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Research Review

Efficacy and Impact of COVID-19 mRNA Vaccines on Patients With Compromised Immune Systems

In the wake of the COVID-19 pandemic, health care leaders and researchers have dedicated efforts to pinpointing and deploying the most effective vaccines to curb the virus and counter various variants. Evaluating the effectiveness of each vaccine aids health care professionals in identifying the optimal treatment approach for patients. Comparing vaccination effectiveness enables them to tailor their interventions to individual patient requirements, ensuring that the chosen vaccine is the most effective method in combating COVID-19 and preventing reinfection.

This holds particular significance for individuals with compromised immune systems. In a dedicated study comparing the outcomes of administering mRNA-1273 and its competitor, BNT162b2, researchers conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 framework.1 The search was executed using the World Health Organization COVID-19 Research Database on April 14, 2022, with subsequent updates on December 19, 2022. Researchers systematically explored various databases, including MEDLINE, International Clinical Trials Registry Platform, Embase, EuropePMC, medRxiv, Web of Science, and ProQuest Central, among others.1

Researchers utilized population information, study and participant attributes, vaccine types and vaccination statuses, underlying health conditions, and clinical outcomes to facilitate their evaluation.1 The patient cohorts encompassed individuals in the US, Spain, Italy, and Singapore, spanning those with organ transplants, undergoing chronic hemodialysis, both immunocompromised and immunocompetent vaccine recipients, patients with multiple sclerosis receiving disease-modifying therapies, individuals with cancer, inflammatory bowel disease, rheumatic disease, and other immunocompromised conditions.1

"Of 5745 unique items retrieved, 34 studies were identified reporting COVID-19 clinical efficacy or effectiveness outcomes in IC individuals ≥18 years of age who received mRNA-1273 or BNT162b2 in the same study," said researchers.1

In a meta-analysis incorporating data from 15 studies detailing SARS-CoV-2 infection in immunocompromised populations, mRNA-1273 demonstrated a statistically significant decrease in the risk of infection compared to BNT162b2 (RR, 0.85 [95% CI, 0.75-0.97], P=0.0151). The risk difference (95% CI) indicated approximately 375 fewer SARS-CoV-2 infections associated with mRNA-1273 when compared to BNT162b2.1

As the efficacy of mRNA-1273 became evident for certain patients, health care professionals aimed to understand if outcomes impacted the administration of multiple mRNA-1273 vaccinations in patients who are immunocompromised. In a study published in JAMA Network Open, researchers sought to examine the rise in mRNA-1273 usage among immunocompromised populations, aiming to enhance their understanding of outcomes after administering multiple vaccination boosters.2

Leveraging the Kaiser Permanente Southern California health system, a comprehensive, integrated health care system serving over 4.7 million members in Southern California, researchers accessed data for immunocompromised patients across various health care settings.2 All cohort members identified were eligible for COVID-19 vaccines without charge. Researchers confined the analysis to patients who exclusively received mRNA vaccines to streamline their analyses and maintain consistency in defining fully vaccinated individuals.2

Based on the study findings, 3606 individuals included in the obtained information from the Kaiser Permanente Southern California database were administered either BNT162b2 or mRNA-1273 vaccinations. In comparison, 1588 individuals received a combination of two monovalent mRNA vaccines.2 Additionally, the analysis included 59 patients who received a fourth dose following CDC recommendations and 78 patients who received a fifth dose before the CDC officially made a fifth dose available.2

"When examining cumulative uptake over time, 78.0% of immunocompromised individuals had received a third dose by the end of the study period (approximately 1 year after the CDC recommendation in August 2021 for immunocompromised individuals to receive a 3-dose primary series)," said researchers.

According to the latest findings, researchers emphasize the critical role of a booster dose in safeguarding patients against adverse COVID-19 outcomes, particularly in the context of emerging variants.2 Despite evidence indicating that some individuals deviated from CDC recommendations for mRNA monovalent COVID-19 booster doses, adherence to these guidelines is deemed crucial, especially for immunocompromised individuals who face an elevated risk of severe COVID-19.2 The reasons behind the hesitation among patients with compromised immune systems to pursue fourth and fifth doses remain somewhat unclear, with a suggested factor being apprehension related to the exclusion of individuals with immunocompromised conditions from clinical trials assessing COVID-19 vaccine efficacy.2

In a separate study featured in JAMA Network Open, researchers explore the potential adverse events that older immunocompromised adults may experience following COVID-19 vaccinations. This investigation aims to offer patients a clearer insight into the possible outcomes they might face after receiving vaccinations and boosters when making the decision to get them.3

The study encompassed over 6 million eligible individuals who received either the mRNA-1273 or BNT162b2 vaccine. In comparison to the BNT162b2 vaccine, mRNA-1273 exhibited a reduced risk of pulmonary embolism (RR, 0.96 [95% CI, 0.93-1.00]; RD, 9 [95% CI, 1-16] events per 100,000 persons).3 Additionally, mRNA-1273 demonstrated a lower risk of thrombotic thrombocytopenic purpura among individuals categorized as nonfrail (11% lower risk).3 Moreover, it was associated with a decreased risk of diagnosed COVID-19 (RR, 0.86 [95% CI, 0.83-0.87]), a benefit that was moderated by the level of frailty (frail: RR, 0.94 [95% CI, 0.89-0.99]).3

In the comprehensive cohort study of older US patients, researchers discovered that, "the mRNA-1273 vaccine was associated with a slightly lower risk of several adverse events compared with BNT162b2, possibly due to greater protection against COVID-19."3

Researchers' collective findings consistently highlight mRNA-1273 as a leading contender in the fight against SARS-CoV-2 infection, severe cases, COVID-19-related hospitalization, and death when contrasted with BNT162b2, particularly in immunocompromised population, drawing from multiple studies assessing the efficacy of mRNA-1273 in comparison to its counterparts.1 Continuous research is advised to assess efficacy and outcomes in the face of evolving variants. Although it’s clear patients with compromised immune systems may be hesitant to receive their first vaccination or receive multiple doses,2 health care professionals should take note of these effective outcomes.

References

  1. Wang X, Haeussler K, Spellman A, et al. Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework. Frontiers in Immunology. 2023;14:1204831. doi:/10.3389/fimmu.2023.1204831
  2. Tartof SY, Slezak JM, Puzniak L, et al. Analysis of mRNA COVID-19 vaccine uptake among immunocompromised individuals in a large US health system. JAMA Netw Open. 2023;6(1):e2251833. doi:10.1001/jamanetworkopen.2022.51833
  3. Harris DA, Hayes KN, Zullo AR, et al. Comparative risks of potential adverse events following COVID-19 mRNA vaccination among older US adults. JAMA Netw Open. 2023;6(8):e2326852. doi:10.1001/jamanetworkopen.2023.26852

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