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We report a case of cerebral venous sinus thrombosis, bilateral adrenal hemorrhage, and thrombocytopenia in a 70-year-old man found dead. He had previously received the ChAdOx1 nCoV-19 vaccine (Vaxzevria®, AstraZeneca) 18 days before, and had since developed unspecific and undiagnosed characteristics of what proved to be a rare case of vaccine-associated thrombocytopenia with thrombosis syndrome (TTS). He was found dead 1 week after the beginning of symptoms (day 25 post-vaccine). Autopsy yielded venous hemorrhagic infarction with the presence of thrombi within dural venous sinuses, and extensive hemorrhagic necrosis of the central part of the adrenal glands. Antibodies against platelet factor 4 (PF4) were strongly positive in postmortem fluids, as measured with an enzyme-linked immunosorbent assay (ELISA). This difficult diagnosis is usually made during the patient's lifetime. After eliminating differential diagnoses, we concluded on a fatal case of vaccine-induced immune TTS with positive anti-PF4 antibodies in cadaveric blood, 3 weeks after ChAdOx1 nCoV-19 vaccination. Specific search for anti-PF4 antibodies in cadaveric blood appears therefore paramount to assess postmortem cases of TTS associated with anti-COVID vaccines.
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Introduction: Vaccination against COVID-19 appears to be a promising approach to mitigate this pandemic. The French agency of medicinal products (ANSM) issued a signal concerning cases of sudden hearing loss (SHL) following vaccination with elasomeran (Spikevax® Moderna) [1] and AZD1222 (Vaxzevria® AstraZeneca) [2]. SHL is defined as a sensorineural hearing loss ≥30 dB within 72 hours [3]. We aimed to investigate the potential signal of SHL associated with COVID-19 vaccines. Material and methods: We queried VigiBase® (World Health Organization pharmacovigilance database), for all reports of "Sudden Hearing Loss" (MedDRA Preferred Term) related to "COVID-19 vaccine" (Active Ingredient), from 1967 to December 30, 2021 [4]. Disproportionality analysis was based on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval (CI) and the Information Component (IC). A positive IC025 is statistically needed to confirm the detection of a signal [5]. Results: In VigiBase®, 1,602 cases of COVID-19 vaccine-associated SHL were collected. Tozinameran (Pfizer-BioNTech) was mostly notified with 1,053 (65.7%) reports, followed by elasomeran (Moderna, 281, 17.5%), AZD1222 (AstraZeneca, 217, 13.5%), and JNJ 78436735 (Janssen, 43, 2.7%). Most cases concerned women (885, 55.2%), with a median age of 51 years, and 827 (51.6%) were considered serious. The association of COVID-19 vaccines and SHL showed significant disproportionality, with a ROR of 7.4 (95% CI 6.9-7.9) and an IC025>0. Tozinameran reached the strongest ROR (8.2;95% CI 7.6-8.8), followed by elasomeran (4.6;95% CI 4.0-5.2), JNJ-78436735 (3.0;95% CI 2.2-4.0), and AZD1222 (2.7;95% CI 2.3-3.1), all with IC025>0. Discussion/Conclusion: Significant disproportionality was identified for COVID-19 vaccines and SHL. Even though this adverse drug event may rely on an inflammatory mechanism, causality cannot be established by this pharmacovigilance study. However, this finding may strengthen the signals issued by ANSM, concerning elasomeran and AZD1222. SHL following COVID-19 vaccination might be evoked and treated as soon as possible.
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Introduction: To contain the COVID-19 pandemic, vaccination is deemed as a promising approach. A French pharmacovigilance survey identified five cases of trigeminal neuralgia (TN) following vaccination with AZD1222 (Vaxzevria®, AstraZeneca) [1]. Furthermore, a case report mentioned such an adverse reaction with tozinameran (Comirnaty®, Pfizer-BioNTech) [2]. TN is characterized by recurrent, unilateral, and brief electric shock-like pain in one or more trigeminal divisions [3]. TN is triggered by innocuous stimuli. We aimed to investigate the potential signal of TN related to COVID-19 vaccines. Material and methods: We queried VigiBase® (World Health Organization pharmacovigilance database) for all reports of "Trigeminal Neuralgia" (MedDRA Preferred Term) associated with "COVID-19 vaccine" (Active Ingredient), from 1967 to December 29, 2021 [4]. Disproportionality analysis relied on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval (CI), and the Information Component (IC). A positive IC025 is statistically needed to confirm the detection of a signal [5]. Results: In VigiBase®, we gathered 1,283 cases of COVID-19 vaccine-related TN. Most reports involved women (998, 77.8%), with a median age of 52 years, and 510 (39.8%) were deemed serious. Tozinameran was mostly reported with 782 (61.0%) cases, followed by AZD1222 (264, 20.6%), elasomeran (Spikevax® Moderna, 185, 14.4%), and JNJ-78436735 (Janssen® Johnson & Johnson, 37, 2.9%). The association of COVID-19 vaccines and TN revealed significant disproportionality, with an IC025>0 and a ROR of 3.1 (95% CI 2.9-3.3). Tozinameran showed the strongest ROR (3.6;95% CI 3.3-3.8), followed by AZD1222 (2.3;95% CI 2.0-2.6), elasomeran (2.0;95% CI 1.7-2.3), and JNJ-78436735 (1.8 95% CI 1.3-2.5), each with IC025>0. Discussion/Conclusion: COVID-19 vaccines and TN showed relevant disproportionality. Albeit this reaction may rely on an immune-mediated inflammation, causality can only remain hypothetical in this pharmacovigilance study. Nonetheless, this finding may suggest a signal, strengthening reports mentioned by literature and French pharmacovigilance. A TN occurring after COVID-19 vaccination should alert the clinician.
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Introduction: Post-mRNA vaccine myocarditis emerged as a rare adverse effect quickly after adolescents and young adult populations started to be vaccinated, and it was labelled as such for both vaccines. This work aimed to study the Reporting rates (Rr) of myocarditis after mRNA-1273 and BNT162b2 injections. Material and methods: mRNA vaccine exposures were retrieved from the French SI-VAC database, while cases of myocarditis were retrieved from the French spontaneous reporting database (Base Nationale de Pharmacovigilance, BNPV) up to 30 September 2021. All cases were routinely evaluated by drug safety medical professionals and repeated at national level in the context of an intensive pharmacovigilance monitoring. Reporting rates (Rr) per 100.000 injections were calculated according to age, gender and injection rank;Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). Results: Over the study period, almost 73 million BNT162b2 and 10 million mRNA-1273 doses were injected, and 376 and 106 confirmed cases of myocarditis were reported, respectively. These occurred in the week following the injection for 76.4% of cases reported after mRNA-1273 (n = 81) vs. 58.4% after BNT162b2 (n = 219). Rr per 100.000 injections was 1.1 (95% CI 0.9 to 1.3) for mRNA-1273 and 0.5 (0.5 to 0.6) for BNT162b2. After the second injection, the difference among vaccines was more pronounced in men aged 18-24 years (13.9 [9.2 to 20.1] for mRNA-1273 vs. 4.3 [3.4 to 5.5] for BNT162b2) and aged 25-29 years (7.0 [3.4 to 12.9] vs. 1.9 [1.2 to 2.9]);in younger people, the low number of cases did not allow any meaningful conclusion. In women, Rrs were globally lower, but differences between vaccines were close to those found for men. Discussion/Conclusion: The present study suggests that mRNA-1273 is related with a higher risk of myocarditis than BNT162b2 in people aged under 30, especially after the second injection.
ABSTRACT
Introduction: Vaccination against COVID-19 appears to be a promising approach to mitigate this pandemic. The French agency of medicinal products (ANSM) issued a signal concerning cases of transient global amnesia (TGA) following vaccination with elasomeran (Spikevax® Moderna) [1]. TGA is characterized by the sudden onset of anterograde amnesia with preservation of other cognitive functions and a spontaneous resolution within 24 h [2]. We aimed to investigate the potential link of TGA with COVID-19 vaccines. Material and methods: We queried the WHO VigiBase® for all reports of "Transient global amnesia" (MedDRA Preferred Term) related to "Covid-19 vaccine"(Active Ingredient), from 1967 to December 6, 2021 [3]. Disproportionality analysis was based on the Reporting Odds Ratio (ROR) with its 95% Confidence Interval [CI] and the Information Component (IC) [4]. A positive IC025 statistically detects a signal [5]. Results: The search yielded 289 COVID-19 vaccine-associated TGAs, 178 of which (61.6%) were deemed serious. Most cases concerned women (187, 64.7%), with a median age of 66 years. Tozinameran (T: Comirnarty® Pfizer-BioNTech) was the most represented with 147 reports (50.8%), followed by AZD1222 (A: Vaxzevria® AstraZeneca) with 69 reports (23,8%), elasomeran (E: Spikevax®, Moderna) with 60 reports (20.8%), and JNJ-78436735 (J: Janssen® Johnson & Johnson) with 12 reports (4.2%). With a IC025 > 0, COVID-19 vaccines proved a significant disproportionality (global ROR 5.1 [4.4-6.0]), with respective RORs at 4.6 [3.9-5.0] for T, E at 4.4 [3.4-6.0], A at 3.8 [3.0-5.0], and J at 3.7 [2.1-6.0]. Discussion/Conclusion: Our analysis of COVID-19 vaccines and TGA shows significant disproportionality. Various mechanisms, such as cerebrovascular, inflammatory, or migrainous, may underlie this association. Yet causality cannot be ascertained solely with this approach, although it strengthens the signal issued by the ANSM. Further studies may help to identify the causality of COVID-19 vaccines in triggering TGAs.
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Introduction: COVID-19 is an unprecedented challenge for physicians and scientists. Several publicized drugs are being used with not much evidence of their efficacy such as hydroxychloroquine, azithromycin or lopinavir-ritonavir. Yet, the cardiac safety of these drugs in COVID-19 deserves scrutiny as they are known to foster cardiac adverse ADRs, notably QTc interval prolongation on the electrocardiogram and its arrhythmogenic consequences.
ABSTRACT
Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.