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SARS-CoV-2(COVID-19),viral load and clinical outcomes;lessons learned one year into the pandemic:A systematic review

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World Journal of Critical Care Medicine 2021年第4期10卷 132-150页

作者： Santosh Shenoy Department of General and Colorectal Surgery KCVA and University of Missouri at Kansas CityMissouriMO 64128United States

BACKGROUND Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections is diagnosed via real time reverse transcriptase polymerase chain reaction(RT-PCR)and reported as a binary assessment of the test being positive or negative.High SARS-CoV-2 viral load is an independent predictor of disease severity and mortality.Quantitative RT-PCR may be useful in predicting the clinical course and prognosis of patients diagnosed with coronavirus disease 2019(COVID-19).AIM To identify whether quantitative SARS-CoV-2 viral load assay correlates with clinical outcome in COVID-19 infections.METHODS A systematic literature search was undertaken for a period between December 30,2019 to December 31,2020 in PubMed/MEDLINE using combination of terms“COVID-19,SARS-CoV-2,Ct values,Log_(10) copies,quantitative viral load,viral dynamics,kinetics,association with severity,sepsis,mortality and infectiousness”.After screening 990 manuscripts,a total of 60 manuscripts which met the inclusion criteria were identified.Data on age,number of patients,sample sites,RT-PCR targets,disease severity,intensive care unit admission,mortality and conclusions of the studies was extracted,organized and is analyzed.RESULTS At present there is no Food and Drug Administration Emergency Use Authorization for quantitative viral load assay in the current pandemic.The intent of this research is to identify whether quantitative SARS-CoV-2 viral load assay correlates with severity of infection and mortality?High SARS-CoV-2 viral load was found to be an independent predictor of disease severity and mortality in majority of studies,and may be useful in COVID-19 infection in susceptible individuals such as elderly,patients with co-existing medical illness such as diabetes,heart diseases and immunosuppressed.High viral load is also associated with elevated levels of TNF-α,IFN-γ,IL-2,IL-4,IL-6,IL-10 and C reactive protein contributing to a hyper-inflammatory state and severe infection.However there is a wide heterogeneity in fluid samples and different phases

关键词： COVID-19 SARS-CoV-2 viral load Severe sepsis Dynamics Mortality

Application of a ddRT-PCR to quantify seasonal influenza virus for viral isolation

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Biosafety and Health 2022年第5期4卷 299-302页

作者： Yimeng Liu Jiachen Zhao Xiaomin Peng Guilan Lu Weixian Shi Zhaomin Feng Hui Xu Shujuan Cui Yang Pan Daitao Zhang Peng Yang Quanyi Wang Institute for Infectious Disease and Endemic Disease Control Beijing Center for Disease Prevention and ControlBeijing 100013China

viral isolation in cell cultures has been regarded for decades as the“gold standard”for the laboratory diagnosis of influenza viral infections.Not all viral strains could be isolated from clinical samples.This study aimed to quantify the viral load in the samples before isolation to save working time and improve working efficiency.Four hundred samples from patients with influenza-like cases were confirmed pdmH1N1 positive(200 cases)and B Victoria(BV)positive(200 cases)by whole-genome sequencing and analyzed by ddPCR for viral load in samples before isolation,and isolation results were verified by hemagglutination(HA)assay and hemagglutination-inhibition(HI)tests.Probit regression analysis was used to calculate the isolation viral load limit with a 95%probability level by SPSS 19.0 software.The results showed that the isolation limit of viral load was 4.9×10^(4)(95%CI:2.5×10^(4)–9.0×10^(4))copies/mL for pdmH1N1 and 1.9×10^(4)(95%CI:7.8×103–3.6×10^(4))copies/mL for BV.The isolation rate of clinical samples is positively correlated with the viral load in clinical samples,which can be used for viral culture,providing important guidance for daily work.

关键词： Influenza virus ddRT-PCR viral load viral isolation

Stroke and HIV: Correlation between viral load and Type of Stroke

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Neuroscience & Medicine 2021年第4期12卷 163-167页

作者： Prince Eliot Galieni Sounga Bandzouzi Ghislain Armel Mpandzou Josué Euberma Diatewa Patience Moudeko M’Foutou Dina Happia Motoula-Latou Charles Godefroy Koubemba Paul Macaire Ossou-Nguiet Donatien Moukassa Faculty of Health Sciences Marien N’GOUABI University Brazzaville Republic of Congo Department of Neurology Loandjili General Hospital Pointe-Noire Republic of the Congo Department of Neurology University Hospital of Brazzaville Brazzaville Republic of Congo

Introduction: The role of immunosuppression of TCD4+ lymphocytes in the onset of stroke in people living with HIV has been reported in numerous studies examining the co-morbidity of stroke and HIV. Objective: To determine the correlation between the viral load and the type of stroke. Methodology: This was a 7-month cross-sectional descriptive study carried out in the Neurology Department of Loandjili General Hospital in Pointe-Noire. The study population consisted of patients living with HIV who had a stroke confirmed by brain scan. The sero-immunological investigation consisted of looking for T lymphocyte typing from two kits: a CD4+ T lymphocyte typing reagent kit (BD FACS Presto TM) and a GeneXpert kit for viral load (Xpert®HIV-1 viral load). The database was made from the 2010 version of Microsoft Excel. Results: We included 16 patients living with HIV, 56% of whom were women with a sex ration of 0.78. The mean age was 56.92 ± 11.21. The mean number of TCD4+ lymphocytes was 413.44 ± 677.95/mm3;minimum: 93/mm3;maximum: 2854/mm3. The mean viral load was 17,996.31 ± 20,982.22/mm3;minimum: 1002/mm3;maximum: 67,229/mm3. No significant difference between the viral load and the occurrence of the stroke (p = 0.13). Conclusion: Our study did not show a causal link between viral load, immunosuppression of TCD4+ lymphocytes and the onset of stroke.

关键词： viral load HIV Stroke

Tracing the origin of large respiratory droplets by their deposition characteristics inside the respiratory tract during speech

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Building Simulation 2023年第5期16卷 781-794页

作者： Yihan Wang Jianjian Wei Caroline X.Gao Tao Jin Li Liu Institute of Refrigeration and Cryogenics Key Laboratory of Refrigeration and Cryogenic Technology of Zhejiang ProvinceZhejiang UniversityHangzhou 310000China Public Health and Preventive Medicine Monash UniversityMelbourneVIC3004Australia Department of Building Science Tsinghua UniversityBeijing 100084China

Origin of differently sized respiratory droplets is fundamental for clarifying their viral loads and the sequential transmission mechanism of SARS-CoV-2 in indoor environments.Transient talking activities characterized by low(0.2 L/s),medium(0.9 L/s),and high(1.6 L/s)airflow rates of monosyllabic and successive syllabic vocalizations were investigated by computational fluid dynamics(CFD)simulations based on a real human airway model.SST k-ωmodel was chosen to predict the airflow field,and the discrete phase model(DPM)was used to calculate the trajectories of droplets within the respiratory tract.The results showed that flow field in the respiratory tract during speech is characterized by a significant laryngeal jet,and bronchi,larynx,and pharynx-larynx junction were main deposition sites for droplets released from the lower respiratory tract or around the vocal cords,and among which,over 90%of droplets over 5μm released from vocal cords deposited at the larynx and pharynx-larynx junction.Generally,droplets’deposition fraction increased with their size,and the maximum size of droplets that were able to escape into external environment decreased with the airflow rate.This threshold size for droplets released from the vocal folds was 10-20μm,while that for droplets released from the bronchi was 5-20μm under various airflow rates.Besides,successive syllables pronounced at low airflow rates promoted the escape of small droplets,but do not significantly affect the droplet threshold diameter.This study indicates that droplets larger than 20μm may entirely originate from the oral cavity,where viral loads are lower;it provides a reference for evaluating the relative importance of large-droplet spray and airborne transmission route of COVID-19 and other respiratory infections.

关键词： respiratory droplets deposition viral load airborne transmission COVID-19

Reasons,safety and efficacy analysis for conversion of HAART to TAF/ FTC/BIC among HIV-infected patients

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Chinese Medical Journal 2023年第24期136卷 2931-2937页

作者： Jiang Xiao Guiju Gao Yi Ding Jialu Li Chengyu Gao Qiuhua Xu Liang Wu Hongyuan Liang Liang Ni Fang Wang Yujiao Duan Di Yang Hongxin Zhao Clinical and Research Center of AIDS Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

Background:This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium(TAF/FTC/BIC)in highly active antiretroviral therapy(HAART)-experienced HIV-infected patients in real-world settings.Methods:We conducted a retrospective cohort study.The treatment conversion rationales,safety,and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.Results:Regimen simplification(990/1684,58.79%)was the most common reason for switching,followed by osteoporosis or osteopenia(375/1684,22.27%),liver dysfunction(231/1684,13.72%),decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat(TAF/FTC/EVG/c)with food restriction(215/1684,12.77%),virological failure(116/1684,6.89%),and renal dysfunction(90/1684,5.34%).In patients receiving non-nucleotide reverse transcriptase inhibitors(NNRTI)-containing regimens,lipid panel changes 1 year after switching indicated a difference of 3.27±1.10 mmol/L vs.3.40±1.59 mmol/L in triglyceride(P=0.014),4.82±0.74 mmol/L vs.4.88±0.72 mmol/L in total cholesterol(P=0.038),3.09±0.70 mmol/L vs.3.18±0.66 mmol/L in low-density lipoprotein(Pviral load suppression,and alanine transaminase(ALT),aspartate transaminase(AST),estimated glomerular filtration rate(eGFR),and serum creatinine levels after the transition(P<0.001).Conclusion:The transition to TAF/FTC/BIC demonstrated good treatment potency.Furthermore,this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios,providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAA

关键词： HIV Antiretroviral therapy,highly active Conversion viral load Efficacy Safety

Characterization of two SARS-CoV-2 subgenomic RNA dynamics in severe COVID-19 patients

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Virologica Sinica 2022年第1期37卷 30-37页

作者： Xiaohui Zou Shengrui Mu Yeming Wang Li Guo Lili Ren Xiaoyan Deng Haibo Li Jiankang Zhao Yulin Zhang Hui Li Binghuai Lu Chaolin Huang Bin Cao Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina-Japan FriendshipHospitalBeijing100029China National Center for Respiratory Medicine Beijing100029China Institute of Respiratory Medicine Chinese Academy of Medical SciencesBeijing100029China Department of Pulmonary and Critical Care Medicine Capital Medical UniversityBeijing100069China Tsinghua University-Peking University Joint Center for Life Sciences Beijing100029China NHC Key Laboratory of Systems Biology of Pathogens and Christophe M erieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&PekingUnion Medical CollegeBeijing100176China Jin Yin-tan Hospital Wuhan430013Hubei ProvinceChina

Little is known about Subgenomic RNA(sgRNA)dynamics in patients with Coronavirus diseases 2019(COVID-19).We collected 147 throat swabs,74 gut swabs and 46 plasma samples from 117 COVID-19 patients recruited in the LOTUS China trial(ChiCTR2000029308)and compared E and orf7a sgRNA load in patients with different illness duration,outcome,and comorbidities.Both sgRNAs were detected in all the three types of samples,with longest duration of 25,13,and 17 days for E sgRNA,and 32,28,and 17 days for orf7a sgRNA in throat,gut,and plasma,respectively.A total of 95%(57/60)of patients had no E sgRNA detected after 10 days post treatment,though 86%of them were still E RNA positive.High correlation on titer was observed between sgRNA encoding E and orf7a gene.sgRNA showed similar variation in the standard care and Lopinavir-Ritonavir group.Patients with diabetes and heart diseases showed higher pharyngeal E sgRNA at the first day(P=0.016 and 0.013,respectively)but no difference at five days after treatment,compared with patients without such commodities.Patients with hypertension and cerebrovascular diseases showed no difference in the pharyngeal sgRNA levels at both one and five days after treatment,compared with patients without these two commodities.E sgRNA levels in the initial infection showed no correlation with the serum antibody against spike,nucleoprotein,and receptor binding domains at ten days later.sgRNA lasted a long period in COVID-19 patients and might have little effect on humoral response.

关键词： SARS-CoV-2 Subgenomic RNA(sgRNA) viral load Antibody

Impact factors of Blastocystis hominis infection in persons living with human immunodeficiency virus:a large-scale,multi-center observational study from China

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Infectious Diseases of Poverty 2023年第5期12卷 95-96页

作者： Shun-Xian Zhang Ji-Chun Wang Zhong-Wei Li Jin-Xin Zheng Wen-Ting Zhou Guo-Bing Yang Ying-Fang Yu Xiu-Ping Wu Shan Lv Qin Liu Mu-Xin Chen Yan Lu Zhi-Hui Dou Da-Wei Zhang Wen-Wen Lv Lei Wang Zhen-Hui Lu Ming Yang Pei-Yong Zheng Yue-Lai Chen Li-Guang Tian Xiao-Nong Zhou Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai China Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research) NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research On Tropical Diseases National Institute of Parasitic Diseases Shanghai China School of Global Health Chinese Center for Tropical Diseases Research-Shanghai Jiao Tong University School of Medicine Shanghai China Department of Science and Technology Chinese Center for Disease Control and Prevention Beijing China Gansu Province People’s Hospital Gansu Provincial Hospital Lanzhou China National Health Commission (NHC) Key Laboratory of Biosafety National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China Gansu Provincial Center for Disease Control and Prevention Lanzhou China National Center for AIDS/STD Control and Prevention China Center for Disease Control and Prevention Beijing China The People’s Liberation Army 302 Hospital Beijing China Clinical Research Institute Shanghai Jiao Tong University School of Medicine Shanghai China

Background Blastocystis hominis(Bh)is zoonotic parasitic pathogen with a high prevalent globally,causing opportunistic infections and diarrhea disease.Human immunodeficiency virus(HIV)infection disrupts the immune system by depleting CD4^(+)T lymphocyte(CD4^(+)T)cell counts,thereby increasing Bh infection risk among persons living with HIV(PLWH).However,the precise association between Bh infection risk and HIV-related biological markers and treatment processes remains poorly understood.Hence,the purpose of the study was to explore the association between Bh infection risk and CD4^(+)T cell counts,HIV viral load(VL),and duration of interruption in antiviral therapy among PLWH.Methods A large-scale multi-center cross-sectional study was conducted in China from June 2020 to December 2022.The genetic presence of Bh in fecal samples was detected by real-time fluorescence quantitative polymerase chain reaction,the CD4^(+)T cell counts in venous blood was measured using flowcytometry,and the HIV VL in serum was quantified using fluorescence-based instruments.Restricted cubic spline(RCS)was applied to assess the non-linear association between Bh infection risk and CD4^(+)T cell counts,HIV VL,and duration of interruption in highly active antiretroviral therapy(HARRT).Results A total of 1245 PLWH were enrolled in the study,the average age of PLWH was 43 years[interquartile range(IQR):33,52],with 452(36.3%)being female,50.4%(n=628)had no immunosuppression(CD4^(+)T cell counts>500 cells/μl),and 78.1%(n=972)achieved full virological suppression(HIV VL<50 copies/ml).Approximately 10.5%(n=131)of PLWH had interruption.The prevalence of Bh was found to be 4.9%[95%confidence interval(CI):3.8-6.4%]among PLWH.Significant nonlinear associations were observed between the Bh infection risk and CD4^(+)T cell counts(Pfor nonlinearity<0.001,L-shaped),HIV VL(Pfor nonlinearity<0.001,inverted U-shaped),and duration of interruption in HARRT(Pfor nonlinearity<0.001,inverted U-shaped).Conclusions The study revealed that VL was a better predicto

关键词： Blastocystis hominis Human immunodeficiency virus viral load Non-linear association Restricted cubic spline Propensity score China

Learning from a rare phenomenon — spontaneous clearance of chronic hepatitis C virus post-liver transplant: A case report

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World Journal of Hepatology 2022年第2期14卷 456-463页

作者： Noreen Singh Mang Ma Aldo J Montano-Loza Rahima A Bhanji Division of Gastroenterology and Liver Unit University of Alberta HospitalEdmonton T6G 2X8AlbertaCanada

BACKGROUND Hepatitis C virus(HCV)can lead to chronic liver damage resulting in cirrhosis and hepatocellular carcinoma.Spontaneous clearance of HCV has been documented after an acute infection in 20%-45%of individuals.However,spontaneously resolved chronic hepatitis C following liver transplant(LT)is rare and has been documented only in a few case reports.The phenomenon of spontaneous clearance of chronic hepatitis C occurs together with other meaningful events,which are typically associated with significant changes in the host immunity.CASE SUMMARY We report three cases of spontaneous resolution of chronic hepatitis C following liver transplantation.These patients either failed or had no HCV treatment prior to transplant,but had spontaneous resolution of HCV post-LT as documented by undetectable polymerase chain reaction(PCR).Diagnosis of HCV was based on viremia through PCR or liver biopsy.All three patients currently undergo surveillance and have no recurrence of HCV.CONCLUSION Examining each patient’s clinical course,we learned about many viral,host and cellular-factors that may have enhanced the host’s immunity leading to spontaneous clearance of HCV.Though HCV treatment has excellent cure rates,understanding this mechanism may provide clinicians with insights regarding timing and duration of treatment.

关键词： Spontaneous resolution of hepatitis C Liver transplantation Hepatitis C Immunosuppression viral load Case report

Virological and immunological outcomes in HIV-1-infected Chinese patients treated with a combination of Efavirenz and Indinavir for 48 weeks

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Chinese Medical Journal 2004年第3期117卷 347-352页

作者：李莉魏飞力梅珊冯鑫姚均金侠曹韵贞 National Center for AIDS Prevention and Control Department of Infections Diaseases Beijing Ditan Hospital Department of Infectious Diseases Rochester University Medical CenterRochester

Background The incidence of HIV-1-related infection d iseases and the mortality of AIDS have dramatically decreased since highly activ e antiretroviral therapy began to be used clinically in China in 1999. And we in itiated a second clinical trial using a combination of Efavirenz and Indinavir to observe the effects of the immunoreaction.Methods Twenty patients with laboratory-confirmed chronic HIV-1 infection were recruited. Blood samples were collected initially and during the weeks after initiation of treatment. Within 48 hours of blood sampling, peripheral blood plasma and mononuclear cells were separated using routine methods. HIV-1 viral load was measured in thawed plasma samples. Within 48 hours of peripheral blood sampling, CD4 + and CD8 + T cell subsets were enumerated.Results The drug regimen was efficient in reducing HIV-1 plasma viral load and increasing total CD4 + T cell counts. The percentage of CD4 + and CD8 + T cel l subsets expressing CD38 and HLA-DR activation markers was positively correlated with plasma viral load and tended to normalize.Conclusions The combination of Efavirenz and Indinavir was generally well tolerated and efficient at reducing HIV-1 RNA. Furthermore, the treatment improved the immunological function.

关键词： HIV/AIDS viral load CD4 + T cell counts activation markers