Click to Enlarge: Source: JAMA Network

SAN FRANCISCO — Veteran patients who received a COVID-19 vaccination series, plus a booster vaccine dose, had a low incidence of hospitalization, death or severe illness from COVID-19, according to a new study.

The retrospective cohort study published in the Journal of the American Medical Association (JAMA) included more than 1.6 million participants who sought care at Veterans Health Administration (VHA) facilities across the United States and received a vaccination series plus one booster against SARS-CoV-2, the virus that causes COVID-19.1

Patients were eligible if they had a primary care visit in the previous two years and documented receipt of all U.S. Food and Drug Administration-authorized doses of the initial mRNA vaccine or viral vector vaccination series after Dec. 11, 2020, and a subsequent booster dose between July 1, 2021, and April 29, 2022. They were followed for 24 weeks from July 1, 2021, to May 30, 2022, after completing the COVID-19 vaccination series and booster.

This analysis was needed to provide critical information, particularly for high-risk populations, on the incidence of severe COVID-19 illness following vaccination and booster with BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) and Ad26.COV2.S (Janssen/Johnson & Johnson) vaccines. The researchers evaluated patient medical records for breakthrough COVID-19 infection and hospitalizations with COVID-19 pneumonia and death, rather than considering all hospitalizations among patients with a positive COVID-19 lab test.

When patients received the vaccination series and booster, the study found the incidence of hospitalization with COVID-19 pneumonia or death was low, 8.9 per 10,000 persons, during the period when the delta and Omicron variants were predominant.

“We found that after 24 weeks of follow-up, incidence of severe disease was very low,” J. Daniel Kelly, MD, PhD, corresponding author of the study and assistant professor of medicine and epidemiology and biostatistics at University of California, San Francisco, told U.S. Medicine during an interview. “We found this among veterans who had average risk, were over the age of 65 without high-risk comorbidities and also had high-risk comorbidities. We found an increased risk of severe disease among veterans with immunocompromising conditions. In general, after three doses of the COVID vaccine across the whole cohort, we found very little evidence of hospitalization due to COVID pneumonia or death.”

“I think what’s reassuring is that higher risk individuals, people who were over the age of 65 and people who have comorbidities like hypertension, kidney disease and liver disease were also at really low risk of being hospitalized due to COVID pneumonia. However, those individuals with immunocompromising conditions did have an increased risk.”

Click to Enlarge: Abbreviation: NC, not calculable.
a) Booster to 24 weeks, using model to make predictions at 24 weeks.
b) Combination mRNA included all possible combinations in which mRNA-1273 and BNT162b2 were received.
c) This combination group received Ad26.COV2.S first then either mRNA-1273 or BNT162b2, or vice versa.
d) Death due to all causes within 30 days of breakthrough COVID-19 infection.
e) Severe pneumonia was defined as having mechanical ventilation or an intubation procedure during hospitalization.
Source: JAMA Network

While higher risk groups are still protected with boosters, additional preventive and therapeutic strategies are necessary for immunocompromised populations. A booster probably isn’t enough for them, Kelly explained.

Advice on Immunocompromised

“Healthcare professionals should be considering post-exposure antiviral therapy and encouraging continued masking for the immunocompromised individuals,” Kelly said. “People at risk or with symptoms of COVID who are immunocompromised should seek urgent medical attention to receive antiviral and other therapies because of their ongoing risk for severe disease.”

Meanwhile, clinicians should be able to provide reassurance to people who are not immunocompromised but have high-risk conditions, that being boosted will protect them from severe disease, Kelly added.

Overall, the study shows the advantages of receiving the COVID-19 vaccination series plus a booster vaccine.

“The benefits are that, if you’re vaccinated and boosted, you’re unlikely to develop severe disease and unlikely to be hospitalized,” Kelly said. “We’re seeing this over a sustained period of time, despite delta and Omicron variant predominance.”

These data provide information that healthcare professionals can use to counsel patients on the importance of COVID-19 vaccination and how to advise if a booster is good enough or whether additional precautions need to be taken if patients become ill. Important conclusions can be drawn from the study, such as people who aren’t vaccinated and haven’t received the booster vaccine may be at risk for severe illness over the winter and should consider getting a vaccine dose, Kelly said.

“This is just additional evidence showing that vaccines and boosters are effective at preventing death and keeping people out of the hospital,” Kelly added. “This should be reassurance and encouragement that getting the vaccine could keep people healthy and enjoying the holidays.”

Further research is needed to understand the effectiveness of booster vaccines, Kelly said.

“We still don’t have enough real-world data on booster effectiveness and over longer periods of follow-up,” Kelly said. “We know that boosters work. We don’t know for how long. These results are significant, because a lot of the studies don’t dig into the high-risk subgroups. I think that was one of the big things about this study—the evaluation of different high-risk groups and showing that risk actually varies among the groups.”

The study had several limitations, Kelly acknowledged.

“Obviously, the virus continues to change, and we don’t know the current effectiveness of the omicron booster yet,” Kelly said. “One limitation is most people are getting the omicron booster right now. There’s no real-world data on the booster, but we suspect that it will do better than the old boosters.”

Also, these data group people in terms of different risk categories, but some of the high-risk comorbid conditions may confer additional risk (for example, individuals who receive hemodialysis or have severe end organ damage, multiple comorbidities, etc.). Many veterans have multiple comorbidities, so there may be particular high-risk comorbidities that confer additional risk. However, this still needs to be explored.

In addition, this study only followed patients for six months. Other research is looking at slightly longer follow-up periods and has found continued protection with the booster. However, as the BA.4 and BA.5 variants have emerged, boosters are starting to wane.

“For people who have gotten a third dose, I would advise getting the omicron booster now,” Kelly said. “That’s not a direct implication of the study, but the bigger picture.”

 

  1. Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, Lum EN, Moss-Vazquez TA, Andino R, Wong JK, Byers A, Bravata DM, Tien PC, Keyhani S. Incidence of Severe COVID-19 Illness Following Vaccination and Booster With BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines. JAMA. 2022 Oct 11;328(14):1427-1437. doi: 10.1001/jama.2022.17985. PMID: 36156706; PMCID: PMC9513709.