COVID-19 Update: April 6th - April 20th
Welcome to the McGraw-Hill COVID-19 channel. In this bi-weekly update we have information on COVID-19 and DVT incidence in outpatients, information about vaccine-induced immune thrombotic thrombocytopenia (VITT) associated with the AstraZeneca and the Johnson & Johnson/Janssen vaccines, information on the immune response to SARS-CoV-2 mRNA vaccines in pregnancy and a link to new recommendations for surface decontamination at home and in public buildings.
The AstraZeneca vaccine is associated with vaccine-induced immune thrombotic thrombocytopenia (VITT) with 62 cases of cerebral venous sinus thrombosis and 24 cases of splanchnic vein thrombosis reported. Six similar cases have been associated with the Johnson & Johnson/Janssen vaccine which has led to a temporary halt in the use of this vaccine in the United States.
The first paper is a report of 23 cases of thrombocytopenia with thrombosis in patients who had gotten the AstraZeneca SARS-CoV-2 vaccine (ChAdOx1 nCoV-19 Vaccination). Presentations included cerebral venous thrombosis (including venous sinus thrombosis) (13), pulmonary embolism, portal vein thrombosis, ischemic stroke, and intracranial hemorrhage. Thirty percent of these cases died. Laboratory evaluation demonstrated an elevated D-dimer and low fibrinogen levels. Notably, 22 of 23 patients had a positive ELISA for anti-PF4 antibodies, the same antibody found in heparin induced thrombocytopenia (HIT). The paper includes a diagnostic and treatment algorithm for VITT which is based on the limited information we have so far. Possible treatments include IVIG, glucocorticoids, and the use of non-heparin anticoagulants when anticoagulation is indicated. Platelet transfusion was associated with progression of thrombosis. They recommend consultation with a hematologist to help guide therapy.
A similar syndrome of cerebral venous sinus thrombosis with thrombocytopenia has been identified in six individuals given the Johnson & Johnson/Janssen vaccine in the United States. It is thought that these may also be associated with anti-PF4 antibodies. These cases have led to a temporary halt in administration of this vaccine in the United States.
Symptoms began three to 13 days after vaccination with a mean time to hospital admission of 15 days post-vaccination. Presenting symptoms included headache (5 cases), backache with subsequent headache (1 case), aphasia, weakness, visual changes nausea, vomiting and abdominal pain. Two patients were diagnosed with portal and splanchnic thromboses.
The CDC suggests that patients seek medical care “urgently” for any of the following within three weeks of the Johnson & Johnson/Janssen vaccine (verbatim):
- severe headache
- new neurologic symptoms
- severe abdominal pain
- shortness of breath
- leg swelling
- tiny red spots on the skin (petechiae)
- new or easy bruising
They point out that these six cases occurred in the setting of almost 7 million vaccinations administered, making this complication exceedingly rare even if causally related. The CDC Health Alert for clinicians can be found here. Clinical information for providers and patients can be found here.
- European Medicine Agency. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. April 7, 2021 available at: https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood
- Scully M, Singh D, Lown R, et. al. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. April 16th 2021 available at https://www.nejm.org/doi/full/10.1056/NEJMoa2105385
- CDC, Emergency Preparedness and Response Health Alert Network, Cases of Cerebral Venous Sinus Thrombosis with Thrombocytopenia after Receipt of the Johnson & Johnson COVID-19 Vaccine April 13th 2021 available at https://emergency.cdc.gov/han/2021/han00442.asp
- CDC, COVID-19. Recommendation to Pause the Use of Johnson & Johnson’s Janssen COVID-19 Vaccine. April 16, 2021 available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/JJUpdate.html
The immune response to SARS-CoV-2 mRNA vaccines administered during pregnancy or lactation is robust and similar to the response in non-pregnant controls. This is a prospective cohort study of antibody response to either the Moderna or Pfizer/BioNTech SARS-CoV-2 mRNA vaccine in 84 pregnant patients, 21 lactating patients, and 16 non-pregnant patients. Vaccine induced antibody levels were also compared to those in 37 pregnant women who were diagnosed with COVID-19.
Vaccine induced antibody levels were not statistically different between pregnant, lactating, and non-pregnant women (p=0.24). Vaccine induced antibody levels were higher than those secondary to COVID-19 infection during pregnancy (p<0.0001). Neutralizing antibodies were found in all umbilical cord samples (N=10) as well as in in all breast milk samples tested.
This is the first data we have looking at the immune response to the two mRNA COVID-19 vaccines in pregnancy. While the numbers are small, the data is reassuring; vaccination during pregnancy seems to generate an adequate immune response and the antibody is transferred to the neonate via the placenta and breast milk. The full study can be found here.
- Gray KJ, Bordt EA, Atyeo C, et.al. COVID-19 vaccine response in pregnant and lactating women: A cohort study, American Journal of Obstetrics and Gynecology (2021), doi: https://doi.org/10.1016/j.ajog.2021.03.023.
The risk of DVT is not elevated in outpatients with a positive SARS-CoV-2 test when compared to those who are SARS-CoV-2 negative. It is clear that inpatients with COVID-19 have an elevated risk of venous thromboembolism (VTE). How about outpatients? This is a retrospective study of 220,588 patients of whom 11.8% tested positive for SARS-CoV-2. They looked at the risk of VTE in the 30 days after testing. A new VTE was found in 0.8% of those who tested positive for SARS-CoV-2 (198 patients) and 0.5% (1008 patients) in those who tested negative for SARS-CoV-2 (p<0.001). However, this difference was entirely explained by those patients who were hospitalized; the risk for VTE in outpatients was the same regardless of SARS-CoV-2 status (1.8 vs. 2.2. cases/1000, p=0.16)
This study suffers from a lack of standardized testing in all patients which would have been impractical given the size of the cohort. The authors also point out that VTE testing patterns may have changed because of SARS-CoV-2, which may have caused some patients not to seek care. However, even with these limitations the risk of a VTE diagnosis in those COVID-19 patients treated as outpatients seems low. The full study can be found here.
- Roubinian NH, Dusendang JR, Mark DG, et al. Incidence of 30-Day Venous Thromboembolism in Adults Tested for SARS-CoV-2 Infection in an Integrated Health Care System in Northern California. JAMA Intern Med. Published online April 05, 2021. doi:10.1001/jamainternmed.2021.0488
Briefly, the CDC has changed SARS-CoV-2 surface cleaning guidelines for non-healthcare facilities and individual homes. The recommendations now differentiate between when to clean with soaps and detergents and when to use a disinfectant. They also note that if it has been greater than 24 hours since an area has been exposed to an individual with COVID-19 that disinfection is not necessary; routine cleaning will do. The guidelines are nuanced and not easily summarized.
- CDC, COVID-19: Cleaning and Disinfecting Your Home: Every Day and When Someone is Sick, April 5, 2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/disinfecting-your-home.html
- CDC, COVID-19: Cleaning and Disinfecting Your Facility: Every Day and When Someone is Sick, April 5, 2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/community/disinfecting-building-facility.html