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1.
Clin Infect Dis ; 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1758700

ABSTRACT

BACKGROUND: To combat the COVID-19 pandemic, nonpharmaceutical interventions (NPI) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARI). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for eight viral pathogens (influenza virus, IFV; respiratory syncytial virus, RSV; human parainfluenza virus, HPIV; human adenovirus; human metapneumovirus; human coronavirus, HCoV; human bocavirus, HBoV, and human rhinovirus, HRV) between 2012 and 2021, were analyzed to assess the changes of respiratory infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. RESULTS: Test positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17·2% for RSV to -87·6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year round, RSV, HPIV, HCoV, HRV HBov resurged and went beyond historical levels during September, 2020-January, 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children younger than 18 years and in Northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315884

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. Methods: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. Findings: The overall CFR in China was estimated to be 4.6% (95% CI 4.5%-4.8%). It increased with age and was higher in males than females. The highest CFR observed was in male patients ≥70 years old. Although the outcome of infection is generally worse for males, this adverse effect from male sex decreased as people get old. Differential age/sex CFR patterns across geographical regions were found: the age effect on CFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher CFR was associated with older age, and male sex. Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher CFR. Interpretation: This up-to-date and comprehensive picture of COVID-19 CFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315883

ABSTRACT

There is no vaccine or specific antiviral treatment for COVID-19. One current focus is drug repurposing research, but those drugs have limited therapeutic efficacies and known adverse effects. The pathology of COVID-19 is essentially unknown. It is therefore challenging to discover a successful treatment to be approved for clinical use. This paper addresses several key biological processes of reactive oxygen, halogen and nitrogen species (ROS, RHS and RNS) that play crucial physiological roles in organisms from plants to humans. These include why superoxide dismutases, the enzymes to catalyze the formation of H2O2, are required for protecting ROS-induced injury in cell metabolism, why the amount of ROS/RNS produced by ionizing radiation at clinically relevant doses is ~1000 fold lower than the endogenous ROS/RNS level routinely produced in the cell and why a low level of endogenous RHS plays a crucial role in phagocytosis for immune defense. Herein we propose a plausible amplification mechanism in immune defense: ozone-depleting-like halogen cyclic reactions enhancing RHS effects are responsible for all the mentioned physiological functions, which are activated by H2O2 and deactivated by NO signaling molecule. Our results show that the reaction cycles can be repeated thousands of times and amplify the RHS pathogen-killing (defense) effects by 100,000 fold in phagocytosis, resembling the cyclic ozone-depleting reactions in the stratosphere. It is unraveled that H2O2 is a required protective signaling molecule (angel) in the defense system for human health and its dysfunction can cause many diseases or conditions such as autoimmune disorders, aging and cancer. We also identify a class of potent drugs for effective treatment of invading pathogens such as HIV and SARS-CoV-2 (COVID-19), cancer and other diseases, and provide a molecular mechanism of action of the drugs or candidates.

4.
BMC Infect Dis ; 21(1): 1282, 2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1634834

ABSTRACT

BACKGROUND: The temporal relationship between SARS-CoV-2 and antibody production and clinical progression remained obscure. The aim of this study was to describe the viral kinetics of symptomatic patients with SARS-CoV-2 infection and identify factors that might contribute to prolonged viral shedding. METHODS: Symptomatic COVID-19 patients were enrolled in two hospitals in Wuhan, China, from whom the respiratory samples were collected and measured for viral loads consecutively by reverse transcriptase quantitative PCR (RT-qPCR) assay. The viral shedding pattern was delineated in relate to the epidemiologic and clinical information. RESULTS: Totally 2726 respiratory samples collected from 703 patients were quantified. The SARS-CoV-2 viral loads were at the highest level during the initial stage after symptom onset, which subsequently declined with time. The median time to SARS-CoV-2 negativity of nasopharyngeal test was 28 days, significantly longer in patients with older age (> 60 years old), female gender and those having longer interval from symptom onset to hospital admission (> 10 days). The multivariate Cox regression model revealed significant effect from older age (HR 0.73, 95% CI 0.55-0.96), female gender (HR 0.72, 95% CI 0.55-0.96) and longer interval from symptom onset to admission (HR 0.44, 95% CI 0.33-0.59) on longer time to SARS-CoV-2 negativity. The IgM antibody titer was significantly higher in the low viral loads group at 41-60 days after symptom onset. At the population level, the average viral loads were higher in early than in late outbreak periods. CONCLUSIONS: The prolonged viral shedding of SARS-CoV-2 was observed in COVID-19 patients, particularly in older, female and those with longer interval from symptom onset to admission.


Subject(s)
COVID-19 , Aged , Female , Humans , Middle Aged , Prospective Studies , RNA, Viral , SARS-CoV-2 , Viral Load , Virus Shedding
6.
Clin Infect Dis ; 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1522157

ABSTRACT

BACKGROUND: To combat the COVID-19 pandemic, nonpharmaceutical interventions (NPI) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARI). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for eight viral pathogens (influenza virus, IFV; respiratory syncytial virus, RSV; human parainfluenza virus, HPIV; human adenovirus; human metapneumovirus; human coronavirus, HCoV; human bocavirus, HBoV, and human rhinovirus, HRV) between 2012 and 2021, were analyzed to assess the changes of respiratory infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. RESULTS: Test positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17·2% for RSV to -87·6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year round, RSV, HPIV, HCoV, HRV HBov resurged and went beyond historical levels during September, 2020-January, 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children younger than 18 years and in Northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

7.
Clin Infect Dis ; 73(2): e513-e522, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1493765

ABSTRACT

BACKGROUND: For pediatric pneumonia, the meteorological and air pollution indicators have been frequently investigated for their association with viral circulation but not for their impact on disease severity. METHODS: We performed a 10-year prospective, observational study in 1 hospital in Chongqing, China, to recruit children with pneumonia. Eight commonly seen respiratory viruses were tested. Autoregressive distributed lag (ADL) and random forest (RF) models were used to fit monthly detection rates of each virus at the population level and to predict the possibility of severe pneumonia at the individual level, respectively. RESULTS: Between 2009 and 2018, 6611 pediatric pneumonia patients were included, and 4846 (73.3%) tested positive for at least 1 respiratory virus. The patient median age was 9 months (interquartile range, 4‒20). ADL models demonstrated a decent fitting of detection rates of R2 > 0.7 for respiratory syncytial virus, human rhinovirus, parainfluenza virus, and human metapneumovirus. Based on the RF models, the area under the curve for host-related factors alone was 0.88 (95% confidence interval [CI], .87‒.89) and 0.86 (95% CI, .85‒.88) for meteorological and air pollution indicators alone and 0.62 (95% CI, .60‒.63) for viral infections alone. The final model indicated that 9 weather and air pollution indicators were important determinants of severe pneumonia, with a relative contribution of 62.53%, which is significantly higher than respiratory viral infections (7.36%). CONCLUSIONS: Meteorological and air pollution predictors contributed more to severe pneumonia in children than did respiratory viruses. These meteorological data could help predict times when children would be at increased risk for severe pneumonia and when interventions, such as reducing outdoor activities, may be warranted.


Subject(s)
Air Pollution , Pneumonia , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Virus Diseases , Air Pollution/adverse effects , Air Pollution/analysis , Child , China/epidemiology , Humans , Infant , Pneumonia/epidemiology , Pneumonia/etiology , Prospective Studies , Weather
8.
Nat Commun ; 12(1): 5026, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1363491

ABSTRACT

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/microbiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Virus Diseases/virology , Viruses/isolation & purification , Adolescent , Adult , Bacteria/classification , Bacteria/genetics , Bacterial Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Prospective Studies , Respiratory Tract Infections/epidemiology , Seasons , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Young Adult
9.
Lancet Reg Health West Pac ; 16: 100268, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1415636

ABSTRACT

BACKGROUND: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. METHODS: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. FINDINGS: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012-2019, with a relative decrease of 71•75% for adenovirus, 58•76% for norovirus, 53•50% for rotavirus A, and 72•07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012-2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66•53% and 90•48% increase respectively. This increase was larger for pediatric patients than for adult patients. INTERPRETATION: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. FUNDING: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.

10.
Vaccines (Basel) ; 9(9)2021 Sep 06.
Article in English | MEDLINE | ID: covidwho-1390818

ABSTRACT

Background: The SARS-CoV-2 vaccine has been widely rolled out globally in the general populations. However, specific data on vaccination confidence, willingness or coverage among health care workers (HCWs) has been less reported. Methods: A cross-sectional online survey was conducted to specify the basic data and patterns of vaccination confidence, willingness and coverage among HCWs nationwide. Results: In total, 2386 out of 2583 (92.4%) participants were enrolled for analysis, and the rates of confidence in vaccine, professional institutes and government were 75.1%, 85.2% and 85.4%, respectively. The overall vaccination coverage rate was 63.6% which was adjusted as 82.8% for participants under current medical conditions or having contraindications. Confidence in vaccine safety was shown to be the most related factor to willingness among doctors, nurses, medical technicians and hospital administrators, while confidence in vaccine effectiveness as well as trust in government played the key role in formulating public health employees' willingness. 130 (7.1% of 1833) participants reporting willingness still not been vaccinated regardless of contraindications. Multivariate analysis among willingness participants showed that males, aged over 30 years, public health employees and higher vaccination confidence had significantly higher vaccination rates with ORs (95% confidence intervals) as 1.64 (1.08-2.49), 3.14 (2.14-4.62), 2.43 (1.46-4.04) or 2.31 (1.24-4.33). Conclusions: HCWs' confidence, willingness and coverage rates to the vaccine were generally at high levels. Heterogeneity among HCWs should be considered for future vaccination promotion strategies. The population's confidence in vaccination is not only the determinant to their willingness, but also guarantees their actual vaccine uptake.

11.
J Microbiol Immunol Infect ; 2021 Aug 25.
Article in English | MEDLINE | ID: covidwho-1370605

ABSTRACT

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0-10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11-20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87-55.16). CONCLUSION: Neurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

12.
PeerJ ; 9: e11397, 2021.
Article in English | MEDLINE | ID: covidwho-1359402

ABSTRACT

BACKGROUND: Air pollution leads to many adverse health conditions, mainly manifested by respiratory or cardiac symptoms. Previous studies are limited as to whether air pollutants were associated to influenza-like illness (ILI). This study aimed to explore the association between air pollutants and outpatient visits for ILI, especially during an outbreak of influenza. METHODS: Daily counts of hospital visits for ILI were obtained from Peking University Third Hospital between January 1, 2015, and March 31, 2018. A generalized additive Poisson model was applied to examine the associations between air pollutants concentrations and daily outpatient visits for ILI when adjusted for the meteorological parameters. RESULTS: There were 35862 outpatient visits at the fever clinic for ILI cases. Air quality index (AQI), PM2.5, PM10, CO and O3 on lag0 days, as well as nitrogen dioxide (NO2) and sulfur dioxide (SO2) on lag1 days, were significantly associated with an increased risk of outpatient visits for ILI from January 2015 to November 2017. From December 2017 to March 2018, on lag0 days, air pollutants PM2.5 [risk ratio (RR) = 0.971, 95% CI: 0.963-0.979], SO2 (RR = 0.892, 95% CI: 0.840-0.948) and CO (RR = 0.306, 95% CI: 0.153-0.612) were significantly associated with a decreased risk of outpatient visits for ILI. Interestingly, on the lag2 days, all the pollutants were significantly associated with a reduced risk of outpatient visits for ILI except for O3. We did not observe the linear correlations between the outpatient visits for ILI and any of air pollutants, which were instead associated via a curvilinear relationship. CONCLUSIONS: We found that the air pollutants may be associated with an increased risk of outpatient visits for ILI during the non-outbreak period and with a decreased risk during the outbreak period, which may be linked with the use of disposable face masks and the change of outdoor activities. These findings expand the current knowledge of ILI outpatient visits correlated with air pollutants during an influenza pandemic.

13.
BMC Infect Dis ; 21(1): 481, 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1244909

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic has been largely controlled in China, to the point where case fatality rate (CFR) data can be comprehensively evaluated. METHODS: Data on confirmed patients, with a final outcome reported as of 29 March 2020, were obtained from official websites and other internet sources. The hospitalized CFR (HCFR) was estimated, epidemiological features described, and risk factors for a fatal outcome identified. RESULTS: The overall HCFR in China was estimated to be 4.6% (95% CI 4.5-4.8%, P < 0.001). It increased with age and was higher in males than females. Although the highest HCFR observed was in male patients ≥70 years old, the relative risks for death outcome by sex varied across age groups, and the greatest HCFR risk ratio for males vs. females was shown in the age group of 50-60 years, higher than age groups of 60-70 and ≥ 70 years. Differential age/sex HCFR patterns across geographical regions were found: the age effect on HCFR was greater in other provinces outside Hubei than in Wuhan. An effect of longer interval from symptom onset to admission was only observed outside Hubei, not in Wuhan. By performing multivariate analysis and survival analysis, the higher HCFR was associated with older age (both P < 0.001), and male sex (both P < 0.001). Only in regions outside Hubei, longer interval from symptom onset to admission, were associated with higher HCFR. CONCLUSIONS: This up-to-date and comprehensive picture of COVID-19 HCFR and its drivers will help healthcare givers target limited medical resources to patients with high risk of fatality.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Hospital Mortality , Hospitalization , SARS-CoV-2 , Adult , Age Factors , Aged , China/epidemiology , Female , Humans , Male , Middle Aged , Risk Factors , Sex Factors , Time-to-Treatment
14.
BMC Infect Dis ; 21(1): 452, 2021 May 19.
Article in English | MEDLINE | ID: covidwho-1236546

ABSTRACT

BACKGROUND: COVID-19 has impacted populations around the world, with the fatality rate varying dramatically across countries. Selenium, as one of the important micronutrients implicated in viral infections, was suggested to play roles. METHODS: An ecological study was performed to assess the association between the COVID-19 related fatality and the selenium content both from crops and topsoil, in China. RESULTS: Totally, 14,045 COVID-19 cases were reported from 147 cities during 8 December 2019-13 December 2020 were included. Based on selenium content in crops, the case fatality rates (CFRs) gradually increased from 1.17% in non-selenium-deficient areas, to 1.28% in moderate-selenium-deficient areas, and further to 3.16% in severe-selenium-deficient areas (P = 0.002). Based on selenium content in topsoil, the CFRs gradually increased from 0.76% in non-selenium-deficient areas, to 1.70% in moderate-selenium-deficient areas, and further to 1.85% in severe-selenium-deficient areas (P < 0.001). The zero-inflated negative binomial regression model showed a significantly higher fatality risk in cities with severe-selenium-deficient selenium content in crops than non-selenium-deficient cities, with incidence rate ratio (IRR) of 3.88 (95% CIs: 1.21-12.52), which was further confirmed by regression fitting the association between CFR of COVID-19 and selenium content in topsoil, with the IRR of 2.38 (95% CIs: 1.14-4.98) for moderate-selenium-deficient cities and 3.06 (1.49-6.27) for severe-selenium-deficient cities. CONCLUSIONS: Regional selenium deficiency might be related to an increased CFR of COVID-19. Future studies are needed to explore the associations between selenium status and disease outcome at individual-level.


Subject(s)
COVID-19/diagnosis , Selenium/analysis , COVID-19/mortality , COVID-19/virology , China/epidemiology , Crops, Agricultural/chemistry , Humans , Micronutrients/analysis , SARS-CoV-2/isolation & purification , Selenium/deficiency , Soil/chemistry , Survival Analysis
15.
Vaccine ; 39(21): 2833-2842, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1180090

ABSTRACT

BACKGROUND: Vaccination against coronavirus disease 2019 (COVID-19) has become an important public health solution. To date, there has been a lack of data on COVID-19 vaccination willingness, vaccine hesitancy, and vaccination coverage in China since the vaccine has become available. METHODS: We designed and implemented a cross-sectional, population-based online survey to evaluate the willingness, hesitancy, and coverage of the COVID-19 vaccine among the Chinese population. 8742 valid samples were recruited and classified as the vaccine-priority group (n = 3902; 44.6%) and the non-priority group (n = 4840; 55.4%). RESULTS: The proportion of people's trust in the vaccine, delivery system, and government were 69.0%, 78.0% and 81.3%, respectively. 67.1% of the participants were reportedly willing to accept the COVID-19 vaccination, while 9.0% refused it. 834 (35.5%) reported vaccine hesitancy, including acceptors with doubts (48.8%), refusers (39.4%), and delayers (11.8%). The current coverage was 34.4%, far from reaching the requirements of herd immunity. The predicted rate of COVID-19 vaccination was 64.9%, 68.9% and 81.1% based on the rates of vaccine hesitancy, willingness, and refusal, respectively. CONCLUSIONS: The COVID-19 vaccine rate is far from reaching the requirements of herd immunity, which will require more flexible and comprehensive efforts to improve the population's confidence and willingness to vaccinate. It should be highlighted that vaccination alone is insufficient to stop the pandemic; further efforts are needed not only to increase vaccination coverage but also to maintain non-specific prevention strategies.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , China , Cross-Sectional Studies , Humans , SARS-CoV-2 , Vaccination
16.
Rev Med Virol ; 31(4): e2195, 2021 07.
Article in English | MEDLINE | ID: covidwho-938541

ABSTRACT

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19/pathology , Cytokines/metabolism , Humans , Killer Cells, Natural/immunology , Leukocytes/immunology , Severity of Illness Index , T-Lymphocytes/immunology
17.
Clin Infect Dis ; 72(4): 626-633, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-851733

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , COVID-19/mortality , China/epidemiology , Humans , Laboratories , Prognosis , Retrospective Studies
18.
Euro Surveill ; 25(40)2020 10.
Article in English | MEDLINE | ID: covidwho-841040

ABSTRACT

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.


Subject(s)
Coronavirus Infections/transmission , Coronavirus/pathogenicity , Infectious Disease Incubation Period , Pneumonia, Viral/transmission , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Child , Child, Preschool , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Epidemiologic Studies , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Young Adult
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