Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients

Agha, Mounzer; Blake, Maggie; Chilleo, Charles; Wells, Alan; Haidar, Ghady

doi:10.1101/2021.04.06.21254949

Cited by 103 publications

(133 citation statements)

References 14 publications

(17 reference statements)

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“…As suggested by different authorities (e.g., UK Joint Committee on Vaccination and Immunisation), individuals with immunosuppression should be prioritized for the COVID-19 vaccination [ 27 ]. However, on the other hand, these individuals may reveal a diminished response to the vaccine, while some, as confirmed for two cases reported in our study, could be subject to vaccine failure [ 17 ]. Therefore, it is pivotal to advise these patients to continue to adhere to preventive measures, particularly at a time of a high number of infections in the population, and to test the serum level of anti-SARS-CoV-2 IgG antibodies following the vaccination.…”

Section: Discussionsupporting

confidence: 74%

“…Additionally, reduced immunogenicity after a single dose and after the full vaccination regime must be taken into account in the case of some elderly subjects, cancer patients, and other immunocompromised individuals [ 14 , 15 , 16 ]. Importantly, some of these vaccine recipients may not produce any antibodies and may remain highly susceptible to the SARS-CoV-2 infection [ 17 ]. The exact percentage of individuals falling into the non-responders category is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Characteristics of Hospitalized COVID-19 Patients Who Received at Least One Dose of COVID-19 Vaccine

et al. 2021

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The clinical trials of the COVID-19 vaccines that are authorized in the European Union have revealed high efficacy in preventing symptomatic infections. However, during vaccination campaigns, some vaccine recipients, including those partially and fully vaccinated, will experience severe COVID-19, requiring hospitalization. This may particularly concern patients with a diminished immune response to the vaccine, as well as non-responders. This work has retrospectively analyzed the 92 cases of patients who were hospitalized between 27 December 2020 and 31 May 2021 in four Polish healthcare units due to COVID-19, and who have previously received the COVID-19 vaccine (54.3% ≤ 14 days after the first dose, 26.1% > 14 days after the first dose, 7.6% ≤ 14 days after the second dose, and 12% > 14 days after the second dose). These patients represented a minute fraction (1.2%) of all the COVID-19 patients who were hospitalized during the same period in the same healthcare institutions. No significant differences in white blood count, absolute lymphocyte count nadir, C-reactive protein, interleukin-6, procalcitonin, oxygen saturation, lung involvement, and fever frequency were found between the recipients of the first and second vaccine dose. A total of 15 deaths were noted (1.1% of all fatal COVID-19 cases in the considered period and healthcare units), including six in patients who received the second dose (five > 14 days after the second dose)—three of these subjects were using immunosuppressive medicines, and two were confirmed to be vaccine non-responders. The study reassures that severe COVID-19 and deaths are not common in vaccinated individuals, highlights that the clinical course in such patients may not reveal any distinctive features, and advocates for close monitoring of those at a higher risk of vaccine failure.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Clinical Characteristics of Hospitalized COVID-19 Patients Who Received at Least One Dose of COVID-19 Vaccine

et al. 2021

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“…Vaccination is encouraged in these immunosuppressed patient groups, although it is possible that the immune responses will be less robust, as has been seen in response to natural infection. 152 153 Indeed, early studies are showing comparable safety, but reduced immunogenicity has been observed for these populations, including patients with HM, 154–156 SOTRs, 157 and those with rheumatological diseases. 158 159 To achieve comparable vaccine efficacy, further strategies employing altered vaccine schedules, doses, or adjustment to immunosuppression during vaccination might be needed, and should be accomplished only in the context of a clinical trial.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

Goldman

Robinson

Uldrick

et al. 2021

J Immunother Cancer

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SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.

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“…Many individuals with a compromised immune system, including transplant patients, patients with cancer and individuals taking immunosuppressive drugs, do not mount strong responses to vaccines, including those for SARS-CoV-2 [5][6][7][8] . At present, the messaging from regulatory agencies states that "antibody tests should not be used to evaluate a person's level of immunity or protection from COVID-19. "…”

Section: Florian Krammermentioning

confidence: 99%

A correlate of protection for SARS-CoV-2 vaccines is urgently needed

Krammer

2021

Nat Med

188

158

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Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients

Cited by 103 publications

References 14 publications

Clinical Characteristics of Hospitalized COVID-19 Patients Who Received at Least One Dose of COVID-19 Vaccine

Clinical Characteristics of Hospitalized COVID-19 Patients Who Received at Least One Dose of COVID-19 Vaccine

COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies

A correlate of protection for SARS-CoV-2 vaccines is urgently needed

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