RESEARCH BRIEFING – WEEK IN REVIEW

Evidence continues to favor the efficacy of the covid-19 vaccines, most recently in the form of data from the HEROES-RECOVER network, released this week in the CDC's Morbidity and Mortality Weekly Report. This confidence boost adds to last week's letters published in the New England Journal of Medicine that touted vaccines amongst healthcare workers in the United States. The results from this new data set focus not only on healthcare workers, but also first responders and essential frontline workers, such as teachers, hospitality staff, delivery people and retail personnel.  

Promisingly, the data showed that there was a 35-fold difference in infection rates when comparing those who were vaccinated to those who were not. In other words, the vaccines demonstrated 90 percent effectiveness at preventing SARS-CoV-2 infection, as measured 14 days after the second dose. Even after the first dose, an 80 percent efficacy rate was achieved. 

Data were collected between December and March from nearly 4,000 research subjects from a diverse group of jurisdictions around the United States, including Arizona, Florida, Oregon, Minnesota, Texas and Utah, some of which experienced critically high levels of covid-19 disease during the time that the study covered. However, Arizona was by far the most tested region. At the time of analysis, nearly 64 percent of the cohort of people being followed had received two doses of an mRNA vaccine and another 12 percent had received one shot. Subjects tended to be more often female, between the age of 18-49 years, and White. 

 These data should be easily applicable to the general population and should provide further reassurance of vaccine importance, assuming that major changes in these dynamics do not emerge due to new SARS-CoV-2 variants. Nevertheless, given the preponderance of White subjects in this study, future studies showing effectiveness among Hispanic, Black, and other populations may help increase vaccine interest in non-White groups. 31 March 2021.

While the Oxford/AstraZeneca vaccine has been in use in many countries around the world, recent fears surrounding a potentially related blood disorder have led to concern regarding the shot, which has resulted in a number of countries temporarily suspending its use. Last week, the "Ontario Covid-19 Science Advisory Table" released information documenting our current understanding of the disorder, dubbed (perhaps prematurely) as "vaccine-induced prothrombotic immune thrombocytopenia," or VIPIT. (Note: prothrombotic means "encouraging of thick or clotted blood", thrombocytopenia is the medical term for a low number of platelets, the type of blood cell involved in clotting) Importantly, these results have not yet been peer-reviewed.

The purported documented cases of VIPIT came from individuals who received the vaccine across various countries in Europe. As reported, the condition affected primarily women under 55 years old, but no clear predisposing risk factors were identified, including prior history of bleeding disorders. Furthermore, even if the condition truly is vaccine "induced" (rather than coincident, which at these numbers is hard to prove), the researchers estimate that the incidence of VIPIT would fall somewhere between 1 in 125,000 to 1 in 1 million vaccinated persons.

Let's unpack the two primary clinically relevant components of VIPIT. The first aspect is a disease known as cerebral sinus venous thrombosis (CSVT), which refers to blood clots forming in the veins surrounding the brain. Unlike strokes, which affect the arteries of the brain, CSVT is caused by blood clots in the veins. CVST is a rare disorder that primarily affects women under the age of 50. It is more often found in those who are already at high risk for blood clots due to underlying conditions, medications, or pregnancy. Its initial symptoms typically include a severe headache, sometimes with neurologic deficits, like weakness. It is rare, found in at most two people per 100,000 per year. And interestingly, of the 20 million people who have received the Oxford/AstraZeneca vaccine, only 18 cases have been identified. As mentioned above, this is actually a smaller percentage than the "background rate" expected in the general population. This calls into question whether the vaccine is causing these events or whether it is merely an innocent bystander.

Thrombocytopenia, on the other hand, is significantly more common, and has numerous causes. The particular type found amongst those who received the vaccine is similar in nature to a disease called heparin-induced thrombocytopenia (HIT), which is an uncommon and paradoxical disorder that occurs after patients receive the blood thinning medication, heparin. Similar to the physiology in HIT, those who develop VIPIT are described as having developed antibodies that attack and destroy the body's own platelets, ultimately resulting in blood clotting (again, a paradox, as blood thinning and clotting are generally thought to be on opposite sides of the blood thickness spectrum). Once again, however, the rate of VIPIT does not seem to be any greater than the rate of a number of other forms of thrombocytopenia that would be expected among the same number of people who did not receive the Oxford/AstraZeneca vaccine.

Ultimately, although VIPIT sounds frightening, there is simply not enough evidence to suggest a true causal relationship with the Oxford/AstraZeneca vaccine, nor even data to show that it is happening more frequently than would be expected amongst the general population. Before we truly think about shelving this particular vaccine, which has some significant storage and cost advantages, much more data should be required. 29 March 2021.

New data published in The Lancet Global Health examined the effect of the covid-19 pandemic on maternal and fetal outcomes. Researchers reviewed the body of literature from January 2020 to January 2021 and found approximately 40 studies that point to an increase in stillbirths, maternal death and postpartum depression since the start of the covid-19 pandemic.

While those were the headline results, there were a number of other findings from the research worth noting. The increase in maternal deaths occurred primarily in low- and middle-income countries. Meanwhile, preterm births decreased in high income countries (findings on this topic have varied across multiple studies, as we have covered in the past here at Brief19). However, these data did not show a change in pregnancy-related diabetes, high blood pressure in pregnancy, induction of labor or modes of labor (e.g. vaginal deliveries versus instrumental-assisted deliveries or c-section). Additionally, no differences were seen in rates of postpartum hemorrhage and neonatal mortality.

These results are meaningful, yet not without limitations. There is bound to be a significant possibility of publication bias; studies that show significant changes in outcomes are more likely to have been published, while researchers who "found nothing," might have been less likely to move forward with the peer-review process. Furthermore, the vast majority of the referenced studies came from high-income countries, which is particularly problematic, as the lower proportion of studies from low- and middle-income nations suggests that the worst of the problems may be of greater magnitude than this report suggests.

Nevertheless, these results offer insight into the stark reality that social determinants of health continue to influence outcomes with respect to healthcare disparities both in relation to covid-19 and in general. More research that sheds more light on these disparities as they relate to maternal and fetal outcomes during and after the pandemic are expected. 2 April 2021.