Understanding SARS-CoV-2 in Diabetic Pregnancies
Imagine two global health crises converging in a single vulnerable population—this is the reality faced by pregnant women living with diabetes during the COVID-19 pandemic.
As the world grappled with the relentless spread of SARS-CoV-2, researchers quickly identified that certain groups faced heightened risks, particularly those with chronic conditions like diabetes. When this vulnerability intersects with pregnancy—a state already requiring careful medical management—the clinical implications become increasingly complex and concerning 1 .
Approximately 20 million (16%) of live births worldwide are affected by some form of hyperglycemia in pregnancy, with gestational diabetes representing the majority of these cases 1 .
The European prevalence of gestational diabetes sits at about 16.3%, while North America experiences even higher rates at approximately 20.8% 1 .
Diabetes in pregnancy exists along a continuum, with different types requiring distinct management approaches:
Representing approximately 84% of hyperglycemia cases in pregnancy, GDM typically emerges in the second or third trimester and usually resolves after delivery 1 .
About 7.9% of diabetic pregnancies involve women diagnosed with type 1 or type 2 diabetes prior to pregnancy 1 .
Approximately 8.5% of cases represent first observations of type 1 or type 2 diabetes during pregnancy 1 .
Pregnancy itself represents a unique immunological state characterized by modified immune responses to accommodate the growing fetus. This adaptation, while necessary for successful pregnancy, may increase susceptibility to certain viral infections 6 .
The entry of SARS-CoV-2 into human cells relies heavily on the angiotensin-converting enzyme 2 (ACE2) receptor, which acts as the primary doorway for viral invasion .
In diabetic pregnancies, the expression of ACE2 receptors may be enhanced, particularly in the presence of hyperinsulinemia, creating more potential entry points for the virus 4 .
Diabetes is characterized by a state of chronic low-grade inflammation, with higher baseline levels of pro-inflammatory cytokines 1 .
When SARS-CoV-2 infection occurs in this already primed inflammatory environment, it can trigger an exaggerated immune response known as a "cytokine storm" .
Hypoxia, or insufficient oxygen supply to tissues, represents another key intersection between COVID-19 and diabetic pregnancies .
In pregnancy, where oxygen demands are already elevated, hypoxia can have particularly serious implications for both maternal and fetal health .
The combination of diabetic and COVID-19-related inflammation may create what researchers describe as a "double-hit" scenario, with implications for both immediate pregnancy outcomes and long-term offspring health 1 .
Diabetes creates a baseline state of low-grade inflammation with elevated pro-inflammatory cytokines.
SARS-CoV-2 infection triggers an exaggerated immune response, potentially leading to a cytokine storm.
The synergistic effect creates a "double-hit" scenario with amplified risks for both mother and fetus.
To better understand how gestational diabetes influences COVID-19 outcomes in pregnancy, researchers established the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study conducted across 115 hospitals in Germany and Austria 4 .
Between April 3, 2020, and August 24, 2021, researchers enrolled 1,490 pregnant women with clinically confirmed COVID-19 at any stage of pregnancy 4 .
Gestational diabetes was diagnosed according to International Diabetes in Pregnancy Study Groups criteria, using a two-step approach 4 .
Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes 4 .
| Patient Group | Adjusted Odds Ratio for Adverse Maternal Outcome | 95% Confidence Interval |
|---|---|---|
| Overweight with GDM | 2.90 | 1.21-6.95 |
| Obese with GDM | 2.54 | 1.13-5.67 |
| Overweight/Obese with Insulin-Treated GDM | 3.05 | 1.38-6.73 |
Table 1: Maternal Outcomes in Women with COVID-19 and Gestational Diabetes 4
Adverse maternal outcomes based on timing of COVID-19 diagnosis relative to GDM diagnosis:
Studying the complex relationship between SARS-CoV-2 and diabetic pregnancies requires specialized tools and methodologies.
| Reagent/Method | Function/Application | Example of Use |
|---|---|---|
| ACE2 Antibodies | Detect and quantify ACE2 receptor expression | Mapping receptor distribution in placental and fetal tissues 6 |
| TMPRSS2 Antibodies | Identify cells expressing this critical protease | Determining co-expression patterns with ACE2 in trophoblastic cells 6 |
| SARS-CoV-2 RT-PCR Tests | Confirm active infection through viral RNA detection | Diagnosing COVID-19 in pregnant study participants 4 |
| Oral Glucose Tolerance Tests (OGTT) | Diagnose gestational diabetes | Identifying GDM cases in research cohorts 4 |
| Single-Cell RNA Sequencing | Analyze gene expression in individual cells | Characterizing cellular tropism of SARS-CoV-2 at maternal-fetal interface 6 |
| Cytokine Panels | Measure inflammatory markers | Quantifying cytokine storm magnitude in severe COVID-19 cases 1 |
| HbA1c Testing | Assess long-term glycemic control | Identifying pre-existing diabetes in early pregnancy 7 |
Table 3: Essential Research Reagents and Methods for Studying SARS-CoV-2 in Diabetic Pregnancies
The pandemic has accelerated the adoption of digital health technologies that show particular promise for managing diabetic pregnancies.
Telemedicine platforms, remote glucose monitoring systems, and smartphone applications offer innovative approaches to maintaining continuity of care while reducing infection exposure risks 1 .
One of the most intriguing aspects involves the concept of transgenerational programming—the idea that perturbations during critical developmental windows can have lifelong consequences 1 .
The combination of maternal dysglycemia and COVID-19-related inflammation may "program" the offspring for increased risk of metabolic disorders later in life 1 .
While early reports suggested minimal vertical transmission of SARS-CoV-2, more recent evidence confirms that transplacental infection can occur, though it remains relatively uncommon with estimates around 3.28% 6 .
Research indicates that the abundance of both ACE2 and TMPRSS2 is actually much higher in multiple embryonic tissues than in the placenta, suggesting that while the placenta provides a somewhat effective barrier, certain fetal tissues—particularly the intestine in the 20th week of development—may be at higher risk if the virus does cross the placental barrier 6 .
Estimated vertical transmission rate
The collision of the diabetes and COVID-19 pandemics in pregnancy represents a significant challenge for clinicians, researchers, and patients alike. The evidence reviewed here reveals a complex biological interplay characterized by shared pathophysiological mechanisms including ACE2-mediated viral entry, exaggerated inflammatory responses, and hypoxia-related tissue damage.
The CRONOS registry and other studies have identified particularly vulnerable subgroups, especially women with gestational diabetes who also have overweight or obesity, and those requiring insulin therapy. These findings highlight the importance of tailored prevention strategies and vigilant monitoring for this population.
As we continue to navigate the COVID-19 pandemic and prepare for future public health challenges, the lessons learned from studying this complex intersection will undoubtedly enhance our ability to protect maternal and fetal health in the face of emerging threats.
This article was based on a systematic scoping review published in BMC Pregnancy and Childbirth (2021) and subsequent related research. For complete details and methodological considerations, readers are referred to the original scientific publications.