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Limit J&J COVID Vaccine in Women Under 50?

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center. Use of mRNA COVID-19 vaccines should be considered as the preferable option in the US rather than Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in women under the age of 50 years, according to one group of experts. The group makes…

Editor’s note: Find the most recent COVID-19 news and guidance from Medscape’s Coronavirus Resource Center.

Use of mRNA COVID-19 vaccines must be deemed as the preferable option in the US as opposed to Johnson & Johnson’s (J&J) Janssen COVID-19 vaccine in girls under the age of 50 decades, according to one group of experts.

The team makes their recommendation in an editorial at JAMA published online April 30, accompanying a newspaper describing details of 12 example reports of cerebral venous sinus thrombosis (CVST) using thrombocytopenia following the J&J COVID-19 vaccine, also referred to as the Ad26.COV2. S vaccine.

The editorialists are Ruth A. Karron, MD, professor of international health at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland; Nigel S. Key, MD, professor of hematology in University of North Carolina at Chapel Hill; and Joshua M. Sharfstein, MD, associate dean for public health practice at Johns Hopkins Bloomberg School of Public Health.

They note that after an initial pause following reports of thrombosis with thrombocytopenia syndrome (TTS) connected into this J&J vaccine, and on the recommendation of the Advisory Committee on Immunization Practices, the US has allowed the use of their J&J vaccine in all adults with advice on the chance of TTS added to instructional materials.

The editorialists point out that no instances of TTS have been confirmed following government of over 180 million doses of the mRNA vaccines in the US.

They state that although the J&J vaccine will nevertheless be required for individuals with allergies to elements of their mRNA vaccines and also for people who reside in remote locations in which the cold chain for transport and storage of mRNA vaccines can’t be preserved,”US public health agencies and clinicians should consider recommending mRNA vaccines as safer options for those who may be at substantially higher risk for TTS after Ad26.COV2. S vaccination, currently women younger than 50 years.”

In the main JAMA paper, a group led by Isaac See, MD, Centers for Disease Control and Prevention (CDC) COVID-19 Response Team, report complete details of 12 cases of CVST with thrombocytopenia after the J&J COVID-19 vaccine reported to the US Vaccine Adverse Event Reporting System (VAERS).

The 12 US case reports, three of which have been deadly, reveal many similarities to cases described in Europe after the AstraZeneca vaccine.

The authors note that by April 12, approximately 7 million doses of the J&J vaccine had been awarded in the US. The 12 instances of CVST and thrombocytopenia following receipt of this vaccine were reported to VAERS between March 2 and April 21. All of 12 cases were in white ladies, 11 of whom were under 50 years old.

As of April 25, a further two cases have been confirmed and reported to VAERS; one in a person younger than 40 years, another in a female aged between 40 and 59 years.

In the 12 cases reported in detail, symptoms started between 6 and 6 15 days post vaccination.

At least 1 risk factor for CVST was diagnosed in seven patients (obesity in 6, hypothyroidism in 1, and also use of combined oral contraceptives in 1). None of those patients had been pregnant or over 12 weeks postpartum, had prior thrombosis, a personal or family history of thrombophilia, or recorded before exposure to heparin.

In addition to CVST, seven patients needed intracerebral hemorrhage and eight had non-CVST thromboses.

One patient reported a history of SARS-CoV-2 disease approximately 4 months prior to vaccination. Of the other 11 patients, four had negative serologic tests and seven weren’t tested.

All 12 patients were hospitalized and 10 were admitted to an intensive care unit (ICU). In the time of the last follow-up, three patients had died (all of whom had intraparenchymal hemorrhage), three stayed in the ICU, two were still hospitalized but not in an ICU, and four were discharged home.

The authors point out that the US instances of CVST using thrombocytopenia following the J&J vaccine have many similarities to those reported in Europe after the AstraZeneca vaccine, occurring mostly in women younger than 40 years and in patients without diagnosed thrombophilia. Both European and US patients experienced a median platelet nadir count of 19×103/µL and many had non-CVST large-vessel thrombosis.

In the European instances of CVST with thrombocytopenia, 50percent of patients died, in comparison with 25% of US patients.

Like the European cases, the US cases had positive heparin-PF4 HIT antibody ELISA tests in the absence of previous exposure to heparin, as could be observed in autoimmune HIT.

However, in the initial European CVST reports, 88% of patients tested with practical platelet HIT antibody tests had positive results, in comparison with only 11% of the US cases. But the authors note that absence of standardization in functional platelet HIT antibody assays may lead to differences in outcomes by different laboratories.

“It may be important to notify testing laboratories that post-vaccination TTS is being evaluated, so that testing methods can be adjusted if needed,” they state.

They conclude that these case reports suggest that the pathogenesis of TTS might be like autoimmune HIT, triggered by the formation of antibodies directed against PF4, a part of platelet alpha granules released during platelet activation. Compared to classic HIT in which exogenous heparin triggers antibody formation, in autoimmune HIT, an endogenous polyanion activates PF4 antibody formation.

They notice that the exact mechanism of TTS in regard to COVID-19 vaccination hasn’t yet been established. The Global Advisory Committee on Vaccine Safety has stated that a platform-specific mechanism related to adenovirus vector vaccines can’t be excluded. Both the J&J and AstraZeneca vaccines use an adenoviral vector, but they’re distinct; J&J utilizes an individual vector, while AstraZeneca utilizes a chimpanzee vector.

They also point out that CVST and thrombocytopenia following SARS-CoV-2 infection has been reported in at least two cases, but HIT testing was not done in such scenarios. There have not so far been any reports to VAERS of CVST with thrombocytopenia after mRNA COVID-19 vaccines.

The authors say these findings have important clinical and public health consequences, noting that the CDC has upgraded its interim clinical concerns for use of approved COVID-19 studies to indicate that girls aged 18 to 49 years should know about the heightened risk of TTS after receipt of their J&J vaccine, and to utilize a nonheparin anticoagulant in suspected cases.

They note that a subacute presentation of headache is present in 90% of patients with average CVST. While headache is a frequent symptom after the J&J vaccination, many headaches start and fix within 2 days. Whereas in the US instances of CVST after maternity, aggravation symptoms started at six days after vaccination and lasted for at least a week to many.

“Urgent consultation with a neurologist is prudent when a patient is suspected or confirmed to have CVST. In addition, since the median time from symptom onset to hospitalization was seven days in the US CVST case series, patient and clinician education might shorten the time to clinical evaluation and therefore treatment,” they say.

The authors also note that VAERS is a passive surveillance system, therefore cases of CVST using thrombocytopenia may be underreported.

In their corresponding article, Karron et al point out in addition to the 12 patients with CVST with thrombocytopenia explained within this case series, at least three patients with no CVST but meeting diagnostic criteria for TTS have been reported to VAERS (as of April 21), all in girls aged 18 into 59 years (median age, 37 years).

The editorialists report that the rate of CVST using thrombocytopenia following the J&J vaccine is approximately 5 per million women aged 18 to 50 years. This is in comparison with a background rate of roughly 0. 05 to 0. 13 a million each month.

They state that the access to an interim standardized case definition of this adverse effect will facilitate potential case ascertainment through inspection of large connected databases and active case finding.

This will also permit greater comprehension of whether people that are otherwise at increased risk for hypercoagulation in general and for CVST specifically (by way of example, women taking hormonal contraceptive pills drugs or who are pregnant) are also at greater risk for TTS.

Obtaining this information will encourage dynamic country-specific evaluations of the risks of each vaccine compared with the danger of COVID-19 disorder because of their own populations and subpopulations, they add.

JAMA. Published online April 30, 2021. Full text, Editorial

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