Immunopathogenesis of patients with COVID-19: from the perspective of immune system 'evolution' and 'revolution'.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system 'evolution' as well as 'revolution' that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.

Exploring the Immunopathogenesis of Pregnancy With COVID-19 at the Vaccination Era.

Since December 2019, Wuhan, China, has experienced an outbreak of coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pregnant women are deductively considered to be in immunosuppressive condition for the safety of semi-allograft fetuses, which increases the risk of being infected by the virus. In this review, we analyzed the unique immunological characteristics of pregnant women and reviewed their known outcomes at different trimesters from the perspective of underlying mechanisms that have been studied and speculated so far.

Molecular evidence suggesting the persistence of residual SARS-CoV-2 and immune responses in the placentas of pregnant patients recovered from COVID-19.

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.

COVID-19 and Pregnancy: A Case Study.

The 2019 novel coronavirus disease is spreading all over the world. Pregnant women and infants require particular concern, owing to the special immune conditions. A case of a pregnant woman who was exposed to SARS-CoV-2 at 34+1 weeks gestation and chose to continue pregnancy is reported. Without obvious symptoms or signs, the woman did not receive any treatment before delivery, and gave birth at 37+5 weeks to a neonate with positive immunoglobulin G for SARS-CoV-2 and negative nucleic acid tests. The mother was given anti-infection, oxytocin, and fluid rehydration treatment after delivery. Both mother and infant recovered well after a three-month follow-up. Continued expectation to deliver at term instead of preterm can decrease the potential risk of severe perinatal and infant complications and is beneficial to the development of the neonate. More studies are required to confirm the presence of vertical transmission.

Clinical Characteristics and Outcomes of Childbearing-Age Women With COVID-19 in Wuhan: Retrospective, Single-Center Study.

BACKGROUND: Since December 2019, an outbreak of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly in Wuhan and worldwide. However, previous studies on pregnant patients were limited. OBJECTIVE: The aim of this study is to evaluate the clinical characteristics and outcomes of pregnant and nonpregnant women with COVID-19. METHODS: This study retrospectively collected epidemiological, clinical, laboratory, imaging, management, and outcome data of 43 childbearing-age women patients (including 17 pregnant and 26 nonpregnant patients) who presented with laboratory-confirmed COVID-19 in Tongji Hospital, Wuhan, China from January 19 to March 2, 2020. Clinical outcomes were followed up to March 28, 2020. RESULTS: Of the 43 childbearing-age women in this study, none developed a severe adverse illness or died. The median ages of pregnant and nonpregnant women were 33.0 and 33.5 years, respectively. Pregnant women had a markedly higher proportion of history exposure to hospitals within 2 weeks before onset compared to nonpregnant women (9/17, 53% vs 5/26, 19%, P=.02) and a lower proportion of other family members affected (4/17, 24% vs 19/26, 73%, P=.004). Fever (8/17, 47% vs 18/26, 69%) and cough (9/17, 53% vs 12/26, 46%) were common onsets of symptoms for the two groups. Abdominal pain (n=4, 24%), vaginal bleeding (n=1, 6%), reduced fetal movement (n=1, 6%), and increased fetal movement (n=2, 13%) were observed at onset in the 17 pregnant patients. Higher neutrophil and lower lymphocyte percent were observed in the pregnant group compared to the nonpregnant group (79% vs 56%, P<.001; 15% vs 33%, P<.001, respectively). In both groups, we observed an elevated concentration of high-sensitivity C-reactive protein, erythrocyte sedimentation rate, aminotransferase, and lactate dehydrogenase. Concentrations of alkaline phosphatase and D-dimer in the pregnant group were significantly higher than those of the nonpregnant group (119.0 vs 48.0 U/L, P<.001; 2.1 vs 0.3µg/mL, P<.001, respectively). Both pregnant (4/10, 40%) and nonpregnant (8/15, 53%) women tested positive for influenza A virus. A majority of pregnant and nonpregnant groups received antiviral (13/17, 76% vs 25/26, 96%) and antibiotic (13/17, 76% vs 23/26, 88%) therapy. Additionally, both pregnant (2/11, 18%) and nonpregnant (2/19, 11%) recovered women redetected positive for SARS-CoV-2 after discharge. CONCLUSIONS: The epidemiology and clinical and laboratory features of pregnant women with COVID-19 were diverse and atypical, which increased the difficulty of diagnosis. Most pregnant women with COVID-19 were mild and moderate, and rarely developed severe pneumonia or severe adverse outcomes.

Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital, China.

Based on the New Diagnosis and Treatment Scheme for Novel Coronavirus Infected Pneumonia (Trial Edition 5), combined with our current clinical treatment experience, we recently proposed a revision of the first edition of "Guidance for maternal and fetal management during pneumonia epidemics of novel coronavirus infection in the Wuhan Tongji Hospital". This article focused on the issues of greatest concern of pregnant women including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnostic criteria, inspection precautions, drug treatment options, indications and methods of termination of pregnancy, postpartum fever, breastfeeding considerations, mode of mother-to-child transmission, neonatal isolation and advice on neonatal nursing, to provide valuable experience for better management of SARS-CoV-2 infection in pregnant women and newborns.

Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study.

BACKGROUND: In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19. METHODS: In this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed. FINDINGS: Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29-34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of follow-up was Feb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth. INTERPRETATION: The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature. FUNDING: National Natural Science Foundation of China, Hubei Provincial Natural Science Foundation of China.