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A regime of three doses of COVID-19 vaccine, compared with two doses, is associated with a greater than 90% decrease in COVID-19-related deaths among patients with multiple chronic conditions, data suggest.
Booster vaccination can play a crucial role in protecting vulnerable groups as the pandemic continues to evolve, the study authors write.
Dr Esther Chan
“People with multimorbidity are known to be at increased risk of SARS-CoV-2 infection and severe complications and thus are one of the most vulnerable populations amid the pandemic,” senior author Esther Wai Yin Chan, PhD, an associate professor of pharmacology and pharmacy with the Centre for Safe Medication Practice and Research in the Li Ka Shing Faculty of Medicine at the University of Hong Kong, told Medscape Medical News.
“Given the newly emerging viral strains and waning protection from the priming doses, it is important to investigate and demonstrate the effectiveness of a timely booster shot among this high-risk population,” she said.
The study was published January 30 in the Canadian Medical Association Journal.
“Drastic Differences”
When the BA.2 Omicron variant wave hit Hong Kong in 2021, the city reported the highest COVID-19 mortality rate worldwide, relative to its population of 7.5 million, the authors write. In November 2021, high-priority vulnerable groups became eligible to receive a booster dose, including older adults and healthcare professionals. In January 2022, eligibility was extended to everyone, and more than 3 million people received a third shot during the first 4 months of 2022.
In a territory-wide retrospective cohort study, the researchers analyzed routine clinical records from public health facilities in Hong Kong. They compared the risk for COVID-19-related death between adults with two or more chronic conditions who received a third dose between November 2021 and March 2022 and those who received only two doses. Multimorbidity included 30 conditions, such as high blood pressure, diabetes, and chronic kidney disease.
The researchers included 120,724 patients who received the BNT162b2 mRNA vaccine from Fosun-BioNTech (equivalent to Pfizer-BioNTech outside of China), including 87,289 who received a booster dose and 127,318 patients who received Sinovac’s CoronaVac shot. Of the latter patients, 94,977 received a booster. In general, those who received a booster dose were slightly older. There were more COVID-19-related deaths among CoronaVac recipients.
Overall, the risk for mortality was lower among those who received a third dose of either vaccine. Among BNT162b2 recipients, there were five COVID-19-related deaths among booster-vaccinated patients and 34 COVID-19-related deaths among two-dose recipients, yielding incidence rates per million person-days of 1.3 and 23.4, respectively. Among CoronaVac recipients, there were 26 COVID-19-related deaths among booster-vaccinated patients and 88 COVID-19-related deaths among two-dose recipients, yielding incidence rates per million person-days of 5.3 and 53.1, respectively.
For both vaccines, a booster dose was associated with a more than 90% decrease in mortality rate amid the Omicron wave, the authors write. Subgroup and sensitivity analyses yielded similar results for booster vaccination.
“We were slightly surprised at the drastic differences,” said Chan. “We did expect great effectiveness before the analyses, but 90% is an incredible finding, particularly as this was a real-world study and not a controlled clinical trial with strict patient inclusion criteria — it is often in controlled trials where we see comparatively higher effectiveness.”
Chan and colleagues are continuing to conduct research on COVID-19 vaccines and antivirals in vulnerable groups to understand how public health measures can reduce complications as the pandemic continues. They also plan to analyze how COVID-19 sequelae may increase the incidence of multimorbidity among those with ongoing symptoms.
Chan attributes the notable mortality differences between groups in this study to a higher baseline COVID-19-related mortality risk among patients with multimorbidity, as well as the long duration since the second dose. Many two-dose recipients received their last shot more than 6 months before the Omicron wave, which likely led to waning protection, she noted.
Vaccination Saves Lives
Commenting on the study for Medscape, Antonios Diab, PhD, a postdoctoral fellow with the Canadian Society of Pharmacology and Therapeutics and Dalhousie University’s College of Pharmacy in Halifax, Nova Scotia, said, “It is becoming increasingly clear that vaccination against COVID-19 saves lives and that booster doses are needed. What remains to be addressed is how long after a booster dose does an individual remain protected, and how does this change between populations? Do those with multimorbidity need more frequent vaccination?”
Dr Antonios Diab
Diab, who wasn’t involved with this study, has researched COVID-19 pathophysiology and pharmacology in clinical vaccine and drug trials authorized by Health Canada. He and his colleagues are assessing best practices and gaps in trial design in ordewr to create guidelines for future trials.
“Unfortunately, in many jurisdictions, as public health measures wane, so does active monitoring of the virus, and this increases the uncertainty of the risk of infection,” he said. “The ideal situation, including with the XBB.1.5 variant, would be timing booster doses with periods of increased risk — defined as the convergence of waning immunity, increased chance of exposure, and preexisting health conditions, such as multimorbidity. However, we need the proper research, monitoring, and data to be able to assess risk.”
The study was funded by a research grant from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region through the Health and Medical Research Fund Research on COVID-19. Chan has received grants from the Research Grants Council of Hong Kong, the Research Fund Secretariat of the Food and Health Bureau of Hong Kong, the National Natural Science Fund of China, the Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and the Narcotics Division of the Security Bureau of Hong Kong outside of the current study. She has also received an honorarium from the Hong Kong Hospital Authority. Diab has disclosed no relevant financial relationships.
CMAJ. Published January 30, 2023. Full text
Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.
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