Effectiveness of Tocilizumab in COVID-19 patients with pneumonia: A systematic review

Background and Objective@#COVID-19 contributes significantly to global morbidity and mortality. Age-related comorbidities elevate the risk of severe cases. Studies have recently demonstrated that widely available medications, including tocilizumab (TCZ), can manage severe symptoms. However, its effectiveness is unclear, particularly among the older population. Therefore, this review aimed to evaluate TCZ’s efficacy in managing severe pneumonia in individuals aged 50 and older.@*Methods@#We systematically search several databases and gray literature including Web of Science, CINAHL, Academic Search Complete, PsycINFO, PsycArticles, SocINDEX, CENTRAL/Cochrane Library, PubMed/MEDLINE for original research articles in English across several study designs published in the year 2020-2022. A narrative synthesis was conducted to summarize the evidence. We employed the NIH quality assessment tool for observational cohort studies to evaluate risk of bias. Additionally, we utilized GRADE to appraise the certainty of evidence.@*Results@#Among 539 screened articles, only five studies met the selection criteria. Tocilizumab's impact on severe COVID-19 pneumonia revealed a diverse effect on mortality rate, with 29% in the TCZ group, and 40% in the controls died within 30 days of intubation (OR 0.61; 95% CI, 0.27-1.36). It is also reported that TCZ was not associated with mortality, despite faster decline in pulmonary function and prolonged fever. Hospital mortality in the TCZ group was significantly lower than in the controls, and age over 60 was the only significant risk factor. Moreover, administering TCZ reduced mechanical ventilation needs, with 82% extubated compared to 53% in controls. However, 45% in TCZ group was associated with a higher ventilator-associated pneumonia rate than in the untreated group which was 20% (P < 0.001). Despite this, TCZ-treated patients had shorter hospital stays.@*Conclusions@#The effects of tocilizumab on reducing mortality risk and improving the survival rate of COVID-19 patients with pneumonia remained inconclusive. Yet, the majority of results suggested that giving tocilizumab leads to shorter hospital stays, lowers the requirement for mechanical ventilation, and decreases the likelihood of ICU transfer. Tocilizumab is linked to the incidence of secondary infections; hence, this medication should be closely monitored for side effects.

Spatial epidemiological analysis of severe hand, foot and mouth disease in Guangxi, 2014-2018 / 中国热带医学

@#Abstract: Objective　To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods　Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results　From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions　Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

Analysis of the epidemiological characteristics of severe and deceased cases of hand, foot and mouth disease in Hebei province between 2010 and 2016 / 中华实验和临床病毒学杂志

Objective@#To analyze the epidemiological characteristics of severe and deceased cases of hand, foot and mouth disease (HFMD) in Hebei province, so as to provide reference for prevention and control of the disease.@*Methods@#Severe and deceased HFMD cases reported from the National Disease Surveillance Information Management System and the laboratory testing result in Hebei province from 2010 to 2016 were analyzed. Descriptive epidemiological method involving the distribution of population, area, time and pathogeny were used for the analysis.@*Results@#From 2010 to 2016, 3 803 severe HFMD cases and 162 deceased cases were reported in Hebei province, and the ratio of severe cases among all HFMD patients was 0.75%. A chi-square test showed that the incidence of severe HFMD between males and females was significantly different (χ2=239.37, P<0.001), and scattered children were the main patient. Infants less than six months of age had the highest ratio of severe HFMD cases, the group of one-year-old and younger children had the highest proportion of severe HFMD cases. The severe ratio and severe incidence of Xingtai, Langfang and Hengshui were the top three prefectures having the highest proportions of severe cases. The number of severe cases fluctuated over the past 7years, but showed a downward trend. The constituent ratios of EV-A71 in severe cases and deaths were 79.25% and 92.66%, respectively.@*Conclusions@#Severe HFMD epidemics showed a declining trend in Hebei province. EV-A71 is still the main pathogen of both severe and fatal cases. It is necessary to strengthen the prophylactic and therapeutic measures for the young children (< 2 years).

Alert: Severe cases and deaths associated with Chikungunya in Brazil

Abstract Since the detection of the Chikungunya virus in America in 2013, two million cases of the disease have been notified worldwide. Severe cases and deaths related to Chikungunya have been reported in India and Reunion Island, estimated at 1 death per 1,000 inhabitants. Joint involvement in the acute and chronic phase is the main clinical manifestation associated with Chikungunya. The severity of the infection may be directly attributable to viral action or indirectly, owing to decompensation of preexisting comorbidities. In Brazil, the virus was identified in 2014, and recently, there has been a significant increase in the number of deaths caused by the Chikungunya virus infection, especially in Pernambuco. However, the numbers of fatalities are probably underreported, since for many cases, the diagnosis of Chikungunya infection may not be considered, for deaths by indirect causes. An increase in the mortality rate within months of epidemic occurrence, compared to previous years has also been reported and may be associated with Chikungunya virus infection. An in-depth investigation of reported mortality in Brazil is necessary, to measure the actual impact of the deaths, thereby, allowing the identification of possible causes. This will alert professionals about the risks, and hence, enable creation of protocols that target reducing mortality.

Severe cases with hand, foot and mouth disease: data based on national pilot hand, foot and mouth disease surveillance system / 中华流行病学杂志

Objective To investigate the clinical severity,etiological classification and risk factors of severe cases with hand,foot and mouth disease (HFMD).Methods A total of 1 489 records on severe and fatal HFMD cases reported to the national pilot surveillance system of HFMD were used to analyze the demographic,medical treatment,etiological classification of the cases.Treatment outcome related risk factors were also studied with multi-variable stepwise logistic regression method.Results Seven out of the 1 489 severe HFMD cases died of this disease.A total of 960 (72.9％) were under three years old and 62.9％ were male and most of the cases (937,62.9％) resided in rural areas.Among all the cases,494 (33.2％) went to seek the first medical assistance at the institutions of village or township level.Durations between disease onset and first medical attendance,being diagnosed as the disease or diagnosed as severe cases were 0(0-1) d,1 (0-2) d and 2 (1-4) d,respectively.In total,773 (51.9％) of the severe HFMD cases were diagnosed as with aseptic meningitis,260 (17.5％) with brainstem encephalitis,377 (25.3 ％) with non-brainstem encephalitis,6 (0.4％) with encephalomyelitis,1 (0.1％) with acute flaccid paralysis,4 (0.3％) with pulmonary hemorrhage/pulmonary edema and 68 (4.6％) with cardiopulmonary failure.Of the etiologically diagnosed 1 217 severe and fatal HFMD cases,642 (52.8％) were with EV71,other enterovirus 261 (21.5％),Cox A16 36 (3.0％),1 (0.1％) with both EV71 and Cox A16.However,277 (22.8％) showed negative on any pathogenic virus.Complication (Z=3.15,P=0.002) and duration between onset and diagnosed as severe cases (Z=3.95,P＜0.001) were shown as key factors related to treatment outcomes.Conclusions Most severe HFMD cases appeared in boys,especially living in the rural areas.Frequently seen complications would include aseptic meningitis,non-brainstem encephalitis and brainstem encephalitis.EV71 was the dominant etiology for severe and fatal cases.Early diagnosis and complication control were crucial,related to the treatment outcome of HFMD.

Severe cases with hand, foot and mouth disease: data based on national pilot hand, foot and mouth disease surveillance system / 中华流行病学杂志

Objective To investigate the clinical severity,etiological classification and risk factors of severe cases with hand,foot and mouth disease (HFMD).Methods A total of 1 489 records on severe and fatal HFMD cases reported to the national pilot surveillance system of HFMD were used to analyze the demographic,medical treatment,etiological classification of the cases.Treatment outcome related risk factors were also studied with multi-variable stepwise logistic regression method.Results Seven out of the 1 489 severe HFMD cases died of this disease.A total of 960 (72.9％) were under three years old and 62.9％ were male and most of the cases (937,62.9％) resided in rural areas.Among all the cases,494 (33.2％) went to seek the first medical assistance at the institutions of village or township level.Durations between disease onset and first medical attendance,being diagnosed as the disease or diagnosed as severe cases were 0(0-1) d,1 (0-2) d and 2 (1-4) d,respectively.In total,773 (51.9％) of the severe HFMD cases were diagnosed as with aseptic meningitis,260 (17.5％) with brainstem encephalitis,377 (25.3 ％) with non-brainstem encephalitis,6 (0.4％) with encephalomyelitis,1 (0.1％) with acute flaccid paralysis,4 (0.3％) with pulmonary hemorrhage/pulmonary edema and 68 (4.6％) with cardiopulmonary failure.Of the etiologically diagnosed 1 217 severe and fatal HFMD cases,642 (52.8％) were with EV71,other enterovirus 261 (21.5％),Cox A16 36 (3.0％),1 (0.1％) with both EV71 and Cox A16.However,277 (22.8％) showed negative on any pathogenic virus.Complication (Z=3.15,P=0.002) and duration between onset and diagnosed as severe cases (Z=3.95,P＜0.001) were shown as key factors related to treatment outcomes.Conclusions Most severe HFMD cases appeared in boys,especially living in the rural areas.Frequently seen complications would include aseptic meningitis,non-brainstem encephalitis and brainstem encephalitis.EV71 was the dominant etiology for severe and fatal cases.Early diagnosis and complication control were crucial,related to the treatment outcome of HFMD.

A study on epidemiological characteristic of severe hand -foot -mouth disease in Fengtai District,Beijing / 预防医学

Objective To learn the epidemiological characteristics of severe hand,foot,mouth disease (HFMD)in Fengtai District,and to provide the theoretical basis for the prevention and intervention of severe hand,foot,mouth disease cases. Methods Descriptive epidemiological analysis was conducted on the incidence data of severe cases of HFMD in Fengtai District,2010 -2015.Results The reported number of severe cases of HFMD was highest in 2010.The cases decreased year by year,and the annual incidence peak was present during June -August.The most cases were young children aged 1 -5 years. EV71 was the major pathogen,but other intestinal virus presented a rising trend.Cases were mainly floating population and presented regional distribution of small commodity wholesale market.Clinical features were mainly fever,rash,accompanied by more nervous system symptoms.The clinical symptoms include fever and rash usually accompanied by symptoms of the nervous system.Conclusion Severe cases presented a decline trend,and the proportion of other intestinal virus pathogen was increasing.More attention should be paid to other enterovirus infection of hand,foot and mouth disease among children.

Correlation of nutrient levels and state of severe cases with HFMD / 中国免疫学杂志

Objective:To detect the levels of PA,FN,RBP,CRP,Iron,Zinc,VitD in peripheral blood of children with HFMD and to explore the relationship between them and the disease .Methods:The levels of PA,FN,RBP and CRP were detected by immune turbidimetric assay;and the levels of Iron and Zinc were detected by flame atomic absorption spectrometry ;while the levels of VitD were detected by electro chemilumin escence .Results:The levels of PA,FN,RBP,Iron,Zinc and VitD in the severe group were lower than those in other groups ,while the levels of CRP were higher than those in other groups ( P0.05 ) .The levels of PA,FN,RBP,Fe,Zn and VitD in the convalescence were higher than those in the acute phase of the severe cases (P0.05).There were negative correlation between the levels of PA ,FN,RBP and the state of HFMD(P<0.05),while there were positive correlation between the levels of CRP and the state of HFMD (P<0.05). And there were low negative correlation between the levels of Iron , Zinc, VitD and the state of HFMD ( P <0.05 ), respectively.Conclusion:There were nutritional deficiency in severe cases of HFMD ,and the nutritional status should be assessed dy-namically,then proper amount of nutrition should be supplement .

Study on the score criteria of severe hand, foot and mouth disease cases / 中华流行病学杂志

Objective To explore the score criteria of severe hand, foot and mouth disease (HFMD) cases and to provide evidence for unified criteria and treatment on severe HFMD cases.Methods All severe cases and partial mild cases reported by two designated hospitals of HFMD in Fuyang during March to June, 2008 were scored by the methods of criteria constructed in advance.ROC curve was adopted to evaluate the score criteria and the gold standard was defined according to ICU, intubation and clinical outcomes, etc. Sensitivity, specificity and Youden' s index were used to determine the division scores on critical, severe and mild cases. Results 97% of the cases (34 cases) were scored less than 6 points. 88% of cases (24 cases) who were intubated or mechanical ventilated had the scores of 6 points or higher. 79% of deaths (11 cases) were scored 10 points or higher. The area of receiver operation characteristic (ROC) curve was 0.90 (95% CI: 0.83-0.98)between severe and mild cases and the area of ROC curve was 0.95 (95%CI: 0.92-0.98) between critical and severe, mild cases. When comprehensively considering the sensitivity and specificity,severe cases were best judged when score was 4 points (sensitivity, specificity and Youden' s index were 0.94, 0.68 and 0.62 respectively). When score was 6 points, critical cases were judged very well (sensitivity, specificity and Youden' s index were 0.92, 0.84 and 0.76 respectively). Conclusion Score criteria could be quantified to determine the degree of seriousness and with high-value for diagnosis on HFMD.