Clinical characteristics of patients with acquired immunodeficiency syndrome complicated with nontuberculous mycobacteria disease / 中华传染病杂志

Objective:To explore the clinical characteristics of acquired immunodeficiency syndrome (AIDS) complicated with nontuberculous mycobacteria (NTM) disease.Methods:The clinical data of 190 patients with AIDS complicated with NTM disease diagnosed by Shanghai Public Health Clinical Center, Fudan University from January 1, 2019 to December 31, 2021 were analyzed retrospectively. NTM diseases were divided into disseminated NTM disease group and non-disseminated NTM disease group. The independent sample t test, Mann Whitney U test and chi-square test were used for statistical analysis. Results:The 190 patients with AIDS complicated with NTM disease included 182 males and eight females. The age was (42±13) years old, and the first hospital stay was 15(6, 26) days. Pneumocystis carinii pneumonia was the most common co-infection in 12.1%(23/190) of patients, 87 cases (45.8%) were disseminated NTM disease. The clinical symptoms of patients were common in fever (55.8%(106/190)), cough (50.0%(95/190)), and expectoration (28.9%(55/190)). The proportions of fatigue (31.0%(27/87) vs 7.8%(8/103)), poor appetite (21.8%(19/87) vs 10.7%(11/103)) in the AIDS patients with disseminated NTM disease group were higher than those in the non-disseminated NTM disease group, and the differences were statistically significant ( χ2=16.99, P<0.001 and χ2=4.42, P=0.036, respectively). There was no significant difference in the proportions of deaths between AIDS patients with disseminated NTM disease and those without disseminated NTM disease (17.2%(15/87) vs 12.6%(13/103), χ2=0.80, P=0.371). The most common NTM species was Mycobacterium avium (67.1%(49/190)), followed by Mycobacterium kansasii (15.1%(11/190)). Hemoglobin ((90.3±23.9) g/L vs (110.1±24.2) g/L), albumin ((29.7±5.5) g/L vs (34.7±5.6) g/L), CD4 + T lymphocyte count (11(5, 30)/μL vs 52(16, 96)/μL) and CD8 + T lymphocyte count ((362±320)/μL vs (496±352)/μL) in the disseminated NTM disease group were lower than those in non-disseminated NTM disease group ( t=-5.63, P<0.001; t=-6.18, P<0.001; Z=-5.90, P<0.001; and t=-2.73, P=0.007, respectively), while procalcitonin (0.24(0.10, 0.77) μg/L vs 0.10 (0.04, 0.51) μg/L) was higher than that in the non-disseminated NTM disease group ( Z=-3.09, P=0.002), with statistical significance. The most common imaging features were lung patch and strip shadow (67.4%(128/190)). Conclusions:The most common type of AIDS patients complicated with NTM disease is disseminated NTM disease, and Mycobacterium avium is the most common NTM species. The clinical manifestations (fatigue, anorexia) and laboratory tests (hemoglobin, albumin, procalcitonin, CD4 + T lymphocyte count, CD8 + T lymphocyte count) of AIDS patients with disseminated NTM disease and non-disseminated NTM disease are different, while the prognosis is not significantly different.

Current status and influencing factors of different initiation time of antiretroviral therapy in HIV/AIDS patients / 上海预防医学

ObjectiveTo investigate the status of different antiretroviral therapy（ART） initiation times in patients with HIV/AIDS and analyze the relevant characteristics and influencing factors of delayed ART. MethodsFrom December 2018 to December 2020， a survey was conducted among adult HIV/AIDS patients treated in 28 designated AIDS prevention and treatment institutions in Beijing， Shanghai， Guangdong， Jiangsu， Henan， Jiangxi， Guangxi， Yunnan and other places. Data of the basic demographic information， lifestyle and chronic disease prevalence， and characteristics of diagnosis and treatment were collected. The characteristics and related factors of delayed ART were compared and analyzed. ResultsThe median age of 1 741 patients was 41 years old （IQR： 32‒52）. The initial CD4 count of most patients was less than 200 cells·μL-1（51.4%）. Among them， 1 027 patients had delayed ART （59.0%）， and the association between ART initiation time and initial CD4 count varied with the time of diagnosis of HIV infection. Multivariate logistic analysis showed that the older age （aOR=0.99， 95%CI： 0.98‒0.99） was associated with a higher rate of starting ART within 1 month after diagnosis， while those diagnosed before 2017 and with the initial CD4 count >200 cells·μL-1 were more likely to delay ART. Delayed initiation of ART may be a risk factor for poor sleep quality and co-infection in HIV/AIDS patients. ConclusionWith the expansion of free ART in China， the proportion of delayed ART with HIV/AIDS shows a downward trend. Timely ART management should be strengthened for the young HIV/AIDS patients and patients with high CD4 counts.

The past, present and future of tuberculosis treatment / 浙江大学学报·医学版

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.

ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells

Backgroud & AimsCurrently, the COVID-19 pandemic, caused by SARS-CoV-2 infection, represents a serious public health problem worldwide. Although it has been shown that ACE2 serves as the main receptor for SARS-CoV-2 entry into host cells, studies have shown that ACE2 is expressed at extremely low levels in various tissues, especially in some organs where virus particles have been found, such as the heart and liver. Therefore, these organs potentially express additional SARS-CoV-2 receptors that have not yet been discovered. Methods & ResultsHere, by a genome-wide CRISPR-Cas9 activation library screening, we found that ASGR1 promoted SARS-CoV-2 infection of 293T cells. In Huh-7 and HepG2 cell lines, simultaneous knock out of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary liver parenchymal cells, both of which hardly express ACE2, SARS-CoV-2 could successfully establish an infection. After treatment with ASGR1 antibody, the infection rate significantly reduced. This suggests that SARS-CoV-2 infects liver cells mainly through an ASGR1-dependent mechanism. Finally, we also found that the soluble ASGR1 could not only prevent the SARS-CoV-2 pseudovirus, which binds to the ASGR1 receptors, from infecting host liver cells, but also had a protective effect on those expressing ACE2, indicating that administration of soluble ASGR1 protein may represent a new treatment approach. ConclusionsColletively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of liver cells. Lay SummaryWe show that ASGR1 is a candidate receptor for SARS-CoV-2 to infect liver cells.

Expert recommendations on booster immunization strategies of 2019-nCoV vaccines / 中华临床感染病杂志

Since the end of 2019, the COVID-19 caused by 2019-nCoV has emerged and the pandemic ravaged the world, which seriously threatens global public health security and economic development. 2019-nCoV vaccine is an effective weapon to combat the viral infection, however, studies have shown that vaccine-induced immune protection decreases over time, coupled with some novel and immune escape variants continual emerging. Therefore, it is urgent to complete booster immunization to improve protection. At present, 2019-nCoV vaccines based on a variety of technical platforms have been approved and available in China. Therefore, we developed this sequential vaccination strategy guide to provide documentation guidance for the prevention and control of the epidemic caused by 2019-nCoV and its variant strains.

Optimization of emergency management practice for emergent infectious diseases / 中华医院管理杂志

The study analyzed the application of failure mode and effect analysis(FMEA)in the emergency management of emergent infectious diseases. In February 2020, optimization of emergency management procedures for emergent infectious diseases was identified as the research theme. Subsequently, FMEA was applied to study the emergency management process of emergent infectious diseases and analyze corresponding potential failure modes in an infectious disease hospital. The appraisal identified four prioritized risk exposures to correct, including non-standardized personnel protection, delayed personnel arrival, unqualified specimens and inadequate ward preparation. Accordingly pertinent countermeasures were formulated. Three months after measures were taken, the risk priority numbers of the above four risks were decreased significantly. On the other hand, evident increase was found in the on-duty rate of emergency personnel, the rate of standard protection, the qualification rate of sample collection and disposal, as well as the serviceability rate of respirators, ECG monitors and protective equipment in emergency wards. The application of FMEA is conducive to optimizing the emergency response process of emergent infectious diseases, and to upgrading emergency management at large.

Rational medication in clinical practice for COVID-19 guided by Shanghai expert consensus / 中华临床感染病杂志

The outbreak of COVID-19 occurred in January 2020, the epidemic is still rampant around the world. The Shanghai Expert Consensus on Comprehensive Treatment and Management of Corona Virus Disease 2019 was issued in early March 2020, which provided the guidance of the standardized treatment and rational medication for COVID-19. The administration of " four agents (glucocorticoids, heparin, high-dose vitamin C, Interferon-κ) and one peptide (thymic peptide)" recommended by the consensus is the key to successfully block and treat critical illness.

Value of CD4 + and CD8 + T-lymphocyte counts for clinical diagnostic classification and prognosis of coronavirus disease 2019 / 中华传染病杂志

Objective:To assess the value of CD4 + and CD8 + T-lymphocyte counts for the diagnostic classification and prognosis of coronavirus disease 2019 (COVID-19). Methods:A total of 95 COVID-19 adult patients admitted to Shanghai Public Health Clinical Center, Fudan University from January to March 2020 were recruited. The CD4 + and CD8 + T-lymphocyte counts among ordinary, severe and critical patients, as well among the cured, improved, unimproved and death patients were compared. The area under receiver operating characteristic curve (AUROC) was used to evaluate the value of CD4 + and CD8 + T-lymphocyte counts for the clinical diagnosis and prognosis of COVID-19. The comparison among groups was performed by Mann-Whitney U test. Results:A total of 95 COVID-19 cases including 68 common, 11 severe and 16 critical cases were enrolled. The counts of CD4 + and CD8 + T-lymphocyte of patients in common, severe and critical groups were 419 (309, 612), 267 (212, 540), 141 (77, 201)/μL, and 238 (153, 375), 128 (96, 172), 92 (51, 144)/μL, respectively, with significant differences ( Z=24.322 and 15.956, respectively, both P<0.01). The counts of CD4 + and CD8 + T-lymphocyte of the death, unimproved, improved, and cured patients were 149 (143, 349), 315 (116, 414), 344 (294, 426), 745 (611, 966)/μL, and 106 (43, 501), 176(67, 279), 194(188, 432), 429(276, 564)/μL, respectively, with significant differences ( Z=36.083 and 16.658, respectively, both P<0.01). The optimal cut-off point of CD4 + T-lymphocyte counts was 237/μL for critical COVID-19 with AUROC 0.911 (95% confidence interval ( CI) 0.833-0.989, P<0.01), with the sensitivity of 86.1% and specificity of 87.5%. For predicting severe and critical cases, the optimal cut-off point of CD4 + T-lymphocyte counts was 405/μL with AUROC 0.863 (95% CI 0.727-0.999, P=0.001), with the sensitivity of 78.6% and specificity of 74.6%. Conclusions:The conditions of patients with COVID-19 are aggravated with CD4 + and CD8 + T-lymphocyte counts decreasing. CD4 + T-lymphocyte counts may be an indicator for diagnostic classification of COVID-19 and prognostic indicator for severe and critical patients.

Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network

The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

Olfactory and Gustatory Dysfunction as An Early Identifier of COVID-19 in Adults and Children: An International Multicenter Study

ObjectiveEvaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study DesignMulticenter Case Series Setting5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. ResultsOf 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. ConclusionsOlfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio for predicting clinical outcomes in COVID-19

BackgroundThe epidemic of 2019 novel coronavirus (COVID-19) struck China in late December, 2019, resulting in about 200000 deaths all over the world. Numerous observational studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte proportion and the platelet-to-lymphocyte ratio (PLR) are inflammatory markers. Our study aimed to detect the role of NLR, PLR in predicting the prognosis of COVID-19. MethodsFour hundred and fifteen consecutive patients were enrolled in Shanghai Public Health Clinical Center affiliated to Fudan University, between 20 January and 11 April 2020 with confirmed COVID-19. Epidemiology, symptoms, signs, and laboratory examinations during the hospital stay were collected and compared between non-severe and severe patients. Statistical analysis was performed by SPSS 25.0 software. ResultsFour hundred and fifteen laboratory-confirmed COVID-19 patients were included in our study, among which 386 (93%) patients were not severe, and 27 (7%) were severe. The proportion of males in severe cases is higher than in non-severe cases (75.86% vs. 50.52%, P=0.008). The age between the two groups is different (p=0.022). Compared with non-severe patients, severe patients exhibited more comorbidities, including hypertension (48.28% vs. 19.43%, p<0.001), diabetes (20.69% vs. 6.99%, p=0.009), chronic obstructive pulmonary disease (51.72% vs. 6.22%, p<0.001), and fatty liver (37.93% vs. 15.8%, p=0.002), respectively. NLR and PLR showed significant difference (p<0.001). Diabetes (OR 0.28; 95% CI 15.824-187.186), fatty liver (OR 21.469; 95% CI 2.306-199.872), coronary heart disease (OR 18.157; 95% CI 2.085-158.083), NLR (OR 1.729; 95% CI 1.050-2.847) were significantly associated with severe cases with COVID-19. The NLR of patients in severe group had a 1.729-fold higher than that of no-severe group (OR 1.729; 95% CI 1.050-2.847, P=0.031). ConclusionsNLR is an independent risk factor of severe COVID-19 patients. PLR, NLR were significantly different between severe and non-severe patients, so assessment of NLR, PLR may help identify high risk cases with COVID-19.

Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications

BackgroundThe COVID-19 pandemic caused by SARS-CoV-2 coronavirus threatens global public health. Currently, neutralizing antibodies (NAbs) versus this virus are expected to correlate with recovery and protection of this disease. However, the characteristics of these antibodies have not been well studied in association with the clinical manifestations in patients. MethodsPlasma collected from 175 COVID-19 recovered patients with mild symptoms were screened using a safe and sensitive pseudotyped-lentiviral-vector-based neutralization assay. Spike-binding antibody in plasma were determined by ELISA using RBD, S1, and S2 proteins of SARS-CoV-2. The levels and the time course of SARS-CoV-2-specific NAbs and the spike-binding antibodies were monitored at the same time. FindingsSARS-CoV-2 NAbs were unable to cross-reactive with SARS-CoV virus. SARS-CoV-2-specific NAbs were detected in patients from day 10-15 after the onset of the disease and remained thereafter. The titers of NAb among these patients correlated with the spike-binding antibodies targeting S1, RBD, and S2 regions. The titers of NAbs were variable in different patients. Elderly and middle-age patients had significantly higher plasma NAb titers (P<0.0001) and spike-binding antibodies (P=0.0003) than young patients. Notably, among these patients, there were ten patients whose NAb titers were under the detectable level of our assay (ID50: < 40); while in contrast, two patients, showed very high titers of NAb, with ID50 :15989 and 21567 respectively. The NAb titers were positive correlated with plasma CRP levels but negative correlated with the lymphocyte counts of patients at the time of admission, indicating an association between humoral response and cellular immune response. InterpretationThe variations of SARS-CoV-2 specific NAbs in recovered COVID-19 patients may raise the concern about the role of NAbs on disease progression. The correlation of NAb titers with age, lymphocyte counts, and blood CRP levels suggested that the interplay between virus and host immune response in coronavirus infections should be further explored for the development of effective vaccine against SARS-CoV-2 virus. Furthermore, titration of NAb is helpful prior to the use of convalescent plasma for prevention or treatment. FundingMinistry of Science and Technology of China, National Natural Science Foundation of China, Shanghai Municipal Health Commission, and Chinese Academy of Medical Sciences

Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China

BackgroundSince mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai. MethodsCases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. ResultsOf 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5{degrees} C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. ConclusionsIn this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5{degrees}C, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease.

A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention

ObjectiveTo describe and evaluate the impact of diseases control and prevention on epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai. DesignA retrospective descriptive study SettingChina ParticipantsEpidemiology information was collected from publicly accessible database. 265 patients admitted to Shanghai Public Health Center with confirmed COVID-19 were enrolled for clinical features analysis. Main outcome measurePrevention and control measures taken by Shanghai government, epidemiological, demographic, clinical, laboratory and radiology data were collected. Weibull distribution, Chi-square test, Fishers exact test, t test or Mann-Whitney U test were used in statistical analysis. ResultsCOVID-19 transmission rate within Shanghai had reduced over 99% than previous speculated, and the exponential growth has been stopped so far. Epidemic was characterized by the first stage mainly composed of imported cases and the second stage where >50% of cases were local. The incubation period was 6.4 (95% CI 5.3 to 7.6) days and the mean onset-admission interval was 5.5 days (95% CI, 5.1 to 5.9). Median time for COVID-19 progressed to severe diseases were 8.5 days (IQR: 4.8-11.0 days). By February 11th, proportion of patients being mild, moderate, severe and critically ill were 1.9%(5/265), 89.8%(238/265), 3.8%(10/265), 4.5%(12/265), respectively; 47 people in our cohort were discharged, and 1 patient died. ConclusionStrict controlling of the transmission rate at the early stage of an epidemic in metropolis can quickly prohibit the spread of the diseases. Controlling local clusters is the key to prevent outbreaks from imported cases. Most COVID-19 severe cases progressed within 14 days of disease onset. Multiple systemic laboratory abnormalities had been observed before significant respiratory dysfunction.

Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection / 医学前沿

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4

Clinical analysis of risk factors for severe patients with novel coronavirus pneumonia / 中华传染病杂志

Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.

Pathogenic microorganisms in ocular fluid of infectious uveitis patients with acquired immunodeficiency syndrome / 中华眼底病杂志

Objective:To study the distribution of pathogenic microorganisms in the ocular fluid of patients with acquired immunodeficiency syndrome (AIDS) and infectious uveitis.Methods:It was a retrospective case analysis. From June 2018 to December 2019, 31 AIDS patients with infectious uveitis who were hospitalized or outpatient at Shanghai Public Health Clinical Center were included in the study. Among them, there were 30 males and 1 female; the average age was 38.51±11.17 years. There were 20 cases of panuveitis, 10 cases of posterior uveitis, and 1 case of infectious endophthalmitis. Serum CD4 +T lymphocyte count (CD4 +TC) were 0 - 239/μl during the same period. The second-generation gene sequencing technology was used to detect the collected intraocular fluid. Among 31 specimens, aqueous humor and vitreous humor were 27 and 4 respectively. Results:Among 31 specimens, 18 samples (58.1%, 18/31) of cytomegalovirus (CMV) were detected; varicella-zoster virus (VZV) were detected in 5 samples (16.1%, 5/31); Epstein-Barr virus were detected in 9 samples (29.0%, 9/31); human beta herpes virus type 6 (HHV6) were detected in 3 samples (9.7%, 3/31), human papillary molluscum virus (HPV), human polyoma virus, type G hepatitis virus were separately detected in 1 sample (3.2%, 1/31), all coexisting with other microorganisms. Parvovirus were detedcted in 8 samples (25.8%, 8/31); treponema pallidum were detedcted in 5 samples (16.1%, 5/31); toxoplasma gondii and Harmon coccidia were detedcted in 1 sample (3.2%, 1/31); synitelium Polycarpum were detedcted in 1 sample (3.2%, 1/31); mycobacterium tuberculosis complex, fungi, and microbacteria coexist were detedcted in 1 sample (3.2%, 1/31). Among the 18 CMV specimens, the number of gene sequences was more than 1059 (50.0%), and 104-1055 (27.7%). Among the 5 specimens of VZV, the number of gene sequences was>1044 (80.0%). In one specimen, the mycobacterium tuberculosis complex, fungi, and microbacteria coexist, and the number of gene sequences were all <100. The number of gene sequences of HHV6, HPV, human polyoma virus, type G virus, and parvovirus in all specimens was small. Among 31 specimens, 15 (48.4%) of pathogenic microorganisms were detected at least 2 species.Conclusions:CMV and VZV are the main pathogenic microorganisms of infective uveitis in patients with serum CD4 +TC <100/μl; treponema pallidum, toxoplasma gondii or other protozoa, mycobacterium tuberculosis, and fungi cause more infectious uveitis which are common in AIDS patients with serum CD4 +TC >100/μl. The coexistence of two or more microorganisms can be detected in the intraocular fluid of AIDS patients with infectious uveitis.

Effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker on clinical characteristics of coronavirus disease 2019 patients with hypertension / 中华内科杂志

Objective:To analyze the effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) on coronavirus disease 2019 (COVID-19) patients with hypertension, and to provide an evidence for selecting antihypertensive drugs in those patients.Methods:Clinical data were retrospectively analyzed in 58 COVID-19 patients with hypertension admitted to Shanghai Public Health Clinical Center from January 20 to February 22, 2020, including epidemiological history, clinical manifestations, laboratory findings, chest CT and outcome. Patients were divided into ACEI/ARB group and non-ACEI/ARB group.Results:Twenty-six patients were in ACEI/ARB group and the other 32 patients in non-ACEI/ARB group, with median age 64.0 (49.5, 72.0) years and 64.0 (57.0, 68.8) years respectively. The median time to onset was 5(3, 8) days in ACEI/ARB group and 4 (3, 7) days in non-ACEI/ARB group, the proportion of patients with severe or critical illness was 19.2% and 15.6% respectively. The main clinical symptoms in two groups were fever (80.8% vs. 84.4%) and cough (23.1% vs. 31.3%). The following parameters were comparable including lymphocyte counts, C-reactive protein, lactate dehydrogenase, D-dimer, bilateral involvement in chest CT (76.9% vs. 71.9%), worsening of COVID-19 (15.4% vs. 9.4%), favorable outcome (92.3% vs. 96.9%) between ACEI/ARB group and non-ACEI/ARB group respectively (all P>0.05). However, compared with non-ACEI/ARB group, serum creatinine [80.49 (68.72, 95.30) μmol/L vs. 71.29 (50.98, 76.98) μmol/L, P=0.007] was higher significantly in ACEI/ARB group. Conclusions:ACEI/ARB drugs have no significant effects on baseline clinical parameters (serum creatine and myoglobin excluded) , outcome, and prognosis of COVID-19 patients with hypertension. Antihypertensive drugs are not suggested to adjust in those patients, but the potential impairment of renal function as elevation of serum creatinine should be paid attention in patients administrating ACEI/ARB drugs.

Clinical analysis of risk factors for severe patients with corona virus disease 2019 / 中华传染病杂志

Objective:To analyze the clinical features of patients with corona virus disease 2019 (COVID-19) in Shanghai and the risk factors for disease progression to severe cases.Methods:The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory tests were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using chi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results:Among the 292 patients, there were 21 severe cases with the rate of 7.2%. One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.5±15.7) years old, and 19 (90.5%) were male, 11 (52.4%) had underlying diseases, seven (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, and 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t=-4.730, χ2=12.930, 5.938 and 4.744, respectively, all P<0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin, D-dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum cardiactroponin I (cTn I) in severe patients were all significantly higher ( U=2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 947.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 747.5 and 1 258.0, respectively, all P<0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U=1 263.5, t=4.716, U=1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P<0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR)=0.806, 95% confiderce interval ( CI)0.675-0.961), serum myoglobin ( OR=1.010, 95% CI 1.004-1.016), CRP ( OR=1.016, 95% CI 1.000-1.032), CD3 + T lymphocyte count ( OR=0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR=1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P<0.05). Conclusions:Severe patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.

Renal Pathology and clinical features of patients with human immunodeficiency virus infection complicated with kidney diseases / 中华传染病杂志

Objective:To analyze the pathological patterns, clinical features, and prognosis in patients with human immunodeficiency virus (HIV) infection complicated with kidney disease.Methods:A retrospective analysis of 21 renal damage cases in HIV-infected patients undergoing renal biopsy from June 2016 to November 2019 in Shanghai Public Health Clinical Center, Fudan University was conducted. The clinical features, renal pathological patterns, therapies and outcomes were summarized and analyzed.Results:The age of 21 patients was (45.4±11.0) years. There were 19 men and two women. The CD4 + T lymphocyte count was (473.7±218.4) cells/μL. The HIV RNA levels were measured in 20 patients, and 13 cases (65.0%) were less than 40 copies/mL. A total of 18 cases (85.7%) had initiated antiretroviral therapy before renal biopsy, and the treatment time was 12 (1, 47) months. As for the clinical diagnosis, 14 cases (66.7%) were nephrotic syndrome and seven cases (33.3%) were nephritic syndrome. Renal pathology reports showed that HIV immune-complex kidney disease was the most common pathology pattern, accounting for 42.9% (9/21), followed by podocytopathy and diabetic nephropathy, both accounting for 23.8% (5/21), respectively. The IgA nephropathy (23.8%, 5/21) was the most common subtype of HIV immune-complex kidney disease, while minimal change disease (19.0%, 4/21) was the most common one of podocytopathy. However, classic HIV-associated nephropathy was not found in the study. The follow-up period was (12.5±9.2) months. During this period, the nephropathy conditions of nine patients were improved, eight were stable, two deteriorated, and two died. Conclusions:IgA nephropathy, minimal change disease and diabetic nephropathy are the top three patterns of renal pathology in patients with HIV infection. Most cases have good prognosis after treatments. For HIV-infected patients with serious renal damage, timely kidney biopsy is vital to determine pathological pattern, and to subsequently guide the clinical treatment and evaluate the prognosis.