Scientists tie platelet factor 4 to AstraZeneca COVID vaccine-related clots
UK researchers have uncovered the novel mechanism behind rare abnormal blood clotting seen in some AstraZeneca/Oxford vaccine recipients, according to a study today in the New England Journal of Medicine.
The study involved clinical and lab evaluation of 23 previously healthy patients who experienced blood clots and thrombocytopenia (low platelet counts) 6 to 24 days after receiving the first dose of the AstraZeneca vaccine. Most clots were cerebral venous thrombosis, while some were arterial thrombosis and venous thromboembolisms such as pulmonary embolisms.
Twenty-one patients had antibodies for clot-promoting platelet factor 4 (PF4) on enzyme-linked immunosorbent assay (ELISA) before heparin administration. They appeared to be of the immunoglobulin G (IgG) subtype. Functional heparin-induced thrombocytopenia (HIT) testing confirmed the positive PF4 ELISA result in five of seven patients tested.
"These findings confirmed the presence of platelet activation similar to that seen in patients with HIT, as measured by the addition of donor platelets to patient serum in the absence of heparin," the researchers wrote. "This effect was not increased with the addition of heparin in physiologic doses but was fully suppressed with the addition of an excess of heparin."
Seven of 23 patients (30%) died. Autopsy results were available for one patient, who had evidence of clotting in many small blood vessels, particularly in the lungs, intestine, cerebral veins, and venous sinuses, and extensive hemorrhage in the brain.
All patients had normal or low concentrations of fibrinogen, which is involved in blood clotting, and high levels of D-dimer, a sign of blood clots. Median patient age was 46 years, and 61% were women.
The authors said that while COVID-19 vaccination remains critical to pandemic control, "a pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 [AstraZeneca] vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications."
The researchers recommended against the use of platelet transfusions in these patients because of the risk of worsening the blood clotting and suggested the use of a nonheparin anticoagulant agent and intravenous immunoglobulin for treatment of the first blood clot occurrence.
Apr 16 N Engl J Med study
Study notes 10% of Marines who had COVID-19 experience reinfections
Previous COVID-19 infection did not completely protect young US Marines in a study led by scientists from the Naval Medical Research Center and published yesterday in the Lancet Respiratory Medicine.
Of the 2,346 otherwise healthy quarantined Marine recruits studied from May 11 to Nov 2, 2020, 189 were seropositive, or had antibodies against COVID-19 in their blood, indicating previous coronavirus infection, while 2,247 were seronegative.
Of the 189 seropositive participants, 19 (10%) tested positive for COVID-19 during the 6-week follow-up period, compared with 1,079 (48%) of seronegative participants (rate ratio, 0.18). Most participants were men 18 to 20 years old. Overall, there were 1,098 (45%) new infections during the study period.
Sixteen of 19 infected seropositive Marines (84%) and 732 of 1,079 seronegative participants (68%) had no or mild symptoms, and none were hospitalized.
Infection was more likely in seropositive recruits with lower baseline full-length spike protein immunoglobulin G concentrations than in those with higher levels (hazard ratio, 0.45). The viral loads of infected seropositive Marines were roughly 10 times lower than those of infected seronegative participants.
Baseline neutralizing antibodies were found in 45 of 54 (83%) of uninfected participants and 6 of 19 (32%) infected recruits during the 6-week observation period.
In a Lancet news release, senior study author Stuart Sealfon, MD, of Icahn School of Medicine at Mount Sinai, said it's important to remember that previously infected young people are vulnerable to reinfection and may pass the virus to others. "Immunity is not guaranteed by past infection, and vaccinations that provide additional protection are still needed for those who have had COVID-19," he said.
In a commentary in the same journal, Maria Velasco, MD, PhD, and Carlos Guijarro, MD, PhD, of Hospital Universitario Fundacion Alcorcon in Madrid, Spain, said that the high rate of reinfection in the Marines could be tied to close contact in crowded conditions or to greater detection from regular screening in asymptomatic participants.
"Overall," they said, "these results indicate that COVID-19 does not provide an almost universal and long-lasting protective immunity, unlike that seen in measles, for example."
Apr 15 Lancet Respir Med study and commentary
Apr 15 Lancet news release