Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Application value of cardiovascular MR T 1 mapping in patients recovered from COVID-19 / 中华放射学杂志

Objective:To explore the value of cardiovascular MR (CMR) T 1 mapping in evaluating myocardial injury in patients recovered from COVID-19. Methods:The clinical and image data of 15 patients with COVID-19 (9 with moderate clinical manifestation, 6 with severe clinical manifestation) who underwent CMR screening at 3 months after being discharged from the Second People′s Hospital of Fuyang City during May 2020 to June 2020 were prospective collected. Fifteen COVID-19 patients were selected as case group, and another 11 healthy volunteers were selected as control group. A standardized CMR protocol included cine, native and enhanced T 1 mapping, late gadolinium enhancement (LGE). Cardiac functional parameters, native T 1 value of left ventricular and extracellular volume fraction (ECV) were measured. One way ANOVA was used to assess the difference between CMR parameters among moderate and severe manifestation groups and control group, and LSD- t was used to assess the difference between the three groups. Results:LGE value was negative in all subjects. ECV values were higher in recovered COVID-19 patients with either moderate (27.9%±2.7%) or severe manifestation (30.0%±3.7%) than control group (23.2±1.9%) ( P<0.05); there was no significant difference of ECV values between recovered COVID-19 patients with moderate and severe manifestation ( P=0.100). There was no difference of native T 1 values and other functional and morphologic parameters of left ventricular and right ventricular among recovered COVID-19 patients with moderate and severe manifestation and control group ( P>0.05). Conclusion:CMR myocardial tissue ECV increase in patients who recovered from COVID-19, suggesting subclinical myocardial injury.

Evaluation of the auxiliary diagnostic value of antibody assays for the detection of novel coronavirus (SARS-CoV-2).

The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has taken on pandemic proportions, affecting over 100 countries in a matter of weeks. The goal of this study was to assess the diagnostic values of different methods of detecting and estimating the SARS-CoV-2 infection, and the auxiliary diagnostic potential of antibody assays. By retrospectively analyzing the data of viral RNAs and serum immunoglobulin M-immunoglobulin G antibodies against SARS-CoV-2 from 38 cases with confirmed coronavirus disease 2019 in the Second People's Hospital of Fuyang, we found that, in the early phase of the illness, the viral RNA was most abundant in the sputum specimens, followed by that in the throat swabs, while the antibody assays identified fewer positive cases at this stage. However, the sensitivity of the antibody assays overtook that of RNA test from the eighth day of disease onset. Simultaneous use of antibody assay and reverse transcription-quantitative real-time polymerase chain reaction improved the sensitivity of the diagnoses. Moreover, we found that most of these cases with no detectable viral RNA load during the early stages were able to be seropositive after 7 days. Our findings indicate that the antibody detection could be used as an effective supplementary indicator of SARS-CoV-2 infection in suspected cases with no detectable viral RNA, and in conjunction with nucleic acid detection in confirming the infection.

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

ObjectivesTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. DesignMulticenter, open-label, randomized controlled trial. Setting16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. InterventionsHCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. ResultsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. ConclusionsThe administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registrationChiCTR2000029868 What is already known on this topic-- The pandemic of coronavirus disease 2019 (COVID-19) imposes substantial burdens on individuals, communities, health-care facilities, markets, governments, etc. globally. -- There is no specific treatment approved for COVID-19 or vaccine to prevent infection with the novel coronavirus. -- During the urgent pandemic, media headlines the utility of drugs without solid evidence but buries the side-effects of these drugs. What this study adds-- In this randomized clinical trial of patients mainly with persistent mild to moderate COVID-19, exposure to hydroxychloroquine led to a similar probability of virus elimination comparing to the current standard-of-care. -- Adverse events, mostly gastrointestinal related, were significantly increased in patients who received hydroxychloroquine. -- Overall, the results from our trial do not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19. Print abstractO_ST_ABSStudy questionC_ST_ABSTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. MethodsThis is a multicenter, open-label, randomized controlled trial conducted in 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. A total of 150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. Among them, 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention to treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Study answer and limitationsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70) with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. What this study addsOur trial does not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19 due to limited effects on virus eliminating and significantly increased adverse events. Funding, competing interests, data sharingThis work was supported by the Emergent Projects of National Science and Technology (2020YFC0844500), National Natural Science Foundation of China (81970020, 81770025), National Key Research and Development Program of China (2016YFC0901104), Shanghai Municipal Key Clinical Specialty (shslczdzk02202, shslczdzk01103), National Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Discipline for Respiratory Diseases (2017ZZ02014), National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304007), Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period (2018ZX09206005-004, 2017ZX10202202-005-004, 2017ZX10203201-008). All authors declared no competing interests. Anonymized datasets can be made available on reasonable request after approval from the trial management committee. Study registrationChiCTR2000029868

Analysis of the clinical characteristics of novel coronavirus pneumonia and the influencing factors of severe disease progress / 中华急诊医学杂志

Objective:To analyze the clinical characteristics of patients with novel coronavirus pneumonia (COVID-19) and the factors influencing mild cases developing into severe cases, so as to provide a basis for clinical screening, prevention and treatment of potential severe cases.Methods:Retrospective analysis was performed on the clinical characteristics of 168 cases who were admitted to two tertiary general hospitals in Anhui province and diagnosed with COVID-19 from January 20 to March 4, 2020. According to the classification criteria in the COVID-19 diagnosis and treatment program (trial version 6) issued by the National Health Commission, the mild and common cases were classified as the mild group ( n=137), and the severe and critical cases were classified as the severe group ( n=31). The general data, epidemiological history, clinical manifestations, laboratory examination and imaging indexes of the two groups were compared. Univariate analysis was performed. Then multivariate Logistic regression analysis was conducted on the factors with statistically significant differences in univariate analysis to obtain independent influencing factors of the occurrence of severe COVID-19. Results:Among the 168 COVID-19 patients, 95 were male and 73 were female, with an average age of 42.6±15.8 years old. The mean age of the mild group was younger than that of the severe group (40.5±15.5 vs 51.6 ±14.1, P<0.01). The proportion of patients combined with hypertension (29.0% vs 10.9%), diabetes (25.8% vs 2.2%, P=0.005) and two or more underlying diseases (29.0% vs 4.4%, P=0.006) in the severe group were significantly higher than those in the mild group. In the severe group, the proportion of patients receiving initial treatment in Medical institutions below secondary hospitals was significantly higher than that in the mild group ( P<0.01), and the time between symptom onset and diagnosis was longer [(8.00±3.27) d vs (6.49±3.90) d, P=0.048]. There was no significant difference in the initial symptoms between the mild group and the severe group. However, the body temperature was higher in the severe group [(38.80±0.67)℃ vs (37.9±0.60)℃, P<0.01]. At the time of admission, the lymphocyte percentage of the severe group was significantly lower than that of the mild group [(18.20±9.13)% vs (24.43±10.43)%, P<0.01], while C-reactive protein, interleukin-6 (IL-6), D-dimer, LDH, aspartate and aminotransferase were significantly higher than that of the mild group ( P<0.01). CT imaging showed that 11 (8%) patients in the mild group had lesions confined to a single lobe of the lung, while all patients in the severe group had multi-lobe lesions ( P<0.01). All the 168 COVID-19 patients in this study were cured, and the length of hospital stay in the severe group was significantly longer than that in the mild group [(24.71±7.72) d vs (20.28±7.67) d, P=0.021]. According to multivariate binary Logistic regression analysis, age ( P=0.042), diabetes ( P=0.021), body temperature at admission ( P=0.001), and IL-6 measured at admission ( P=0.008) were independent factors affecting COVID-19 to severe progress. Conclusions:Strengthening the professional knowledge training of primary hospitals is helpful for early diagnosis of COVID-19. Patients with older age, combined with diabetes, high initial fever and significantly increased IL-6 level are more possibly to develop into severe disease. Early identification and prevention should be carried out.

Analysis of the clinical characteristics and early warning model construction of severe/critical coronavirus disease 2019 patients / 中华危重病急救医学

Objective:To analyze the clinical characteristics of critical patients with coronavirus disease 2019 (COVID-19), build an early warning model for severe/critical type, and aim at providing reference for the prediction of severe/critical COVID-19.Methods:The clinical data of COVID-19 patients treated in the Second People' Hospital of Fuyang City from January 20th to February 18th in 2020 were retrospective analyzed, including the demographic and epidemiological date, vital signs and hematology indexes, etc. on admission. Patients were divided into the normal type (set as normal group) and severe/critical type (set as severe group) according to the COVID-19 treatment plan classification standard published by National Health Commission of the People's Republic of China. The differences between two groups were compared, and the variables with statistical significance were incorporated in the multivariate binary unconditional Logistic regression analysis to screen the risk factors of severe/critical type. Risk factors were summarized to establish an early warning model, and the receiver operating characteristic (ROC) curve was carried out to evaluate the significance of the early warning model in the screening of critically COVID-19.Results:A total of 155 patients with COVID-19 were admitted, including 125 patients of normal type and 30 patients of severe/critical type. ① Compared with normal group, patients in severe group were older, and with higher proportion of basic diseases, higher body mass index (BMI), higher incidence of tachypnea, persistent high fever, peripheral blood oxygen saturation (SpO 2) < 0.95, while the white blood cell count (WBC), CD4 + T lymphocyte, CD8 + T lymphocyte, lymphocyte count (LYM) were decreased obviously, the levels of interleukin-6 (IL-6), C-reactive protein (CRP) and serum amyloid a protein (SAA), and CT showed higher incidence of multi-pulmonary lobe lesions. There were no significant differences of gender, travel history from Wuhan, smoking history, shock index (SI) and CD4 +/CD8 + ratio between the two groups. ② Multivariate Logistic regression analysis showed that age ≥60 years old [odds ratio ( OR) = 1.620, P = 0.031], combined with underlying diseases ( OR = 1.521, P = 0.044), persistent high fever ( OR = 2.469, P = 0.014), WBC < 2.0×10 9/L and/or LYM < 0.4×10 9/L ( OR = 3.079, P = 0.006), pulmonary multilobar lesions ( OR = 1.367, P = 0.047), and IL-6 ≥ 30 ng/L ( OR = 2.426, P = 0.010) were the risk factors of severe/critical COVID-19. ③ The OR value corresponding to each risk factors were scored by rounding. Two points were scored for age≥60 years old, with underlying diseases, persistent high fever and IL-6 ≥ 30 ng/L, 3 points for WBC < 2.0×10 9/L and/or LYM < 0.4×10 9/L, 1 point for pulmonary multilobar lesions, and totally calculated as early warning model scores. The early warning model score of the severe group was significantly higher than that of the normal group (9.33±2.79 vs. 5.04±2.38, t = 9.010, P = 0.001). ④ The ROC curve analysis showed the area under ROC curve (AUC) of early warning model on the early screening of severe/critical patients in COVID-19 was 0.944, and 95% confidence interval (95% CI) was 0.903-0.985; and the sensitivity and specificity were 93.3% and 72.0% respectively while the cut-off was 6.5. Conclusions:There are many differences between severe/critical and mild COVID-19 patients. The establishment of early warning model could help to screen severe/critical patients at an early stage, with certain significance for guiding treatment.

Analysis of blood-borne occupational exposure of intern nurses in a tertiary infectious disease hospital / 中华劳动卫生职业病杂志

Objective@#To explore the risk factors of occupational exposure of intern nurses in an infectious disease hospital, and put forward prevention and control strategies.@*Methods@#A retrospective analysis was made of 82 reported cases of occupational exposure of intern nurses in a tertiary infectious disease hospital from 2013 to 2017. The occupational exposure rate, pathogens, occurrence sites and exposure links of the intern nurses were analyzed.@*Results@#The overall occupational exposure rate of internship nurses in 2013-2017 was 6.20% (82/1322) .The pathogens were mainly HBV, 52 cases, accounting for 63.4%. The site of occurrence was mainly finger, 75 cases, accounting for 91.5%. In the occurrence of the process, 35 cases were taken, accounting for 42.7%; 20 cases of arteriovenous puncture, accounting for 24.4%; 17 cases of separation needles and finishing materials, accounting for 20.7%.@*Conclusion@#The incidence of blood-borne occupation of intern nurses is higher, which needs special attention in infectious disease hospitals. To prevent blood-borne occupational exposure of intern nurses, occupational safety education should be strengthened, clinical operation should be standardized and humanized management should be provided.

Clinical Observation of Doxofylline Combined with Ceftazidime in the Treatment of Elderly Patients with Chronic Emphysema / 中国药房

OBJECTIVE:To observe the efficacy and safety of doxofylline combined with ceftazidime in the treatment of elder-ly patients with chronic emphysema. METHODS:Data of 78 elderly patients with ceftazidime was collected and divided into single drug group(31 cases)and combined medication group(47 cases)according to different treatment methods. All patients adopted flu-id infusion,oxygen inhalation and nutrition support. Based on it,single drug group received 0.05 g Doxofylline injection,once ev-ery 12 h. Combined medication group additionally received 1.0 g Ceftazidime for injection,once every 12 h. If the symptoms were out of control,20 mg prednisone was given,twice a day. The courses of 2 groups were 10 d. Total efficacy,pulmonary functions [maximum mid-expiratory flow(MMEF),1s forced expiratory volume percent predicted(FEV1%),peak expiratory flow(PEF)] before and after treatment,American Concise Health Survey Questionnaire(SF-36 scale)(QLS)and the incidence of adverse reac-tions in 2 groups were observed. RESULTS:The total effective rate in combined medication group was significantly higher than sin-gle drug group,the difference was statistically significant (P0.05). After treatment,MMEF,FEV1%,PEF and QLS scores in 2 groups were significantly higher than before,and combined medication group MMEF,FEV1%、PEF were higher than single drug group,the difference was statistically significant (P0.05). And there was no significant difference in the incidence of adverse reactions in 2 groups (P>0.05). CONCLUSIONS:Based on conventional treatment,doxofylline combined with ceftazidime shows better efficacy than doxofylline alone in the treat-ment of elderly patients with chronic emphysema,it can improve pulmonary functions,with better safety.

Clinical study of pleural effusion controlled by interrupted drainage via central venous catheter / 中国医师进修杂志

Objective To explore the therapeutic effect,advantages and shortcomings of pleural effusion controlled by interrupted drainage via central venous catheter.Methods The research group had 52 cases with pleural effusion controHed by interrupted drainage via central venous catheter,and the control group had 50 cases with pleural effusion controlled by conventional pleuracentesis.Pleural effusion disappearing time,average hospitalization time,pleuracentesis frequency,related therapy expenses and complications of two groups were observed and compared.Results The pleuracentesis frequency,pleural effusion disappearing time,average hospitalization time,related therapy expenses and per capita incidence of complications of the research group were(1.06±1.30)times,(4.31±2.20)days,(9.87±2.30)days,(264.77±37.20)yuan and 9.62%and in the control group were(4.20±2.60)times,(9.92±3.70)days,(15.08±5.80)days,(487.62±55.56)yuan and 38.00%.The differences between two groups were particularly remarkable.Conclusion The method of pleural effusion controlled by interruptod drainage via central venous catheter is safe,eonvenient,economical and microtraumatic,and it is worth using more widely.