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, Volume 49 Issue 2 Previous Issue   
Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)
CHEN Zhimin,FU Junfen,SHU Qiang,WANG Wei,CHEN Yinghu,HUA Chunzhen,LI Fubang,LIN Ru,TANG Lanfang,WANG Tianlin,WANG Yingshuo,XU Weize,YANG Zihao,YE Sheng,YUAN Tianming,ZHANG Chenmei,ZHANG Yuanyuan
J Zhejiang Univ (Med Sci), 2020, 49(2): 139-146.   https://doi.org/10.3785/j.issn.1008-9292.2020.02.01
Abstract( 1261 )   HTML( 254 )     PDF(1074KB)( 895 )

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Management of COVID-19: the Zhejiang experience
XU Kaijin,CAI Hongliu,SHEN Yihong,NI Qin,CHEN Yu,HU Shaohua,LI Jianping,WANG Huafen,YU Liang,HUANG He,QIU Yunqing,WEI Guoqing,FANG Qiang,ZHOU Jianying,SHENG Jifang,LIANG Tingbo,LI Lanjuan
J Zhejiang Univ (Med Sci), 2020, 49(2): 147-157.   https://doi.org/10.3785/j.issn.1008-9292.2020.02.02
Abstract( 1805 )   HTML( 226 )     PDF(1114KB)( 1717 )

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium, so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

Pharmaceutical care for severe and critically ill patients with COVID-19
JIANG Saiping,LI Lu,RU Renping,ZHANG Chunhong,RAO Yuefeng,LIN Bin,WANG Rongrong,CHEN Na,WANG Xiaojuan,CAI Hongliu,SHENG Jifang,ZHOU Jianying,LU Xiaoyang,QIU Yunqing
J Zhejiang Univ (Med Sci), 2020, 49(2): 158-169.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.01
Abstract( 563 )   HTML( 56 )     PDF(1156KB)( 279 )

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.

Principles and suggestions on biosafety protection of biological specimen preservation during prevalence of COVID-19
ZHANG Xiaoyan,SUN Wei,SHANG Shiqiang,MAO Jianhua,FU Junfen,SHU Qiang,JIANG Kewen
J Zhejiang Univ (Med Sci), 2020, 49(2): 170-177.   https://doi.org/10.3785/j.issn.1008-9292.2020.02.04
Abstract( 370 )   HTML( 46 )     PDF(1070KB)( 205 )

Coronavirus disease 2019 (COVID-19) is a grade B infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In pace with the spreading of the disease, biosafety risk of the biological specimen preservation in biobanks has been significantly increased and biosafety protection during biological specimen preservation become increasingly important. According to the related national rules and the corresponding guidelines of Chinese Medical Association, this paper introduced the etiology about SARS-CoV-2, epidemiology about COVID-19, and the biosafety protection principles of individuals and biological specimen storage places in the process of personal protection, protection of collection, transport, handling, preservation, detection, post-detection disposal and emergencies of biological specimen. Emphasized to carry out a strict biosafety-risk assessment on biological specimen basing on virus load information, infectivity, and sample type (possible contact transmission, aerosol transmission, and fecal oral transmission).

Study on the epidemic development of COVID-19 in Hubei province by a modified SEIR model
CAO Shengli,FENG Peihua,SHI Pengpeng
J Zhejiang Univ (Med Sci), 2020, 49(2): 178-184.   https://doi.org/10.3785/j.issn.1008-9292.2020.02.05
Abstract( 1197 )   HTML( 138 )     PDF(2555KB)( 656 )

Objective: To establish a SEIR epidemic dynamics model that can be used to evaluate the COVID-19 epidemic, and to predict and evaluate the COVID-19 epidemic in Hubei province using the proposed model. Methods: COVID-19 SEIR transmission dynamics model was established, which took transmission ability in latent period and tracking quarantine interventions into consideration. Based on the epidemic data of Hubei province from January 23, 2020 to February 24, 2020, the parameters of the newly established modified SEIR model were fitted. By using Euler integral algorithm to solve the modified SEIR dynamics model, the epidemic situation in Hubei province was analyzed, and the impact of prevention and control measures such as quarantine and centralized treatment on the epidemic development was discussed. Results: The theoretical estimation of the epidemic situation by the modified SEIR epidemic dynamics model is in good agreement with the actual situation in Hubei province. Theoretical analysis showed that prevention and control quarantine and medical follow-up quarantine played an important inhibitory effect on the outbreak of the epidemic.The centralized treatment played a key role in the rapid decline in the number of infected people. In addition, it is suggested that individuals should improve their prevention awareness and take strict self-protection measures to curb the increase in infected people. Conclusion: The modified SEIR model is reliable in the evaluation of COVID-19 epidemic in Hubei province, which provides a theoretical reference for the decision-making of epidemic interventions.

Diagnostic efficacy of three test kits for SARS-CoV-2 nucleic acid detection
SHEN Lihua,HUANG Fei,CHEN Xiang,XIONG Zuan,YANG Xiaoyu,LI Hui,CHENG Feng,GUO Jian,GONG Guofu
J Zhejiang Univ (Med Sci), 2020, 49(2): 185-190.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.09
Abstract( 471 )   HTML( 23 )     PDF(1055KB)( 101 )

Objective: To compare the diagnostic efficacy among three RT-PCR test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection. Methods: The throat swab samples from 40 hospitalized patients clinically diagnosed as coronavirus disease 2019 (COVID-19) and 16 hospitalized non-COVID-19 patients were recruited. The SARS-CoV-2 nucleic acid was detected in throat swab samples with RT-PCR test kits from Sansure Biotech ("Sansure" for short), Jiangsu Bioperfectus Technologies ("Bioperfectus" for short) and BGI Genomics ("BGI" for short). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa value were analyzed. The viral nucleic acid was extracted from the throat swab samples by one-step cleavage and magnetic bead methods, and the efficacy of two extraction methods was also compared. The results of magnetic bead method for nucleic acid extraction by two different extractors (Sansure Natch CS S12C Fully Automated Nucleic Acid Extraction System vs. Tianlong NP968-C Nucleic Acid Extractor) were also compared. Results: The sensitivity, specificity, PPV, NPV and kappa value were 95.00%, 87.50%, 95.00%, 87.50%and 0.825 for Sansure kit; 90.00%, 87.50%, 94.74%, 77.78%and 0.747 for the Bioperfectus kit, and 82.50%, 81.25%, 91.67%, 65.00%and 0.593 for the BGI kit, respectively. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by one-step cleavage and magnetic bead methods were 95.24%, 100.00%, 96.43%and 0.909, respectively, but the one-step cleavage method took only 25 min, while the magnetic bead method required 180 min. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by the two different nucleic acid extractors were 85.00%, 100.00%, 89.29% and 0.764, respectively. Conclusion: The detection efficacy for SARS-CoV-2 nucleic acid by the Sansure kit is relatively higher and the one-step cleavage method has advantages of convenient operation and less time consuming.

Dynamic changes of chest CT imaging in patients with COVID-19
WANG Jincheng,LIU Jinpeng,WANG Yuanyuan,LIU Wei,CHEN Xiaoqun,SUN Chao,SHEN Xiaoyong,WANG Qidong,WU Yaping,LIANG Wenjie,RUAN Lingxiang
J Zhejiang Univ (Med Sci), 2020, 49(2): 191-197.   https://doi.org/10.3785/j.issn.1008-9292.2020.02.03
Abstract( 582 )   HTML( 66 )     PDF(12251KB)( 401 )

Objective: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). Methods: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. Results: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare, the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). Conclusion: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.

CT imaging features of patients with different clinical types of COVID-19
ZHONG Qi,LI Zhi,SHEN Xiaoyong,XU Kaijin,SHEN Yihong,FANG Qiang,CHEN Feng,LIANG Tingbo
J Zhejiang Univ (Med Sci), 2020, 49(2): 198-202.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.05
Abstract( 476 )   HTML( 32 )     PDF(4462KB)( 159 )

Objective: To investigate the CT findings of patients with different clinical types of coronavirus disease 2019 (COVID-19). Methods: A total of 67 patients diagnosed as COVID-19 by nucleic acid testing were collected and divided into 4 groups according to the clinical stages based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6). The CT imaging characteristics were analyzed among patients with different clinical types. Results: Among 67 patients, 3(4.5%) were mild, 35 (52.2%) were moderate, 22 (32.8%) were severe, and 7(10.4%) were critical ill. No significant abnormality in chest CT imaging in mild patients. The 35 cases of moderate type included 3 (8.6%) single lesions, the 22 cases of severe cases included 1 (4.5%) single lesion and the rest cases were with multiple lesions. CT images of moderate patients were mainly manifested by solid plaque shadow and halo sign (18/35, 51.4%); while fibrous strip shadow with ground glass shadow was more frequent in severe cases (7/22, 31.8%). Consolidation shadow as the main lesion was observed in 7 cases, and all of them were severe or critical ill patients. Conclusion: CT images of patients with different clinical types of COVID-19 have characteristic manifestations, and solid shadow may predict severe and critical illness.

Clinical analysis of suspected COVID-19 patients with anxiety and depression
LI Xin,DAI Tian,WANG Hong,SHI Junnian,YUAN Wei,LI Jing,CHEN Lijun,ZHANG Tianming,ZHANG Shanshan,KONG Yan,YUE Ning,SHI Hui,HE Yuping,HU Huifang,LIU Furong,YANG Caixia
J Zhejiang Univ (Med Sci), 2020, 49(2): 203-208.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.02
Abstract( 261 )   HTML( 31 )     PDF(1055KB)( 117 )

Objective: To explore the risk factors of anxiety and depression in patients with suspected coronavirus disease 2019 (COVID-19) so as to achieve early intervention and better clinical prognosis. Methods: Seventy-six patients with suspected COVID-19 in fever isolation wards of Second Hospital of Lanzhou University were enrolled From January 31, 2020 to February 22, 2020. Their clinical baseline data were collected. The anxiety of patients was assessed by Hamilton Anxiety Scale, and the depression of patients was assessed by Hamilton Depression Scale. Multivariate Logistic regression analysis was performed to explore the risk factors of anxiety and depression in these patients. Results: Female patients are more likely to have anxiety (OR=3.206, 95%CI:1.073-9.583, P < 0.05) and depression (OR=9.111, 95%CI:2.143-38.729, P < 0.01) than male patients; patients with known contact history of epidemic area and personnel in epidemic area are more likely to have depression (OR=3.267, 95%CI:1.082-9.597, P < 0.05). Conclusion: During the isolation treatment of suspected COVID-19 patients, early psychological intervention should be carried out for the female patients with known contact history of epidemic area and personnel in epidemic area, and drug treatment should be given in advance if necessary.

Roles of multidisciplinary team in diagnosis and treatment of suspected cases of COVID-19
DING Shubo,YU Shi'an,CHEN Haijun,ZHANG Dehe,XU Yejin,ZHU Dan,CHENG Kun
J Zhejiang Univ (Med Sci), 2020, 49(2): 209-214.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.15
Abstract( 308 )   HTML( 21 )     PDF(1052KB)( 32 )

Objective: To analyze the roles of multidisciplinary team (MDT) in the diagnosis and treatment of suspected cases of coronavirus disease 2019 (COVID-19). Methods: The clinical data of 48 patients with suspected COVID-19 admitted in Jinhua Municipal Central Hospital from January 21, 2020 to March 20, 2020 were retrospectively analyzed. Results: In the 48 suspected cases, 18 were diagnosed with COVID-19, and 30 were excluded. Each of the confirmed cases were discussed among MDT for 2 to 12 times with an average of (4.7±3.2) times; while for non-COVID-19 patients were discussed for 2 to 4 times with an average of (2.3±0.6) times. With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination. Except one transferred patient, all 17 confirmed COVID-19 patients were cured and discharged. There was no cross-infection occurred in suspected patients during the hospitalization. There were no deaths and no medical staff infections. Conclusion: The efficiency of diagnosis and treatment for suspected COVID-19 patients can be improved with MDT, particularly for complicated cases.

A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19
CHEN Jun,LIU Danping,LIU Li,LIU Ping,XU Qingnian,XIA Lu,LING Yun,HUANG Dan,SONG Shuli,ZHANG Dandan,QIAN Zhiping,LI Tao,SHEN Yinzhong,LU Hongzhou
J Zhejiang Univ (Med Sci), 2020, 49(2): 215-219.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.03
Abstract( 119658 )   HTML( 2512 )     PDF(1044KB)( 23548 )

Objective: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). Methods: We prospectively enrolled 30 treatment-naïve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1:1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). Results: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1, 9) days in HCQ group, which is comparable to that in the control group [2 (1, 4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0, 2) day after hospitalization, which was also comparable to that in the control group [1 (0, 3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). Conclusions: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.

Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids
ZHAGN Sheng,LI Danping,CHEN Huazhong,ZHENG Dan,ZHOU Yiping,CHEN Baoguo,SHI Weiwu,LIN Ronghai
J Zhejiang Univ (Med Sci), 2020, 49(2): 220-226.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.10
Abstract( 150 )   HTML( 17 )     PDF(4582KB)( 92 )

Objective: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient. Methods: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3+T, CD4+ T, CD8+ T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored. Results: On D1 of admission, the numbers of peripheral blood CD3+ T, CD4+ T, CD8+ T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3+ T, CD8+ T and CD4 + T cells gradually recovered and showed a linear growth trend (linear fitting equation: Y=18.59X+109.4, P < 0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90. Conclusion: In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.

Clinical observation of 6 severe COVID-19 patients treated with plasma exchange or tocilizumab
LUO Song,YANG Lijuan,WANG Chun,LIU Chuanmiao,LI Dianming
J Zhejiang Univ (Med Sci), 2020, 49(2): 227-231.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.06
Abstract( 383 )   HTML( 32 )     PDF(1042KB)( 232 )

Objective: To observe the clinical effect of plasma exchange and tocilizumab in treatment of patients with severe coronavirus disease 2019 (COVID-19). Methods: Six patients with severe COVID-19 admitted in First Affiliated Hospital of Bengbu Medical College from January 25 to February 25, 2020. Three patients were treated with plasma exchange and three patients were treated with tocilizumab. The effect on excessive inflammatory reaction of plasma exchange and tocilizumab was observed. Results: The C-reactive protein (CRP) and IL-6 levels were significantly decreased and the lymphocyte and prothrombin time were improved in 3 patients after treatment with plasma exchange; while inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in 3 patients treated with tocilizumab. Conclusion: For severe COVID-19 patients with strong inflammatory reaction, plasma exchange may be preferred.

Clinical experience of high-flow nasal cannula oxygen therapy in severe COVID-19 patients
HE Guojun,HAN Yijiao,FANG Qiang,ZHOU Jianying,SHEN Jifang,LI Tong,PU Qibin,CHEN Aijun,QI Zhiyang,SUN Lijun,CAI Hongliu
J Zhejiang Univ (Med Sci), 2020, 49(2): 232-239.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.13
Abstract( 59 )   HTML( 16 )     PDF(1077KB)( 40 )

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial flow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.

Pregnant women complicated with COVID-19: a clinical analysis of 3 cases
CHEN Xu,LI Yang,WANG Jinxi,CAI Hongliu,CAO Hongcui,SHENG Jifang
J Zhejiang Univ (Med Sci), 2020, 49(2): 240-244.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.08
Abstract( 249 )   HTML( 21 )     PDF(2811KB)( 149 )

Objective: To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19). Methods: The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed. Results: There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring. Conclusion: The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.

Management of a colon cancer patient complicated with COVID-19
YE Ziqi,HONG Yun,WU Xiuhua,HONG Dongsheng,ZHANG Yanfang,DONG Xihao,RAO Yuefeng,LU Xiaoyang
J Zhejiang Univ (Med Sci), 2020, 49(2): 245-248.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.12
Abstract( 146 )   HTML( 30 )     PDF(1028KB)( 126 )

Objective: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). Methods: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. Results: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. Conclusion: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

Anesthesia management in cesarean section for patient with COVID-19: a case report
KANG Xianhui,ZHANG Rong,HE Huiliang,YAO Yongxing,ZHENG Yueying,WEN Xiaohong,ZHU Shengmei
J Zhejiang Univ (Med Sci), 2020, 49(2): 249-252.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.04
Abstract( 322 )   HTML( 50 )     PDF(1025KB)( 277 )

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.

Establishment of a rapid identification of adverse drug reaction program in R language implementation based on monitoring data
HONG Dongsheng,NI Jian,SHAN Wenya,LI Lu,HU Xi,YANG Hongyu,ZHAO Qingwei,ZHANG Xingguo
J Zhejiang Univ (Med Sci), 2020, 49(2): 253-259.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.07
Abstract( 136 )   HTML( 18 )     PDF(1085KB)( 49 )

Objective: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. Methods: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). Results: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. Conclusion: In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.

Analysis of medication characteristics of traditional Chinese medicine in treating COVID-19 based on data mining
FAN Tiantian,CHEN Yongcan,BAI Yu,MA Fengqi,WANG Hengcang,YANG Yiping,CHEN Jinxu,LIN Yuqi
J Zhejiang Univ (Med Sci), 2020, 49(2): 260-269.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.14
Abstract( 76 )   HTML( 17 )     PDF(1290KB)( 36 )

Objective: To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19). Methods: We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed. Results: The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were Liquorice, Scutellariabaicalensis, Semen armeniacaeamarae, and Gypsum. The commonly used traditional formulations included Maxing Shigan decoction, Yin Qiao powder, and Xuanbai Chengqi decoction. The Chinese patent drugs included Angong Niuhuang pill, Xuebijing injection, and Lianhua Qingwen capsule. The most common paired medications were Ephedra and Semen armeniacaeamarae, Fructusforsythiae and Liquorice. Two core combinations and one novel formula were discovered in the study. Conclusions: Yin Qiao powder and Huopo Xialing decoction are the basic formulations for Weifen syndrome of COVID-19. In addition, Maxing Shigan decoction, Liang Ge powder, Qingwen Baidu decoction and Da Yuan decoction are the basic formulations for Qifen syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.

Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19
LI Youjiang,HU Yingying,ZHANG Xiaodong,YU Yuanyuan,LI Bin,WU Jianguo,WU Yingping,XIA Xiaoping,XU Jian
J Zhejiang Univ (Med Sci), 2020, 49(2): 270-274.   https://doi.org/10.3785/j.issn.1008-9292.2020.03.11
Abstract( 237 )   HTML( 25 )     PDF(1758KB)( 193 )

Objective: To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid. Methods: Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method. Results: There was no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria. Conclusion: There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.

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