scholarly journals Pathogenic antibodies induced by spike proteins of COVID-19 and SARS-CoV viruses

2021 ◽  
Author(s):  
Huiru Wang ◽  
Qiuchi Chen ◽  
Yue Hu ◽  
Xiancong Wu ◽  
Lin Dai ◽  
...  
Keyword(s):  
Cytokine Release ◽  
Lung Epithelium ◽  
Highly Pathogenic ◽  
Neonatal Deaths ◽  
Still Births ◽  
Pregnant Mice ◽  
Pathogenic Antibodies ◽  
Epithelium Cells ◽  
Pathogenic Effects ◽  
Spike Proteins

Abstract This study, using a virus-free mouse model, explores the pathogenic roles of certain antibodies specific to the spike proteins of highly pathogenic coronaviruses such as the COVID-19 and the SARS-CoV viruses. Our data showed that these pathogenic antibodies, through a mechanism of Antibody Dependent Auto-Attack (ADAA), target and bind to host vulnerable cells or tissues such as damaged lung epithelium cells, initiate a self-attack immune response, and lead to serious conditions including ARDS, cytokine release, and death. Moreover, the pathogenic antibodies also induced inflammation and hemorrhage of the kidneys, brain, and heart. Furthermore, the pathogenic antibodies can bind to unmatured fetal tissues and cause abortions, postpartum labors, still births, and neonatal deaths of pregnant mice. Novel clinical interventions, through disrupting the host-binding of these pathogenic antibodies, can be developed to fight the COVID-19 pandemic. In addition, the new concept of ADAA explored by this study may be applicable to other infectious diseases, such as the highly pathogenic influenza infections. It should be noted that the majority of anti-spike antibodies are non-pathogenic, as only 2 of 7 monoclonal antibodies tested showed significant pathogenic effects.

scholarly journals Pathogenic antibodies induced by spike proteins of COVID-19 and SARS-CoV viruses

2021 ◽  
Author(s):  
Huiru Wang ◽  
Qiuchi Chen ◽  
Yue Hu ◽  
Xiancong Wu ◽  
Lin Dai ◽  
...  
Keyword(s):  
Immune Response ◽  
Lung Epithelium ◽  
Highly Pathogenic ◽  
Neonatal Deaths ◽  
Pregnant Females ◽  
Still Births ◽  
Pathogenic Antibodies ◽  
Epithelium Cells ◽  
Pathogenic Infection ◽  
Spike Proteins

Abstract This study, using a virus-free mouse model, explores the pathogenic roles and novel mechanism of action of certain antibodies specific to the spike proteins of highly pathogenic coronaviruses such as the COVID-19 and the SARS-CoV viruses. These pathogenic antibodies, induced during a highly pathogenic infection such as the COVID-19 infection, target and bind to host vulnerable cells or tissues such as damaged lung epithelium cells, initiate a persistent self-attack immune response, and lead to serious conditions including ARDS, cytokine storms, and death. Moreover, the pathogenic antibodies may also be responsible for infection-related autoimmune diseases, including those experienced by COVID-19 long haulers. Furthermore, the pathogenic antibodies can bind to the unmatured fetal tissues and cause abortions, postpartum labors, still births, and neonatal deaths of pregnant females. Novel clinical interventions, through disrupting the binding of these pathogenic antibodies, can be developed to fight the COVID-19 pandemic. In addition, the new concept explored by this study may be applicable to other infectious diseases, such as the highly pathogenic influenza infections.

scholarly journals A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines

2021 ◽  
Author(s):  
Huiru Wang ◽  
Xiancong Wu ◽  
Yuekai Zhang ◽  
Qiuchi Chen ◽  
Lin Dai ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Acid Methyl Ester ◽  
Drug Candidate ◽  
Lung Epithelium ◽  
Acetylneuraminic Acid ◽  
Excellent Safety Profile ◽  
Pathogenic Antibodies ◽  
Epithelium Cells ◽  
Unique Mechanism

In a previous study, we reported that certain anti-spike antibodies of COVID-19 and SARS-CoV viruses can have a pathogenic effect through binding to sick lung epithelium cells and misleading immune responses to attack self-cells. We termed this new pathogenic mechanism Antibody Dependent Auto-Attack (ADAA). This study explores a drug candidate for prevention and treatment of such ADAA-based diseases. The drug candidate is a formulation comprising N-acetylneuraminic acid methyl ester (NANA-Me), an analog of N-acetylneuraminic acid. NANA-Me acts through a unique mechanism of action (MOA) which is repairment of the missing sialic acid on sick lung epithelium cells. This MOA can block the antibody binding to sick cells, which are vulnerable to pathogenic antibodies. Our in vivo data showed that the formulation significantly reduced the sickness and deaths caused by pathogenic anti-spike antibodies. Therefore, the formulation has the potential to prevent and treat the serious conditions caused by pathogenic antibodies during a COVID-19 infection. In addition, the formulation has potential to prevent and treat the adverse reactions of COVID-19 vaccines because the vaccines can induce similar antibodies, including pathogenic antibodies. The formulation will be helpful in increasing the safety of the vaccines without reducing the vaccine efficacy. Compared to existing antiviral drugs, the formulation has a unique MOA of targeting receptors, broad spectrum of indications, excellent safety profile, resistance to mutations, and can be easily produced.

scholarly journals Evaluation of maternal and perinatal morbidity and mortality in eclampsia by early termination of pregnancy

2020 ◽  
Vol 8 (10) ◽  
pp. 3629
Author(s):  
Suresh C. Mondal ◽  
Sandip Lahiri
Keyword(s):  
Caesarean Section ◽  
Maternal Mortality ◽  
Termination Of Pregnancy ◽  
Early Termination ◽  
Early Presentation ◽  
Neonatal Deaths ◽  
Still Births ◽  
Significant Difference ◽  
Group A ◽  
Group B

 Background: Eclampsia is one of the leading causes of maternal mortality in India.Methods: A prospective observational study was done on 200 pregnant women admitted with antepartum eclampsia in Malda Medical College from 1 April 2017 to 30 October 2019. Group A included patients who delivered through vaginal route within 10 to 12 hrs of eclampsia by stabilisation of patients while Group B included subjects who underwent early caesarean section for uncontrolled convulsions or poor Bishop score. Maternal and perinatal outcomes were compared between the groups. Data was recorded in a pretested performa and was analyzed using appropriate statistical methods with SPSS.Results: Caesarean section (group B) was done in 130 cases (65%) while vaginal delivery (group A) was done in 65 cases (37.5%). Group A had higher maternal mortality (10.7%) in comparison to group B (4.6%) which was statistically not significant (p=0.1075). There were 32 neonatal deaths (24.6%) and 11 still births (8.46%) in group A while there were 12 neonatal deaths (18.46%) and 3 still births (4.61%) in group B. There was a statistically significant difference (p<0.0001) between the groups with respect to total perinatal deaths.Conclusions: Antenatal and intranatal eclampsia should be managed by early termination of pregnancy preferably with Caesarean section. Early presentation and timely decision to terminate pregnancy will improve the maternal and perinatal outcome.

scholarly journals Perinatal outcomes in abruptio placenta

2019 ◽  
Vol 8 (3) ◽  
pp. 1070
Author(s):  
Zenab Tambawaala ◽  
Deepali Kale
Keyword(s):  
Perinatal Mortality ◽  
Tertiary Care ◽  
Perinatal Outcomes ◽  
Obstetric Care ◽  
Care Hospital ◽  
Perinatal Morbidity ◽  
Abruptio Placentae ◽  
Neonatal Deaths ◽  
Still Births ◽  
Abruptio Placenta

Background: Abruptio placentae is an obstetric emergency where placenta completely or partially separates before delivery of the baby. It occurs approximately in one in 120 deliveries. It is an important cause of perinatal morbidity and mortality.Methods: This was a prospective hospital-based study design conducted over a period of 2 years, in the Department of Obstetrics and Gynecology at a tertiary care hospital in Mumbai comprising of 60 cases.Results: The incidence of abruption placentae in Present study is 0.51%. Authors had perinatal mortality in 6.6% of the cases. Out of 60 cases, 2 deaths occurred in utero. Out of the remaining 58 cases, 24 babies needed NICU care, out of them, 22 went home alive and 2 had neonatal deaths. Perinatal morbidity in the form of hyperbilirubinemia, CNS depression, septicemia, neonatal anemia and neonatal DIC were noted.Conclusions: High incidence of perinatal mortality in abruptio placentae is because of increased number of still births. In our studies, the perinatal mortality is 6.6% as compared to all other studies. This decline in perinatal mortality is due to improved obstetric care and excellent NICU facilities which are required for a majority of the cases.

scholarly journals Study of amniotic fluid index and its pregnancy outcome

2019 ◽  
Vol 8 (12) ◽  
pp. 4727
Author(s):  
Manisha M. Parmar ◽  
Sandeep M. Parmar
Keyword(s):  
Amniotic Fluid ◽  
Maternal Morbidity ◽  
Mode Of Delivery ◽  
Well Being ◽  
Perinatal Morbidity ◽  
Amniotic Fluid Index ◽  
Neonatal Deaths ◽  
Still Births ◽  
Tertiary Teaching ◽  
Nicu Admission

Background: Amniotic fluid is vital to the well-being of the fetus. Severe oligohydramnios and polyhydramnios are associated with increased maternal morbidity and perinatal morbidity and mortality.Methods: This was prospective observational study conducted at tertiary teaching institute from July 2012 to July 2013. Total 200 patients were included in the study. On the basis of amniotic fluid index (AFI), patients were categorized in 3 groups, Normal AFI (8-24 cm), oligohydramnios (AFI <5cm) and polyhydramnios (AFI > = 25 cm). Results were analysed in the form of incidence, mode of delivery and perinatal outcome which includes preterm, low birth weight, still births, NICU admissions and neonatal deaths in all the 3 groups.Results: Out of 200 patients, there was 150 cases of normal AFI, 39 cases of oligohydramnios and 11 cases of polyhydramnios. Incidence of oligohydramnios was 4.1% and polyhydramnios was 1.1%. PIH was the most common etiological factor found in oligohydramnios (30.7%) and in polyhydramnios congenital anomalies (36.3%) followed by idiopathic cause (27.2%) was most common. Incidence of caesarean section was 58.9% in oligohydarmnios and 17.3% in normal AFI group. Incidence of NICU admission was 25.6% in oligohydramnios and 50% in polyhydramnios group in comparison to 9.3% in normal AFI group.Conclusions: Amniotic fluid index is an important part of antepartum fetal surveillance. Abnormalities of AFI are associated with high perinatal morbidity and mortality and maternal morbidity.

Dendritic cells loaded with XAGE-1b protein induce specific antitumor response against lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18080-18080
Author(s):  
Q. Zhou ◽  
Y. L. Wu ◽  
A. L. Guo ◽  
K. Wang ◽  
C. R. Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Lymphocytes ◽  
Cancer Cells ◽  
Expression Vector ◽  
Normal Lung ◽  
Lung Epithelium ◽  
Cytotoxic Assay ◽  
Antitumor Response ◽  
Epithelium Cells

18080 Background: Dendritic cells (DCs) are the most potent antigen-presenting cells for initiating cellular immune response. Cancer-testis antigens (CTA) are the biggest tumor antigens family expressing only in some tumors and genital system but not in normal cells. XAGE-1b gene is one of CTA which highly expresses in lung cancer and has strong immunogenicity. Our study was to examine whether DCs loaded with XAGE-1b protein could induce specific antitumor response against lung cancer cells in vitro. Methods: Tumor tissues and normal lung tissues were obtained by operation from 30 non-small cell lung cancer patients. Cancer cells and normal lung epithelium cells were cultured and saved as target cells. Total RNA were isolated and RT-PCR was done to determine XAGE-1b gene expression. XAGE-1b gene was cloned by constructing expression vector and recombinant protein was expressed and purified by using BL21 (DE3) E. coli and AKTA-FPLC. Peripheral blood monocytes were isolated from 20ml blood and cultured to be DCs in serum-free DCs Medium. DCs were loaded with XAGE-1b protein through coculture and induced T lymphocytes into XAGE-1b-specific cytotoxic T lymphocytes (CTLs). The cytotoxicity of CTLs was then measured by cytotoxic assay. Results: 12/30(40%) lung cancer tissues expressed XAGE-1b gene, most of which were adenocarcinoma (11/12, 91.7%). None of normal tissues expressed it. Gene sequencing and western blot confirmed the expression vector construction and recombinant protein expression. Immunofluorescence identification showed the accumulation of XAGE-1b protein in immature DCs. T lymphocytes were stimulated twice with XAGE-1b protein-loaded DCs. Cytotoxic assay showed that the CTL cytotoxicity was much stronger for XAGE-1b positive tumor cells than for XAGE-1b negative tumor cells and it was almost none for normal lung epithelium cells. Conclusions: Our study indicates that DCs loaded with XAGE-1b protein could induce specific antitumor effect against lung cancer cells in vitro and this model offers a new approach to the immunotherapy for lung cancer. No significant financial relationships to disclose.

scholarly journals Fast and scalable lipid nanoparticle formulation of niclosamide (nano NCM) effectively inhibits SARS-CoV-2 replication in vitro

2020 ◽  
Author(s):  
Guankui Wang ◽  
Hanmant Gaikwad ◽  
Mary K McCarthy ◽  
Mercedes Gonzalez-Juarrero ◽  
Yue Li ◽  
...  
Keyword(s):  
Viral Replication ◽  
Essential Medicine ◽  
Cost Effective ◽  
World Health ◽  
Lung Epithelium ◽  
Antiviral Activities ◽  
Nanoparticle Formulation ◽  
Health Organization ◽  
Epithelium Cells

As exemplified by the COVID-19 pandemic, highly infective respiratory viruses can spread rapidly in the population because of lack of effective approaches to control viral replication and spread. Niclosamide (NCM) is an old anthelminthic drug (World Health Organization essential medicine list) with pleiotropic pharmacological activities. Several recent publications demonstrated that NCM has broad antiviral activities and potently inhibits viral replication, including replication of SARS-CoV-2, SARS-CoV, and dengue viruses. Unfortunately, NCM is almost completely insoluble in water, which limits its clinical use. We developed a highly scalable and cost-effective nanoparticle formulation of NCM (nano NCM) using only FDA-approved excipient and demonstrated potency against SARS-CoV-2 infection in cells (Vero E6 and ACE2-expressing lung epithelium cells). Our ultimate goal is to develop the nano NCM formulation for treatment of COVID-19 patients.

scholarly journals KEMATIAN PERINATAL DI BLU RSU PROF. DR. R. D. KANDOU MANADO

2013 ◽  
Vol 1 (1) ◽  
Author(s):  
Mercy Tumundo ◽  
Hermie Tendean ◽  
Eddy Suparman
Keyword(s):  
Mortality Rate ◽  
Perinatal Mortality ◽  
Perinatal Death ◽  
Developed Countries ◽  
Perinatal Deaths ◽  
Neonatal Deaths ◽  
Normal Birth ◽  
Perinatal Mortality Rate ◽  
Still Births ◽  
Early Neonatal Deaths

Abstract: Perinatal death is a big problem especially in a developing country. Some of the hospitals in Indonesia have declared that the number of perinatal death in developing countries is higher than in  developed countries. The purpose of this research is to determine the incidence of the factors that affecting perinatal mortality at Prof. DR. R. D. Kandou General Hospital Manado. This research used retrospective descriptive method through medical records of perinatal deaths patients. There were 164 cases of perinatal deaths found where 109 cases still births and 55 cases were early neonatal deaths in 2011, so the number of perinatal mortality rate was 40.17 per mil. The highest number of perinatal death was from multigravide mother, mother with age  ≥ 35 years old, spontaneous parturition. There were unknown caused of still births cases (77,06%) and sepsis in early neonatal deaths. The normal birth weight is also with most include of perinatal deaths. Keywords: still birth, early neonatal death, perinatal deaths, perinatal mortality rate.     Abstrak: Kematian perinatal merupakan masalah besar khususnya di negara sedang berkembang. Beberapa rumah sakit pendidikan di Indonesia melaporkan angka kematian perinatal yang tinggi dibandingkan dengan laporan angka kematian perinatal di negara – negara maju yang jumlahnya rendah. Tujuan penelitian untuk mengetahui angka kejadian kematian perinatal serta faktor – faktor yang mempengaruhinya. Penelitian ini menggunakan metode deskriptif retrospektif dengan menggunakan data catatan medik pasien. Hasil penelitian yaitu jumlah kematian perinatal pada tahun 2011 sebanyak 164 kasus dengan 109 kasus lahir mati dan 55 kasus kematian neonatal dini sehingga angka kematian perinatal pada tahun 2011 yaitu 40.17 per mil. Kematian perinatal paling banyak pada ibu multigravida, ibu dengan kelompok usia ≥ 35 tahun, menggunakan jenis persalinan spontan. Pada lahir mati 77.06 % penyebab kematiannya tidak diketahui sedangkan sepsis paling banyak menyebabkan kematian neonatal dini. Berat badan lahir normal juga menjadi salah satu faktor terjadinya kematian perinatal. Kata kunci: lahir mati, kematian neonatal dini, kematian perinatal, angka kematian perinatal.

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