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Suboptimal Response to Coronavirus Disease 2019 Messenger RNA Vaccines in Patients With Hematologic Malignancies: A Need for Vigilance in the Postmasking Era.

ABSTRACT: We measured severe acute respiratory syndrome coronavirus 2 immunoglobulin G responses in 67 patients with hematological malignancies after 2 messenger RNA vaccine doses. Forty-six percent were nonresponders; patients with B-cell chronic lymphocytic leukemia were at highest risk (77% nonresponders). Patients with hematological malignancies should continue wearing masks and socially distancing. Studies of revaccination, boosters, and humoral immune correlates of protection are needed.

SUBMITTER: Agha ME

PROVIDER: S-EPMC8320282 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation. Trials (n = 226) were fully assessed for the use of a repurposed drug, identifying a total of 141 therapeutic trials using a repurposed drug to target inflammation in COVID-19 infection. Building on the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial demonstrating the benefit of low dose dexamethasone in COVID-19, repurposed drugs targeting inflammation are promising. Repurposed drugs directed at inflammation in COVID-19 primarily have been drawn from cancer therapies and immunomodulatory therapies, specifically targeted anti-inflammatory, anti-complement, and anti-rejection agents. The proposed mechanisms for many cytokine-directed and anti-rejection drugs are focused on evidence of efficacy in cytokine release syndromes in humans or animal models. Anti-complement-based therapies have the potential to decrease both inflammation and microvascular thrombosis. Cancer therapies are hypothesized to decrease vascular permeability and inflammation. Few publications to date describe using these drugs in COVID-19. Early COVID-19 intervention trials have re-emphasized the subtle, but important cardiotoxic sequelae of potential therapies on outcomes. The volume of trials targeting the COVID-19 hyper-inflammatory phase continues to grow rapidly with the evaluation of repurposed drugs and late-stage investigational agents. Leveraging known clinical safety profiles and pharmacodynamics allows swift investigation in clinical trials for a novel indication. Physicians should remain vigilant for cardiotoxicity, often not fully appreciated in small trials or in short time frames.

Project description:BackgroundRecent reports have raised serious concerns regarding acute myocarditis related to coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. There are only a few reports of fulminant lymphocytic myocarditis that developed after vaccination. Although the diagnostic approach varied among them, no cases with multidisciplinary diagnostic approaches, including cytokine analysis, have been reported.Case summaryA 59-year-old male with no medical history complained of chest pain a day after receiving the first dose of COVID-19 mRNA (BNT162b2) vaccination. On hospital Day 3, he developed a refractory cardiogenic shock and pulseless ventricular tachycardia, requiring mechanical circulatory support secondary to an exacerbation of myocarditis. Based on the clinical course and examination results, including histologic findings showing a diffuse lymphocytic inflammatory infiltrate with abundant T cells and macrophages in the myocardium, and cardiac magnetic resonance (CMR) findings showing a high-intensity signal on the T2-weighted image and late gadolinium enhancement, he was diagnosed with fulminant myocarditis related to COVID-19 mRNA vaccination. His haemodynamic status gradually improved without immunosuppressive or anti-inflammatory therapy, and he was discharged from hospital on Day 47. To investigate the pathogenesis, we performed cytokine analysis, which showed an increase in serum IP-10, MCP-3, and MIG concentrations, suggesting that Th1-type chemokines preferentially promote cellular immunity.DiscussionIn the present case of a patient with fulminant myocarditis following COVID-19 mRNA vaccination diagnosed through histopathological and CMR findings, additional cytokine analysis revealed that elevated levels of cytokines pertaining to Th1 immune response may be involved in disease pathogenesis. A multidisciplinary diagnostic approach is crucial not only to comprehend an individual patient's condition but also to clarify the disease pathogenesis.

Dataset Information

Suboptimal Response to Coronavirus Disease 2019 Messenger RNA Vaccines in Patients With Hematologic Malignancies: A Need for Vigilance in the Postmasking Era.

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