Heightened COVID-19 Vaccine Response following SARS-CoV-2 Infection

BackgroundCurrent recommendations in the United States are that subjects with a previous history of COVID-19 disease receive the full 2 dose mRNA vaccine regimen. We tested the hypothesis that humoral immune responses and reactogenicity to a SARS-CoV-2 mRNA vaccine (BNT-162b2) differ qualitatively and quantitatively in subjects with prior SARS-CoV-2 infection versus infection-naive subjects. MethodsHealth care workers (n=61) from a single academic institution with and without prior COVID-19 received two 30 {micro}g doses of BNT162b2 vaccine 3 weeks apart. The COVID group (n=30) received vaccine approximately 7 months post infection. IgG antibody against the Spike receptor-binding domain (RBD), serum neutralizing activity and vaccine adverse reactions were assessed every 2 weeks for 56 days after the 1st injection. A longitudinal design and long study duration allowed the onset, maximum response and initial decay rate of Spike IgG antibody to be assessed in each subject. In addition, Spike IgG antibody levels are expressed as {micro}g / mL to provide normal values for clinical decision making. FindingsSpike IgG responses were highly variable in both groups. However, the COVID group manifested rapid increases in Spike IgG antibody and serum neutralizing activity post 1st vaccine dose but little or no increase in Spike IgG or serum neutralizing activity after the 2nd dose. In fact, Spike IgG was maximum prior to the 2nd dose in 36% of the COVID group and 0% of controls. Peak IgG antibody was lower but appeared to fall more slowly in the COVID than in the control group. Finally, adverse systemic reactions e.g., fever, headache and malaise, after both the 1st and 2nd injection were more frequent and lasted longer in the COVID group than in the control group. ConclusionsHealth care workers with prior COVID-19 demonstrate a robust, accelerated humoral immune response to the 1st dose of the COVID-19 mRNA vaccine but attenuated response to the 2nd dose. They also experience greater reactogenicity than controls. Accordingly, subjects with prior COVID-19 may require only a single dose of vaccine.

Utility of a Clinical Scoring System for Point of Care Triaging in COVID-19 Pneumonia

BackgroundSurges in COVID-19 disease cases can rapidly overwhelm healthcare resources; triaging to appropriate levels of care can assist in resource planning. At the beginning of the pandemic, we developed a simple triage tool, the Temple COVID-19 Pneumonia Triage Tool (TemCOV) based on a combination of clinical and radiographic features that are readily available on presentation to categorize and predict illness severity. MethodsWe prospectively examined 579 sequential cases admitted to Temple University Hospital who were assigned severity categories on admission. Our primary outcome was to compare the performance of TemCOV in predicting patients who have the highest likely of admission to the ICU at 24 and at 72 hours to other standard triage tools: the National Early Warning System (NEWS), the Modified Early Warning System (MEWS) and the CURB65 score. Additional endpoints included need for invasive mechanical ventilation (IMV) within 72 hours, total hospital admission charges, and mortality. Results26% of patients fell within our highest risk Category 4 and were more likely to require ICU admission at 24 hours (OR 11.51) and 72 hours (OR 8.6). Additionally they had the highest likelihood of needing IMV (OR 29.47) and in-hospital mortality (OR 2.37)., TemCOV performed similar to MEWS in predicting ICU admission at 24 hours (receive operator characteristic (ROC) curve area under the curve (AUC) 0.77 vs. 0.74, p=0.21) but better than NEWS2 and CURB65 (ROC AUC 0.77 vs. 0.69 and 0.77 vs. 0.64, respectively, p<0.01). While all severity scores had a weak correlation to hospital charges, the TemCOV performed the best among all severity scores measured (r=0.18); median hospital charges for Category 4 patients was $170,468 ($96,972-$487,556). ConclusionTemCOV is a simple triage score that can be used upon hospitalization in patients with COVID-19 that predicts the need for hospital resources such as ICU bed capacity, invasive mechanical ventilation and personnel staffing.

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation. METHODS: Retrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings. RESULTS: Out of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage. CONCLUSIONS: Lung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

ROX Index Predicts Intubation in Patients with COVID-19 Pneumonia and Moderate to Severe Hypoxemic Respiratory Failure Receiving High Flow Nasal Therapy.

Use of high flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concern for increased healthcare worker transmission and delays in invasive mechanical Ventilation (IMV). MethodsA retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to May 17, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). HFNT patients were divided into two groups: HFNT only and HFNT progressed to IMV. The primary outcome was the ability of the ROX index to predict the need of IMV. ResultsOf the 837 patients with COVID-19, 129 met inclusion criteria. The mean age was 60.8 ({+/-}13.6) years, BMI 32.6 ({+/-}8), 58 (45 %) were female, 72 (55.8%) were African American, 40 (31%) Hispanic. 48 (37.2%) were smokers. Mean time to intubation was 2.5 days ({+/-} 3.3). ROX index of less than 5 at HFNT initiation was predictive of progression to IMV (OR = 2.137, p = 0,052). Any decrease in ROX index after HFNT initiation was predictive of intubation (OR= 14.67, p <0.0001).{Delta} ROX (<=0 versus >0), peak D-dimer >4000 and admission GFR < 60 ml/min were very strongly predictive of need for IMV (ROC = 0.86, p=). Mortality was 11.2% in HFNT only group versus 47.5% in the HFNT progressed to IMV group (p,0.0001). Mortality and need for pulmonary vasodilators were higher in the HNFT progressed to IMV group. ConclusionROX index is a valuable, noninvasive tool to evaluate patients with moderate to severe hypoxemic respiratory failure in COVID-19 treated with HFNT. ROX helps predicts need for IMV and thus limiting morbidity and mortality associated with IMV.

High Resolution CHEST CT(HRCT) Evaluation in Patients Hospitalized with COVID-19 Infection

IntroductionCurrently the main diagnostic modality for COVID-19 (Coronavirus disease-2019) is reverse transcriptase polymerase chain reaction (RT-PCR) via nasopharyngeal swab which has high false negative rates. We evaluated the performance of high-resolution computed tomography (HRCT) imaging in the diagnosis of suspected COVID-19 infection compared to RT-PCR nasopharyngeal swab alone in patients hospitalized for suspected COVID-19 infection. MethodsThis was a retrospective analysis of 324 consecutive patients admitted to Temple University Hospital. All hospitalized patients who had RT-PCR testing and HRCT were included in the study. HRCTs were classified as Category 1, 2 or 3. Patients were then divided into four groups based on HRCT category and RT-PCR swab results for analysis. ResultsThe average age of patients was 59.4 ({+/-}15.2) years and 123 (38.9%) were female. Predominant ethnicity was African American 148 (46.11%). 161 patients tested positive by RT-PCR, while 41 tested positive by HRCT. 167 (52.02%) had category 1 scan, 63 (19.63%) had category 2 scan and 91 (28.35%) had category 3 HRCT scans. There was substantial agreement between our radiologists for HRCT classification ({kappa} = 0.64). Sensitivity and specificity of HRCT classification system was 77.6 and 73.7 respectively. Ferritin, LDH, AST and ALT were higher in Group 1 and D-dimers levels was higher in Group 3; differences however were not statistically significant. ConclusionDue to its high infectivity and asymptomatic transmission, until a highly sensitive and specific COVID-19 test is developed, HRCT should be incorporated into the assessment of patients who are hospitalized with suspected COVID-19. Key PointsO_ST_ABSKey QuestionC_ST_ABSCan High Resolution CT chest (HRCT) improve diagnostic accuracy of current Nasopharyngeal swab in suspected COVID-19 patients? Bottom LineIn this retrospective analysis, our novel HRCT classification identified 20% of all COVID-19 patients who had negative nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) tests but had HRCT findings consistent with COVID-19 pneumonia. These patients were ruled out for other infections and laboratory markers were similar to other RT-PCR positive patients Why Read onOur new HRCT classification when combined with RT-PCR can improve diagnostic accuracy while promptly improving triaging in COVID-19 patients.

Use of High Flow Nasal Therapy to Treat Moderate to Severe Hypoxemic Respiratory Failure in COVID-19

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of High flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission. MethodsThis was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to April 24, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). Primary outcome was prevention of intubation. ResultsOf the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 ({+/-}13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. SF and chest Xray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital/ventilator associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of VAP/HAP was statistically higher in the progressed to intubation group. ConclusionHFNT use is associated with a reduction in the rate of Invasive mechanical ventilation and overall mortality in patients with COVID-19 infection. Key PointsO_ST_ABSKey QuestionC_ST_ABSWhat is the utility of High Flow Nasal Therapy (HFNT) in COVID-19 related Hypoxemic Respiratory Failure? Bottom LineIn this retrospective analysis of moderate to severe hypoxic respiratory failure for COVID 19 patients, 67 patients (65.4%) were able to avoid intubation despite severely low SF ratio (Mean 121.9). Why Read onHFNT has a significant role in COVID-19 for reducing rate of intubations and associated mortality

Acute toxicity of potassium bichromate and 3,4-dichloroaniline in Chinese rare minnow (Gobiocypris rarus) / 中国实验动物学报

Objective and Methods As a local species, Chinese rare minnow (Gobiocypris rarus) has been one of the standardized test fish for chemical toxicity tests in China .By optimal screening , the acute toxicity of potassium bichromate and 3,4-dichloroaniline (3,4-DCA) was determined to evaluate repeatability and accuracy for Gobiocypris rarus in one laboratory and between different laboratories .Result Based on a proper data analysis , for the two chemicals per-formed with the same fish, all 96 h LC50 values were within mean ( x-) and upper and lower control limits ( ±2s) in both inner test ( in one laboratory ) and outer test ( between different laboratories ) .Conclusions From these results , a valid database could also be established to evaluate one single test .In addition, Gobiocypris rarus will not only be a potential test species for ecotoxicity tests , but also recommended as a standard laboratory animal .

In vitro studies of the effects of high-fat dieton the expression of pancreatic acinar cells' IP3 and amylase release in rats / 中国综合临床

Objective To investigate the effects of high-fat diet on pancreatic acinar cells' IP3 expression and CCK-induced amylase release in rats.Methods Male Wistar rats were divided into high-fat diet group and normal diet group,they were fed for 4 weeks.Blood triglycerides,cholesterol,amylase and glucose levels were determined by automatic biochemical analyzer.Pancreatic tissues were taken for histopathological observations.Pancreatic acinar cells were isolated and cultured,and intracellular inositol 1,4,5-trisphosphate (IP3) was detected using a commercial kit.Amylase release rates were measured after CCK-8 stimulation.Results The rats in high-fat diet group appeared hyperlipidemia,vacuolization of acinar cells and the lymphocytes appeared around the acinar cells can be seen on the pancreatic tissue pathology staining.The levels of IP3 in acinar cells of rats fed a high-fat diet were higher than that of normal rats [(31.807 ± 3.448) pmol/106 cells vs (24.632 ± 3.649) pmol/106 cells,t=7.479,P＜0.001];and amylase release rate in these rats'acinar cells were also higher than those of normal rats [when CCK-8=0.01 nmol/L:( 11.056 ±3.369)％ vs (7.354 ± 2.181) ％,t=3.912,P＜0.001;when CCK-8=1 nmol/L:( 13.854 ± 4.087 ) ％ vs (9.432 ±2.477) ％,t=3.939,P＜0.001 ) after CCK-8 stimulation in different concentrations.Additionally,there was a positive co-relationship between acinar cell's IP3 level and amylase release (r=0.896,P＜0.001 ).Conclusion Chronic high-fat diet induces hypersensitivity for pancreatic acinar cells' exocrine function,and IP3 as a signal molecule may play an important role in this process.