Virus World

BACKGROUND

Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy.

METHODS

From December 14, 2020, to February 28, 2021, we used data from the “v-safe after vaccination health checker” surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons.

RESULTS

A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases).

CONCLUSIONS

Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

Published in NEJM (June 17, 2021):

https://doi.org/10.1056/NEJMoa2104983 

See also NEJM (June 17, 2021):

https://doi.org/10.1056/NEJMe2107070 

It doesn't take an epidemiologist to evaluate vaccine trial results. Answers to just a handful of questions can help anyone do this. Monday marked the first announcement of preliminary results of Phase 3 trials of Covid-19 vaccines, and we expect many more to follow. These results are long awaited: Mass vaccination will give us the most promising path out of the pandemic — but only if people trust the results enough to get the vaccine. A well-informed public is among the most crucial elements of a successful vaccination program. It doesn’t take an epidemiologist to thoughtfully evaluate vaccine trial results. Answers to just a handful of questions can help anyone compare their strengths and weaknesses, distinguish the promising from the inadequate, and know when more information is needed to figure out which is which. Did the vaccine reduce symptomatic infections? No vaccine is 100% protective. The best of the bunch, like vaccines against the measles and hepatitis A, reduce infections in about 95% of people. Yet many other vaccines, such as those for influenza and typhoid, are closer to a coin flip — getting vaccinated reduces the risk of infection by about half. What is the target for Covid-19 vaccines? The FDA has set an efficacy threshold of a 50% reduction in symptomatic infections for consideration of licensure (total and severe infections are harder to measure — more on that later). But experts would like to see something closer to a 60% to 70% reduction, which would bring us closer to approaching herd immunity and potentially allow us to start relaxing physical distancing measures. This is one reason why the 90% reduction reported this week by Pfizer and BioNTech in the first trial results are particularly exciting.

Who participated in the study? Three groups are key: people older than 65; underrepresented racial and ethnic groups, particularly Black and Latino populations; and individuals with medical conditions such as kidney disease, diabetes, or obesity. Study after study after study has shown that these groups suffer the greatest burden of Covid-19-related complications and death. So a vaccine that reduces disease severity in young, healthy white people but has a little effect in these higher-risk groups might have considerably less public health impact. Pharmaceutical companies have been called upon for years to increase diversity in clinical trials, particularly among historically marginalized and exploited groups. Although the Phase 3 trials for Covid-19 vaccines are not large enough to separately show benefit or harm in each of these groups, inclusion of equitable numbers will be crucial for broad public trust in trial results. What do the results reveal about severe infections? On first glance, this might seem like a rehash of the first point, about whether the vaccine reduced symptomatic infections. But the distinction is very important. A vaccine that only moderately prevents infections but that strongly reduces hospitalizations or deaths could still be a winning candidate. It would convert Covid-19 into something akin to the common cold — an annoyance, but not a life-threatening infection. Reducing disease severity may also make people less likely to transmit the virus to others, another win. Because severe Covid-19 infections are relatively uncommon — occurring more often in the elderly, less so in young, healthy people — showing a large benefit in reducing disease severity won’t be easy. For example, the clinical trial plans for the Pfizer/BioNTech vaccine calls for enrolling approximately 43,000 people to detect just 160 symptomatic infections when the final results are released (there were 96 detected symptomatic infections at the time of the preliminary analysis). No data on severe infections have been reported so far, but we would expect only about two dozen of the 160 infected to be hospitalized and a few to die, leaving little chance to show that the vaccine prevents severe complications. Nonetheless, even a modest effect on Covid-19 severity would be welcome, especially if it occurs among the vulnerable groups discussed earlier.

Is it safe? Since vaccines are mainly given to healthy people — and in this case, potentially to billions of them — understanding the safety of a Covid-19 vaccine is essential. Some good news is that the vaccine candidates under consideration are unlikely to have common severe side effects such as a severe allergic reaction or rash requiring hospitalization. They have completed Phase 2 trials that demonstrated safety in hundreds of people. Any vaccine that caused severe side effects in more than 10% of the Phase 2 participants would not have moved ahead into these larger trials....