key: cord-0685088-yaly7mqr authors: Deng, Guangtong; Zeng, Furong; Zhang, Lijuan; Chen, Hui; Chen, Xiang; Yin, Mingzhu title: Characteristics of pregnant COVID-19 patients with liver injury date: 2020-06-20 journal: J Hepatol DOI: 10.1016/j.jhep.2020.06.022 sha: 954cacb74404315690621777a7fe2cdf6af60424 doc_id: 685088 cord_uid: yaly7mqr • Liver injury is not very severe in pregnant COVID-19 patients. • Pregnant COVID-19 patients with liver injury had higher inflammation. • Newborns of COVID-19 patients with liver injury were negative for SARS-CoV-2. Liver injury is not very severe in pregnant COVID-19 patients. Pregnant COVID-19 patients with liver injury had higher inflammation than those without liver injury. All newborns delivered by pregnant COVID-19 patients with liver injury were negative for SARS-CoV-2. 5 To the Editor: The ongoing worldwide pandemic of Coronavirus Disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global threat to human health. Qi et al. 1 and Cai et al. 2 have reported liver injury in general patients with COVID-19. However, little attention has been paid to pregnant COVID-19 patients with liver injury. In this study, we collected the admission data on 37 pregnant COVID-19 patients from Jan 28 to Feb 28, 2020 at Wuhan Union hospital of Huazhong University of Science and Technology. All the patients were laboratory-confirmed cases and classification of the severity of COVID-19 was based on the New Coronavirus Pneumonia Prevention and Control Program in China. 3 As Qi et al. suggested, liver injury was defined as an increase in either of the following parameters: alanine aminotransferase (ALT) > 40 U/L, aspartate aminotransferase (AST) > 40 U/L and total bilirubin (TBIL) > 17.1 μmol/L. 1 Synthetic inflammatory markers were calculated from the admission full blood count, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systematic immune-inflammation-based prognostic index (SII). 4 These parameters have been reported to be associated with the severity of COVID-19. 5 Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range, IQR) for normally or abnormally distributed data, followed by unpaired t-test or Wilcoxon rank sum test. Categorical variables were summarized as counts (percentages) and compared using the Fisher's exact test. P < 0.05 was considered statistically significant. This retrospective study 6 was approved by the ethics committee of Union Hospital of Huazhong University of Science and Technology. A total of 37 pregnant patients were enrolled in this study ( Table 1 ). In detail, 11 (29.7%) patients had laboratory findings consistent with liver injury and 26 (70.3%) patients had normal baseline AST, ALT and TBIL levels. Of these patients with liver injury, the average age was 31.18 years and two reported a medical history of gestational hypertension and diabetes, separately. Fever (8 [72.5%]) and dry cough (6 [54.5%]) were the most common initial symptoms. In laboratory test, compared with the pregnant patients without liver injury, those with liver injury had a higher level of procalcitonin (PCT), interleukin (IL)-6, AST, ALT and lactic dehydrogenase. There were no statistical differences in signs, severity of COVID-19, the interval from onset to hospitalization, hospital stay, radiological findings and obstetric management between pregnant patients with and without liver injury. Four patients with liver injury in third trimester chose cesarean section voluntarily, two had vaginal delivery, and the rest did not reach the delivery time. Finally, six livebirths were recorded with no fetal death, neonatal death or neonatal asphyxia observed. Moreover, we did not detect the presence of SARS-CoV-2 by RT-PCR in breastmilk (n=6), neonatal throat swab (n=4) or neonatal anal swab (n=1). In this study, we reported, for the first time, the clinical, laboratory, and radiological data between pregnant COVID-19 patients with and without liver injury. We found 7 that the prevalence of liver injury in pregnant COVID-19 patients was 29.7%. In Chen et al.'s study, they demonstrated that 23.8% -44.4% pregnant COVID-19 patients had liver injury in all the Wuhan laboratory-diagnosed pregnant patients, which was consistent with our finding. 6 However, Qi et al. reported that 45.7% general patients had liver injury, which was higher than that in pregnant patients. 1 Additionally, we found that inflammatory markers including PCT and IL-6 levels were higher in pregnant COVID-19 patients with liver injury. Accumulating evidence has suggested that hyperinflammation plays an essential role in the mortality of COVID-19. 7 SARS-CoV-2-induced inflammation response can recruit macrophages, monocytes and T cell to establish a pro-inflammatory feedback loop, causing cytokine storms and aggravations. 8 Besides, we recently showed that elevated inflammatory markers were positively correlated with the severity of COVID-19, 9 suggesting that fully monitoring and evaluation of liver function in pregnant patients is appropriate. Interestingly, the elevation of inflammatory markers in pregnant patients was not as marked as in non-pregnant patients. Mor et al. demonstrated that the second trimester of pregnancy reflected anti-inflammatory phase, 10 indicating that pregnancy might confer some protection against higher inflammation and developing severe COVID-19. However, only 5 [13.5%] patients were in second trimester of pregnancy in our study. Previous data showed that younger and female patients had lower rates of severe COVID-19 than older and male patients 11 . Therefore, age and gender effects could mainly account for the low rates of severe COVID-19 in pregnant patients compared with general patients. Considering the low-grade inflammation and 8 non-severe pneumonia in pregnant patients, it seems that pregnant patients are less likely to be treated with the drugs such as lopinavir/ritonavir that are associated with liver injury. 12 To date, though inflammatory cells could be found in the hepatic sinuses from a non-pregnant COVID-19 patient, 2 how and why pregnant patients with liver injury had higher inflammation than those without liver injury still remains to be clarified. Notably, six pregnant patients with liver injury gave six healthy babies without neonatal death, neonatal asphyxia or SARS-CoV-2 infection. That means that there is currently no evidence that liver injury can increase the poor outcomes of neonates. In summary, our study demonstrated that pregnant patients with liver injury had a higher inflammation than those without liver injury. Monitoring and evaluation of liver function in pregnant patients should be performed. Admittedly, our conclusions are limited by the small sample size, and larger researches are needed to validate these findings. Continuous variables with normal distribution were expressed as mean ± standard deviation (SD) and compared with unpaired t-test. Continuous data with abnormally distribution were presented as median (interquartile range, IQR) and compared with Wilcoxon rank sum test. Categorical variables were summarized as counts (percentages) and compared using the Fisher's exact test. Multicenter analysis of 9 clinical characteristics and outcome of COVID-19 patients with liver injury COVID-19: Abnormal liver function tests National Health Commission of China. The notice of launching guideline on diagnosis and treatment of the novel coronavirus pneumonia A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients Clinical Characteristics of Pregnant Women with Covid-19 in Wuhan, China COVID-19: consider cytokine storm syndromes and immunosuppression The trinity of COVID-19: immunity, inflammation and intervention Association of inflammatory markers with the severity of COVID-19: a meta-analysis Inflammation and pregnancy: the role of the immune system at the implantation site Clinical Characteristics of Coronavirus Disease 2019 in China Clinical Features of COVID-19-Related Liver Damage We thank all the hospital staff members for their efforts in collecting the information that used in this study; thank the patients who participated in this study, their families, and the medical, nursing, and research staff at the study centers.