key: cord-0999954-5a2wosu1
authors: Radan, Anda-Petronela; Fluri, Mihaela-Madalina; Nirgianakis, Konstantinos; Mosimann, Beatrice; Schlatter, Bettina; Raio, Luigi; Surbek, Daniel
title: Gestational diabetes is associated with SARS-CoV-2 infection during pregnancy: A case-control study
date: 2022-04-21
journal: Diabetes Metab
DOI: 10.1016/j.diabet.2022.101351
sha: 1a7464de11ce4a9e0f92914bdc5e6c8d5ec8e2ab
doc_id: 999954
cord_uid: 5a2wosu1

AIM: Individuals with SARS-CoV-2 infection and (pre-existing) diabetes, including pregnant women, present with more severe morbidity, as compared to non-diabetic subjects. To date, evidence is limited concerning the role of gestational diabetes (GDM) in severity of SARS-CoV-2 infection during pregnancy, or vice versa. The aim of our study was to investigate the prevalence of GDM in a SARS-CoV-2 infected pregnant population and evaluate risk factors for and from severe infection in these patients. METHODS: A case-control study with prospective data collection for the case group and 1:2 matching with historical controls based on parity, BMI and ethnicity was conducted (n=224). GDM screening was performed at 26 weeks’ gestation. Multivariate binary logistic regression analysis was performed to assess risk factors for GDM and inpatient COVID-19 management. RESULTS: 34.6% of the patients in the case group suffered from GDM, vs. 16.1% in the control group (p=0.002). 35.7% patients were diagnosed with GDM after, vs. 33.3% before SARS-CoV-2 infection (OR (95%CI) 1.11(0.40-3.08), p=0.84), with no correlation between time point of infection and GDM diagnosis. SARS-CoV-2 (OR (95%CI) 2.79 (1.42, 5.47), p=0.003) and BMI (OR (95%CI) 1.12 (1.05, 1.19), p=0.001) were significant independent risk factors for GDM. CONCLUSION: Data suggests that GDM increases the risk of infection in SARS-CoV-2 infected pregnant women. Meanwhile, SARS-CoV-2 during pregnancy might increase the risk of developing GDM. Vaccination and caution in using protective measures should be recommended to pregnant women, particularly when suffering from GDM.

Individuals with SARS-CoV-2 infection and (pre-existing) diabetes, including pregnant women, 23 present with more severe morbidity, as compared to non-diabetic subjects. To date, evidence is 24 limited concerning the role of gestational diabetes (GDM) in severity of SARS-CoV-2 infection during 25 pregnancy, or vice versa. The aim of our study was to investigate the prevalence of GDM in a SARS-26

CoV-2 infected pregnant population and evaluate risk factors for and from severe infection in these 27 patients. 28

A case-control study with prospective data collection for the case group and 1:2 matching with 30 historical controls based on parity, BMI and ethnicity was conducted (n=224). GDM Diabetes mellitus (DM) is one of the most frequent comorbidities in individuals with SARS-CoV-2 62 infection [1] [2] . Evidence shows that individuals suffering from diabetes present higher morbidity and 63 mortality as compared to non-diabetic subjects [1] . 64

Analogue to the general population, pregnant women suffering from preexisting diabetes seem to 65 present with a higher severity degree of SARS-CoV-2 infection [3, 4 ]. An international case control 66 analysis comparing data stratified by the severity of maternal disease identified pulmonary 67 comorbidities, hypertensive disease and DM as risk factors associated with a severe form of SARS-68

CoV-2 infection in pregnancy [5] . Furthermore, it has been previously suggested that hyperglycemia 69 generally increases viral replication and decreases anti-viral response, making a causal relationship 70 between diabetes and SARS-CoV-2 biologically plausible [1, 2] . However, there is limited data so far 71 whether these elaborations also apply to gestational diabetes (GDM). 72 GDM is a major public health issue, with an abrupt increase in prevalence in the last decade, and 73 international committees report a so-called `metabolic pandemic` [6]. According to The 74

Hyperglycemia and Adverse Pregnancy Outcome Study, the level of glycaemia during pregnancy is 75 directly linked to the presence of adverse obstetrical outcomes [7] [8] . 76

Prevalence of GDM lies worldwide between 9,3% and 25,5% [8]. A British study described a 33.8% 77 increase in GDM since the onset of the pandemic, attributing this mainly to reduced exercise levels 78 and psychical stress [9] . 79 SARS-CoV mediated pancreatic islet cell damage is not a newly described phenomenon, as earlier 80 experiences with MERS and SARS teach us [10]. DM is a multifactorial disease, and its development is 81 linked to genetic and environmental influences. Indeed, a causal relationship between viral infections 82 and acute glycemic decompensation with onset of Type I diabetes has been previously described 83

In this context, increasing evidence shows that SARS-CoV-2 can trigger severe diabetic ketoacidosis in 85 persons with new-onset Type I diabetes, most probably due to high angiotensin converting enzyme 2 86 5 (ACE2) expression in the endocrine part of the pancreas. The mechanism seems to involve cell 87 apoptosis with decreased pancreatic insulin secretion [11] . 88

The aim of our study was to investigate the prevalence of GDM in a SARS-CoV-2 infected pregnant 89 population and evaluate risk factors for and from severe infection in these patients. 90

We included 224 pregnant women in our case-control study. The case group consisted of 75 women 92 with SARS-CoV-2 infection during pregnancy, irrespective of the severity of the symptoms. We 93 included all SARS-CoV-2 positive women who were managed at our tertiary hospital between May 94 2020 and July 2021. Data from these individuals were collected prospectively within the international 95 COVI-Preg register. Cases were matched 1:2 with a historical cohort of women who delivered before 96 the SARS-CoV-2 pandemic between 01.01.2016 and 31.10.2019, based on parity, body mass index 97 (BMI) and ethnicity. In one woman, only one matching control was found, so that the control group 98 consisted of 149 individuals. Screening for GDM by 75mg oral glucose tolerance test (OGTT) was 99 performed at 26 weeks' gestation in all 224 women. Normal blood sugar values were defined as 100 follows: fasting < 5,1mmol/l, one hour after glucose ingestion < 10mmol/l, two hours after glucose 101 ingestion < 8,5mmol/l. All women where OGTT was not available were previously excluded. 102

First trimester was defined as conception to 13 + 6 weeks, second trimester from 14 + 0 to 26 + 6 103 weeks and third trimester as more than 27 + 0 weeks of gestation. Baseline characteristics of the study population and delivery outcomes are depicted in Table 1 . Higher exposition to hospital visits in women suffering from GDM could be cofounding factor for 172 SARS-CoV-2 infection in pregnancy. We mention that patient management was adapted in our center 173 during the major SARS-CoV-2 pandemic surges, mostly by conversion to teleconsultations. Diabetes 174 testing protocols remained unaltered. 175

In both our study groups, GDM rate was higher than in the general pregnant population in 176

Switzerland, which could be explained by the higher proportion of high-risk pregnancies as well as by 177 the high number of women of South Asian ethnicity being followed at our institution [8] . 178

The rate of hospital admission in SARS-CoV-2 infection in our population was in line with previous 179 reports [5]. We noted a significantly higher incidence of premature delivery in the case group, 180 whereas in the control group, incidence was similar to that of the general pregnant population in our 181 country [14] . The 17.33% rate of preterm delivery in the SARS-CoV-2 infected women in our cohort is 182 in line with results from a large previous meta-analysis [15] .

One major strength of our report is the prospective data assessment in the case group and the case-184 control approach. Homogeneity of testing is another major strength, since standard OGTT was 185 carried out in each patient in both groups, which distinguishes us from previous publications. The 186 ability to classify the COVID-19 infection in respect to the symptoms is a further strength of our 187 study. The major limitation is the cohort size as well as not having matched for further comorbidities 188 or lower socioeconomic status, which is a known risk factor for both GDM as well as SARS-CoV-2 189 infection, because of incomplete records. 

Risks of and From SARS-CoV-2 Infection and 210

COVID-19 in People With Diabetes: A Systematic Review of Reviews. Diabetes Care

Diabetic ketoacidosis and mortality in COVID-19