2020 Volume 22 Issue 6 Published: 28 June 2020
  

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  • Success both in rescue and scientific research: comparison of medical papers published by Chinese in two epidemics
    Cai Haodong, Wang Yuqin
    2020, 22(6): 329-332. https://doi.org/10.3760/cma.j.cn114015-20200519-00549
    Abstract ( ) PDF ( )
    Facing the unprecedented epidemic situation of novel coronavirus pneumonia (COVID-19), medical workers in China have not only successfully controlled the spread of the epidemic in Chinese mainland in just 4 months, but also have made great achievements in scientific research on COVID-19. In the past 4 months, a total of 1-033 English papers about COVID-19 written by Chinese scholars have been published and included in PubMed database, which is 6.6 times the number of articles published in 2003. The proportion of papers published by authors in Chinese mainland has increased from 48.7% （76/156） during the SARS epidemic in 2003 to 84.8% （876/1-033） with 4 months in 2020. The papers were also published significantly earlier than before. Chinese researchers identified the novel coronavirus that caused the outbreak less than 1 month after the COVID-19 outbreak (on January 7, 2020) and reported it to the WHO. They also published articles on the genetic sequence and transmission dynamics of the virus and clinical characteristics of COVID-19 patients in that month. China pays more attention to drug safety of patients. The proportion of English and Chinese literature published by pharmaceutical authors increased from 0 and 0.2% (10/4-023) in 2003 to 2.3% (24/1-032) and 9.3% (215/2-317) from January to April in 2020, respectively. China has not only become a model for the world in epidemic control, but also made important contributions to the relevant academic research.
  • Efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia： a systematic review based on current and previous antiviral therapy
    Li Yun, Jin Yueping, Ge Qinggang, Liu Fang, Cheng Yinchu, Yang Li, Zhao Rongsheng
    2020, 22(6): 333-342. https://doi.org/10.3760/cma.j.cn114015-20200608-00646
    Abstract ( ) PDF ( )
    Objective To systematically evaluate the efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia (COVID-19).　Methods Randomized controlled trials (RCTs), cohort studies, and case-control studies on the efficacy and safety of arbidol for COVID-19, influenza, and other respiratory virus infections were collected by searching related database at home and abroad and network platform for preprint of Health Science Papers (medRxiv) (up to April 25, 2020). Quality of the enrolled studies was evaluated by bias risk assessment tool of Cochrane collaboration network and Newcastle- Ottawa Scale (NOS). Meta-analysis and descriptive analysis of relevant outcome indicators were performed using RevMan 5.3-software.　Results A total of 15-studies were enrolled in the study, including 7 cohort studies with high-quality and 8 RCTs, 6 of which were with low bias risk and the other 2 of which were with medium bias risk. Among these studies, 8 were on arbidol treatment for COVID-19, including 5 retrospective cohort studies, 2 prospective cohort studies, and 1 RCT, and involving 809 patients (479 patients in the arbidol group and 330 in the control group); 7 were RCTs on arbidol treatment for influenza or other respiratory virus infections, involving 1-471 patients (745 patients in the arbidol group and 726 in the control group).In these studies, patients were treated with arbidol (0.15-1.2 g daily for 5-21 d) in the arbidol group while with the other antiviral agents or without any antiviral drug in the control group. Meta analysis on the efficacy and safety of arbidol in treatment for COVID-19-showed that the novel coronavirus (2019-nCoV) nucleic acid negative conversion rate in the arbidol group was significantly higher than that in the control group ［71.7% (109/152) vs. 58.8% (94/160), relative risk (RR)=1.30, 95% confidence interval (CI): 1.01-1.67, P=0.04］; the difference of time taken for 2019-nCoV nucleic acid negative conversion between the 2 groups was not statistically significant (standardized mean difference=-0.17, 95%CI: -0.72-0.38, P=0.55); the difference of disease improvement rate shown by chest CT on day 7 after treatment between the 2 groups was not statistically significant ［46.2% (30/65) vs. 50.7% (36/71)， RR=0.88， 95%CI: 0.39-1.98， P=0.76］; and the difference of incidence of adverse reactions between the 2 groups was not statistically significant ［16.9% (39/231) vs. 19.2% (47/245), risk difference (RD)=-0.03, 95%CI: -0.10-0.04， P=0.44］. Meta analysis on the safety of arbidol in treatment for influenza and other respiratory virus infections showed that the incidence of adverse reactions in the arbidol group was significantly lower than that in the control group ［5.9% (44/745) vs. 11.3% (82/726), RR=0.52, 95%CI: 0.37-0.74, P<0.01］.　Conclusion Arbidol could effectively increase the 2019-nCoV nucleic acid negative conversion rate and it might be safe to treat COVID-19 using arbidol.
  • Analysis of fatal cardiac adverse events caused by chloroquine: a study based on the related data from the WHO global database of individual case safety reports
    Zhang Qingxia, Bai Xiangrong, Yue Qunying
    2020, 22(6): 343-349. https://doi.org/10.3760/cma.j.cn114015-20200302-00197
    Abstract ( ) PDF ( )
    Objective To analyze the clinical characteristics of fatal cardiac adverse events associated with chloroquine, which was recommended for the antiviral treatment of novel coronavirus pneumonia, and provide reference for clinical safe drug use.　Methods The fatal cardiac adverse events associated with chloroquine were searched from the World Health Organization global database of individual case safety reports (VigiBase). The clinical characteristics of the individual cases with well-documented reports (VigiGrade completeness score ≥0.80 or with detailed original reports) were analyzed. The adverse events were coded using the systematic organ classification (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) version 22.1 of International Conference on Harmonization (ICH).　Results Up to 23 February 2020, a total of 45 reports of fatal heart injuries related to chloroquine were reported in VigiBase, which were from 16 countries. Of them, 30 reports were fully informative. Among the 30 reports, 20 cases developed fatal cardiac adverse events after a single large dose of chloroquine. Of them, 17 cases′ fatal cardiac adverse events were caused by overdose of chloroquine (15 cases were suicide or suspected suicide, and 2 children took chloroquine by mistake); 3 cases′ fatal cardiac adverse events were caused in clinical treatment; 18 cases showed arrhythmia and cardiac arrest; 6 cases showed prolonged QRS wave or QT interval; 6 cases were with hypokalemia, including 4 severe ones. Among the 30 reports, 10 cases deve- loped fatal cardiac adverse events after multiple administration of chloroquine, of which 4 cases were treated with chloroquine for 23 days to 2 months and died of heart failure, cardiac arrest or myocardial infarction; 6 cases were treated with chloroquine for 20 months to 29 years and all of them had cardiomyopathy, which were confirmed by endomyocardial biopsy to be caused by chloroquine in 3 cases.　Conclusion Cardiac toxicity was the primary cause of fatal adverse events caused by chloroquine; the main manifestation of single large dose of chloroquine was arrhythmia and the manifestation of multiple administration was cardiomyo- pathy.
  • Clinical observation on safety of chloroquine phosphate treatment in patients with novel coronavirus pneumonia
    Liu Miaona, Qian Wenjing, Li Wei, Xiao Wei, Jian Yanlin, Wang Zhaoqin
    2020, 22(6): 350-354. https://doi.org/10.3760/cma.j.cn114015-20200311-00255
    Abstract ( ) PDF ( )
    Objective To explore the safety of chloroquine phosphate treatment in patients with novel coronavirus pneumonia (COVID-19) and provide references for clinical safety medication.　Methods Active monitoring for adverse events (AE) was carried out in the Third People′s Hospital of Shenzhen from February to March 2020 during the treatment with chloroquine phosphate in patients with COVID-19. The causal relationship between AE and chloroquine phosphate was evaluated.　Results A total of 33 patients were entered in the study, including 16 males and 17 females, aged (43±13) years. The clinical types of COVID-19 in 26 patients (78.8%) were mild, in 7 patients (21.2%) were common. There were 7 patients (21.2%) with basic diseases, including 6 with hypertension and 1 with hypothyroidism. The treatment course of chloroquine phosphate was (8±3) days. During the treatment, a total of 28 cases of AE in 24 (72.7%) of the 33 patients which were probably or possibly related to chloroquine phosphate were detected. The clinical manifestations of AE included abnormal liver function (8/33, 24.2%), gastrointestinal reactions (8/33, 24.2%), neuropsychiatric system reactions (8/33, 24.2%), cardiovascular system reactions (5/33, 15.2%), eye and vision abnormality (2/33, 6.1%), and skin injury (1/33, 3.0%). The severity of AE was grade 1 or grade 2. After drug withdrawal or symptomatic treatments, all the patients′ symptoms were improved and the laboratory tests results returned to normal.　Conclusion The adverse effects of chloroquine phosphate in the treatment of patients with COVID-19 are mild, but it is still necessary to strengthen the monitoring.
  • Clinical case analysis of novel coronavirus pneumonia complicated with pulmonary hypertension
    Wang Lianshuang, Bai Li, Yu Jing, Wang Liping, Wang Xuemei, Xiang Pan, Gao Xuesong, Zhang Yao
    2020, 22(6): 355-359. https://doi.org/10.3760/cma.j.cn114015-20200509-00506
    Abstract ( ) PDF ( )
    Objective To report the clinical features of pulmonary hypertension diagnosed by echocardiography in 5 patients with novel coronavirus pneumonia (COVID-19) in order to understand the special clinical manifestations of COVID-19 and explore the possible mechanism.　Methods The echocardiographic data and clinical characteristics of COVID-19 patients complicated with pulmonary hypertension diagnosed by echocardiography in Beijing Ditan Hospital, Capital Medical University were analyzed descriptively from February 5 to March 31, 2020.　Results A total of 15 patients with severe and critical COVID-19 patients underwent echocardiography. Of them, 7 patients were diagnosed with pulmonary hypertension, 5 of which were confirmed as complications of COVID-19. Among the 5 patients, 4 were female and 1 was male, aged 62-78 years; 4 were with hypertension, 3 were with diabetes, and 1 was with coronary atherosclerotic heart disease. All 5 critically ill patients with COVID-19 were given ventilator-assisted breathing, 2 of which were given extracorporeal membrane oxygenation at the same time. According to echocardiography, the systolic pressure of pulmonary artery in 5 patients was 43-65-mmHg, with an average of 54-mmHg. The severity of pulmonary hypertension was graded as mild in 1 patient and moderate in 4 patients. During the follow-up, pulmonary artery systolic pressure gradually decreased to normal in 4 patients, and then ventilator and ECMO were withdrawn; 1 patient died due to respiratory failure and persistent pulmonary hypertension.　Conclusions Patients with COVID-19 may be complicated by pulmonary hypertension, which is often found in the critical patients. Echocardiography is an important imaging diagnostic method for pulmonary hypertension in patients with COVID-19.
  • Analysis on occurrence and risk factors of drug-induced liver injury in patients with novel coronavirus pneumonia
    Deng Xuanyu, Huang Juanjuan, Sun Ji, Huang Shiqiong, Li Yanfei, He Gefei
    2020, 22(6): 360-365. https://doi.org/10.3760/cma.j.cn114015-20200331-00322
    Abstract ( ) PDF ( )
    Objective To analyze the occurrence and risk factors of drug-induced liver injury (DILI) in patients with novel coronavirus pneumonia (COVID-19).　Methods The medical records of patients with COVID-19 who were discharged from the First Hospital of Changsha from January 15 to March 7, 2020 were collected and the patients were divided into the DILI group and the non-DILI group based on DILI diagnostic criteria. Basic information of patients in the 2 groups including gender, age, underlying diseases, classification of COVID-19, liver function test results on admission and after medication, drug use, time to DILI onset after medication, and treatments and outcomes of DILI were recorded and compared. The incidence of DILI in patients with COVID-19 was calculated, and the factors whose P<0.05 in inter-group comparison were included in the multivariate logistic regression analysis to calculate the odds ratio (OR) and 95% confidence interval (CI).　Results A total of 203 discharged patients with COVID-19 met the inclusion criteria. Of them, 36 patients developed DILI, the incidence was 17.73%. Between the DILI group and the non-DILI group (167 patients), the differences were statistically significant in gender distribution, proportion of patients with underlying diseases such as hypertension, fatty liver, and cholelithiasis, clinical classification of COVID-19, and the kinds of drug use (P<0.05 for all), but not statistically significant in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) on admission (P>0.05 for all). The levels of ALT and AST in patients in the DILI group after medication were higher than those before medication, and the differences were statistically significant (P<0.001 for all). The median time for time to DILI onset after medication was 8 (6, 11) days and none of the patients had obvious clinical signs and symptoms. After the occurrence of DILI, 16 patients stopped the suspicious drugs and received liver- protective treatments, 6 patients only stopped the suspicious drug without additional treatments, and 14 patients received liver-protective treatments without drug withdrawal. Among the 36 patients in the DILI group, liver function were improved in 34 patients but did not returned to normal in 2 patients when they were discharged from the hospital. Multivariate logistic regression analysis showed that male (OR=3.939，95%CI: 1.426-10.883, P=0.008), being severe and critical in clinical classification (OR=6.433, 95%CI: 2.411-17.162，P<0.001), fatty liver (OR=3.815, 95%CI: 1.298-11.215, P=0.015), cholelithiasis (OR=16.347, 95%CI: 1.267-210.990, P=0.032), and the kinds of drug use >8 (OR=10.181, 95%CI: 3.606-28.744, P<0.001) were the independent risk factors of DILI in patients with COVID-19.　Conclusions The incidence of DILI in COVID-19 patients discharged from the First Hospital of Changsha is 17.73%. Male, being severe and critical in clinical classification of COVID-19, fatty liver, cholelithiasis, and the kinds of drug use >8 are the independent risk factors for DILI patients with COVID-19.
  • Research progress in antiviral therapy for novel coronavirus pneumonia
    Xu Jinghang, Liang Rongyue, Yu Yanyan
    2020, 22(6): 366-372. https://doi.org/10.3760/cma.j.cn114015-20200516-00539
    Abstract ( ) PDF ( )
    Since the outbreak of novel coronavirus pneumonia (COVID-19), a number of clinical studies have been carried out globally in order to explore efficacy and safety of drugs for novel coronavirus (2019-nCoV). These studies were mainly focused on drugs with anti-2019-nCoV activity tested in vitro and those previously used for the treatment of SARS and Middle East respiratory syndrome, including remdesivir, lopinavir/ritonavir, chloroquine, hydroxychloroquine, arbidol, interferon, ribavirin, and etc. The recent clinical studies on anti-2019-nCoV drugs are reviewed in this article, but the current research results are inconsistent, which are insufficient to constitute evidence for the efficacy and safety of these drugs in the treatment of COVID-19. In the absence of specific antiviral agents, remdesivir can be a treatment option for patients with critical illness or rapid progress. Some clinical studies are still in progress. We are looking forward to more large-scale and multicenter clinical trials to provide safe and effective evidence for antiviral treatment in the future.
  • Rashes caused by arbidol in a patient with novel coronavirus pneumonia
    Xiong Yu, Bian Yuan, Tang Xiting, Tong Rongsheng, Cui Xiaojiao, Jiang Min, Yang Zhiyong
    2020, 22(6): 373-374. https://doi.org/10.3760/cma.j.cn114015-20200316-00281
    Abstract ( ) PDF ( )
    A 50-year-old male patient with agitated depression and hyperlipemia received oral amoxicillin and clavulanate potassium 0.5 g once daily and 2 lopinavir and ritonavir tablets twice daily for novel coronavirus infection, based on previous drugs including quetiapine, clonazepam, and atorvastatin calcium. After 3 days, lopinavir and ritonavir was changed to oral arbidol 200-mg, thrice daily due to suspicious drug interaction. After taking arbidol for 3 days, the patient developed red papules on the whole body. Considering that it might be related to amoxicillin and clavulanate potassium, the drug was stopped and loratadine was given. But the rashes were aggravated. Considering that the drug eruption was caused by arbidol, arbidol was discontinued and the rashes subsided in a large area the next day. Then vitamin C injection, calcium gluconate injection, and ribavirin were added. After 5 days, the rashes subsided completely. After 17 days, the patient recovered from pneumonia.
  • Hyperkalemia caused by Qingfei Paidu decoction(清肺排毒汤) in a patient with novel coronavirus pneumonia
    Han Maozhi, Li Shasha, Li Jing, Li Xianchao, Gao Linlin, Lu Yan, Zhou Ziyu
    2020, 22(6): 375-376. https://doi.org/10.3760/cma.j.cn114015-20200309-00240
    Abstract ( ) PDF ( )
    A 23-year-old male patient received moxifloxacin, recombinant human interferon α-2b for injection, and lopinavir and ritonavir for 7 days for novel coronavirus pneumonia. There was no abnor-malityof serum potassium. Moxifloxacin was stopped, Qingfei Paidu decoction(清肺排毒汤) was given, and then the patient′s serum potassium began to rise. On day 10 after taking the decoction, laboratory tests showed serum potassium 5.7-mmol/L and the patient was diagnosed with hyperkalemia. Insulin injection 4 U diluted to 5% glucose injection 250-ml was given once by IV infusion, and then the serum potassium decreased to 5.0-mmol/L 6 hours later and 4.6-mmol/L 2 days later. After 5 days, the serum potassium rose again and finally to 5.4-mmol/L on day 17 after taking the decoction. Insulin was given once that day and 2 days later once daily according to the previous method. Then the serum potassium decreased and did not rise again. The patient recovered from novel coronavirus pneumonia and was discharged on day 28 after hospitalization.
  • Oligohydramnios caused by exposure to losartan during pregnancy
    Song Chunrong, Wei Qiang, Zhang Li, Xu Yi, Duan Meifan
    2020, 22(6): 377-378. https://doi.org/10.3760/cma.j.cn114015-20190930-00791
    Abstract ( ) PDF ( )
    A 32-year-old female patient with nephrotic syndrome got pregnant during treatments with losartan potassium tablets (50-mg once daily), methylprednisolone tablets(12-mg every other day), and dipyridamole tablets(50-mg once daily). She continued these drugs during pregnancy. Ultrasonographic examination at 24+2 weeks of gestation indicated oligohydramnios, which lasted until 32+2 weeks of gestation. The amniotic fluid volume ranged 1.1-3.4-cm, and the amniotic fluid indexes were 1.9-6.9-cm. Losartan and methylprednisolone were discontinued, and nifedipine controlled released tablets (30-mg once daily) were given to reduce blood pressure. Amniotic fluid volume gradually increased to normal. At 34+4 weeks of gestation, her blood pressure rose to 177/113-mmHg. Preeclampsia was diagnosed. She was treated with magnesium sulfate (IV infusion at a speed of 1 g/h), oral nifedipine controlled released tablets（60-mg once daily） and labetalol (200-mg twice daily). Then her blood pressure was 143/82-mmHg and urinary protein detection was positive (++). At 35+3 weeks of gestation, a baby boy was delivered by cesarean section, with a body length of 43-cm and a weight of 2 200 g. Neonatal Apgar scores at 1-min and 5-min were both 10, and no birth defects were found. During the follow-up to 24 months of age, his growth and development were good, and intellectual development and physical exercise were normal.
  • Sodium valproate-induced hyperlactatemia with metabolic acidosis
    Wang Zhizhou, Cheng Hongqin, Bai Xiangrong, Jin Ying, Jiang Dechun, Zhang Shengpeng
    2020, 22(6): 379-380. https://doi.org/10.3760/cma.j.cn114015-20181221-01269
    Abstract ( ) PDF ( )
    A 45-year-old male patient underwent craniotomy and biopsy for intracranial lesions. In order to prevent epilepsy, sodium valproate 800-mg dissolved in 0.9% sodium chloride injection 8-ml was injected intravenously after operation, and then the sodium valproate solution of this concentration was continuously pumped at a speed of 0.6-ml/h. One hour after administration, the serum lactate level of the patient increased gradually, reaching the highest level of 14.7-mmol/L, accompanied by metabolic acidosis and compensatory respiratory alkalosis, and with the lowest pH of 7.09 and the lowest base excess of -26.3. The patient fell into a coma. The hyperlactatemia and metabolic acidosis were considered to be related to sodium valproate. Sodium valproate was stopped, intravenous infusion of 5% sodium bicarbonate injection and blood purification were given at the same time. After 3 days, the lactate level of the patient returned to normal, metabolic acidosis was basically corrected, and his mind was clear.
  • Kidney injury caused by esomeprazole magnesium enteric-coated tablets
    Gao Feimeng, Song Zhihui
    2020, 22(6): 381-382. https://doi.org/10.3760/cma.j.cn114015-20200305-00219
    Abstract ( ) PDF ( )
    A 56-year-old male patient received an IV infusion of methylprednisolone 500-mg/d, which was changed to oral prednisone 40-mg/d after 3 days, for thyroid associated ophthalmopathy. Calcium carbonate, calcitriol, alendronate sodium, and esomeprazole magnesium enteric-coated tablets were given orally to prevent hormone-related adverse reactions. The renal function of the patient was normal in the past, but continued to decline after 1 month of medication. And at the end of 3 months after medication, the lowest estimated glomerular filtration rate (eGFR) was 33.1-ml/(min·1.73 m2). Renal diseases and urinary tract obstruction were excluded by routine urine analysis and color Doppler ultrasound examination of the kidneys. Kidney injury caused by esomeprazole magnesium enteric-coated tablets was considered. Then the drug was replaced by famotidine and the other drugs were continued. After 9 days, the renal function of the patient gradually recovered, with the eGFR of 74.0 ml/(min·1.73 m2) at discharge.
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