COVID-19 vaccination and immune thrombocytopenia

Pishko, Allyson M.; Bussel, James B.; Cines, Douglas B.

doi:10.1038/s41591-021-01419-1

Cited by 30 publications

(19 citation statements)

References 12 publications

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“…An immunologic correlate of protection against SARS-CoV-2 has not yet been established [36]. Our model, however, allows us to make a clinicallyguided qualitative prediction for a humoral-based immunologic correlate of protection.…”

Section: Discussionmentioning

confidence: 99%

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Korosec

Farhang‐Sardroodi

Dick

et al. 2021

Preprint

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Background. The lipid nanoparticle (LNP)-formulated mRNA vaccines are a widely adopted two-dose vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described the immunogeneicity of the vaccine, albeit within a limited study time frame. Our aims were to use a within-host mathematical model for LNP-formulated mRNA vaccines, informed by available clinical trial data, to project a longer term understanding of humoral immunity as a function of vaccine type, dosage amount, age, and sex. Methods. We developed a mathematical model describing the immunization process of LNP-formulated mRNA vaccines, and fit our model to twenty-two clinical humoral and cytokine BNT162b2 or mRNA-1273 human two-dose vaccination data sets. We incorporated multi-dose effects in our model to specify whether the dosage is standard or low-dose. We further specify the age groups 18-55, 56-70, and 70+ in our fits for two-standard doses of mRNA-1273, and sex in our fits for two-standard doses of BNT162b2. We used non-linear mixed effect models to fit to all similar data types (e.g. standard two-dose BNT162b2 or mRNA-1273, or two low-dose mRNA-1273). Therefore, in our fits all estimated parameters are statistically correlated, which allowed us to determine the underlying 'population-dynamics' structure common to a data type. We therefore made accurate long-term predictions informed by all clinical data used in this study. Findings. We estimate that two standard doses of either mRNA-1273 or BNT162b2, with dosage times separated by the company-mandated intervals, results in individuals loosing more than 99% humoral immunity relative to peak immunity by eight months following the second dose. We predict that within an eight month period following dose two (corresponding to the CDC time-frame for administration of a third dose), there exists a period of time longer than one month where an individual has less then 99% humoral immunity relative to peak immunity, regardless of which vaccine was administered. We further find that age has a strong influence in maintaining humoral immunity; by eight months following dose two we predict that individuals aged 18-55 have a four-fold humoral advantage compared to aged 56-70 and 70+ individuals. We find that sex has little effect on the vaccine uptake and long-term IgG counts. Finally, we find that humoral immunity generated from two low doses of mRNA-1273 decays substantially slower relative to peak immunity gained than compared to two standard doses of either mRNA-1273 or BNT162b2. Interpretation. For the two dose mRNA vaccines, our predictions highlight the importance of the recommended third booster dose in order to maintain elevated levels of antibodies. We further show that age plays a critical role in determining the antibody levels. Hence, a third booster dose may confer an immuno-protective advantage in older individuals.

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Section: Discussionmentioning

confidence: 99%

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Korosec

Farhang‐Sardroodi

Dick

et al. 2021

Preprint

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“…COVID-19 typically presents with endotheliopathy with microvascular microthrombosis in the lungs, causing ARDS, and occasionally thrombocytopenia, MAHA, and other organ syndromes, which have been called TTP-like syndrome [3,4]. However, vaccine-associated endotheliopathy does not cause TTP-like syndrome, but instead is manifested as "silent" immune thrombocytopenic purpura (ITP) [12,13], which can be called ITP-like syndrome. In addition, CVST [14,15] and multiorgan inflammatory syndrome (MOIS) [16,17] have occurred after vaccination.…”

Section: Endotheliopathymentioning

confidence: 99%

Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis

Chang

Hawley

2021

Medicina

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Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by “attenuated” sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included “silent” immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, “consumptive” thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined “micro-macrothrombosis” composed of binary components of “microthrombi strings” from vEA-VMTD and “fibrin meshes” from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on “two-path unifying theory” of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.

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“…Pishko et al propose that perhaps through molecular mimicry, mRNA-based vaccines against SARS-CoV-2 generate cross-reactive immunity or alter a host protein, thereby influencing the emergence of pre-existing autoreactive antibodies into the immune system. 2 Currently, in the literature, there has only been one reported case of a young man who developed ITP after receiving the Pfizer-BioNTech BNT16B2b2 mRNA vaccine. 3 To our knowledge, this would be the first reported case of ITP and acute liver injury secondary to the Moderna mRNA-1273 SARS-CoV-2 vaccine.…”

Section: Case Reportmentioning

confidence: 99%

Immune thrombocytopenic purpura and acute liver injury after COVID-19 vaccine

et al. 2021

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A 26-year-old woman was sent to the emergency room by her primary care physician for a new petechial rash and thrombocytopenia 2 weeks after receiving the Moderna mRNA-1273 SARS-CoV-2 vaccine. Her hospital course was complicated by transaminitis. Her platelet count improved to normal on hospital day 5 after receiving intravenous steroids and intravenous immunoglobulin to treat her suspected diagnosis of immune thrombocytopenic purpura. Extensive workup for her thrombocytopenia and transaminitis was unremarkable including ruling out infectious, autoimmune and toxic causes. A liver biopsy was unrevealing and her transaminitis was improved on discharge. Although not proven, the temporal relationship of her vaccination with thrombocytopenia and abnormal liver enzymes points towards the Moderna mRNA-1273 SARS-CoV-2 vaccine as the most likely inciting factor.

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COVID-19 vaccination and immune thrombocytopenia

Abstract: COVID-19 vaccination and immune thrombocytopeniaA prospective cohort analysis finds a link between the ChAdOx1 vaccine and an autoimmune disorder known as immune thrombocytopenia-but questions remain and causality is yet to be established.

Cited by 30 publications

References 12 publications

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis

Immune thrombocytopenic purpura and acute liver injury after COVID-19 vaccine

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