Omicron and the Immunocompromised: A Guide for Those at High Risk for COVID-19

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Over the past month, the new COVID-19 variant Omicron has thrown the world into a whirlwind of skyrocketing cases, return to office delays, school closures, and — for many immunocompromised patients — a renewed sense of stress, uncertainty, and fear of getting sick with COVID-19.

However, if you’re prepared with the latest data, preventive measures, and treatment plans available for Omicron, you can turn at least some of the uncertainty into action. Here’s what to know about the new variant if you’re immunocompromised because of an autoimmune or inflammatory health condition or taking immunosuppressant medication.

What Is So Unique About Omicron?

The Omicron variant of the coronavirus, also known as B.1.1.529, has upward of 50 mutations. This includes 30 mutations along the spike protein, which is responsible for facilitating infection and is a key immunogen (a substance used to create an immune response) in currently available vaccines, per the American Society for Microbiology.

A preprint study (meaning it has not been peer-reviewed yet) conducted in South Africa found that Omicron had exponential growth over a four-week period in one province and spread with an estimated doubling time of 3.2 to 3.6 days. That is larger than but comparable to the doubling times first seen during the COVID-19 outbreaks of spring 2020, when prior immunity did not exist and no intervention methods had been implemented.

Some early data suggests that Omicron may lead to less severe cases of COVID-19 than previous variants, but many experts are hesitant to draw conclusions quite yet — especially for people with chronic health problems and are already at increased risk for COVID complications.

“Emerging evidence is suggesting that this particular variant likes to cause more issues in the upper airway than in the lower airway such as the lungs, but the caveat is there’s only been a month of Omicron,” says Aditya Shah, MD, an infectious disease consultant at the Mayo Clinic. “If that holds true as we get more data, then there is a chance that the outcomes with regard to hospitalizations and mortality could be less severe for Omicron as compared to Delta.”

While many generally healthy people already seem to be taking this news to heart — and acting as though catching Omicron is no big deal — it’s no reason to throw precaution to the wind.

Omicron is spreading at a rate not seen with any previous variant and experts are concerned that people are dismissing it as “mild,” per the World Health Organization. A case of COVID-19 that doesn’t require hospitalization or oxygen can still be incredibly impactful and leave you ill for quite some time. Having a compromised immune system only complicates matters.

“Omicron is very transmissible and I don’t think we can apply the severity of disease from the general population for people who are on immunomodulatory and immunosuppressive medications,” says Jean Liew, MD, Assistant Professor of Medicine at Boston University School of Medicine and member of the COVID-19 Global Rheumatology Alliance (GRA), which conducts data collection, analysis, and dissemination of the impact of the COVID-19 pandemic on individuals with rheumatic disease. “While it might be reassuring [to hear that Omicron may be milder], I would act as though that isn’t true — because you don’t know if it’s going to be true for you.”

What’s more, hospitalization and mortality are often dependent on how overburdened your local health care system is. Even if Omicron turns out to cause more mild disease than Delta, more infected people means more patients in the hospital.

How Risky Is Omicron If You’re Immunocompromised?

While each person’s individual risk depends on underlying conditions, medication use, and exposure level (based on region, occupation, living situation, and more), immunocompromised patients likely have a higher chance of acquiring Omicron even after the vaccine and booster than immunocompetent people, says Dr. Shah.

“Immunocompromised patients may or may not mount an adequate immune response to their vaccine plus the booster,” says Dr. Shah. “That sets them up to not have enough vaccine-generated antibodies, in combination with this more transmissible strain.”

However, you’re likely to fare better if your underlying chronic disease is well-controlled. While we don’t have GRA data specific to Omicron yet (most data published on COVID-19 so far has looked at variants before Omicron), Dr. Liew says we can apply what we know from previous variants.

“Risk of poor COVID-19 outcomes based on what underlying condition you have and what medication you’re on still hold true,” says Dr. Liew. “For example, if you have a condition that’s very active and you currently have a lot of inflammation, I would still say that you’re at higher risk for being sicker with COVID-19 than if you were someone who had the same condition but everything was very controlled and your blood test levels look good.”

Other research (not strictly from the GRA) has shown that certain medications like B cell-depleting drugs (like rituximab) can increase the risk of breakthrough COVID infections in general. Other medications used autoimmune or inflammatory diseases, like glucocorticoids, may also hamper the immune response. See our recap of the latest research on COVID-19 and COVID-19 vaccines.

It’s expected that anyone with Omicron infection can spread the virus to others, even if they are vaccinated or aren’t experiencing symptoms, per the U.S. Centers for Disease Control and Prevention (CDC).

Breakthrough infections in those who are fully vaccinated are likely to occur with Omicron. However, it’s important to remember that the current COVID-19 vaccines are expected to protect against severe illness, hospitalizations, and deaths due to Omicron variant infection — which underscores the importance of full vaccination and booster shots in both the general population and immunocompromised patients.

Why Are Additional Vaccine Doses So Important for the Immunocompromised?

“For immunocompromised people, the meaning of being fully vaccinated was already shifting before this was a consideration for the general population,” says Dr. Liew. “People who are on immunomodulatory or immunosuppressant medications need three shots as their primary regimen — for these people, a booster would be a fourth shot, after the third.”

In other words, what’s considered a “booster” for the general population would be comparable to a fourth dose in the immunosuppressed, which can now be administered five months after the third dose.

“Each time the immune system safely encounters a germ or an antigen, it enables the antibody response to really blossom — not only in terms of how much antibody you make but also how diverse that antibody response is,” says researcher Alfred Kim, MD, Assistant Professor of Medicine, Pathology, and Immunology at Washington University, who has extensively studied how immunosuppressant medication affects COVID-19 vaccine effectiveness. “This means it can anticipate new variants, even though it has never seen them before. The boost or any additional doses really play a critical role in optimizing the antibody response, even in the immunocompromised.”

Emerging data, including Dr. Kim’s own research in Med, on TNF inhibitor biologic patients (a very commonly prescribed medication class) shows that their immune system’s ability to fight off variants like Delta in a culture dish is highly eroded with the regular, standard dosing of the vaccine. But when they receive an extra dose, that response becomes much stronger.

Boosters are also recommended for immunocompetent people because the immune response naturally declines over time and additional doses may help protect against variants like Omicron. If you’re immunocompromised, it’s very important for those around you to get their COVID booster.

When Can Immunocompromised People Get a Fourth Vaccine?

People who are immunocompromised because of high-risk health conditions or because of immunosuppressant medication can get a fourth COVID-19 vaccine five months after their third dose.

That means immunocompromised patients who received the third mRNA shot after it was approved in August 2021 would be able to get a fourth shot is January 2022.

“There’s some data in solid organ transplant patients on fourth doses,” says Dr. Kim. “Most importantly, it remains safe. In organ transplant cases where immunosuppression is substantially burdensome — they have some of the highest, most aggressive immunosuppressive regimens out there — there are increasing numbers of people starting to respond to fourth doses, even though they did not respond to the first two or three doses.”

“The data is starting to emerge that getting a fourth dose is probably going to be part of what we look forward to in 2022 for many of our immunocompromised patients,” says Dr. Kim.

How to Reduce Your Risk from Omicron If You’re Immunocompromised

There are actionable steps you can take to reduce your risk of contracting the Omicron variant if you’re immunocompromised — many of which you’ll recognize from throughout the pandemic.

“I don’t want people to worry and think ‘I can’t see my family again and I have to go into extreme isolation,’ but everyone needs to be prepared and know what options are available to lower the risk of having severe outcomes if you do get infected,” says Dr. Liew. “I think a lot of people are doing the right thing but still getting infected because this variant is so transmissible.”

Get the COVID vaccine, including boosters or fourth doses when you’re eligible 

Your doctor may recommend a base series of three doses of the mRNA vaccine if you’re immunocompromised, plus a booster five months later.

“If you haven’t gotten your third shot of the initial series, definitely get the third shot,” says Dr. Liew. “Getting fully vaccinated is a big one because that’s what’s going to protect you from having a very severe outcome.”

Ask your doctor about preventive COVID treatment

The U.S. Food & Drug Administration (FDA) recently authorized monoclonal antibody as a preventive treatment. AstraZeneca’s Evusheld contains tixagevimab and cilgavimab and is authorized for those with:

• Moderate to severely compromised immune systems due to a medical condition or from immunosuppressive medications or treatments and may not mount an adequate immune response to COVID-19 vaccination or
• A history of severe adverse reactions to a COVID-19 vaccine and/or component of the vaccine, and therefore vaccination with an available COVID-19 vaccine is not recommended

It is also only authorized for adults and children (12 years of age or older and weighing at least 40 kilograms, or about 88 pounds) who are not currently infected with the coronavirus virus and who have not recently been exposed to an infected individual, per the FDA.

Evusheld provides about six months of protection with two shots given the same day. Pre-exposure prophylaxis (PrEP) like this will play a key role in protecting immunocompromised patients in the coming year, says Dr. Kim.

GlaxoSmithKline (GSK) and Vir Biotechnology are also partnering to determine if sotrovimab, an investigational monoclonal antibody, can prevent symptomatic COVID-19 infection in uninfected immunocompromised adults, per GSK.

The one roadblock that may occur early on is distribution, so it’s important to talk to your doctor about accessibility of preventive treatments now.

“Right now, PrEP is available in very limited doses,” says Dr. Kim. “But 3 percent of Americans are eligible for PrEP, which is about 10 million people — so there’s a huge gap here in terms of numbers. Obviously production is going to be increasing dramatically, but until it catches up, we’re going to see some similar supply issues as we did with vaccination when it first rolled out.”

Know about COVID treatment options

Formulate a game plan for what you’ll do if you do become infected.

“More important than knowing your risk of a bad outcome is actually knowing where you can act to try and protect yourself,” says Dr. Liew. “I know it’s an even greater burden on people who have already been burdened for two years on how to stay safe and protect themselves, but unfortunately I think that’s where we’re at.”

Now is the time to talk to your doctor about potential treatment options should you become infected with COVID-19. These include:

Antiviral pills: Both Merck and Pfizer have received FDA authorization for antiviral pills, which need to be taken within five days of symptom onset to be effective. These are now becoming available at pharmacies with a doctor’s prescription.

Monoclonal antibody treatments: Ask your doctor where you can get these treatments — particularly Sotrovimab, which is the monoclonal antibody treatment that works against Omicron.

“With Omicron, most of the monoclonal antibody treatments we were using before are not effective,” says Dr. Liew. “The one that is effective, Sotrovimab, is in short supply and it’s hard to figure out how to get an infusion at this point.”

Gather your research now and try to plan ahead. Like antiviral pills, monoclonal antibody treatments work best when administered early on.  Sotrovimab should be given as soon as possible after positive test results and within 10 days of symptom onset. It is administered as a single intravenous infusion over 30 minutes, per GSK.

Remdesvir: This is an antiviral drug administered to hospitalized patients. It prevents viral replication by stopping RNA transcription prematurely, per the National Institutes of Health. However, it’s not always helpful by the time a patient is hospitalized with COVID-19.

“Remdesivir is an intravenous drug only approved for people who are very sick in the hospital with COVID-19,” Monica Gandhi, MD, MPH, Professor of Medicine and Associate Division Chief of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/San Francisco General Hospital, told us previously. “And in fact, by that point, the inflammation is usually so severe that an antiviral doesn’t make a difference. We’ve already shown that very soon after you develop symptoms, your viral load decreases quite quickly.”

For that reason, a mainstay therapy in hospitals for COVID-19 is the steroid dexamethasone and other anti-inflammatories. However, there is emerging evidence that remdesevir could also work in an outpatient setting to prevent hospitalization of patients.

Get tested early

You can greatly reduce your risk of severe outcomes by getting tested for COVID-19 as soon as you have symptoms. That’s because several treatments available for COVID-19, including Omicron, work best when they’re taken immediately. Keep a rapid antigen test on hand at home so you can know if you’re positive without having to wait in line with others who are potentially infected with COVID-19. These can be hard to come by, so keep trying online sites like Walmart and Walgreens.

Use a more protective mask

If you can, upgrade your mask for Omicron. “Cloth or fabric masks are not recommended at this point,” says Dr. Liew. “Surgical is better than the cloth mask, but even then, it’s not recommended if you can get a better mask. If you can get a N95 or a KN95 mask, that would be the best bet for grocery shopping, riding on public transportation, or going to work in a place where you’re around other people.”

For a trusted source of N95 masks, Dr. Liew recommends Project N95.

Wear your mask regularly

“Right now, everyone — including the immunocompetent — need to be repeating what we did in most of 2020,” says Dr. Kim. That includes wearing a mask indoors around others: The CDC recommends wearing a mask in public indoor settings regardless of vaccination status.

Avoid crowded spaces

You can likely continue everyday tasks, but take precautions like wearing a protective mask and social distancing. “Running errands or going into work are different from going to a concert or ballgame,” says Dr. Shah. “If you’re thinking about going to a concert or ballgame, I would recommend against it because there is a larger population density there than in a grocery store. If you’re going to the grocery store, while there is a chance you may come across someone with the Omicron variant or COVID-19 in general, the chances of you acquiring infection if you maintain distance from them, stay masked, and are boosted is way less.”

Speak with your supervisor about potential work from home options if your office has reopened (and working from home is possible for your job). That said, while there’s no such thing as zero risk against COVID-19, if your workplace has mandated vaccines and boosters, masks, has good ventilation, and you follow social distancing, there is a lower risk of infection than in workplaces without these measures.

Control your underlying disease 

Don’t stop taking any medications without speaking to your doctor and work on managing your condition to maintain a good baseline of health.

Is Omicron Like Returning to March 2020 or Lockdown All Over Again?

If it feels like you’re reliving the early days of the pandemic with Omicron, you’re not alone Here’s how to cope emotionally with the letdown of another variant or spike in cases.

“In a lot of ways, we’re reliving the early- to mid-2020 time period,” says Dr. Kim. “Not only should the immunocompromised be thinking about doing the best they can to mitigate risk, but there also needs to be a concerted effort to really make sure the immunocompetent people around them are doing their best to [reduce risk].”

However, there’s reason for hope: At the beginning of the pandemic, we knew much less about how COVID-19 spreads and had far fewer ways to prevent and treat it.

“There are many reasons as to why now is different from the start of the pandemic — number one is that we have vaccines and boosters,” says Dr. Shah. “Number two is that we know good masking can prevent infection. Number three, we have several treatment strategies in terms of antivirals that have recently been approved. We also have monoclonal antibody cocktails, which we did not have at the beginning of the pandemic.”

All of these developments are key for those who are immunocompromised and high risk for COVID-19. While our current situation may feel eerily familiar, know that there is hope ahead with emerging data, preventive measures, and treatment.

“Even though immunocompromised people may not have that initial level of immunity other people have, and they may feel like their tank is running empty because they’ve done everything they can to protect themselves, there is light at the end of the tunnel,” says Dr. Kim.

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