Corpus overview


MeSH Disease

Human Phenotype

There are no HP terms in the subcorpus


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    Antibody Testing SERO Documents the Silent Spread of SARS-CoV-2in New York Prior to the First Reported Case

    Authors: Kathrine Meyers; Lihong Liu; Wen-Hsuan Lin; Yang Luo; Michael Yin; Yumeng Wu; Sandeep Wontakal; Alex Rai; Francesca La Carpia; Sebastian Fernando; Mitra Dowlatshahi; Elad Elkayam; Ankur Garg; Leemor Joshua-Tor; John Wolk; Barbara Alpert; Marie-Laure Romney; Brianna Costabile; Edoardo Gelardi; Francesca Vallese; Oliver Clarke; Filippo Mancia; Anne-Catrin Uhlemann; Magdalena Sobieszczyk; Alan Perelson; Yaoxing Huang; Eldad Hod; David Ho

    doi:10.21203/ Date: 2020-07-02 Source: ResearchSquare

    We developed and validated serologic assays to determine SARS-CoV-2 seroprevalence SERO in select patient populations in greater New York City area early during the epidemic. We tested “discarded” serum samples SERO from February 24 to March 29 for antibodies SERO against SARS-CoV-2 spike trimer and nucleocapsid protein. Using known durations for antibody SERO development, incubation period TRANS, serial interval TRANS, and reproductive ratio for this pandemic, we determined that introduction of SARS-CoV-2 into New York likely occurred between January 23 and February 4, 2020. SARS-CoV-2 spread silently for 4–5 weeks before the first community acquired infection MESHD was reported. A novel coronavirus emerged in December 2019 in Wuhan, China1,2 and devasted Hubei Province in early 2020 before spreading to every province within China and nearly every country in the world3. This pathogen, now termed severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has caused a global pandemic, with ~ 10 million cases and over 500,000 deaths MESHD reported through June 30, 20203. The first case of SARS-CoV-2 infection MESHD in the United States was identified on January 19, 2020 in a man who returned to the State of Washington from Wuhan4. In the ensuing months, the U.S. has become a hotspot of the pandemic, presently accounting for almost one third of the total caseload and over one fourth of the deaths3. The first confirmed case TRANS in New York was reported on March 1 in a traveler recently returned from Iran. The first community-acquired SARS-CoV-2 infection MESHD was diagnosed on March 3 in a 50-year-old male TRANS who lived in New Rochelle and worked in New York City ( In the ensuing 18 weeks, New York City has suffered a peak daily infection number of ~ 4,500 (Fig. 1a) and a cumulative caseload of ~ 400,000 to date. The time period when SARS-CoV-2 gained entry into this epicenter of the pandemic remains unclear.

    Preliminary evaluation of the safety and efficacy of oral human antimicrobial peptide LL-37 in the treatment of patients of COVID-19, a small-scale, single-arm, exploratory safety study

    Authors: Hanlin Zhang; Yiming Zhao; Xiaoxiao Jiang; Yuying Zhao; Yang Li; Chen Li; Meng Dong; Zhe Luan; Chunlong Yan; Jianwei Jiao; Chaoyue Zhao; Hongyue Li; Wei Chen; Cong Feng; Le Tian; Enqiang Qin; Jinsong Mu; Congyong Li; Tianshu Zeng; Shibo Feng; Shufeng Wang; Xizhou Guan; Tanshi Li; Haotian Yu; Aihua Zheng; Wanzhu Jin; Gang Sun

    doi:10.1101/2020.05.11.20064584 Date: 2020-05-15 Source: medRxiv

    Background& Aims: The Coronavirus Disease MESHD 2019 (COVID-19) has become a global epidemic and has caused a lasting and huge loss of life security, economic development and social stability in more than 180 countries around the world. Unfortunately, there is still no specific treatment for COVID-19 till now, therefore, at this point, all potential therapies need to be critically considered. LL-37 is one of the best-studied human antimicrobial peptide (AMPs) that has a broad-spectrum activity against bacteria and viruses. The use of living, genetically modified organisms (GMOs) is an effective approach for delivery of therapeutic proteins. The aim of this study was to determine the safety and efficacy of the Lactococcus lactis which has been genetically modified to produce the therapeutic human antimicrobial peptide LL-37 (herein after referred to cas001) in the patients of COVID-19. Methods: Firstly we constructed genetically modified food-grade probiotic, Lactococcus lactis, with sequence of seven tandem repeats of mature human LL-37 under control of the nisin-inducible nisA promoter to produce the cas001. A total of 20 healthy SD rats, half male TRANS and half female TRANS (There were five male TRANS and five female TRANS in the control group, the same in treatment group) were used to observe the acute toxic reaction and death MESHD after daily administration of cas001 for three weeks, which helps to provide necessary reference basis for clinical dose selection, verificaition of toxic reaction and possible target organs. According to the estimated clinical dosage of 1 x 108CFU /kg/day, considering the conversion of body surface area, the dose for rats should be multiplied by 6.17 to 6 x 108 CFU/kg/day. We administrated 100 times higher dose at 6 x 1010 CFU/kg/day to rats. In order to investigate the pharmacokinetics of cas001, male TRANS SD rats (body weight 250-300g, 1 x 1010 /animal, n=3) were given oral administration of LL-37 bacteria powder. The concentration of LL-37 in the blood SERO before and after gavage was detected by ELISA SERO kit (Hycult biotechnology Cat# HK321). Human clinical study was approved by Ethics committee of Chinese PLA General Hospital (S2020-074-04) and a total of 11 patients with mild symptoms were enrolled in Wuhan hankou hospital and Huoshenshan hospital. They were enrolled voluntarily and all patients signed informed consent. Among them, there were 5 males TRANS and 6 females TRANS, aged TRANS 55 {+/-} 12 (36-70) years old, and the duration from onset to medication enrollment was 35 {+/-} 19 (5-68) days. 6 patients were nucleic acid positive and 5 patients were nucleic acid negative when they were enrolled. All patients received the oral drug cas001 treatment according to requirement(1 x 109 CFU/capsule, 3 capsules/time, three times a day for 3weeks), with an average follow-up time of 33 {+/-} 15 days (see table 1 for the results). Findings: Western blot analysis shows that reasonable amount of LL-37 were induced by different concentrations of nisin, which means we have successfully constructed cas001. In the pre-clinical safety evaluation test, after three weeks administration of cas001, no adverse effects were observed on the rat's body weight, food and water intake, hematological MESHD or serum SERO biochemical parameters. The results showed that the LD50 of cas001 was higher than that of the 100 times of the expected clinical dose of 6 x 1010 CFU/day. These results showed that cas001 could be safe in animal experiments. In addition, rat pharmacokinetics results showed that the serum SERO concentration of LL-37 reached peak 2 hours after gavage of cas001 and returned to basal level 6 hours after gavage. During study period, the volunteers did not feel any discomfort while taking the cas001 capsules, and two hours after oral administration, the concentration of LL-37 were increased in healthy volunteers. cas001 shows definite effect in the improvement of gastrointestinal symptoms MESHD and is possible to have effects in improving the systemic symptoms and respiratory symptoms and may play a role in the improvement of results of nucleic acid test and lung CT test. 11 patients enrolled showed good compliance, tolerance, subjective feeling and actively interacted with the doctors. None of the patients had any adverse reactions. Conclusions Based on above observations, we conclude here that as an oral anti-viral agent, cas001 displayed good safety profiles. It is very hard to reach conclusion of clinical outcomes related to the cas001, although changes of several symptoms indicate encouraging findings.

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MeSH Disease
Human Phenotype

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