Inflammatory biomarkers in pregnant women with COVID-19: a retrospective cohort study

Lombardi, Andrea; Duiella, Silvia F.; Piani, Letizia Li; Comelli, Agnese; Ceriotti, Ferruccio; Oggioni, Massimo; Muscatello, Antonio; Bandera, Alessandra; Gori, Andrea; Ferrazzi, Enrico

doi:10.1038/s41598-021-92885-7

Cited by 23 publications

(24 citation statements)

References 24 publications

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“…CRP can be used to monitor the evolution of COVID-19 disease. Study by Lombardi et al 18 concluded that CRP was related with severity of disease or mortality. As the 116-amino acid precursor of calcitonin hormone, PCT can be synthesized in many extra thyroid tissues during bacterial infection, which is mediated by increased concentrations of tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6.…”

Section: Discussionmentioning

confidence: 99%

Determining laboratory parameters in pregnant women with severe COVID-19

et al. 2022

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Objective: Coronavirus disease causes a wide spectrum of clinical picture in pregnant women. There are still a few studies concerning laboratory parameters to differentiate the severity of coronavirus disease-19 in pregnant patients. This article aims to identify the cut-off on laboratory parameters between pregnant women with asymptomatic/mild/moderate and severe/critical coronavirus disease-19 illness. Methods: All coronavirus disease-19 pregnant women coming to Dr. Cipto Mangunkusumo hospital between January and August 2021 were recruited into this cross-sectional study. All data extracted from medical records were classified into demographic characteristics and laboratory parameters. We defined demographic characteristics as age, parity, systolic, and diastolic blood pressure, heart rate, temperature, respiratory rate, and oxygen saturation. Laboratory parameters measured in this study consisted of complete blood count, renal function test including urea, creatinine, liver function test including aspartate transferase, alanine transferase, infection marker test including procalcitonin, C-reactive protein, interleukin-6, cycle threshold values, ferritin, coagulation test including d-dimer, fibrinogen, random blood glucose, albumin, electrolytes. Data analysis was performed using SPSS statistics. Results: There were 159 cases assessed in this study consisting of 130 (81.8%) patients with asymptomatic/mild/moderate illness and 29 (18.2%) patients with severe/critical illness of coronavirus disease-19. Of 28 laboratory parameters, 12 of them were significant statistically; thus, it resulted to make a cut-off using receiver operating characteristic curve and show relative risk, and 95% confidence interval. In multivariate analysis that aspartate transferase, D-dimer, and albumin were laboratory parameters impacted to the severity of coronavirus disease-19 in pregnant women. The area under receiver operating characteristic curve was 0.834 (95% CI 0.736–0.932). Conclusion: Of all laboratory parameters, urea, aspartate transferase, alanine transferase, procalcitonin, C-reactive protein, lactate dehydrogenase (LDH), ferritin, D-dimer, random blood glucose, cycle threshold values, albumin, and chloride differs between asymptomatic/mild/moderate, and severe/critical illness coronavirus disease-19 in pregnant women; aspartate transferase, D-dimer, and albumin were laboratory parameters impacted the most to the severity of coronavirus disease-19 in pregnant women.

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Section: Discussionmentioning

confidence: 99%

Determining laboratory parameters in pregnant women with severe COVID-19

et al. 2022

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“…Maternal infection and inflammation associated with COVID-19 could prompt potential pregnancy complications through this “cytokine storm”. Several studies reported increased expression of inflammatory biomarkers in pregnant women with COVID-19 ( 21 , 30 , 43 ). Thus, we assessed the impact of SARS-CoV-2 infection during pregnancy on placental inflammation as a potential cause of adverse pregnancy outcomes.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Proinflammatory Molecules and Tissue Factor by SARS-CoV-2 Spike Protein in Human Placental Cells: Implications for SARS-CoV-2 Pathogenesis in Pregnant Women

et al. 2022

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SARS-CoV-2 infects cells via binding to ACE2 and TMPRSS2, which allows the virus to fuse with host cells. The viral RNA is detected in the placenta of SARS-CoV-2-infected pregnant women and infection is associated with adverse pregnancy complications. Therefore, we hypothesize that SARS-CoV-2 infection of placental cells induces pro-inflammatory cytokine release to contribute to placental dysfunction and impaired pregnancy outcomes. First, expression of ACE2 and TMPRSS2 was measured by qPCR in human primary cultured term cytotrophoblasts (CTBs), syncytiotrophoblast (STBs), term and first trimester decidual cells (TDCs and FTDCs, respectively), endometrial stromal cells (HESCs) as well as trophoblast cell lines HTR8, JEG3, placental microvascular endothelial cells (PMVECs) and endometrial endothelial cells (HEECs). Later, cultured HTR8, JEG3, PMVECs and HEECs were treated with 10, 100, 1000 ng/ml of recombinant (rh-) SARS-CoV-2 S-protein ± 10 ng/ml rh-IFNγ. Pro-inflammatory cytokines IL-1β, 6 and 8, chemokines CCL2, CCL5, CXCL9 and CXCL10 as well as tissue factor (F3), the primary initiator of the extrinsic coagulation cascade, were measured by qPCR as well as secreted IL-6 and IL-8 levels were measured by ELISA. Immunohistochemical staining for SARS-CoV-2 spike protein was performed in placental specimens from SARS-CoV-2–positive and normal pregnancies. ACE2 levels were significantly higher in CTBs and STBs vs. TDCs, FTDCs and HESCs, while TMPRSS2 levels were not detected in TDCs, FTDCs and HESCs. HTR8 and JEG3 express ACE2 and TMPRSS2, while PMVECs and HEECs express only ACE2, but not TMPRSS2. rh-S-protein increased proinflammatory cytokines and chemokines levels in both trophoblast and endothelial cells, whereas rh-S-protein only elevated F3 levels in endothelial cells. rh-IFNγ ± rh-S-protein augments expression of cytokines and chemokines in trophoblast and endothelial cells. Elevated F3 expression by rh-IFNγ ± S-protein was observed only in PMVECs. In placental specimens from SARS-CoV-2-infected mothers, endothelial cells displayed higher immunoreactivity against spike protein. These findings indicated that SARS-CoV-2 infection in placental cells: 1) induces pro-inflammatory cytokine and chemokine release, which may contribute to the cytokine storm observed in severely infected pregnant women and related placental dysfunction; and 2) elevates F3 expression that may trigger systemic or placental thrombosis.

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“…While evaluating the laboratory profile we observed significantly raised NLR (p=0.002), CRP (p<0.001), D-Dimer (p=0.002) and abnormal chest X-ray findings (p<0.001) in CW2 obstetrical patients. Lombardi et al also noted raised median values of NLR, CRP and D-dimer (4.4, 1.66 mg/dL and 1,727 μg/L, respectively) [ 11 ]. The umbrella review by A Ciapponii including 66 systematic reviews of observational studies related to COVID-19 in pregnancy reported raised CRP in 28%-96%, lymphocytopenia 33.6% to 80% and abnormal radiological findings in 7.1% to 99% cases [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…They observed that for every 1,000 lymphocyte cells decrease, the risk for oxygen supplementation increases by 26%. Since there is a physiological rise in D-dimer and a fall in serum Ferritin levels during pregnancy, they questioned their prognostic role and inferred that compared to D-dimer and ferritin, CRP is a reliable predictor for obstetrical outcome [ 11 ]. Bernard et al again observed a positive association of CRP with mortality (HR 1.002, 95% CI 1.001-0.004, p 0.0064) [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Severity of Maternal COVID-19 Infection on Perinatal Outcome and Vertical Transmission Risk: An Ambispective Study From North India

Sharma¹,

Verma²,

Solanki³

et al. 2022

Cureus

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Background In contrast to the first wave, the second COVID-19 wave has taken a huge toll affecting maternal outcomes adversely. The aim of this study was to investigate the consequences of the severity of maternal disease on perinatal outcomes and the risk of vertical transmission and to find out the factors associated with adverse fetomaternal outcomes. Materials and methods This was an ambispective observational study including COVID-19 infected pregnant patients; 20-40 years of age irrespective of gestational age admitted at Government Institute of Medical Sciences, UP, India. The patients were divided into two groups: CW 1 (COVID-19 Wave 1): Patients admitted between April 1, 2020 and December 31, 2020 and CW 2 (COVID-19 Wave 2): Patients admitted between April 1, 2021 to May 31, 2021. Data in two groups were compared and analyzed with respect to the clinical profile, laboratory parameters, fetomaternal outcome and the risk of vertical transmission of COVID-19 infection. Results We included 134 eligible patients in the CW1 group and 58 in the CW2 group. Significantly more patients were symptomatic in CW2 (23.1% versus 60.3%, p= <0.001). In CW2, maternal neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP) and D-Dimer were significantly raised along with abnormal chest x-rays. There was a significant increase in maternal mortality in CW2 (1.5% vs 13.7%; p≤0.001). A total of 76 patients delivered in CW1 and 26 in CW2 with increased incidence of cesarean section (43.4%; 42.3%), preterm deliveries (28.2%; 37%) and low birth weight (34.6%; 25.9%) in both waves, the difference among two groups being statistically insignificant. Compared to CW1, perinatal mortality was significantly increased in CW2 (2.2% vs 15.5%; p<0.001). Though nasopharyngeal swab tested positive in four neonates in CW1 and two neonates in CW2, no evidence of vertical transmission was observed even with increased severity of maternal illness. On regression analysis, D-Dimer and CRP were found to have a positive association with maternal and perinatal mortality. Conclusion The severity of maternal illness proportionately affects the neonatal outcome with no impact on the risk of vertical transmission of infection. D-Dimer and CRP have emerged as independent predictors for maternal and perinatal mortality and hence can be utilized in obstetrics decision-making.

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Inflammatory biomarkers in pregnant women with COVID-19: a retrospective cohort study

Cited by 23 publications

References 24 publications

Determining laboratory parameters in pregnant women with severe COVID-19

Determining laboratory parameters in pregnant women with severe COVID-19

Regulation of Proinflammatory Molecules and Tissue Factor by SARS-CoV-2 Spike Protein in Human Placental Cells: Implications for SARS-CoV-2 Pathogenesis in Pregnant Women

Impact of Severity of Maternal COVID-19 Infection on Perinatal Outcome and Vertical Transmission Risk: An Ambispective Study From North India

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