Severe Type Patients Research Articles

The Correlation of Muscle Mass and Walking Distance with Joint Health and Functional Status in Hemophilic Arthropathy Among People with Hemophilia a (PwHA)

Introduction: Hemophilic arthropathy resulting from repeat joint bleeding is a common complication for people with hemophilia (PWH), despite the current prophylaxis therapy. Monitoring the status of musculoskeletal health for PWH is necessary. Muscle plays a critical role in maintaining and promoting the joint health. Muscle atrophy is one of the key features of haemophilic arthropathy. Up to date, there are more studies focusing on joint health of PWH but few having attention on the impact of limbs muscles on joint status of PWH. Clinical assessments such as muscle circumference and manual muscle strength tests fail to detect subtle muscle changes. The study aimed to evaluate the ultrasound measurement of muscle thickness in people with hemophilia A (PwHA) and its correlation to joint health and functional impairments. Methods and Materials: In the observational cross-sectional study, 29 PwHA (median age 35 years; range 13-63) were enrolled, including 27 severe-type diseases on prophylaxis therapy and 2 moderate-type diseases on episodic treatment. Muscle thickness of quadriceps and medial gastrocnemius were measured by ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), Haemophilia Quality of Life Questionnaire for Adults (Haemo-A-QoL), and Haemophilia Activities List (HAL). 6-Minute Walking Test (6MWT) for global functional evaluation. Results: At the time when the 29 patients receiving this survey of joint health, there were 28 on rFVIIIFc treatment for an average of 31.2 months (mean: 33.5, range 19.5－43), among whom 26 severe-type patients had rFVIIIFc prophylaxis and 2 moderate-type patients had on-demand therapy with rFVIIIFc. Only one severe-type patient had received non-rFVIIFc product prophylaxis for > 3 years. Totally 174 joints were examined. By correlation analysis, a significant correlation was found between both quadriceps and calf muscle thickness and the HJHS knee and ankle scores, respectively, with a negative correlation ( r= -0.45, p=0.015*, right quadriceps; r= -0.60, p<0.001***, left quadriceps; r= -0.39, p=0.039*, right calf; r= -0.58, p<0.001***, left calf). A significant correlation between muscle thickness and HEAD-US was observed between quadriceps muscle and knee score, with a negative correlation ( r= -0.56, p=0.017*, right quadriceps; r= -0.36, p=0.0048**, left quadriceps). Therefore, Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was significantly associated with the HJHS ankle. Muscle thickness was also observed to correlate with Haem-A-QoL and HAL. 6MWT was found to significantly correlated with HJHS total, HEAD-US total, Haem-A-QoL, and HAL ( r= -0.42, p=0.0231*, HJHS; r= -0.52, p=0.0037**, HEAD-US; r= -0.60, p<0.0001***, Haem-A-QoL; r= 0.64, p<0.001***, HAL). Conclusion: For the first time, limbs muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PwHA. Ultrasound measurement of muscle thickness appears to be a reliable tool for the assessment of muscle mass in PwHA.The 6MWT also appears to be useful tool for assessment of physical capacity and endurance in PwHA. Disclosures: No relevant conflicts of interest to declare.

Dynamic Characteristics of Blood Platelet Count in COVID-19 Patients

Background and purpose: Coronavirus disease 2019 (COVID-19) was spreading all over the world. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) primarily invades and infects the lungs of humans leading to COVID-19. Mild to severe clinical symptoms such as fever, cough, and shortness of breath were existed in those patients. One of the most common changes in these patients was abnormal blood routine. However, uncertainty remains regarding the dynamic characteristics of platelet in COVID-19 patients due to limited data. Therefore, we aimed to analyze the association between dynamic characteristics of blood platelet and disease severity, and to identify new monitoring indicators to treat the COVID-19 patients. Methods: In this cohort study, 398 COVID-19 patients treated in the Shenzhen Third People’s hospital from December 16, 2019 to March 26, 2020 were collected and participated. All data of participants including the clinical characteristics, imaging and laboratory information were collected. All patients included in our study were classified as four groups (mild, common, severe, and critical types) regarding clinical symptoms and relevant severe failures based on the Diagnosis Criteria. Platelet count was examined at the baseline and every 3–5 days during hospitalization. Results: The platelet count varied with clinical classifications. The platelet count in mild type was normal without significant fluctuation. While the blood platelet count of most common and severe patients had obvious fluctuations, showing as a dynamic change that first rose and then fell to the level at admission, which was consistent with the trend of lung inflammation. Bone marrow smears further showed that bone marrow hyperplasia was normal in mild, common and severe type patients, and megakaryocytes and their platelet-producing functions were not abnormal. Conclusions: Our results suggested that the dynamic changes of platelet count might be a predictor of lung inflammation alteration for COVID-19 patients. The changes in platelet count might be a responsive pattern secondary to lung inflammation. The function of bone marrow may be slightly affected by SARS-CoV-2 infection.

The Investigation of Pulmonary Function Changes of COVID-19 Patients in Three Months.

Background Novel coronavirus disease 2019 (COVID-19) was discovered in December 2019 and has infected more than 80 million people worldwide, and more than 50 million people have achieved a clinical cure. In this study, the pulmonary function results of patients after clinical medicine for three months were reported. Objective To investigate the effect of COVID-19 on lung function in patients. Methods A retrospective analysis was performed on 56 COVID-19-infected patients who were cured after the clinical treatment at Taizhou Public Health Medical Center in Zhejiang Province from January 31, 2020, to March 10, 2020. At discharge and three months after discharge, lung function was measured, including inspiratory vital capacity (IVC), forced vital capacity (FVC), forced expiratory volume in first second (FEV1), forced expiratory volume in first second to inspiratory vital capacity (FEV1/IVC), maximum mid-expiratory flow rate (MEF), peak expiratory flow rate (PEF), and carbon monoxide dispersion (DLCO). Results At discharge, there were 37 patients (66.1%) with pulmonary dysfunction, 22 patients (39.3%) with ventilation dysfunction, 31 cases (55.4%) with small airway dysfunction, and 16 cases (28.6%) with restricted ventilation dysfunction combined with small airway dysfunction. At 3 months after discharge, 24 of the 56 patients still had pulmonary dysfunction and all of them had small airway dysfunction, of which 10 patients (17.9%) were restricted ventilation dysfunction combined with small airway dysfunction. DLCO was measured three months after discharge. Twenty-nine patients (51.8%) had mild to moderate diffuse dysfunction. All pulmonary function indexes of 56 patients recovered gradually after 3 months after release, except FEV1/IVC, and the difference was statistically significant (P < 0.05). There were 41 patients of normal type (73.2%) and 15 patients of severe type (26.8%). Among the 15 severe patients, 8 patients (53.3%) had ventilation dysfunction at discharge, 9 patients (60%) had small airway dysfunction, 4 patients (26.7%) still had ventilation dysfunction 3 months after discharge, 7 patients (46.7%) had small airway dysfunction, and 10 patients (66.7%) had diffuse dysfunction. Among the 41 common type patients, 14 patients (34.1%) had ventilation dysfunction at discharge, 22 patients (53.7%) had small airway dysfunction, 6 patients (14.6%) still had ventilation dysfunction 3 months after discharge, 17 patients (41.5%) had small airway dysfunction, and 19 patients (46.3%) had diffuse dysfunction. Patients with severe COVID-19 had more pulmonary impairment and improved pulmonary function than normal patients. Conclusion COVID-19 infection can cause lung function impairment, manifested as restricted ventilation dysfunction, small airway dysfunction, and diffuse dysfunction. The pulmonary function of most patients was improved 3 months after clinical cure and discharge, and some patients remained with mild to moderate diffuse dysfunction and small airway dysfunction.

Meta-Analysis of D-Dimer, hsCRP and Cytokines in COVID-19 Severe/Critical Patients in China

Objective: To analyze the relationship between D-dimer, inflammatory markers, cytokines and disease severity, and the possibility of early identification of COVID-19 critical type patients. Methods: PubMed, EMBASE and CNKI databases were searched by computer, and references of related reviews and systematic reviews were manually searched as supplements. The retrieval deadline is February 9, 2021. According to the inclusion and exclusion criteria, the literatures were screened and the quality was evaluated, and then the data were extracted for meta-analysis. The fixed/random effects model was used to calculate the weighted mean difference (WMD) and 95% CI to evaluate whether the levels of D-dimer, hsCRP, IL-6, IL-8, IL-10 and TNF-α in critical type patients were statistically different from those in severe type patients. If there were statistical differences, logistic regression analysis was used, and establish the receiver operating characteristic curve (ROC) and area under the curve (AUC) of each index for the diagnosis of critical type patients. The best diagnostic value of COVID-19 critical type patients was calculated by Youden index. Results: A total of 3519 literatures entered the screening process. According to the inclusion and exclusion criteria, 40 articles were finally included in this study, and all of them were high-quality studies after evaluation. The results of meta-analysis showed that the levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in critical type group were significantly higher than those in severe type group (P<0.05). Based on ROC curve, the AUC of D-dimer was 0.785 (95% CI: 0.671-0.899), AUC of hsCRP was 0.884 (95% CI: 0.632-1.000), AUC of IL-6 was 0.819 (95% CI: 0.700-0.939), which had diagnostic significance for critical type patients (P<0.05). The optimal diagnostic threshold of D-dimer was ≥2.00 mg/L (sensitivity 89.3%, specificity 64.0%); the optimal diagnostic threshold of hsCRP was ≥64.22 mg/L (sensitivity 75.0%, specificity 100%); the optimal diagnostic threshold of IL-6 was ≥33.01 ng/L (sensitivity 68.0%, specificity 92.0%). Conclusion: The levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in COVID-19 critical type patients were significantly higher than those in severe type patients. Our results might be helpful in identify and risk reduction of mortality in critical types patients infected with COVID-19. DisclosuresNo relevant conflicts of interest to declare.

Clinical Predictors and Prediction Models for Frequency of Total and Joint Hemorrhage in Severe-Type Patients with Hemophilia a (PwHA) with/without Intermediate-Dose Prophylaxis Therapy with rFVIII

Introduction: It was well-known that severe-type patients with hemophilia A (PwHA) had great variability in bleeding phenotypes. Factors effecting bleeding patterns of PwHA include at least treatment modality and interindividual various procoagulant and anticoagulant levels. We aimed to investigate what clinical variables could predict bleeding frequency of severe PwHA and to develop models for predicting bleeding phenotypes among severe PwHA with/without FVIII prophylaxis therapy.Methods and materials: Totally 51 severe-type previously-treated PwHA from two Hemophilia Centers in Taiwan were enrolled, who received standard half life (SHL) rFVIII products with complete consecutive bleeding records at least more than 6 months, and their medical charts 2017－2018 were retrospectively viewed. The clinical data were collected for analysis, including age, body mass index (BMI), body weight (BW), ABO blood groups, hemoglobin (Hb), hematocrit (Hct), HCV infecton, HIV infection, treatment modality, baseline VWF levels, and genetic defects. Baseline VWF activity meant the data via VWF:ACL activity or VWF:RCo. Clinical variables for annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were evaluated by multivariate linear regression (MVLR) analysis.Results: The cohort of 51 severe-type PwHA included 8 boys and 43 adults, aged 8-64. For treatment modality, there were 19 patients receiving episodic treatment (ET) and 32 receiving prophylaxis therapy (PT) with intermediate-dose standard half life (SHL) rFVIII. The mean study period was 11.9 months, range 10－14.5 months. Among them, there were 31 with HCV infection and 4 with HIV infection. PwHA with non-O blood group were 31 and those with O blood group 20. The mean baseline VWF:Ag was 115.6±55.5%, range 50%－294.7%. The mean baseline VWF:activity was 105.4±52.1%, range 41.3%－307%. ABR of ET group and PT group were 46.1±29.2 and 6.8±7.1, respectively. (p<0.0001***) AJBR of ET group and PT group were 37.3±27.7 and 6.0±6.8, respectively. (p=0.0001***) By MVLR analysis, both treatment modality and baseline VWF:Ag were recognized as inverse predictors of ABR and AJBR, and HCV infection recognized a predictor for AJBR. Age, inhibitor histroy, BMI, BW, ABO blood groups, Hct, Hb, HIV infection, and missense mutation or not were eliminated as predictors. The predictive equations by MVLR were as the following two:(1) Predictive ABR = 56.5 - 37.8 * (Treatment model) - 11.8 * baseline VWF:Ag (IU/mL).(2) Predictive e AJBR = 41.9 - 28.6 * (Treatment model) - 12.0 * baseline VWF:Ag (IU/mL) + 10.0 * (HCV infection).(1 if Treatment model is PT, 0 if Treatment model is ET. 1 if HCV infection or anti-HCV antibody is positive, 0 if HCV infection or HCV antibody is negative.) Separate prediction models developed from MVLR analysis could explain 52.51% of the ABR variability and 50.56% of the AJBR variability. The correlation between predicted and observed bleeding frequency was significantly strong.(P-rank>0.7, p-value<0.0001***) Mean difference between predicted ABRs and observed ABRs was 1.75 and that between predicted AJBRs and observed AJBRs was 1.27. Predicted ABR deviated <21 (<2 per month) of observed ABR in 42/50 patients (84%). Predicted AJBR deviated < 24 (<2 per month) ofobserved AJBR in 44/50 patients (88%).Conclusion: Prophylaxis therapy and baseline VWF:Ag levels were the strongest two inverse predictors for ABR and AJBR. Positive HCV infection was another predictor for AJBR. The prediction models provided with an insight into personal bleeding quantified patterns and may identify PwHA with high bleeding risks based on individual characteristics of treatment modality, baseline VWF:Ag, and HCV infection. Our approach is of help for individualized treatment and refining of dosing strategies. DisclosuresNo relevant conflicts of interest to declare.

Real-World Bleeding Outcomes, Weekly Factor Consumption Doses, Annualized Factor Costs in Severe-Type Patients with Hemophilia a (PwHA) before and after Switching to Extended Half-Life rFVIII-Fc Prophylaxis

Introduction: Stand half-life (SHL) rFVIII had been used in patients with hemophilia A (PwHA) for episodic treatment (ET) and prophylaxis therapy (PT) for years. Extended half-life (EHL) rFVIII had been available since 2014, also available in Taiwan since 2018, and resulted in markedly increased willingness for PT because it reduced injection burden. We aimed to investigate the real-world bleeding outcomes, weekly factor doses, and factor costs of severe-type PwHA with pre-switch SHL rFVIII and post-switch EHL rFVIIIFc prophylaxis in Taiwan, and made a pre-switch and post-switch comparison.Methods and Materials: There were totally 51 non-inhibitor, severe-type PwHA, with complete bleeding records before and after switching from SHL rFVIII to EHL rFVIII-Fc, enrolled from two hemophilia centers during Nov, 2018－July, 2019. Most of them had various degree of one to more major joints arthropathy, except children. The medical charts were retrospective reviewed and data were collected, including body features and factor regimen, etc. Patients' annualized bleeding/joint-bleeding rate (ABR/AJBR), weekly doses (WD), annualized factor costs (AFC) were obtained from the chart records of pre-switch 12 months and post-switch at least more-than 6-month until July, 2019. Data from scheduled operation or hospitalization due to trauma or accidence were excluded.Results: There were 8 boys and 43 adults, the median age of all PwHA when switching was 35.6 years (10.5-62). Before switching, these 51 PTP treated with SHL rFVIII who received ET (ET group), irregular prophylaxis (IP group), and regular prophylaxis (RP group) were 19 (37.3%), 7 (13.7%), and 25 (49%), respectively. Bleeding records of 51 PTP treated with SHL rFVIII were traced back with 11.8±0.9 months. After switching to rFVIII-Fc, 3 PwHA receiving ET were excluded, and bleeding records of 48 received RP were obtained with 14.7±4.6 months. Pre-switch and post-switch prophylaxis rate were 62.7% (32/51) and 94.1% (48/51), respectively. For comparison of pre-switch and post-switch outcomes: Median ABR was reduced from 48, 12, and 4 to 1.15, 1.9, and 1.5 for ET, IP, and RP group, respectively. Median AJBR was reduced from 32, 11, and 4 to 0.95, 0.7, and 1.2 for ET, IP, and RP group, respectively. Median WD was increased from 38.4, 52.9, and 63.6 IU/kg/wk to 84.6, 84.5, and 84.9 IU/kg/wk for ET, IP, and RP group, respectively. Median AFC was increased from 4,141,800, 4,064,000 and 5,129,700 NTD to 7,042,325, 5,835,450, and 5,762,810 NTD for ET, IP, and RP group, respectively. Comparing pre-switch and post-switch outcomes of children and adults who received pre-switch and post-switch prophylaxis, median ABR was reduced from 3 and 5 to 1.35 and 1.85 for children and adults, respectively. Median AJBR was reduced from 3 and 4 to 1.35 and 1.15 for children and adults, respectively. Median WD was increased from 58.8 and 58.3 IU/kg/wk to 87.85 and 83.85 IU/kg/wk for children and adults, respectively. Median AFC was increased from 4,104,225 and 5,879,025 NTD to 4,419,800 and 6,024,916 NTD for children and adults, respectively. For all PwHA, zero ABR accounted for 5.9% (3/51) with pre-switch SHL rFVIII treatment and for 20.8% (10/48) with post-switch rFVIII-Fc prophylaxis. Zero AJBR accounted for 9.8% (5/51) with SHL rFVIII treatment and for 33.3% (16/48) with rFVIII-Fc prophylaxis. For PwHA with pre- and post-switch prophylaxis, zero ABR accounted for 12.5% (1/8) and 8.3% (2/24), respectively, for children and adults on SHL rFVIII prophylaxis and 25% (2/8) and 25% (6/24) respectively, for children and adults on rFVIII-Fc prophylaxis. Zero AJBR accounted for 12.5% (1/8) and 16.7% (4/24), respectively, for children and adults on SHL rFVIII prophylaxis and 25% (2/8) and 37.5% (9/24) respectively, for children and adults on rFVIII-Fc prophylaxis.Conclusion: In real-world setting, for pre-switch ET group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR reduced >95%, and mean WD increased >50%. For pre-switch IP group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR reduced >80%, and mean WD increased >35%. For pre-switch RP group, switch to rFVIII-Fc prophylaxis made both mean ABR and AJBR also reduced >45%, and mean WD increased >20%. The proportions in zero ABR and zero AJBR as post-switch rFVIII-Fc prophylaxis were increased. No matter in ET, IP, or RP group, after switching to RP with rFVIII-Fc, improvement for bleeding outcomes was quite evident. DisclosuresNo relevant conflicts of interest to declare.

Baseline VWF:Ag Level and Body Mass Index Are Inverse Influencing Factors of Annualized Total Bleeding Rate and Annualized Joint Bleeding Rate Respectively in Severe-Type Adult Patients with Hemophilia a (PwHA) with Episodic Treatment with rFVIII

Introduction: Bleeding phenotypes of severe-type patients with hemophilia A (PwHA) vary greatly, which influence factor consumption and medical cost. Factors affecting bleeding patterns of PwHA include various procoagulant and anticoagulant factors, joint condition and physical activity, etc. We aimed to investigate clinical factors influencing by-nature bleeding frequency of severe-type PwHA during episodic treatment.Methods and materials: There were 19 non-inhibitor, severe-type, previously treated PwHA aged >20 years, who had at least one to five major joints arthropathy, retrospectively enrolled from two hemophilia centers for analysis. They had been refusing prophylaxis therapy with FVIII product due to heavy burden of frequent intravenous FVIII injection and had long-term episodic treatment. Clinical informations were collected from November 2017 to November 2018, including age, body mass index (BMI), body weight, ABO blood grouping, HCV and HIV infection status, baseline VWF:Ag and VWF:activity, mutation of F8 gene. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR), weekly doses and annualized factor consumption costs (calculated by new Taiwan dollars, NTD) were obtained from the patients' medical records.Results: The PwHA with ABR <24 had significantly lower proportion of blood-group-O patients, higher baseline VWF:Ag and VWF:activity than those with ABR >24.(P-value <0.05) The PwHA with AJBR <13 had significantly higher BMI than those with AJBR >13.(P-value <0.05) There was no significant difference in ABR, AJBR, weekly dose, and annualized factor cost between PwHA with O blood group and non-O blood group. Compared with PwHA with baseline VWF:Ag or VWF:activity <145%, those with baseline VWF:Ag or VWF:activity >145% had significantly older age (34.9 vs 53.2 years, P-value <0.05), higher BMI (25.2 vs 29.9, P-value <0.05), lower ABR (58.2 vs 12.2 per year, P-value<0.01), lower AJBR (46.8 vs 10.8 per year, P-value<0.01), lower weekly dose (42.4 vs 10.6 IU/kg/wk, P-value<0.01), and lower annualized factor consumption costs (4,177,732 vs 1,120,704 NTD, P-value<0.01). Compared with PwHA with BMI <28, those with BMI >28 had significantly lower ABR (58.2 vs 12.2 per year, P-value<0.05), lower AJBR (46.8 vs 10.8 per year, P-value<0.05), higher baseline VWF:activity (94.6% vs 190.2%, P-value <0.05), and lower weekly dose (38.5 vs 17.1 IU/kg/wk, P-value <0.05). By backward-stepwise multivariate linear regression, baseline VWF:Ag and BMI were identified as independent and significant inverse influencing factors for ABR and AJBR, respectively.(P-value <0.05)Conclusion: For severe-type adult PwHA with episodic treatment, baseline VWF:Ag or VWF:activity >145% was associated with lower ABR, AJBR, weekly dose, and annualized factor cost. BMI >28 was associated with lower ABR, AJBR, and weekly dose consumption. Baseline VWF:Ag and BMI were revealed as inverse influencing factors for ABR and AJBR, respectively. The results of our study could be useful for clinicians to have an insight into diversity of bleeding phenotypes of by-nature severe-type PwHA. For developing countries where factor concentrate resources are not enough, these clinical influencing factors might be helpful for the management of therapeutic strategies and resource allocation for severe PwHA. DisclosuresNo relevant conflicts of interest to declare.

Prognostic Role and Diagnostic Power of Seven Indicators in COVID-19 Patients.

The prognostic role and diagnostic ability of coronavirus disease 2019 (COVID-19) disease indicators are not elucidated, thus, the current study aimed to investigate the prognostic role and diagnostic ability of several COVID-19 disease indicators including the levels of oxygen saturation, leukocytes, lymphocytes, albumin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer in patients with COVID-19. The levels of oxygen saturation, lymphocytes, and albumin were significantly higher in the common and severe clinical type patients compared with those in critical type patients. However, levels of leukocytes, CRP, IL-6, and D-dimer were significantly lower in the common and severe type patients compared with those in critical type patients (P < 0.001). Moreover, the current study demonstrated that the seven indicators have good diagnostic and prognostic powers in patients with COVID-19. Furthermore, a two-indicator (CRP and D-dimer) prognostic signature in training and testing datasets was constructed and validated to better understand the prognostic role of the indicators in COVID-19 patients. The patients were classified into high-risk and low-risk groups based on the median-risk scores. The findings of the Kaplan–Meier curve analysis indicated a significant divergence between the high-risk and low-risk groups. The findings of the receiver operating curve (ROC) analysis indicated the good performance of the signature in the prognosis prediction of COVID-19. In addition, a nomogram was constructed to assist clinicians in developing clinical decision-making for COVID-19 patients. In conclusion, the findings of the current study demonstrated that the seven indicators are potential diagnostic markers for COVID-19 and a two-indicator prognostic signature identification may improve clinical management for COVID-19 patients.

Computed tomography findings and clinical manifestations in different clinical types of coronavirus disease 2019

OBJECTIVE: Since the coronavirus disease 2019 (COVID-19) outbreak in Wuhan in 2019, the virus has spread rapidly. We investigated the clinical and computed tomography (CT) characteristics of different clinical types of COVID-19. MATERIALS AND METHODS: We retrospectively analyzed clinical and chest CT findings of 89 reverse transcription polymerase chain reaction confirmed cases from five medical centers in China. All the patients were classified into the common (n = 65), severe (n = 18), or fatal (n = 6) type. CT features included lesion distribution, location, size, shape, edge, density, and the ratio of lung lesions to extra-pulmonary lesions. A COVID-19 chest CT analysis tool (uAI-discover-COVID-19) was used to calculate the number of infections from the chest CT images. RESULTS: Fatal type COVID-19 is more common in older men, with a median age of 65 years. Fever was more common in the severe and fatal type COVID-19 patients than in the common type patients. Patients with fatal type COVID-19 were more likely to have underlying diseases. On CT examination, common type COVID-19 showed bilateral (68%), patchy (83%), ground-glass opacity (48%), or mixed (46%) lesions. Severe and fatal type COVID-19 showed bilateral multiple mixed density lesions (56%). The infection ratio (IR) increased in the common type (2.4 [4.3]), severe type (15.7 [14.3]), and fatal type (36.9 [14.2]). The IR in the inferior lobe of both lungs was statistically different from that of other lobes in common and severe type patients (P &lt; 0.05). However, in the fatal type group, only the IR in the right inferior lung (RIL) was statistically different from that in the right superior lung(RUL), right middle lung (RML), and the left superior lung (LSL) (P &lt; 0.05). CONCLUSION: The CT findings and clinical features of the various clinical types of COVID-19 pneumonia are different. Chest CT findings have unique characteristics in the different clinical types, which can facilitate an early diagnosis and evaluate the clinical course and severity of COVID-19.

Ocular manifestations in Chinese adult patients with NLRP3-associated autoinflammatory disease

NLRP3-associated autoinflammatory disease (NLRP3-AID) is a rare autosomal dominant disorder involving multiple systems. We aim to assess the ocular manifestations of Chinese adult patients with NLRP3-AID. Twelve adult patients (> 18 years old) were diagnosed as NLRP3-AID at the Department of Rheumatology, Peking Union Medical College Hospital. All patients underwent ophthalmologic evaluation by an ophthalmologist. Clinical and genetic features of these patients were collected and compared with those from Caucasian population. A total of 7 NLRP3-AID patients (58%) 14 eyes had ocular manifestations. Five NLRP3 variants were identified, and 3 patients (43%) with severe ocular damages were all found to have the NLRP3 T348M variant. The incidences of papilledema and optic atrophy in the Chinese adult NLRP3-AID patients of moderate type were similar to those in the Caucasian NLRP3-AID patients of severe type. This is the first cohort of Chinese adult NLRP3-AID patients with ocular involvement. Ocular manifestations were diverse and even severe in NLRP3-AID, particularly in patients with the moderate phenotype, and may have relationship with genotypes. Awareness of these manifestations by rheumatologists and ophthalmologists could help to avoid the irreversible ocular damages.

Quantitative and semi-quantitative CT assessments of lung lesion burden in COVID-19 pneumonia

This study aimed to clarify and provide clinical evidence for which computed tomography (CT) assessment method can more appropriately reflect lung lesion burden of the COVID-19 pneumonia. A total of 244 COVID-19 patients were recruited from three local hospitals. All the patients were assigned to mild, common and severe types. Semi-quantitative assessment methods, e.g., lobar-, segmental-based CT scores and opacity-weighted score, and quantitative assessment method, i.e., lesion volume quantification, were applied to quantify the lung lesions. All four assessment methods had high inter-rater agreements. At the group level, the lesion load in severe type patients was consistently observed to be significantly higher than that in common type in the applications of four assessment methods (all the p < 0.001). In discriminating severe from common patients at the individual level, results for lobe-based, segment-based and opacity-weighted assessments had high true positives while the quantitative lesion volume had high true negatives. In conclusion, both semi-quantitative and quantitative methods have excellent repeatability in measuring inflammatory lesions, and can well distinguish between common type and severe type patients. Lobe-based CT score is fast, readily clinically available, and has a high sensitivity in identifying severe type patients. It is suggested to be a prioritized method for assessing the burden of lung lesions in COVID-19 patients.

Analysis of drug therapy of 53 patients with Corona Virus Disease-2019

Objective:To explore safe and effective treatment strategies for the patients with Corona Virus Disease-2019 (COVID-19). Methods: The clinical data and treatment strategies of COVID-19 patients were collected and retrospectively analyzed. Results: Major clinical manifestations of the patients with COVID-19 were fever (75. 5%) and cough (41. 5%). Of the 53 COVID-19 patients, 42 were of common type, 6 were of severe type and 5 were of critical type. Most of the critical type patients were the elderly with basic diseases. Serum lymphocyte count decreased when they were admitted into hospital. During hospitalization,C-reactive protein significantly increased in critical type patients. Liver injury was observed in severe type and critical type patients. With regard to treatment, 30 patients in the common type were treated with traditional Chinese medicine alone, 8 patients were treated with traditional Chinese medicine combined with lopinavir/ritonavir(LPV/r), 2 patients were given traditional Chinese medicine combined with other drugs, and still another 2 patients were given interferon alone. One severe type patient was treated with LPV/r combined with glucocorticoids, traditional Chinese medicine was given to other 5 severe type patients, including 2 patients with methylprednisolone sodium succinate combined treatment and one patient with interferon combined treatment. The treatment of the critically ill patients was relatively complex, including antiviral, diuretic, cardiotonic treatment, as well as nutritional support. Conclusion;Traditional Chinese medicine was beneficial to the recovery of COVID-19 patients. However, definite benefits of combined treatment with LPV/r or glucocorticoids were not clearly observed. © 2020 Publishing House of Pharmaceutical Care and Research. All rights reserved.

Comparison of Clinical Characteristics of First and Second Generation Cases of COVID-19

Purpose — To explore the differences in clinical characteristics of the first and second generation cases of COVID-19. Methods — 63 patients with COVID-19 and asymptomatic infections admitted to the Third People's Hospital of Wuhu City and the Fourth People's Hospital of Ma'anshan City from January 24, 2020 to March 3, 2020 were selected as the research objects. The patients were divided into the first and second generation case groups according to the history of epidemiology, and the differences of clinical data between the two groups were compared. Results — There was no significant difference between the two groups of patients in gender, age, and number of smokers (P&gt;0.05). In the first generation group, the number of people with underlying diseases was lower than that in the second generation group (86.80%, 92.00%), and the number of patients of severe or critical type was higher than that in the second generation group (18.40%, 0.00%). The difference was statistically significant (P&lt;0.05). The symptoms of the two groups were compared: fever (84.20%, 64.00%), cough (78.9%, 40.00%), chest tightness (44.70%, 12.00%), nausea (2.60%, 36.00%). The difference was statistically significant (P&lt;0.05). The distribution of lesions in the two groups was compared: bilateral lung lesions (77.80%, 66.70%), unilateral lesions (17.80%, 5.50%), and no lesions (4.40%, 27.80%). The difference was statistically significant (P&lt;0.05). There was no statistically significant difference between the two groups in laboratory tests (P&gt;0.05). Conclusions — Compared with the first generation cases, the second generation cases have different degrees of relief in clinical classification, lower respiratory symptoms and the number of lung lesions; the differentiation of the transmission generation has a certain reference value for the evaluation of the disease condition.

Chest CT features and progression of patients with coronavirus disease 2019.

Objectives:Coronavirus disease 2019 (COVID-19) is a major public health emergency. It poses a grave threat to human life and health. The purpose of the study is to investigate the chest CT findings and progression of the disease observed in COVID-19 patients.Methods:Forty-nine confirmed cases of adult COVID-19 patients with common type, severe and critically severe type were included in this retrospective single-center study. The thin-section chest CT features and progress of the disease were evaluated. The clinical and chest imaging findings of COVID-19 patients with different severity types were compared. The CT severity score and MuLBSTA score (a prediction of mortality risk) were calculated in those patients.Results:Among the 49 patients, 35 patients (71%) were common type and 14 patients (28%) were severe and critically severe type. Nearly all patients (98%) had pure ground-glass opacities (GGO) in CT imaging. Of the severe and critically severe type patients, 86% exhibited GGO with consolidation, in comparison with 54% of the patients with common type. Fibrosis presented in 79% of the severe and critically severe type patients and 43% of the common type patients. The severe and critically severe type patients were significantly more prone to experience five-lobe involvement compared to the common type patients (p = 0.002). The severe and critically severe type patients also had higher CT severity and MuLBSTA scores than the common type patients (5.43 ± 2.38 vs 3.37 ± 2.40, p < 0.001;and 10.21 ± 3.83 vs 4.63 ± 3.43, p < 0.001, respectively). MuLBSTA score was positively correlated with admittance to the intensive care unit (p = 0.005, r = 0.351). Nineteen patients underwent three times CT scan. The interval between first and second CT scan was 4[4,8] days, second and third was 3[2,4] days. There were greater improvements in the third CT follow-up findings compared to the second (p = 0.002).Conclusions:The severe and critically severe type patients often experienced more severe lung lesions, including GGO with consolidation. The CT severity score and MuLBSTA score may be helpful for the assessment of COVID-19 severity and progression.Advances in knowledge:Chest CT has the value of evaluated radiographical features of COVID-19 and allow for dynamic observation of the disease progression. Considering coagulation disorder of COVID-19, MuLBSTA score may need to be updated to increase new understanding of COVID-19.

Phage Therapy to Prevent Nosocomial Bacterial Pneumo-nia in Patients with Severe COVID-19 in 2020

The COVID-19 was reported to be a pandemic, according to the World Health Organization (WHO). Secondary bacterial pneumonia exacerbates respiratory problems and increases mortality in patients with COVID-19. Recently, 50% of the causes of death in these patients have been reported as nosocomial pneumonia in these cases. These bacteria have become multidrug-resistant. Phage production is a cost-benefit. Inhalation of phage cocktail with mesh nebulizer can be suitable to prevent secondary bacterial pulmonary infection in patients with severe COVID-19. To prevent secondary bacterial pneumonia and reduce mortality in patients with severe type COVID-19 and patients who are under a ventilator for a long time, the use of phage cocktail product by inhalation with mesh nebulizer device is recommended.

Association of D-dimer, inflammatory markers, cytokines abnormality, and disease severity in COVID-19 severe/critical patients in Wuhan

目的分析2019新型冠状病毒肺炎（COVID-19）重型及危重型患者D-二聚体、炎症指标、细胞因子水平与疾病严重程度的关系。方法收集华中科技大学同济医院中法新城院区山西援鄂国家医疗一队2020年2月8日至3月25日收治的41例COVID-19患者病例资料，重型28例，危重型13例，比较不同临床分型COVID-19患者的基本临床特征，入院时D-二聚体、炎症指标[WBC、ANC、降钙素原（PCT）、超敏C-反应蛋白（hsCRP）]、细胞因子（IL-2R、IL-6、IL-8、TNF-α）水平；比较有无D-二聚体异常患者的细胞因子（IL-2R、IL-6、IL-8、TNF-α）水平；并比较抗凝治疗前后患者D-二聚体、细胞因子指标（IL-2R、IL-6、IL-8、TNF-α）水平变化。结果41例患者中，男23例（56.1%），女18例（43.9%），平均年龄（55.4±11.9）岁。危重型患者平均年龄[（61.1±10.4）岁]高于重型患者[（52.8±11.7）岁]，差异有统计学意义（t=2.264，P=0.032）。危重型患者合并高血压（χ2=10.420，P=0.001）、心血管疾病（χ2=6.972，P=0.008）、脑血管疾病（χ2=6.972，P=0.008）比例高于重型患者。危重型患者出现呼吸困难、盗汗及乏力症状比例均高于重型患者，差异均有统计学意义（χ2分别为14.898、6.972、7.823，P值分别为<0.001、0.008、0.005）。危重型患者D-二聚体、WBC、ANC、PCT、hsCRP、IL-8水平均高于重型患者，差异均有统计学意义（P值均<0.05）。D-二聚体异常患者IL-2R、IL-8、TNF-α水平均较D-二聚体正常者增高，差异均有统计学意义（P值均<0.05）。8例预防性抗凝治疗患者D-二聚体、IL-2R、IL-6、IL-8抗凝治疗后比治疗前水平降低。结论COVID-19危重型患者存在更严重的凝血-免疫功能紊乱，动态监测D-二聚体、细胞因子水平有助于早期识别COVID-19危重型患者，抗凝治疗可能通过纠正凝血-免疫功能紊乱促进疾病好转。

Semiquantitative lung ultrasound scores in the evaluation and follow-up of critically ill patients with COVID-19: a single-center study

Rationale and ObjectivesChest CT is not suitable for critically ill patients with COVID-19 and lung ultrasound (LUS) may play an important role for these patients. In this study, we summarized the findings of LUS and explore the value of semiquantitative LUS scores in evaluation and follow-up of COVID-19 pneumonia.Materials and MethodsRetrospectively studied the LUS and chest CT imaging of 128 critically ill patients with COVID-19. The imaging data were reviewed to acquire the LUS and CT scores. The correlation between LUS scores and CT scores were made to evaluate the accuracy of LUS. A cut-off point of LUS score was calculated to distinguish critical-type patients from severe-type patients. LUS follow-up of 72 patients were compared with the gold standard chest CT.ResultsThe most common LUS features of COVID-19 pneumonia were crowded or coalescent B-lines with multifocal small consolidations in multi-zone. The mean LUS score was 8.1 points in severe-type patients and 15.7 points in critical-type patients (P<0.05). The correlation between LUS scores and CT scores was high (r=0.891, p<0.01) and it was higher in critical-type patients than that in severe-type patients. The LUS score higher than 10.5 points had a 97.4% sensitivity and 75.0% specificity to distinguish critical-type patients. The consistency of LUS and chest CT in follow-up was 0.596, with higher consistency in diagnosis of lesion progression (Kappa values was 0.774).ConclusionOur scoring system provides a more quantitative use of LUS findings and accurate evaluation of lung damage for critically ill patients with COVID-19.

Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia

Timely analysis of the laboratory characteristics associated with 2019 novel coronavirus pneumonia (COVID-19) can assist with clinical diagnosis and prognosis. This study is a collection of clinical data from 54 hospitalized adult patients diagnosed with COVID-19 in the Zhongfa Xincheng district of China at Tongji Hospital of Huazhong University of Science and Technology from January 28, 2020 to February 11, 2020. The average age of the patients was 61.8 ± 14.5 years, and the predominant age group was 50–79. The proportion of critical-type patients with comorbidities was higher than that of severe-type patients. Lymphocyte counts were significantly reduced in routine bloodwork for all patients, but significantly lower in critical-type patients than that in severe-type patients. Prolongation of prothrombin times (PT) and elevation of fibrinogen degradation products (FDPs) and D-dimers (D-Ds) were detected in coagulation function tests, and more significant changes were observed in critical-type patients compared to severe-type patients. Serum ferritin levels were sensitive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but could not be used for disease assessment. In addition, levels of two inflammatory factors, soluble interleukin-2 receptor (sIL-2R) and interleukin-6 (IL-6) were significantly increased in all patients, but higher in critical-type patients than in severe-type patients. Moreover, kidney injury was the second-most common organ affected by COVID-19 followed by heart and liver. Kidney and heart injury were more severe in critical-type patients than in severe-type patients. All of the 31 severe-type patients recovered. Of the critical-type patients, six died and 17 recovered. The length of hospital stay for critical-type patients was significantly longer for severe-type patients. In summary, increased lymphocyte counts, prolonged PT, secondary increases in fibrinolytic activity and increases in sIL-2R and IL-6 are typical features of COVID-19 and are associated with disease severity.

The underlying changes and predicting role of peripheral blood inflammatory cells in severe COVID-19 patients: A sentinel?

BackgroundThe underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. Material and methodsThis retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. ResultsCompared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR = 7.701, 95%CI:1.265–46.893, P = 0.027), eosinopenia (OR = 5.595, 95%CI:1.008–31.054, P = 0.049), and worse one-month outcome (OR = 8.984; 95%CI:1.021–79.061, P = 0.048). ConclusionLymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.

Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian, China.

PurposeWe aimed to report the clinical characteristics of 194 cases coronavirus disease-19 (COVID-19) in Huanggang, Hubei and Taian, Shandong.MethodsWe retrospectively investigated the clinical, laboratory characteristics and CT imaging of confirmed cases of COVID-19 from January 22 to February 28, 2020 in Huanggang Central Hospital and The Second Affiliated Hospital of Shandong First Medical University. Real time PCR was used to detect the new coronavirus in respiratory samples. Immunohistochemical staining was used to detect the expressions of ACE2 in tissues.ResultsAmong the 194 patients infected with COVID-19, 108 patients were male, with a median age of 48.3 years. The average preclinical period was 7.44 day. Except for 37 severe or critically ill patients, the rest of the 157 patients exhibited mild or moderate symptoms. 190 (97.94%) patients were confirmed during the three times nucleic acid test. The main clinical symptom of the patients were fever, sore throat and cough, which accounted for 146 cases (75.26%), 98 (50.52%) and 86 cases (44.33%), respectively. 30 patients (15.46%) showed liver dysfunction. Imaging examination showed that 141 patients (72.68%) showed abnormal density shadow, while 53 cases (27.32%) had no obvious abnormality in the parenchyma of both lungs. Up to now, 109 cases have been discharged from the hospital, and 9 patients died. The ACE2 expression levels were up-regulated in patients of severe type and critically ill type.ConclusionClinical symptoms, laboratory tests and CT imaging should be combined for comprehensive analysis to diagnose COVID-19. ACE2 may be the receptor of COVID-19.Electronic supplementary materialThe online version of this article (10.1007/s15010-020-01440-5) contains supplementary material, which is available to authorized users.