Immunoglobulin may benefit those with COVID vaccine-related blood clots

High doses of intravenous immunoglobulin (IVIG) in conjunction with an anticoagulant were associated with resolved vaccine-induced immune thrombotic thrombocytopenia (VITT) in three patients, according to a report yesterday in the New England Journal of Medicine.

VITT occurs when antibodies attack protein factor 4 (PF4), leading to blood clumping and clots.

The patients, one woman and two men, were 63 to 72 years old and received the AstraZeneca/Oxford COVID-19 vaccine in Canada from Mar 31 to Apr 13. (At that time, Canada restricted AstraZeneca use to those older than 55 because VITT is mostly observed in younger populations.)

Two patients with no comorbidities were diagnosed as having leg clots and initially had leg pain. The third, who had arterial and venous brain clots, had headaches and confusion as well as a history of non–insulin-dependent diabetes, high blood pressure, obstructive sleep apnea, pre-stage prostate cancer, and heparin exposure 9 months prior followed by daily aspirin use.

One patient with leg clots was discharged with an oral anticoagulant when IVIG treatment was associated with platelet counts of 114,000 per cubic millimeter (mm³) during a 2-day period. The other's platelets increased to 640,000 per mm³ 7 days after IVIG treatment began, but he still faced foot amputation because of lingering clots.

The patient with the cerebral clots needed four IVIG doses because the third dose's effects appeared to wane. With therapeutic plasma exchange, he achieved normal platelet levels of 158,000 per mm³ by day 62 post-vaccination. No new or progressive blood clots were associated with IVIG use.

To help measure VITT, the researchers used an enzyme-linked immunosorbent assay (ELISA) test with a reaction well for PF4 without heparin. They say its results support its use before administration of IVIG and that ELISA reactivity was not inhibited by the treatment.

While the researchers know using high-dose IVIG for clotting is unusual, they point to the association between IVIG's serum-induced platelet-activating properties and increased platelet counts.

"Increasing the platelet count is especially important when patients have severe thrombocytopenia and multiple unusual thromboses that require therapeutic-dose anticoagulation, especially in the context of hemorrhagic transformation after cerebral infarction," write the researchers. "Since patients with VITT can have severe thrombocytopenia that potentially lasts for several weeks, early administration of IVIG may be an important adjunct therapy to anticoagulation for the management of VITT."
Jun 9 N Engl J Med study

Improved heart health may result in better COVID-19 outcomes

A consolidation of 32 literature reviews on COVID-19 and heart health or comorbidities found that high blood pressure, smoking, obesity, heart disease, and diabetes were associated with worse COVID-19 outcomes, according to the European Heart Journal - Quality of Care & Clinical Outcomes yesterday. 

The reviews were published from Mar 2 to Aug 11, 2020, and all were either considered of moderate quality (31) or high quality (1) according to the AMSTAR 2 appraisal tool.

Comorbidities associated with both mortality and severe infection in COVID-19 patients were renal disease (odds ratio [OR], 3.07), cerebrovascular disease (risk ratio [RR], 2.75), cardiovascular disease (OR, 2.65), high blood pressure (OR, 2.50), diabetes (OR, 2.09), and smoking history (relative risk [RR], 1.26). Liver disease had higher odds of mortality but not severe infection, as did obesity (ORs, 2.81 and 2.18, respectively). Current smoking had the opposite effect, with greater risk of severity but not mortality (RR, 1.80).

All listed odds and risk ratios are for mortality, but the study includes severity ratios as well. The compiled data also showed that those hospitalized with COVID-19 experienced venous thromboembolism (25%), pulmonary embolism (19%), arrhythmias (19%), myocardial injury (10%), angina (10%), deep vein thrombosis (7%), myocardial infarction (4%), and acute heart failure (2%).

Not all reviews looked at all factors. Subject matter data ranged from one review for alcohol (consisting of one study and 30 patients) and one for multiple cardiovascular risk factors (consisting of 21 studies and more than 77,000 people) to 18 on diabetes and COVID-19 outcomes, with the largest diabetes review covering 63 studies.

"Our study indicates that COVID-19 patients with heart disease or its risk factors are at greater risk of hospitalisation, ventilation or death due to COVID-19 and might need more intense treatment and monitoring," study author Stephanie Harrison, PhD, of the University of Liverpool, said in a European Society of Cardiology (ESC) press release.

"Promoting heart health may be another way to improve outcomes for COVID-19 patients. More research is needed on the long-term impact of COVID-19 on the heart."
Jun 9 Eur Heart J Qual Care Clin Outcomes study
Jun 10 ESC press release

MERS sickens man in Saudi Arabia

Saudi Arabian health officials reported a new MERS-CoV case, which involves a 63-year-old man from Taif who had contact with camels, a known risk factor.

In an update, the Ministry of Health (MOH) said the man is not a health worker and listed the man's source of MERS-CoV (Middle East respiratory syndrome coronavirus) as primary, meaning he didn't likely contract it from another person. Taif is in western Saudi Arabia.

The latest case brings the country's total to nine so far this year. The World Health Organization aid in a recent update that it has received reports of 2,574 cases, at least 886 fatal, since the first human infections were detected in 2012. The vast majority are from Saudi Arabia.
Jun 8 Saudi MOH update

Study: Wolbachia-treated mosquitoes reduce dengue incidence

An Indonesian study published today in the New England Journal of Medicine, shows that the introduction of Wolbachia-treated mosquitoes reduced dengue incidence, and resulted in fewer hospitalizations due to the virus.

In recent years, scientists have sought ways to harness infections with Wolbachia bacteria, which renders the offspring of Aedes aegypti mosquitoes sterile, to limit the spread of vector-borne disease, including Zika and dengue.

To conduct the study, called the Applying Wolbachia to Eliminate Dengue (AWED) trial, researchers treated some mosquitoes in a 26-square-kilometer site, which was divided into 24 clusters. Twelve clusters were randomly divided to receive the Wolbachia-treated mosquitoes through 9 to 14 rounds of introductions beginning in 2017, and the others were untreated controls. 

Wolbachia-treated mosquitoes were 77.1% effective in preventing confirmed dengue infections, and 86.2% effective in preventing hospitalizations due to dengue in a study of 8,144 participants who had acute undifferentiated fever during the trial. The protective efficacy was similar for all four dengue serotypes.

"These impressive results show the efficacy of wolbachia introgression into A. aegypti populations as a method for the prevention of dengue in an urban setting in which dengue is endemic," said David Hamner, MD, in an accompanying commentary. "This trial has several major strengths, including community engagement, use of constrained randomization, adequate power (despite disruption of the trial because of the Covid-19 pandemic), and use of virologically confirmed infection for the primary end point."
Jun 10 N Engl J Med study
Jun 10 N Engl J Med commentary

High-path H5 avian flu strikes wild birds in 3 countries

South Africa reported seven outbreaks involving highly pathogenic H5N1 avian flu in wild and zoo birds in Western Cape province, including in and around Cape Town, according to a Jun 8 report to the World Organization for Animal Health (OIE). Earlier this year the country reported H5N1 outbreaks in poultry.

Taken together, the virus killed 15 of 110 susceptible birds. So far, the source of the virus isn't know, and officials have applied quarantine measures.

Elsewhere, Germany reported highly pathogenic H5N4 in a wild bird in Lower Saxony state, and Estonia reported highly pathogenic H5N1 in wild birds in six different locations.
Jun 8 OIE report on H5N1 in South African wild birds
Jun 4 OIE report on H5N4 in Germany
Jun 10 OIE report on H5N1 in Estonia