Many patients with chronic conditions may have low antibodies after second COVID-19 vaccine

One-fifth of patients with chronic medical conditions who received two doses of an mRNA COVID-19 vaccine had insufficient antibody levels at least 14 days after the second dose, researchers reported in Chest.

In a new study, Michael E. Wechsler, MD, director of the National Jewish Health Cohen Family Asthma Institute in Denver, and colleagues identified 360 patients (mean age, 62 years; 63% women) with chronic medical conditions evaluated at the respiratory specialty clinic who received two doses of the Pfizer/BioNTech (64%) or Moderna (36%) mRNA vaccines from December 2020 to July 2021 and subsequently had spike antibody results at least 14 days following the second dose.

At a mean of 96 days after the second dose, 21% of patients had no antibodies. Twenty-four percent of patients who received the Pfizer-BioNTech vaccine and 16% of patients who received the Moderna vaccine had negative antibody responses.

Interstitial lung disease (OR = 0.37; 95% CI, 0.18-0.76), chronic heart failure (OR = 0.22; 95% CI, 0.07-0.65), biologic use (OR = 0.3; 95% CI, 0.15-0.63) and immunosuppressant use (OR = 0.35; 95% CI, 0.18-0.69) were significant risk factors for a negative antibody response after adjusting for other variables.

Healio spoke with Wechsler to discuss the results of this study.

Healio: Why did you and your colleagues conduct this study in people with chronic conditions?

Wechsler: When we started to look at people who’ve been fully vaccinated, we found that close to 22% of patients here at National Jewish Health had insufficient levels of antibodies despite being vaccinated. Since pulmonary patients are at higher risk for complications of viral infections, and since National Jewish Health has a large contingency of patients with lung disease, we decided to look at who these people are, how frequent this is occurring, predictors of lack of production of antibodies and other factors, including T-cell response, that are potentially apparent in this patient population and might put them at risk for developing a breakthrough SARS-CoV-2 infection.

Healio: What are the take-home messages of this study?

Wechsler: It’s important for physicians to educate patients, particularly those with underlying lung disease that, even if they are fully vaccinated, they still need to take precautions, because over 1 in 5 of those patients may not have sufficient antibodies. One strategy would be to check spike protein antibody levels, and people with lower levels following a second vaccine dose should get a booster dose. Even if they’ve been boosted once, they might need a fourth shot dose if they still don’t have adequate antibodies. It is important to monitor and evaluate which patients are responding and which are not responding to the vaccine. In patients with asthma and COPD, in particular, we found a relatively large contingency of patients who continue to have an insufficient antibody response. For instance, 14% of asthma patients, 15% of COPD patients and 36% of ILD patients failed to make antibodies after a second vaccine dose. That means that 1 in 3 ILD patients, 1 in 6 COPD patients and 1 in 7 asthma patients are making insufficient antibodies.

Healio: What was the most surprising finding?

Wechsler: The frequency of nonresponders to the vaccine was the most surprising finding, but it wasn’t just in people who were on immunosuppressants. When we looked at medication use, almost 40% of patients were on biologics or JAK inhibitors and tended to have an insufficient antibody response, and 27% of people were on systemic steroids and had insufficient antibody production as well. This suggests we should be checking antibody levels in these patients and adding a level of precision medicine to our approach.

Healio: Any speculation as to why more than one-fifth of patients with chronic medical conditions may continue to have insufficient antibody levels to fight COVID-19?

Wechsler: That’s something we’re studying right now. Many questions remain to be answered. Is it something with the disease itself that is causing impairment? Is it because of the medications? Is it simply because antibody levels wane over time? Is there something about the immune system of an individual with lung disease that causes them to be nonresponsive to the vaccine?

Healio: What advice would you share for physicians who treat patients with chronic medical conditions like those in this study?

Wechsler: It is important to be cognizant of the fact that not everyone who is vaccinated is protected, and I would advocate for testing in this high-risk population. The results of this study can also be extrapolated beyond the COVID vaccine. Flu shots to patients on an annual basis and perhaps we should be checking their responsiveness to that vaccine, especially those at higher risk for complications from influenza, older patients and those with lung disease.

Healio: What is needed in terms of further research?
We are analyzing B-cell responses and T-cell responses to the COVID-19 vaccines in our patients to try to ascertain the mechanisms in these vulnerable patients. Another question is what about kids? Are they more or less likely to be susceptible to have this apparent immune response?

For more information:

Michael E. Wechsler, MD, can be reached at wechslerm@njhealth.org.

References:

• Liao SY, et al. Chest. 2022;doi:10.1016/j.chest.2021.12.654.
• Study confirms that many patients with chronic illness have low antibody levels after second vaccination dose. Published Jan. 14, 2022. Accessed Feb. 9, 2022.