Clinical characteristics of 57 cases of Brucella infection in Shenzhen City / 中华传染病杂志

Objective:To analyze the clinical characteristics of Brucella infection in Shenzhen City, and to provide reference for clinical diagnosis and treatment of patients with Brucella infection. Methods:The clinical characteristics of 57 patients with Brucella infection from January 1, 2018 to December 31, 2020 in The Third People′s Hospital of Shenzhen were retrospectively analyzed. The clinical characteristics of patients with brucellosis and latent Brucella infection, patients with or without comorbidities were compared respectively, and magnetic resonance imaging (MRI) and lumbar puncture examination findings of 57 patients were also analyzed. Statistical analysis was performed using Wilcoxon rank sum test and chi-square test. Results:Among the 57 patients with Brucella infection, 10 cases (17.5%) were latent infections and 47 cases (82.5%) were brucellosis patients. Among brucellosis patients, 91.5%(43/47) had fever and 74.4%(32/43) had maximum body temperature ≥38.1 ℃, 40.4%(19/47) had chills orshivering, 25.5%(12/47) had hyperhidrosis, 17.0%(8/47) had fatigue, 21.3%(10/47) had headache, 23.4%(11/47) had neck/back/low back pain, and 31.9%(15/47) had joint pain. A total of 18 cases (38.3%) had comorbidities. Cases with positive blood cultures in latent infection and brucellosis were seven and 39, respectively. The time from symptom onset to diagnosis was 30.0 (15.0, 67.5) days in 18 patients of brucellosis with comorbidity, which was longer than 20.0 (13.0, 30.0) days in 29 patients without comorbidity. Neck/back/low back pain and joint pain occurred in patients with brucellosis with comorbidity were seven and nine, respectively, and those without comorbidity were four and six, respectively, with statistically significant differences ( Z=-2.00, χ2=3.90 and 4.39, respectively, all P<0.050). Of the 11 brucellosis patients with neck/back/low back pain, six had spondylitis. Of the 15 brucellosis patients with joint pain, six had arthritis. Lumbar puncture examination did not indicate meningitis in six cases of latent infection, while revealed six cases of brucellosis meningitis in 32 brucellosis patients. Fifty-four patients had good outcomes, and three patients were cured after an extended course of treatment. Conclusions:Although patients with latent Brucella infection have no comorbidities, they have a high positive blood culture rate. Active standardized anti- Brucella treatment is recommended. MRI examination of relevant sites is recommended in brucellosis patients with joint, neck/back/low back pain, and lumbar puncture is recommended in brucellosis patients regardless of headache.

Persistent while declined neutralizing antibody responses in the convalescents of COVID-19 across clinical spectrum during the 16 months follow up

Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400[~]480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with [≥] 50% decrease in MN titers when comparing the available peak and current MN titers ([≥] 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.

Efficacy of antiviral therapy for chronic hepatitis B with nonalcoholic fatty liver disease / 临床肝胆病杂志

Objective To investigate the influence of nonalcoholic fatty liver disease (NAFLD) on the antiviral response of patients with chronic hepatitis B (CHB), and to provide a reference for clinical treatment of such patients. Methods A total of 187 patients who attended Shenzhen Third People's Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients, NAFLD group with 41 patients, and CHB+NAFLD group with 103 patients. Related indices were measured at enrollment different time points of follow-up, including body height, body weight, alanine aminotransferase (ALT), aspartate aminotransferase, four blood lipid parameters, four indicators of liver fibrosis, aspartate aminotransferase-to-platelet ratio index, HBsAg, HBeAg, anti-HBe, and HBV DNA quantification, and the CHB patients and the CHB+NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12, 24, 48, 72, and 96 of antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the NAFLD group at baseline, the CHB group and the CHB+NAFLD group had significantly lower platelet count, ALT, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, and right lobe of liver oblique diameter (all P 0.05). At week 12 of antiviral therapy, there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB+NAFLD group (all P > 0.05); compared with the CHB+NAFLD group at weeks 24 and 48, the CHB group had significantly greater reductions in ALT ( Z =-2.128 and -3.055, both P < 0.05) and GGT ( Z =-2.025 and -1.631, both P < 0.05); at week 48, the CHB group and the CHB+NAFLD group had a significant reduction in HBV DNA ( Z =-6.445 and -4.415, both P < 0.001), and the CHB group had a significantly greater reduction. The CHB+NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy ( χ 2 =14.237, 13.961, 15.226, 10.462, and 13.030, all P < 0.05). At week 48 of antiviral therapy, the CHB+NAFLD group had a significantly lower HBeAg clearance rate than the CHB group ( χ 2 =5.309, P =0.021), while there was no significant difference between the two groups at week 96 ( χ 2 =0.117, P =0.732). At weeks 24, 48, 72, and 96 of antiviral therapy, the CHB+NAFLD group had a significantly lower ALT normalization rate than the CHB group ( χ 2 =12.049, 5.287, 11.407, and 11.375, all P < 0.05). Conclusion NAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy.

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic / 医学前沿

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

Viral shedding and immunological features of children COVID-19 patients

BackgroundSARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed. MethodsEpidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines. Results40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. ConclusionCOVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.

Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study

SummaryO_ST_ABSBackgroundC_ST_ABSManaging discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk. MethodsA population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts. FindingsOf 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29-38 years). The median discharge-to-RP length was 8 days (95% CI: 7-14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1{middle dot}9-5{middle dot}7 log10 copies/mL (median: 3{middle dot}2, 95% CI: 3{middle dot}1-3{middle dot}5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of [≥]1:32. InterpretationRP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of [≥] 1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials. FundingSanming Project of Medicine in Shenzhen, China National Science and Technology Major Projects Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Shenzhen Committee of Scientific and Technical Innovation grants.

Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications

IMPORTANCEHow to appropriately care for patients who become PCR-negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still not known. Patients who have recovered from coronavirus disease 2019 (COVID-19) could profoundly impact the health care system if a subset were to be PCR-positive again with reactivated SARS-CoV-2. OBJECTIVETo characterize a single center COVID-19 cohort with and without recurrence of PCR positivity, and develop an algorithm to identify patients at high risk of retest positivity after discharge to inform health care policy and case management decision-making. DESIGN, SETTING, AND PARTICIPANTSA cohort of 414 patients with confirmed SARS-CoV-2 infection, at The Second Affiliated Hospital of Southern University of Science and Technology in Shenzhen, China from January 11 to April 23, 2020. EXPOSURESPolymerase chain reaction (PCR) and IgM-IgG antibody confirmed SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURESUnivariable and multivariable statistical analysis of the clinical, laboratory, radiologic image, medical treatment, and clinical course of admission/quarantine/readmission data to develop an algorithm to predict patients at risk of recurrence of PCR positivity. RESULTS16.7% (95CI: 13.0%-20.3%) patients retest PCR positive 1 to 3 times after discharge, despite being in strict quarantine. The driving factors in the recurrence prediction model included: age, BMI; lowest levels of the blood laboratory tests during hospitalization for cholinesterase, fibrinogen, albumin, prealbumin, calcium, eGFR, creatinine; highest levels of the blood laboratory tests during hospitalization for total bilirubin, lactate dehydrogenase, alkaline phosphatase; the first test results during hospitalization for partial pressure of oxygen, white blood cell and lymphocyte counts, blood procalcitonin; and the first test episodic Ct value and the lowest Ct value of the nasopharyngeal swab RT PCR results. Area under the ROC curve is 0.786. CONCLUSIONS AND RELEVANCEThis case series provides clinical characteristics of COVID-19 patients with recurrent PCR positivity, despite strict quarantine, at a 16.7% rate. Use of a recurrence prediction algorithm may identify patients at high risk of PCR retest positivity of SARS-CoV-2 and help modify COVID-19 case management and health policy approaches. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the characteristics, clinical presentations, and outcomes of COVID-19 patients with PCR retest positivity after resolution of the initial infection and consecutive negative tests? Can we identify recovered patients, prior to discharge, at risk of the recurrence of SARS-CoV-2 PCR positivity? FindingsIn this series of 414 COVID-19 inpatients discharged to a designated quarantine center, 69 retest positive (13 with 2 readmissions, and 3 with 3 readmissions). A multivariable model was developed to predict the risk of the recurrence of SARS-CoV-2 PCR positivity. MeaningRate and timing of the recurrence of PCR positivity following strict quarantine were characterized. Our prediction algorithm may have implications for COVID-19 clinical treatment, patient management, and health policy.

A non-competing pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design. One Sentence SummaryA pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity.

Development and validation of an early warning score (EWAS) for predicting clinical deterioration in patients with coronavirus disease 2019

BackgroundSince the pandemic outbreak of coronavirus disease 2019 (COVID-19), the health system capacity in highly endemic areas has been overwhelmed. Approaches to efficient management are urgently needed. We aimed to develop and validate a score for early prediction of clinical deterioration of COVID-19 patients. MethodsIn this retrospective multicenter cohort study, we included 1138 mild to moderate COVID-19 patients admitted to 33 hospitals in Guangdong Province from December 27, 2019 to March 4, 2020 (N =818; training cohort), as well as two hospitals in Hubei Province from January 21 to February 22, 2020 (N =320; validation cohort) in the analysis. ResultsThe 14-day cumulative incidences of clinical deterioration were 7.9% and 12.1% in the training and validation cohorts, respectively. An Early WArning Score (EWAS) (ranging from 0 to 4.5), comprising of age, underlying chronic disease, neutrophil to lymphocyte ratio, C-reactive protein, and D-dimer levels, was developed (AUROC: 0.857). By applying the EWAS, patients were categorized into low-, medium-, and high risk groups (cut-off values: two and three). The 14-day cumulative incidence of clinical deterioration in the low-risk group was 1.8%, which was significantly lower than the incidence rates in the medium-(14.4%) and high-risk (40.9%) groups (P <.001). The predictability of EWAS was similar in the validation cohort (AUROC =0.781), patients in the low-, medium-, and high-risk groups had 14-day cumulative incidences of 2.6%, 10.0%, and 25.7%, respectively (P <.001). ConclusionThe EWAS, which is based on five common parameters, can predict COVID-19-related clinical deterioration and may be a useful tool for a rapid triage and establishing a COVID-19 hierarchical management system that will greatly focus clinical management and medical resources to reduce mortality in highly endemic areas.

Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test

BackgroundIt has been reported that several cases recovered from COVID-19 tested positive for SARS-CoV-2 after discharge (re-detectable positive, RP), however the clinical characteristics, significance and potential cause of RP patients remained elusive. MethodsA total of 262 COVID-19 patients were discharged from January 23 to February 25, 2020, and were enrolled for analysis of their clinical parameters. The RP and non-RP (NRP) patients were grouped according to the disease severity during their hospitalization period. The clinical characterization at re-admission to the hospital was analyzed. SARS-CoV-2 RNA and plasma antibody levels were detected using high-sensitive detection methods. FindingsUp to March 10, 2020, all of patients were followed up for at least 14 days, and 38/262 of RP patients (14.5%) were present. The RP patients were characterized by being less than 14-years old and having mild and moderate conditions as compared to NRP patients, while no severe patients became RP. Retrospectively, the RP patients displayed fewer symptoms, more sustained remission of CT imaging and earlier RNA negative-conversion but similar plasma antibody levels during their hospitalization period as compared to those NRP patients. When re-admitted to the hospital, these RP patients showed no obvious clinical symptoms or disease progression indicated by normal or improving CT imaging and inflammatory cytokine levels. All 21 close contacts of RP patients were tested negative for SARS-CoV-2 RNA, and no suspicious clinical symptoms were reported. However, 18/24 of RNA-negative samples detected by the commercial kit were tested to be positive for virus RNA using a hyper-sensitive method, suggesting the carrier status of virus possibly existed in patients recovered from COVID-19. InterpretationOur results showed that young and mild COVID-19 patients seem to be RP patients after discharge, who show no obviously clinical symptoms and disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients during follow-up. Our findings provide empirical information and evidence for the effective management of COVID-19 patients during their convalescent phase.

Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients

BackgroundThe novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. MethodsIn this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. FindingsAmong the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. InterpretationElderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. FundingNational Natural Science Foundation of China, Chinese Academy of Medical Sciences Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published up to March 15, 2020 using keywords "2019-nCoV", "SARS-CoV-2", "novel coronavirus", and COVID-19 AND "ARB", and "angiotensin II receptor blocker" for papers published in both English and Chinese. We found three papers: one from our group, published in Science China Life Science that demonstrated an elevated Angiotensin II level in blood samples from COVID-19 patients; another a perspective article in Chinese recommending ACEI and ARBs as potential remedies for SARS-CoV-2 infections; the third a retrospective study in Chinese identifying no significant difference between ACEI/ARB associated with outcomes in 112 COVID-19 patients with CVD comorbidity. The International society of Hypertension stated on March 16th, 2020: "there are no clinical data in human to show that ACE-inhibitors or ARBs either improve or worsen susceptibility to COVID-19 infection nor do they affect the outcomes of those infected". Added value of this studyWe retrospectively reviewed different types of anti-hypertensive drugs taken by COVID-19 patients with hypertension comorbidity prior to entering the hospital. We discovered that ARB hypertensive drugs were associated with a decreased risk of severe disease in elderly (age>65) COVID-19 patients (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025), the first evidence of ARBs association to COVID-19 infections in human. We conducted a meta-analysis in the literature and found that ARB has positive effects associated with morbidity and mortality of pneumonia. Implications of all the available evidenceARB drugs are widely used in the population with hypertension. Treatments with ACEI and ARBs should be continuous according to medical guidelines. RCT trials of ARB associated with morbidity and mortality of SARS-CoV-2 infection are recommended in the future.

A retrospective study of the clinical characteristics of COVID-19 infection in 26 children

BackgroundThe outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children. MethodThis study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020. ResultNine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients. ConclusionThe clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis. MainpointCOVID-19 is a kind of new infectious disease.The clinical characteristics of 2019-nCoV infection in children may different from adult. Myocardium likely less affected by 2019-nCoV in children.

Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.

Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

BackgroundThe novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. MethodsA total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. ResultsAmong 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). ConclusionsThe antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

Laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections

BackgroundThe outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidating the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this disease. MethodsRespiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information. FindingsExcept for BALF, the sputum possessed the highest positive rate (74.4%[~]88.9%), followed by nasal swabs (53.6%[~]73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected [≥] 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%[~]61.1%. The positive rate of throat swabs collected [≥] 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground-glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples. InterpretationSputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP. FundingNational Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.

Clinical and epidemiological characteristics of 34 children with 2019 novel coronavirus infection in Shenzhen / 中华儿科杂志

Objective@#To describe the characteristics of clinical manifestations and epidemiology of children with 2019 novel coronavirus (2019-nCoV) infection.@*Methods@#All 34 children with laboratory-confirmed 2019-nCoV infection by quantitative real-time reverse transcription-PCR through nasopharyngeal swab specimens were admitted to the Third People’s Hospital of Shenzhen from January 19 to Febuary 7, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed.@*Results@#Among the 34 cases, 14 were males, and 20 were females. The median age was 8 years and 11 months. No patients had underlying diseases. There were 28 children (82%) related with a family cluster outbreak. There were 26 children (76%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 22 (65%) common cases, 9 (26%) mild cases and 3 (8.8%) asymptomatic cases. No severe or critical cases were identified. The most common symptoms were fever (17 cases, 50%) and cough (13 cases, 38% ). In the 34 cases, the white blood cell counts of 28 cases (82%) were normal. Five cases had white blood cell counts more than 10×109/L. One case had white blood cell counts less than 4×109/L. Neutropenia and lymphopenia was found in one case, respectively. C-reactive protein levels and erythrocyte sedimentation rates were elevated in 1 and 5 case, respectively. Elevated procalcitonin was found in 1 case and D-Dimer in 3 cases. The levels of lactic dehydrogenase (LDH) were more than 400 U/L in 10 cases. The CT images of these patients showed bilateral multiple patchy or nodular ground-glass opacities and/or infiltrating shadows in middle and outer zone of the lung or under the pleura. Twenty patients were treated with lopinavir and ritonavir. Glucocorticoids and immunoglobulin were not used in any cases. All the cases improved and were discharged from hospital. Further following up was need.@*Conclusions@#The clinical manifestations in children with 2019-nCoV infection are non-specific and are milder than that in adults. Chest CT scanning is heplful for early diagnosis. Children's infection is mainly caused by family cluster outbreak and imported cases. Family daily prevention is the main way to prevent 2019-nCoV infection.

Epidemiological and clinical characteristics analysis of 30 childhood cases with 2019 novel coronavirus infection in Shenzhen / 中华传染病杂志

Objectives@#To analyze the epidemiological and clinical characteristics of children with 2019 novel coronavirus (2019-nCoV) infection in Shenzhen.@*Methods@#The data of 30 children diagnosed with 2019-nCoV infection in the Third People’s Hospital of Shenzhen from 16th January 2020 to 9th February 2020were collected.@*Results@#Among the 30 children, 14 were boys and 16 were girls. There were 10 mild cases, 13 common cases and one severe case, and six cases with asymptomatic infection. The age ranged from 7 months to 18 years old with the median age of 7 years old. Twenty out of 30 cases (66.7%) were school children. The common clinical characteristics were fever (30.0%, 9/30) and cough (23.3%, 7/30). The body temperature waved below 37.5 ℃. Mostly the auscultations of the lungs were no rales and there was no extrapulmonary complication. A total number of one case had wheezes and hypoxia, and one case had diarrhea and vomiting. There was no critical and death case. There were 29 cases with travelling experience in Hubei province within two weeks, and 24 cases (80.0%) had relatives (parents or grandparents) diagnosed with 2019-nCoV infection. Elevated white blood cell counts (﹥12×109/L), C reaction protein level, lactate dehydrogenase level and the low proportion of T help cells occurred in three, five, five and three cases, respectively. Some cases were coinfected with human respiratory syncytial virus, mycoplasma pneumonia, human herpesvirus, influenza B virus and rubella virus. The predominant pattern of computed tomography findings of childhood patients with 2019-nCoV infection presented with patchy film and ground-glass opacities in bilateral or unilateral lung. The median time for nucleic acid to turn negative was eight days among the enrolled cases. All the cases were cured and discharged home, and the days in hospital waved from 5 - 16 days (the median time was 12 days).@*Conclusions@#The majority of the childhood cases are the school-age children with family cluster. Most cases present mild and common symptoms with good prognosis. Some patients may be complicated with multiple infections.

ECMO application of patients with Critical Corona Virus Disease 2019 and fulminant myocarditis / 中华实验和临床病毒学杂志

Objective To evaluate the clinical experience of extracorporeal membrane oxygenation (ECMO) treatment on two cases of infection with the critical Corona Virus Disease 2019 (COVID-19) complicated by fulminant myocarditis (FM) . Methods This study selects two COVID-19 cases comorbid with fulminant myocarditis and had been treated with ECMO in Shenzhen Third People's Hospital from January 2020 to February 2020. We compare the index of inflammation, immunization, D-dimer and lactic acid before and after ECMO treatment in 24 and 96 hours, cardiopulmonary function before and after ECMO treatment in 24, 48, 72, 96 hours,. We also analyze the complications and clinical outcomes of the two cases during the ECMO treatment. Results Both patients were elderly obese men with chronic cardiopulmonary disease. Comparing the laboratory test results and imaging data of the two patients, the acute lung injury score, oxygenation index, albumin level, hypersensitive C-reactive protein, lactate and lactate dehydrogenase levels in 2 patients after ECMO treatment were improved as compared with those before ECMO treatment. Finally, case 1 died of multiple organ failure and his cardiac function continued to deteriorate, while, case 2 successfully withdrew and his cardiac function gradually improved. Conclusions For critical COVID-19 patients with fulminant myocarditis, ECMO treatment can improve pulmonary function in the short term, provide valuable time for rescuing COVID-19 patients with fulminant myocarditis.

Risk factor and hepatitis B virus makers during the first trimester in villi tissues of HBsAg-positive pregnant women / 中华实验和临床病毒学杂志

Objective@#To determine whether intrauterine infection with hepatitis B virus (HBV) occurs in early pregnancy and to characterize associated virulence factors.@*Methods@#Villi tissues and blood samples of 45 HBV surface antigen (HBsAg)-positive pregnant women were collected during the first trimester and HBV DNA loads were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of GCM1, HBsAg and hepatitis B core antigen (HBcAg) in villi tissues were detected by immunohistochemical method.@*Results@#Data from qRT-PCR showed that HBV DNA was detected in 14 of 45 villi tissues (positive rate of 31.11%), and 24 of 45 blood samples (positive rate of 53.33%), further statistical analysis showed that the positive rates of HBV DNA between blood samples and villi tissues were not significantly different (χ2=4.555, P=0.054). Among them, 12 samples were consistently positive between the villi and blood specimens, and HBsAg, HBeAg, HBeAb, HBV DNA from peripheral blood in these pregnant women were significantly higher than those of the other women (P value was 0.007, 0.004, 0.000, and 0.000 respectively). The multivariate logistic regression analysis showed that blood HBV DNA greater than 106 IU/ml was independently associated with HBV DNA positive in villi, and the HBsAg, HBeAg, villi tissues HBV DNA positive rates of these pregnant women were significantly higher than those of the other pregnant women (all P value were 0.000). Immunohistochemistry results showed that all 45 cases were positive for GCM1 expression in the cell nucleus. Nine cases also had HBsAg expression in the cytoplasm. Only one case was found to express HBV core antigen (HBcAg) in the nucleus.@*Conclusions@#HBV DNA and HBsAg can be detected from villi tissues harvested during the first trimester in HBsAg-positive pregnant women, and the results suggest an early occurrence of intrauterine infection of fetuses with high HBV levels.

Combined anluohuaxianwan and entecavir treatment significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective@#To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks.@*Methods@#Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations.@*Results@#Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29).@*Conclusion@#Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.