Lisa Sammaritano, MD, Talks About COVID-19, Pregnancy, and Rheumatic Disease – What We Know So Far

The Delta variant of SARS-CoV-2, which was considered approximately 50% more transmissible than the preceding Alpha variant, became predominant in the US in July 2021.¹

A recently published study authored by Adhikari EH et al showed increased morbidity among pregnant patients with COVID-19, especially among those who were unvaccinated, during the Delta surge.² The authors concluded that although the pathophysiologic mechanisms associated with increased COVID-19 severity are still unclear, the urgency of prevention measures, including vaccination, must be emphasized among certain populations including in pregnancy.²

Very little is known about the specific effects of the Omicron variant on pregnancy; however, currently available data on the safety and efficacy of COVID-19 vaccines in pregnancy are promising, with unvaccinated individuals at increased risk for severe disease.³

It has long been established that a rheumatic disease (RD) diagnosis increases the risk for poor maternal and neonatal health outcomes, with pregnancy outcomes dependent on disease activity, medication usage, and the presence of certain autoantibodies.⁴ Now, the COVID-19 pandemic has placed an additional burden on providers and patients with RD, especially pregnant persons, with regard to the adverse effects of the virus on immunocompromised systems and health outcomes.

However, published data regarding outcomes of SARS-CoV-2 infection in patients with RD who are pregnant or considering pregnancy are limited.

To inform rheumatologists in practice who are at the helm of providing care and treatment to this population, Bermas and colleagues have shed further light on pregnancy outcomes in RD and COVID-19, using data collected from the COVID-19 Global Rheumatology Alliance. Results of this study showed that the majority of pregnant women with RD and COVID-19 had favorable outcomes.⁵

In a recent editorial published in The Journal of Rheumatology,⁶ Lisa Sammaritano, MD, provided an overview of the available literature on the effects of COVID-19 on pregnant patients with RD.

To talk more about this paper and the clinical implications of published research in this area, we spoke with Dr Sammaritano, a professor of clinical medicine and an attending physician in rheumatology at Weill Cornell Medicine and the Hospital for Special Surgery in New York City.

In your recent editorial, you mentioned that the early data on pregnancy, RD, and COVID-19 were “reassuring.”⁶ Can you provide a clinical overview on what is known thus far about the effects of SARS-CoV-2 infection on pregnancy and RD?

Dr Sammaritano: The available data are reassuring despite the obvious cause for concern. The largest study is by Bermas and colleagues, recently published in The Journal of Rheumatology, reporting data from 39 women with RD who contracted COVID-19 infection during pregnancy.⁵

There are 2 concerning factors for pregnant patients with RD who develop COVID-19. First, women with RD are already at a higher risk for adverse pregnancy outcomes compared with the general population, with risk depending on diagnosis, disease activity, autoantibody status, medications, and other factors. Second, COVID-19 infections in pregnant women tend to be more severe due to altered immune responses of pregnancy.

Despite a higher rate of hospitalization, the pregnant patients with RD, in the Bermas et al study, did well. None of the patients required intensive care unit (ICU) admission or mechanical ventilation, despite the additional risk factor of pregnancy. There were no patient deaths. Patients may have done well in part due to their overall young age, relatively quiet disease activity, and limited use of immunosuppressive medications. Of note, these data were collected during the early part of the COVID-19 pandemic when the overall outcomes were more severe and risk of mortality was higher.⁵

The effect of the current Omicron variant on pregnant women may be less severe, although data have not yet been reported.

Are there certain factors, such as race, ethnicity, and socioeconomic background that play a role in differential outcomes of COVID-19 infection in pregnancy?

Dr Sammaritano: Differences in race, ethnicity, and socioeconomic background appear to be associated with varying risk, along with the previously well-defined medical factors.

A review of 192 studies by Allotey et al reporting on the outcomes of COVID-19 during pregnancy found that pregnant women with COVID-19 who were [hospitalized] were more likely to require admission to the ICU or need mechanical ventilation.⁷

Comorbidities identified as risk factors for severe COVID-19 in pregnancy included non-White ethnicity, hypertension, diabetes, high maternal age, and high body mass index. These risk factors align with those identified in the general (nonpregnant) population. Additional risk factors for the (nonpregnant) RD patient population include the presence of active disease and certain medications.

How can rheumatologists counsel their patients with RD who are pregnant or considering pregnancy during the COVID-19 pandemic? How does this differ from guidance for pregnant persons in the general population?

Available reports provide limited but reassuring information for clinical rheumatologists seeking to counsel their patients with RD who are currently pregnant or are considering pregnancy during the COVID-19 pandemic. All patients considering pregnancy should be encouraged to be vaccinated and to minimize the risk for exposure. In general, patients with RD planning pregnancy are already encouraged to have a low level of or quiet disease activity to optimize maternal and fetal outcomes.

What advice can rheumatologists provide to pregnant patients with RD who present with symptoms of COVID-19? Can you shed some light on the available treatments and treatment goals for these patients because we know that some medications may be associated with poorer outcomes?

If a pregnant patient with RD tests positive for COVID-19, the patient should be encouraged to receive monoclonal antibody therapy. Pregnancy is recognized as a risk factor for severe COVID-19. Even if not receiving immunosuppressive medication, pregnant patients with RD are at increased risk [for severe disease] and are encouraged to seek treatment.

The Omicron variant has changed our use of monoclonal therapies, with only sotrovimab considered effective. Patients receiving immunosuppressive medications should stop [receiving] these (if possible) during acute infection. Paxlovid, an oral COVID-19 antiviral medication, is discouraged for use during pregnancy and breastfeeding due to lack of data, but it may be considered if benefits are thought to outweigh risks.

Although there have been limited studies conducted on neonatal outcomes in COVID-19, what available data can be beneficial during the management of pregnant patients with RD?

Pregnancy itself increases the risk for some infections with negative effects on maternal health and fetal/neonatal outcomes. Certain infections acquired in utero (or during delivery) can cause fetal/neonatal mortality and childhood developmental anomalies, such as the classic TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex virus) infections and others (eg, parvovirus B19 and Zika virus).

In contrast to the significant risk for intrauterine infection, the corona and influenza viruses pose the greatest threat to maternal health rather than directly to fetal health. Previous coronaviruses (severe acute respiratory syndrome [SARS] and Middle Eastern respiratory virus [MERS]) and influenza A H1N1 outbreaks have been shown to increase the risk for maternal death and ICU admission, as well as secondary adverse obstetric outcomes such as prematurity, with little risk for vertical transmission.⁸

Studies of COVID-19 in pregnancy suggest risks like those seen with previous coronaviruses. There appears to be little risk for vertical transmission to the fetus, but the pregnant state increases risk for severe maternal infection and adverse outcomes, such as preterm delivery and neonatal ICU (NICU) admission.³

In the Bermas et al study, though the emphasis was on maternal outcomes, limited data on pregnancy outcomes were available for 22 patients. None of the patients had delivered due to COVID-19 infection; most births were at-term, with only 3 preterm births (<37 weeks).⁵

Will COVID-19-related guidance be included in future updates for the management of reproductive health in RD?

Of course, if studies provide evidence adequate to support recommendations regarding COVID-19 that are specific to reproductive health issues.

Reports have shown low uptake of the COVID-19 vaccines among pregnant persons compared with the general population. How can rheumatologists advise pregnant patients with RD on the safety of the COVID-19 vaccines?

The COVID-19 vaccine uptake in pregnant women is lower than in the general population, with significant vaccine hesitancy especially regarding the novel mRNA vaccines. However, data are supportive of vaccine safety during pregnancy. Benefits include a lowered risk for severe COVID-19 for the mother as well as transplacental passage of COVID-19 antibodies to the fetus, providing some protection to the newborn.

Multiple professional organizations have recommended that pregnant women receive a COVID-19 vaccine.⁹ Published reports also support the safety and benefit of COVID-19 vaccination for patients with RD. However, no studies yet have specifically reported on the safety and benefit of COVID-19 vaccines in pregnant patients with RD.

Can you highlight the importance of communication and collaboration between rheumatologists and women’s health specialists/OB-GYNs for the provision of adequate care to this patient population? 

Communication and collaboration between specialists is always important for patient care, whether regarding decisions regarding contraception, planning for in vitro fertilization (IVF), or pregnancy.

The current COVID-19 pandemic further strengthens the need for a team-based approach – patients should be confident that their physicians with differing expertise have discussed their medical history and agreed on recommendations, especially during a particularly challenging time with COVID-19.

References

1. Gov.uk. SPI-M-O: consensus statement on COVID-19. Published June 2, 2021. Accessed January 19, 2022. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/993321/S1267_SPI-M-O_Consensus_Statement.pdf
2. Adhikari EH, SoRelle JA, McIntire DD, Spong CY. Increasing severity of COVID-19 in pregnancy with Delta (B.1.617.2) variant surge. Am J Obstet Gynecol. 2022;226(1):149-151. doi:10.1016/j.ajog.2021.09.008
3. Hall, S. COVID vaccines safely protect pregnant people: the data are in. Nature. Published online January 12, 2022. Accessed January 19, 2022. https://www.nature.com/articles/d41586-022-00031-8
4. Maguire S, O’Shea F. Management of pregnancy in rheumatic disease. EMJ Rheumatol. 2021;8(1):86-93. doi:10.33590/emjrheumatol/21-00034
5. Bermas BL, Gianfrancesco M, Tanner HL, et al. COVID-19 in pregnant women with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance. J Rheum. 2022;1;49(1):110-114. doi:10.3899/jrheum.210480
6. Sammaritano LR. The effect of covid-19 illness on pregnant patients with rheumatic disease: early reassuring data. J Rheum. 2022; 49(1):5-7. doi:10.3899/jrheum.211050
7. Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. doi:10.1136/bmj.m3320
8. Wastnedge EA, Reynolds RM, Van Boeckel SR, et al. Pregnancy and COVID-19. Physiol Rev. 2021;101:303-318. doi:10.1152/physrev.00024.2020
9. Centers for Disease Control and Prevention (CDC). COVID-19 vaccines while pregnant or breastfeeding. Updated December 6, 2021. Accessed January 19, 2022. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html