The in vitro and in vivo potency of CT-P59 against Delta and its associated variants of SARS-CoV-2

The Delta variant originally from India is rapidly spreading across the world and causes to resurge infections of SARS-CoV-2. We previously reported that CT-P59 presented its in vivo potency against Beta and Gamma variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on the Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal study. CT-P59 showed reduced antiviral activity but enabled neutralization against Delta, Epsilon, and Kappa variants in cells. In line with in vitro results, the mouse challenge experiment with the Delta variant substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against the Delta variant infection, hinting that CT-P59 has therapeutic potency for patients infected with Delta and its associated variants. HighlightsO_LICT-P59 exerts the antiviral effect on authentic Delta, Epsilon and Kappa variants in cell-based experiments. C_LIO_LICT-P59 showed neutralizing potency against variants including Delta, Epsilon, Kappa, L452R, T478K and P681H pseudovirus variants. C_LIO_LIThe administration of clinically relevant dose of CT-P59 showed in vivo C_LIO_LIprotection against Delta variants in animal challenge experiment. C_LI

Therapeutic efficacy of CT-P59 against P.1 variant of SARS-CoV-2

P.1. or gamma variant also known as the Brazil variant, is one of the variants of concern (VOC) which appears to have high transmissibility and mortality. To explore the potency of the CT-P59 monoclonal antibody against P.1 variant, we tried to conduct binding affinity, in vitro neutralization, and in vivo animal tests. In in vitro assays revealed that CT-P59 is able to neutralize P.1 variant in spite of reduction in its binding affinity against a RBD (receptor binding domain) mutant protein including K417T/E484K/N501Y and neutralizing activity against P.1 pseudoviruses and live viruses. In contrast, in vivo hACE2 (human angiotensin-converting enzyme 2)-expressing TG (transgenic) mouse challenge experiment demonstrated that a clinically relevant or lower dosages of CT-P59 is capable of lowering viral loads in the respiratory tract and alleviates symptoms such as body weight losses and survival rates. Therefore, a clinical dosage of CT-P59 could compensate for reduced in vitro antiviral activity in P.1-infected mice, implying that CT-P59 has therapeutic potency for COVID-19 patients infected with P.1 variant. HighlightsO_LICT-P59 could bind to and neutralize P.1 variant, but CT-P59 showed reduced susceptibility in in vitro tests. C_LIO_LIThe clinical dosage of CT-P59 demonstrated in vivo therapeutic potency against P.1 variants in hACE2-expressing mice challenge study. C_LIO_LICT-P59 ameliorates their body weight loss and prevents the lethality in P.1 variant-infected mice. C_LI

Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant. HighlightsO_LICT-P59 significantly inhibit B.1.1.7 variant to a similar extent as to wild type virus C_LIO_LICT-P59 showed reduced potency against the B.1.351 variant in in vitro studies C_LIO_LITherapeutic dosage of CT-P59 showed in vivo neutralizing potency against B.1.351 in ferret challenge study. C_LI

Clinical Study of Foreign Body Aspiration in Infants and Children

A clinical study was done on 42 cases of inpatients, who had been admitted for foreign body aspiration form January 1979 to June 1992. We obtained the following results by analysing the records of their treatment during that time. 1) 31(73.8%) of these cases were below the age of 3 years. 25(59.4%) were below the age of 2. The ratio of male to female was 2:1 2) In 23 cases(54.8%) onset of the symptoms and diagnosis was less than 24 hours after aspiration. 3) Most of the cases(83.3%) had a history of foreign body aspiration; 7 other cases did not. 4) The most common symptoms of bronchial foreign bodies were cough, dyspnea and fever, whereas those of laryngotracheal foreign bodies were dyspnea and cough, in that order. 5) Common complications were obstructive emphysema, pneumonia and atelectasis, in that order. These complications were observed more frequently in the cases of vegetable foreign bodies. 6) Chest X-ray at the time of admission showed obstructive emphysema (42.9%) and pneumonia(40.5%). 11 cases(26.2%) were normal. 7) The most comon site of foreign body enlodgement was the right main bronchus(38.1%), and 4 cases(9.5%) were discovered in other bronchial sites. 8) Vegetable foreign bodies occupied 54.8% of the cases, peanuts being the most common.

Diagnostic Value and Relationship of the between Stable Microbubble Rating Test and Shake Test for the Prediction of Neonatal Respiratory Distress Syndrome

Respiratory distress syndrome (RDS) in the newborn infants remains a major cause of mortality and morbidity in the newborn period despite much improvements in neonatal intensive care and artificial ventilatory techniques. Gastric fluid was obtained from 151 patients within 6 hours after delivery. The sensitivity, specificity, and predictive value of the simple shake test (133 cases) and stable microbubble rating (SMR) test (151 cases) were assessed in the diagnosis of RDS, as well as the relation between both tests and RDS. We carried out both tests of on gastric aspirates all newborn who admitted to NICU of Presbyterian Medical Center from June 1991 to August 1992. The results were summarized as follows: 1) Among the total 151 cases, RDS were found in 41 cases(27.2%). 2) RDS occurence rate of the simple shake test was 11/11 in 0 group, 17/26 in +1 group, 8/28 in +2 group, 2/41 in +3 group, and 2/27 in +4 group. RDS occurence rate was high the 0 and +1 group. 3) RDS occurence rate of the SMR test was 4/4 in very weak group, 32/36 in weak group, 1/33 in medium group, and 4/78 in strong group. RDS occurence rate was high in the very weak and weak group. 4) Among the positive group of the SMR test 95 cases, positive group of the shake test were found in 87 cases. Among negative group of the SMR test 38 cases, negative of the shake test were found in 29 cases (correlation coefficient=0.763). 5) Sensitivity of the shake test and SMR test were 70%, 87.8% respectively. Specificity of the shake test and SMR test were 93.3%, 96.4% respectively. Positive predictability were 75.7%, 90% respectively and negative predictability were 87.5%, 95.5% respectively. The shake test, as Well as SMR test, has significant value to diagnosis of the RDS. We predict RDS occurence rate of the SMR test was significantly higher than shake test.

Neurosonographic diagnosis of periventricular-intraventricular hemorrhage in low birth weight infants

Periventricular-intraventricular hemorrhage (PV-IVH)is one of the most important neurologic lesion of the low birth weight infants. Serial neurosonographic exeaminations were performed in 113 low birth weight infants who were admitted to the neonatal intensive care unit of Presbyterian Medical Center from November 1, 1990to July 31, 1991. The results were summarized as follows: 1) The incidence of PV-IVH in the study was 54% 2) According to Papile's grading system of PV-IVH, grade I was 32.8%, grade II was 45.9%, grade IIIwas 11.5% and grade IV was 9.8%. 3) The onset of PV-IVH was within the first 7 days of life in 82%. 4) Poor activity, apnea, bradycardia and hypotension were statistically significant clinical findings associated with PV-IVH(P<0.05). 5) The risk factors associated with PV-IVH were gestational age, birth weight, hyaling membrane disease, patent ductus arteriosus and artifical ventilation. 6) The mortality of PV-IVH was 0% for grade I, 10.7% for grade II,42.9% for grade III and 83.3% for gradeIV.