Is complement the culprit behind COVID-19 vaccine-related adverse reactions?

Mastellos, Dimitrios C.; Skendros, Panagiotis; Lambris, John D.

doi:10.1172/jci151092

Cited by 29 publications

(28 citation statements)

References 24 publications

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“…Without prior heparin exposure, VITT displays findings of acute thrombotic complications and severe thrombocytopenia following administration of the J&J vaccine. A single dose of the adenoviral-associated vaccine prompts the pro-thrombotic activation of anti-PF4 antibodies through IgG-FcγR interactions and FcR-mediated engagement of immune effector cells [16]. C3 activation due to the anti-PF4 complex results in the downstream generation of potent pro-inflammatory effectors that can potentiate inflammation [16].…”

Section: Discussionmentioning

confidence: 99%

“…A single dose of the adenoviral-associated vaccine prompts the pro-thrombotic activation of anti-PF4 antibodies through IgG-FcγR interactions and FcR-mediated engagement of immune effector cells [16]. C3 activation due to the anti-PF4 complex results in the downstream generation of potent pro-inflammatory effectors that can potentiate inflammation [16]. Deregulated complement C3 responses with circulating anti-PF4 immune complexes ignite complement activation of inflammatory properties of monocytes and neutrophils through complement receptors [16].…”

Section: Discussionmentioning

confidence: 99%

“…C3 activation due to the anti-PF4 complex results in the downstream generation of potent pro-inflammatory effectors that can potentiate inflammation [16]. Deregulated complement C3 responses with circulating anti-PF4 immune complexes ignite complement activation of inflammatory properties of monocytes and neutrophils through complement receptors [16]. This development postulates that the role complement may have on vaccine-related adverse reactions.…”

Section: Discussionmentioning

confidence: 99%

“…This development postulates that the role complement may have on vaccine-related adverse reactions. The activation has been implicated as a cause of thromboinflammation of immune complexes in autoimmune pathologies, increasing the risk for blood clots [16].…”

Section: Discussionmentioning

confidence: 99%

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A COVID-Positive 52-Year-Old Man Presented With Venous Thromboembolism and Disseminated Intravascular Coagulation Following Johnson & Johnson Vaccination: A Case-Study

Shazley¹,

Alshazley²

2021

Cureus

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The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Infection by the SARS-CoV-2 increases the risk for systematic multi-organ complications and venous, arterial thromboembolism. The need for an effective vaccine to combat the pandemic prompted the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) to approve a nationwide distribution of the Ad26.COV2.S vaccine manufactured by Johnson & Johnson (J&J). The use of the vaccine was halted after reported cases of cerebral venous sinus thrombosis (CVST) and thrombocytopenia among recipients. Researchers have postulated these rare occurrences as potentially immune-triggered responses associated with complement-mediated thrombotic microangiopathy (TMA). Thrombotic complications and thrombocytopenia increase the risk for blood clot growth due to the inflammation of immune complexes by pro-thrombotic activation of anti-platelet antibodies.A 52-year-old man presented to the intensive care unit (ICU) with severe dyspnea. He required bilevel positive airway pressure (BiPAP) for supplemental oxygen therapy. Endotracheal intubation was performed due to his worsened respiratory deterioration. Lab results suggested respiratory failure due to decreased partial pressure of oxygen (pO 2 ) and increased partial pressure of carbon dioxide (pCO 2 ). Findings of elevated D-dimer levels with decreased fibrinogen and thrombocytopenia with prolonged prothrombin clotting time were consistent for disseminated intravascular coagulation (DIC). Chest radiography displayed moderate to heavy bilateral airspace consolidations, consistent with multifocal pneumonia suspicious for COVID-19. A computed tomography angiogram (CTA) revealed a mildly enlarged right ventricle and interventricular septum consistent for right heart strain due to a saddle pulmonary embolism (PE) that extended into the main pulmonary lobar segmental arteries bilaterally. The patient was transferred to a higher-level (tertiary) care for radiology intervention to remove the pulmonary embolism found on his lungs.This patient presented with severe dyspnea secondary to massive PE and deep venous thrombosis (DVT) due to SARS-CoV2 infection following the administration of the J&J vaccine. Bilateral thrombus opacities and pulmonary emboli are consistent among COVID-19 patients by intravascular coagulation with increased prothrombin time and D-dimer concentration with a low platelet count. Adverse emboli growths with increased D-dimer and thrombocytopenia strikes a similarity in recipients of the AstraZeneca vaccine due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Administrative use of the J&J vaccine resumed in May 2021. The FDA's reassurance stemmed from their conclusive findings that the vaccine's benefits far outweigh these rare developments, which account for less than 0.01% of the total recipient population. Nevertheless, a further detailed analysis must be conducted on the adverse thrombotic manifestations...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A COVID-Positive 52-Year-Old Man Presented With Venous Thromboembolism and Disseminated Intravascular Coagulation Following Johnson & Johnson Vaccination: A Case-Study

Shazley¹,

Alshazley²

2021

Cureus

View full text Add to dashboard Cite

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“…It has been proposed that part of the adenoviral vector vaccine cross-reacts with PF4 on platelets due to molecular mimicry, causing anti-PF4 antibody formation (antibody responses against PF4/polyanion) and may play role in VITT syndrome cases after AstraZeneca COVID-19 vaccine administration [ 72 , 75 , 76 ]. Researchers have hypothesized that complement activation by antibodies against vaccine components can stimulate VITT [ 77 ]. Similar to heparin’s “vaccine-induced COVID-19 mimicry,” production of the soluble spike protein variant encoded by adenoviral vector vaccine acts as a polyanion to mediate PF4 activation and trigger antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity [ 10 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Cerebral Coagulation Complications Following COVID-19 Adenoviral Vector Vaccines: A Systematic Review

et al. 2021

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Emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak identified in late 2019 in Wuhan, China, was declared a pandemic in March 2020. High fatality rate in afflicted patients prompted scientists and physicians to develop various vaccines against the virus. While administration of millions of doses of the adenoviral vector vaccines (e.g., Oxford-AstraZeneca (ChAdOx1 nCoV-19) and Janssen/Johnson & Johnson (Ad26.COV2. S)) has helped control the disease, numerous cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia have been reported in vaccinated individuals. In this article, we aim to review the cases reported thus far and further discuss the association between the vaccine administration and subsequent cerebral thromboembolic events. Our study was performed and reported based on the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Google Scholar and Norris Medical Library databases were searched using the following terms: coronavirus disease 2019 (COVID-19) vaccines (“AstraZeneca” or “AZD1222 COVID vaccine” or “ChAdOx1 nCoV-19 COVID-19 vaccine” or “Janssen” or “Johnson & Johnson COVID vaccine” or “Ad26.COV2 COVID vaccine”), coagulopathy (“cerebral venous sinus thrombosis (CVST)” and “vaccine-induced immune thrombotic thrombocytopenia (VITT)” or “cerebral venous thrombosis (CVT)”) and thrombocytopenia. All the relevant studies within the English literature up to August 1, 2021, were included. Fourteen most recent articles reporting on 66 patients with CVST and VITT after adenoviral vector vaccination were reviewed by two independent authors. Age of the patients ranged from 18 to 60 years. The majority of cases were women (43 females versus 14 males). Platelet count was between 5 and 127 × 10 9 /L. Above-normal D-dimer was found in 86% of the patients. A total of 68% of the patients had positive platelet factor 4 IgG assay in the absence of prior exposure to heparin. Among CVST cases following COVID vaccination, 44% succumbed to death. Early diagnosis and treatment of CVST plays a fundamental role in decreasing morbidity and mortality. Health care professional should be familiar with this rare complication post vaccination against COVID-19. Given the rarity of CVST after the COVID-19 vaccine, the benefit of vaccination outweighs the potential harm.

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Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine–Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis

et al. 2021

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IMPORTANCEThe COVID-19 pandemic saw one of the fastest developments of vaccines in an effort to combat an out-of-control pandemic. The 2 most common COVID-19 vaccine platforms currently in use, messenger RNA (mRNA) and adenovirus vector, were developed on the basis of previous research in use of this technology. Postauthorization surveillance of COVID-19 vaccines has identified safety signals, including unusual cases of thrombocytopenia with thrombosis reported in recipients of adenoviral vector vaccines. One of the devastating manifestations of this syndrome, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), is cerebral venous sinus thrombosis (CVST). This review summarizes the current evidence and indications regarding biology, clinical characteristics, and pharmacological management of VITT with CVST.OBSERVATIONS VITT appears to be similar to heparin-induced thrombocytopenia (HIT), with both disorders associated with thrombocytopenia, thrombosis, and presence of autoantibodies to platelet factor 4 (PF4). Unlike VITT, HIT is triggered by recent exposure to heparin. Owing to similarities between these 2 conditions and lack of high-quality evidence, interim recommendations suggest avoiding heparin and heparin analogues in patients with VITT. Based on initial reports, female sex and age younger than 60 years were identified as possible risk factors for VITT. Treatment consists of therapeutic anticoagulation with nonheparin anticoagulants and prevention of formation of autoantibody-PF4 complexes, the latter being achieved by administration of high-dose intravenous immunoglobin (IVIG). Steroids, which can theoretically inhibit the production of new antibodies, have been used in combination with IVIG. In severe cases, plasma exchange should be used for clearing autoantibodies. Monoclonal antibodies, such as rituximab and eculizumab, can be considered when other therapies fail. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying bleeding risk.CONCLUSIONS AND RELEVANCE Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.

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Is complement the culprit behind COVID-19 vaccine-related adverse reactions?

Cited by 29 publications

References 24 publications

A COVID-Positive 52-Year-Old Man Presented With Venous Thromboembolism and Disseminated Intravascular Coagulation Following Johnson & Johnson Vaccination: A Case-Study

A COVID-Positive 52-Year-Old Man Presented With Venous Thromboembolism and Disseminated Intravascular Coagulation Following Johnson & Johnson Vaccination: A Case-Study

Cerebral Coagulation Complications Following COVID-19 Adenoviral Vector Vaccines: A Systematic Review

Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine–Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis

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