Increasing oxygen requirements and disease severity in pregnant individuals with the SARS-CoV-2 Delta variant.

OBJECTIVE: According to the Centers for Disease Control and Prevention (CDC), the Delta (B.1.617.2) variant of SARS-CoV-2 became the most common variant in certain regions of the United States in July 2021. More than 80% of cases detected in Ohio starting the first week of July, were attributed to the Delta variant.

Although the Delta variant was found to be associated with an increase in disease severity and oxygen requirement in the nonpregnant population, there are limited data on its impact on pregnant individuals. , This study aimed to determine whether the Delta variant was associated with increased oxygen requirement and disease severity in the pregnant population.

STUDY DESIGN: This was a single academic center retrospective cohort study conducted at The Ohio State University Wexner Medical Center. All pregnant individuals who had a positive molecular test for COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) from March 2020 through October 2021 were included. The cohort was divided into 2 groups on the basis of the Delta variant becoming the dominant variant in Ohio starting July 2021. The Delta variant group included positive patients from July 2021 to October 2021, and the pre-Delta (including B.1.1.7, B.1.351, P.1) variants group included positive patients from March 2020 to June 2021. Individuals were not routinely sequenced for the different variants at our institution.

Our primary outcome was need for oxygen supplementation, defined as any oxygen supplementation using a nasal cannula, a high-flow nasal cannula, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Patients with oxygen saturation ≤94% on room air or those with severe or critical disease were started on oxygen supplementation (criteria applied across all time points during study period). The secondary outcomes included disease severity on the basis of the National Institutes of Health criteria (assigned at time of diagnosis or hospital admission), hospitalization for COVID-19, COVID-19 symptoms, laboratory and imaging abnormalities, intensive care unit (ICU) admission, inpatient therapeutics use including remdesivir and corticosteroids, and maternal death. A subgroup analysis, comparing the outcomes for vaccinated and unvaccinated individuals, was performed in the Delta variant cohort. The clinical care of patients was similar regardless of their vaccination status.

The summary statistics were calculated for the baseline variables. Bivariate analyses were performed as appropriate. The association between infection with the Delta variant and the primary and secondary outcomes was determined using multivariable analysis, correcting for the clinically relevant covariates such as body mass index (BMI) and major medical comorbidity (respiratory disease, hypertension, and pregestational diabetes). It was then expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). All the statistical analyses were performed using Stata version 15 (StataCorp, College Station, TX). A P value less than.05 was used for statistical significance. Because this was an exploratory study with convenience sampling, no power calculations or correction for multiple comparisons were performed. This study was approved by the University's institutional review board.

RESULTS: A total of 424 pregnant individuals tested positive for SARS-CoV-2 infection during the study period and were included. Maternal characteristics including age, BMI, gestational age at COVID-19 diagnosis, and medical comorbidities were comparable between the pre-Delta and the Delta groups (Table 1 ). Patients in the pre-Delta group had higher rates of gestational diabetes and were more likely to be delivered by cesarean delivery; no difference was noted in the rates of hypertensive diseases of pregnancy or preterm delivery between the 2 groups (Table 1).

Table 1

Maternal characteristics and pregnancy outcomes

Maternal characteristics (n)	Delta variant group (n=99)	Pre-Delta variant group (n=325)	P value
GA at diagnosisa (wk+d)	29+3 (23+3 to 35+6)	31+5 (17+6 to 37+3)	.64
Nulliparityb	25 (25.3)	75 (23.1)	.69
Agec (y)	29.0 (5.5)	29.5 (5.4)	.48
Medical historyb
Respiratory diseased	7 (7.1)	37 (11.4)	.22
Chronic hypertension	14 (14.1)	33 (10.2)	.27
Pregestational diabetes	5 (5.05)	23 (7.1)	.64
BMI at COVID-19 diagnosisa (kg/m2)	33.0 (26–39)	31.0 (26–37)	.11
Partial COVID-19 vaccine seriesb	21 (21.1)	27 (8.3)	<.01e
Completed COVID-19 vaccine seriesb	17 (17.2)	21 (6.5)	<.01e
Pregnancy outcomes (n)	Delta variant group (n=97)f	Pre-Delta variant group (n=325)	P value
Gestational diabetesb	2 (2.1)	30 (9.2)	.02e
Hypertensive diseases of pregnancyb,g	11 (11.3)	41 (12.6)	.74
Cesarean deliveryb	6 (6.2)	111 (34.2)	<.01e
Postpartum hemorrhageb	2 (2.1)	16 (4.9)	.39
Preterm delivery <37 wkb	21 (21.7)	59 (18.2)	.44
Intrauterine fetal demiseb	1 (1.0)	6 (1.9)	.99

BMI, body mass index; GA, gestational age.

Data are presented as median (interquartile range)

Data are presented as n (%)

Data presented as mean (±standard deviation)

Respiratory diseases include asthma, chronic obstructive pulmonary disease, or any other known underlying respiratory condition

Significant at P<.05

Two with data missing as still pregnant

Hypertensive diseases of pregnancy include gestational hypertension; preeclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; or eclampsia.

Patients in the Delta variant group were more likely to require any form of oxygen supplementation (18.2% vs 6.8%; aOR, 2.76; 95% CI, 1.38–5.50) and have more severe disease (moderate, severe, or critical; 23.2% vs 10.5%; aOR, 2.30; 95% CI, 1.24–4.21) than those in the pre-Delta variant group (Table 2 ). In addition, they were more likely to have laboratory or imaging abnormalities and require admission to the ICU (Table 2). There were 2 maternal deaths in the Delta variant group compared with none in the pre-Delta variant group. Both the patients were unvaccinated.

Table 2

COVID-19 characteristics, severity, treatments, and outcomes

COVID-19 characteristics and treatments	Delta variant group (n=99)	Pre-Delta variant group (n=325)	aOR (95% CI)
Primary outcomea	18 (18.2)	22 (6.8)	2.76 (1.38–5.50)b
Highest level of oxygen supplementation required	6 (6.1)	15 (4.6)	1.19 (0.41–3.04)
Nasal cannula	7 (7.1)	1 (0.3)	22.18 (3.84–418.9)b
HFNC	5 (5.1)	6 (1.9)	2.56 (0.71–8.87)
Mechanical ventilation/ECMO
Moderate/severe/critical disease severityc	23 (23.2)	34 (10.5)	2.30 (1.24–4.21)b
Admission to hospital for COVID-19	18 (18.2)	51 (15.7)	1.27 (0.61–2.03)
Admission to ICU for COVID-19	9 (9.1)	7 (approximately 2.2)	4.25 (1.51–12.39)b
Symptomatic	80 (80.8)	195 (60.0)	2.84 (1.66–5.02)b
Laboratory abnormalitiesd	26 (26.3)	41 (12.6)	2.31 (1.24–4.25)b
Abnormal findings on chest imaging	23 (23.2)	28 (8.62)	2.93 (2.56–5.40)b
Receipt of corticosteroids	18 (18.2)	20 (6.2)	3.05 (1.50–6.05)b
Receipt of remdesivir	20 (20.2)	21 (6.5)	3.29(1.67–6.47)b
Maternal death from COVID-19	2 (2.0)	0 (0)	—
Subgroup analysis of maternal oxygen supplementation and disease severity with Delta variant for vaccinated vs unvaccinated
Variable (n)	Vaccinated (n=17)	Unvaccinated (n=82)	P value
Primary outcomea	0 (0)	18 (22.0)	.04b
Moderate/severe/critical disease severityc	0 (0)	22 (26.8)	.01b
Symptomatic	15 (88.2)	65 (79.3)	.51
Laboratory/chest imaging abnormalitiesd	1 (5.9)	25 (30.5)	.04b
Admission to hospital for COVID-19	0 (0)	18 (22.0)	.04b
Admission to ICU for COVID-19	0 (0)	9 (11.0)	.35
Maternal death from COVID-19	0 (0)	2 (2.0)	.99

Data are presented as number (percentage). aOR presented for obesity (body mass index>30 kg/m2) and co-occurring medical conditions (respiratory disease, chronic hypertension, and pregestational diabetes).

aOR, adjusted odds ratio; CI, confidence interval; ECMO, extracorporeal membrane oxygenation; HFNC, high-flow nasal cannula; ICU, intensive care unit.

Primary outcome=composite of any form of supplemental oxygen used

Significant at P<.05

Defined using the National Institutes of Health criteria: asymptomatic, no symptoms consistent with COVID-19; Mild illness, symptomatic without shortness of breath/dyspnea/abnormal chest imaging; moderate illness, evidence of lower respiratory disease during clinical assessment or imaging and those who have an oxygen saturation (SpO2) ≥94%; severe illness, SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, a respiratory rate >30 breaths/min, or lung infiltrates >50%; critical illness, respiratory failure, septic shock, and/or multiple organ dysfunction

Laboratory abnormalities: defined as platelet count <150 × 103 per uL, or prothrombin time >14 seconds, or partial prothrombin time >35 seconds, or creatinine >1 mg/dL, or aspartate aminotransferase greater than 40 units/L or alanine aminotransferase >35 units/L. Chest imaging abnormalities defined by changes consistent with COVID-19 on chest X-ray or computed tomography.

Eid. Oxygen requirements and disease severity in pregnant individuals with the SARS-CoV-2 Delta variant. Am J Obstet Gynecol MFM 2022.

The rate of COVID-19 vaccination was higher in the Delta variant group, with 17.2% of patients having completed the vaccination series compared with 6.2% in the pre-Delta variant group (Table 1). A subgroup analysis among COVID-19 patients in the Delta variant cohort showed that none of the vaccinated patients required oxygen supplementation, compared with 22% (P=.04) of the unvaccinated patients who also showed more severe forms of the disease (moderate, severe, or critical; 26% vs 0%; P=.01). In addition, the rates of laboratory or imaging abnormalities (30.5% vs 5.9%; P=.04) and admission to the hospital (22% vs 0%; P=.04) were all significantly higher in unvaccinated pregnant individuals with the Delta variant than in those who were unvaccinated (Table 2).

CONCLUSION: A significant increase in oxygen requirement and disease severity was seen in pregnant individuals affected by the SARS-CoV-2 Delta (B.1.617.2) variant. Vaccinated patients were less likely to develop severe disease or require oxygen supplementation with the Delta variant than the nonvaccinated population. The difference in the vaccination rate between the 2 groups may be explained by the increased availability and uptake of the vaccine during the Delta predominance. The results of our study support the importance of COVID-19 vaccination in the pregnant population, as it appears to be protective against severe forms of the disease.