tests should be performed at least three times, 48 hours apart after a high-risk exposure), and you could be infected and spreading the virus without showing any symptoms.

Have a plan. Talk with your primary care provider in advance about what you should do if you are at risk for severe complications from COVID-19 and think you have been exposed or start to show symptoms of COVID-19. For example, some clinicians may prefer you get a more sophisticated PCR test, rather than the simple at-home antigen tests. Some people with COVID-19, notably those over 65 or with other health conditions, might benefit from the antiviral therapy Paxlovid—though this must be taken within five days after symptoms start. Talking to your provider in advance can help you know precisely what to do, such as getting a prescription for Paxlovid, especially if you must take action over the weekend.

Recognize we are all learning to live with COVID-19. This viral disease, much like the flu or the common cold, is not going away. But with some basic precautions, it should not stand in the way of spending time with friends and family.

Learn more from the CDC about COVID-19 and travel

Updated COVID-19 Vaccines: What Are They and Do I Need One?

Oct 14, 2022 | COVID-19, Featured, Vaccines

Over the years of the COVID-19 pandemic, SARS-CoV-2, the virus that causes the disease, has mutated many times. Each new version of the virus is called a variant or subvariant.  The same COVID-19 vaccines that were made available since December 2020 have done a remarkable job in preventing severe disease and death but have become less effective at preventing infections because of the mutations.

That is, until the late summer of 2022, when the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) green-lighted “bivalent” formulations—an updated version of the vaccines—to be used against the newer variants of SARS-CoV-2.

Bernard Camins, MD, MSc, Professor of Medicine (Infectious Diseases) at the Icahn School of Medicine at Mount Sinai and the Medical Director for Infection Prevention for the Mount Sinai Health System, explains what the bivalent vaccines do and the latest guidance on who should receive them and when.

New Guidance on COVID-19 Vaccines: In April 2023, the Food and Drug Administration and the Centers for Disease Control and Prevention announced some major changes for COVID-19 vaccines. Click here to read more about what you need to know.

What does it mean that the vaccines are bivalent?

COVID-19 vaccines with bivalent formulations target the BA.5 subvariant of Omicron—one of the predominant circulating variants—as well as the original SARS-CoV-2 virus, says Dr. Camins. These include the vaccines from Pfizer-BioNTech and Moderna.

An updated vaccine is needed because the virus has mutated several times and is so different from the original strain that the previous monovalent version of the vaccine —targeting only one variant—might not provide adequate protection from infection, he says.

With bivalent vaccines now authorized for use, the monovalent versions of the COVID-19 boosters are no longer authorized. The primary series are still recommended before the bivalent booster can be administered.

How effective and safe is the updated vaccine compared to previous ones?

“It’s pretty much the same as the old vaccine,” Dr. Camins says. The difference is that the genetic makeup of the updated vaccines has an addition to account for the spike protein of BA.5.

The updated vaccines’ side effects are similar to previous versions. The most commonly reported side effects of the bivalent vaccines include pain, redness, and swelling at the injection site, fatigue, headache, muscle pain, joint pain, chills, swelling of the lymph nodes in the same arm of the injection, nausea/vomiting, and fever, according to the FDA.

“You probably would not notice it being different from any of the previous vaccine doses or boosters you’ve received,” Dr. Camins says.

The updated Moderna and Pfizer-BioNTech vaccines have both been studied for effectiveness and safety. Although the studies examined a bivalent formulation involving the original strain and Omicron BA.1, the FDA granted the vaccines authorization based on the totality of evidence, which included clinical and nonclinical data that demonstrated commonalities between BA.1 and BA.4/BA.5.

This method of studying and approving updated COVID-19 vaccines is similar to how new flu vaccines based on circulating strains are handled, he adds: “It is very analogous to what we do with the flu vaccine.”

Who is eligible for the updated vaccine and who should get it?

The Moderna updated booster is authorized for individuals ages 6 and older, while the Pfizer-BioNTech updated booster is authorized for those who are 5 and older.

Where can I get the updated vaccine?

If you live in the New York metropolitan region, you can check the New York State, New York City, New Jersey, or Connecticut websites for locations that offer appointments or walk-in vaccination. Major pharmacy chains are another place to try. If you live elsewhere, Dr. Camins recommends using vaccines.gov or reaching out to local health care providers and pharmacies.

When should I get the updated booster?

The updated vaccine is recommended to individuals two months after completing a primary series or a previous booster.

I got COVID-19 recently. Do I still need the updated booster?

“The updated booster is recommended even for those who have been infected with a previous variant or subvariant of SARS-CoV-2,” says Dr. Camins.

If you have been recently infected, it is reasonable to wait 90 days after symptom onset before receiving an updated booster, he says. However, the CDC has indicated it is also safe to seek an updated booster as soon as you are no longer contagious from a current infection.

Why do I need a booster when people still seem to get COVID-19 despite being vaccinated?

The updated vaccine booster was created to match the current circulating BA.5 subvariant better so it should protect patients from infection better than the previous version, although it’s not a 100 percent guarantee, Dr. Camins says. Receiving the booster could also lessen the chances of developing severe disease especially for patients who are at high risk for complications from COVID-19.

Will I need to keep taking updated boosters if there are new variants?

“We don’t know if future updated boosters are required,” Dr. Camins says. That determination could be based on the current circulating sub-variant, as well as the data from people who have received the updated booster for Omicron BA.5, he adds.

However, Dr. Camins notes that the White House’s COVID-19 Response Team is thinking of moving in the direction of rolling out annual, updated COVID-19 shots matched to current circulating strands. A single annual shot should provide a high degree of protection against serious illness all year, and could prevent thousands of deaths and hospitalizations annually, according to White House officials.

Read more from Mount Sinai experts about vaccines

Curious About the Mpox Vaccine? Here’s What You Need to Know

Updated on Dec 6, 2022 | Featured, Infectious Diseases


As cases of mpox, the disease caused by the monkeypox virus, climb in New York City, health professionals and the city Department of Health and Mental Hygiene (DOHMH) have urged people at high risk of contracting the virus to receive the vaccine. DOHMH is making appointments for the vaccine available as quickly as possible, but the vaccine remains in extremely short supply nationwide. Richard Silvera, MD, MPH, Assistant Professor of Medicine (Infectious Diseases), at the Icahn School of Medicine at Mount Sinai, explains what the vaccine is and who should consider getting a shot.

Has a vaccine been approved by the FDA for mpox, and if so, when?

There are two vaccines approved by the U.S. Food and Drug Administration for mpox and smallpox, which are in the same Orthopoxvirus family. JYNNEOS, initially approved in 2019, is currently being used for mpox vaccination efforts. The other is ACAM2000, which was approved in 2007.

How do the vaccines work?

The JYNNEOS vaccine is approved to be administered as two shots subcutaneously, or into tissue under the skin, delivered at least four weeks apart. On August 9, the FDA granted emergency use authorization for the vaccine to be delivered intradermally, or between layers of the skin, to increase availability of doses up to fivefold. DOHMH adopted this guidance on August 23.

ACAM2000, which is not being used for the current outbreak, is administered as a single dose via multiple punctures into the skin using a bifurcated needle.

Both vaccines contain live vaccinia virus, which is also an Orthopoxvirus like mpox. The JYNNEOS vaccine contains attenuated virus. “What that means is there is a virus in the vaccine that has been medically altered to prevent it from reproducing,” Dr. Silvera said. Vaccinated individuals are unable to pass on vaccinia infections to other people around them, unlike with replication-competent vaccines such as ACAM2000.

The vaccine elicits two types of immunities: humoral and cellular, said Dr. Silvera. Humoral immunity involves the building of antibodies that fight off viruses if the body is exposed to them. Cellular immunity involves teaching cells to recognize cells that are infected with viruses and to eradicate those cells. Vaccinia virus has been used as a vaccine for nearly two centuries to fight off more lethal infections, such as smallpox, which was considered eradicated in the United States in the late 1970s.

Is intradermal administration of the vaccine as effective and safe as subcutaneous?

The guidance for intradermal administration of the JYNNEOS vaccine is only for those ages 18 and older. Individuals who are younger would still require the subcutaneous route.

The authorization was granted based on data of a 2015 clinical study that evaluated a two-dose intradermal regimen compared to a subcutaneous one, with the former administered at one-fifth the volume of the latter route of administration.

Results demonstrated that intradermal administration produced a similar immune response to subcutaneous administration. Administration by the intradermal route resulted in more redness, firmness, itchiness, and swelling at the injection site, but less pain, and that these side effects were manageable.

As per the Centers for Disease Control and Prevention (CDC), the city Health Department has adopted the guidance of using subcutaneous delivery to individuals with a history of developing keloid scars. These are raised scar tissue that might occur after a cut or a skin injury.

Am I protected with the first shot? How effective is the vaccine?

“The vaccine does offer some protection after the first shot, but it takes about two weeks after the vaccine is given before that protection comes into play,” said Dr. Silvera. When the two-shot series is complete, it confers about an 80-85 percent effectiveness against infection at the individual level, but its effectiveness at a community level is currently unknown, he added.

Given limited supplies of the JYNNEOS vaccine, the DOHMH is delaying second doses so that more people can get first doses and have some protection. In DOHMH guidance, it added that it is OK to wait longer than four weeks to receive the second dose. Those who received the first dose will be contacted by the Health Department when second doses are available.

Who is considered high-risk and should consider getting the vaccine?

The city is prioritizing appointments for high-risk groups, which currently include men who have sex with men and transgender or gender non-conforming/non-binary people, if they have had multiple or anonymous sex partners in the last 14 days, and transactional sex workers of any sexual orientation or gender identity.

That guidance may change as the epidemic evolves, Dr. Silvera said, adding that health officials are watching the situation closely.

Mpox, however, should not be stigmatized as a sexually transmitted infection unique to the LGBTQ community, Dr. Silvera pointed out. Infections are spread via intimate skin-to-skin contact and sex happens to be one such activity. “No particular person is at high risk of contracting an infection because of who they are,” he stressed.

Who should not get the vaccine?

People who have an allergy to the ingredients of the JYNNEOS vaccine should not receive it. The ingredients include gentamicin, ciprofloxacin, and egg protein.

Otherwise, people who meet the eligibility criteria should highly consider the vaccine, Dr. Silvera said.

If I had received a routine smallpox vaccine, am I still protected against mpox today?

Up until 1972, the United States had routine smallpox vaccination, which led to the disease being eradicated. However, people who received a smallpox vaccine then would not be considered to have adequate protection against the current mpox outbreak, Dr. Silvera said, adding that if those individuals meet the criteria for getting the JYNNEOS vaccine, they should seek it.

The CDC guidance, however, stipulates that people who previously have been vaccinated against smallpox can receive just one dose of the JYNNEOS vaccine for adequate protection.

Can I receive a mpox vaccine around the same time as a COVID-19 shot or booster?

The current recommendation is to space out four weeks between receiving a JYNNEOS vaccine and a COVID-19 shot or booster that uses mRNA technology, such as those from Pfizer or Moderna. “That’s to help prevent people from any adverse side effect,” Dr. Silvera said.

However, if vaccination is recommended due to a known exposure to mpox, the individual is encouraged to get the JYNNEOS vaccine even if the person recently received a Pfizer or Moderna vaccine, according to city Health Department guidance.

The story has been updated to include that DOHMH has adopted the guidance regarding administering the mpox vaccine intradermally.

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