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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323670

ABSTRACT

【Background】Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown.【Methods】 This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild and severe groups. We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined.【Results】 56.2% of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% cases the level of ALT, AST or TBil ≤ 3 fold of the upper normal range. The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (p<0.05).The percentage of the patients with both elevated ALT and AST was 12.7% in mild cases vs. 46.2% in severe cases (p = 0.001). 34.6% severe group patients started to have abnormal ALT after admission,and 73.4% of all patients had normal ALT before discharge.【Conclusion】Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN,but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322743

ABSTRACT

Background: Towards the end of December 2019, the Wuhan health commission declared an outbreak of clusters of pneumonia in patients. Sequencing indicated that this disease (COVID-19) was caused by a novel coronavirus (SARS-CoV-2). The outbreak of COVID-19 is currently still underway. Methods We recruited 75 SARS-CoV-2 infected patients admitted to the Center of Infectious Disease division 2 of Beijing Ditan Hospital from Jan 20 to Mar 20, 2020. Epidemiological, demographic, clinical, radiological features, laboratory data were analyzed. Results Of the 75 patients, 42(56%) patients were male and 33(44%) patients were female. The mean age of all patients was 41.5 ± 19.4 years. Male patients were more likely to become severe. There were 9 family clusters accounted for 44 patients. Patients classified as being severe had a higher frequency of fever upon admission than patients classified as moderate cases. For moderate patients, the median duration of viral shedding was 25(9.5, 42) days (range 1–63 days) from the first positive nucleic acid test compared to 14(9, 21.25) days (range 2–62 days) for severe cases. The difference between the two groups was statistically significant (p = 0.041). Cox regression analyses indicated that disease status and CRP were the factors that affect the duration of viral shedding. Virus clearance was significantly faster in severe patients compared to moderate patients(p = 0.011), and patients with CRP range in 2–10 times higher than upper limit of normal value had longer duration of viral shedding(p = 0.012). CRP and CD4 + T lymphocyte was negative correlated, and the relationship between CRP and CD4 + T lymphocyte was statistically significant (P = 0.003), with a correlation coefficient of -0.564. During the second week following the onset of illness, severe cases had higher WBC, NEU and CRP, but lower LYM, MON and EOS as compared with moderate cases (all P < 0.05). Severe cases still had lower lymphocyte counts and higher CRP than moderate cases in the third week. Conclusions Viral clearance was significantly prolonged in moderate patients, and those CRP in 2–10 times higher than upper limit of normal value. Immune response may affect the duration of viral shedding. Severe cases had a persistence lower lymphocyte count and higher CRP than moderate cases.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315201

ABSTRACT

The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.

4.
J Med Virol ; 94(5): 2237-2249, 2022 May.
Article in English | MEDLINE | ID: covidwho-1664417

ABSTRACT

As the coronavirus disease 2019 (COVID-19) pandemic is still ongoing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are circulating worldwide, an increasing number of breakthrough infections are being detected despite the good efficacy of COVID-19 vaccines. Data on 88 COVID-19 breakthrough cases (breakthrough infections group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 22, 2021, were extracted from a cloud database established at Beijing Ditan Hospital to evaluate the clinical, immunological, and genomic characteristics of COVID-19 breakthrough infections. Among these 129 COVID-19 cases, 33 whole genomes were successfully sequenced, of which 23 were Delta variants, including 15 from the breakthrough infections group. Asymptomatic and mild cases predominated in both groups, but two patients developed severe disease in the unvaccinated group. The median time of viral shedding in the breakthrough infections group was significantly lower than that in the unvaccinated group (p = 0.003). In the breakthrough infections group, the IgG titers showed a significantly increasing trend (p = 0.007), and the CD4 + T lymphocyte count was significantly elevated (p = 0.018). For people infected with the Delta variant in the two groups, no significant difference was observed in either the quantitative reverse-transcription polymerase chain reaction results or viral shedding time. In conclusion, among vaccinated patients, the cases of COVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, IgG titers were significantly increased and rose rapidly, and the viral shedding time was shorter.


Subject(s)
COVID-19 , Beijing/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Genomics , Humans , SARS-CoV-2/genetics
5.
Cell Rep ; 38(2): 110205, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1588142

ABSTRACT

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.


Subject(s)
COVID-19/virology , Host-Pathogen Interactions/genetics , SARS-CoV-2/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/genetics , Spike Glycoprotein, Coronavirus/genetics , Young Adult
7.
Microbiol Spectr ; 9(1): e0027321, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1341310

ABSTRACT

The SARS-CoV-2 B.1.1.7 variant has increased sharply in numbers worldwide and is reported to be more contagious than the nonvariant. Little is known regarding the detailed clinical features of B.1.1.7 variant infection. Data on 74 COVID-19 cases from two outbreaks in two districts of Beijing, China were extracted from a cloud database, including 41 cases from Shunyi District (Shunyi B.1.470 group) and 33 from Daxing (Daxing B.1.1.7 group) from December 25, 2020 to January 17, 2021. We conducted a comparison of the clinical characteristics. Seven clinical indicators of the Daxing B.1.1.7 group were significantly higher than those of the Shunyi group, including the proportion with fever over 38°C, the levels of C-reactive protein (CRP), serum amyloid A (SAA), creatine kinase (CK), d-dimer (DD), and CD4+ T lymphocytes (CD4+ T), and the proportion with ground-glass opacity (GGO) in the lung (P values of ≤0.05). After adjusting for age, B.1.1.7 variant infection was a risk factor for elevated CRP (P = 0·045), SAA (P = 0·011), CK (P = 0·034), and CD4+ T (P = 0.029) and for the presence of GGO (P = 0.005). The median threshold cycle (CT) value of reverse transcriptase quantitative PCR (RT-qPCR) tests of the N gene target in the Daxing B.1.1.7 group was significantly lower (P = 0.036) than that in the Shunyi B.1.470 group. Clinical features, including a more serious inflammatory response, pneumonia, and a possibly higher viral load, were detected in the cases infected with B.1.1.7 SARS-CoV-2. The B.1.1.7 variant may have increased pathogenicity. IMPORTANCE The SARS-CoV-2 B.1.1.7 variant, which was first identified in the United Kingdom, has increased sharply in numbers worldwide and was reported to be more contagious than the nonvariant. To our knowledge, no studies investigating the detailed clinical features of COVID-19 cases infected with the B.1.1.7 variant have been published. Local epidemics have rarely occurred in China, but occasionally, a small clustered outbreak triggered by an imported SARS-CoV-2 strain with only one chain of transmission could happen. From late 2020 to early 2021, two clustered COVID-19 outbreaks occurred in Beijing, one of which was caused by the B.1.1.7 variant. The COVID-19 patients from the two outbreaks received similar clinical tests, diagnoses, and treatments. We found that the B.1.1.7 variant infection could lead to a more serious inflammatory response, acute response process, more severe pneumonia, and probably higher viral loads. This therefore implies that the B.1.1.7 variant may have increased pathogenicity.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adult , CD4-Positive T-Lymphocytes , China/epidemiology , Cohort Studies , Female , Humans , Lung/virology , Male , Middle Aged , Prospective Studies , Risk Factors , Viral Load , Whole Genome Sequencing
8.
J Infect Public Health ; 14(5): 620-627, 2021 May.
Article in English | MEDLINE | ID: covidwho-1074829

ABSTRACT

INTRODUCTION: Many individuals test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA after recovering from the coronavirus disease (COVID-19), but the incidence of reactivation is unknown. We, therefore, estimated the incidence of reactivation among individuals who had recovered from COVID-19 and determined its predictors. METHODS: In this retrospective cohort study, patients with COVID-19 were followed up for at least 14 days after two consecutive negative SARS-CoV-2 polymerase chain reaction test results obtained ≥24 h apart, and the frequency of SARS-CoV-2 reactivation was assessed. RESULTS: Of the 109 patients, 29 (27%) experienced reactivation, and seven (24%) of these were symptomatic. The mean period for the real-time PCR tests for SARS-CoV-2 from negative to positive results was 17 days. Compared with patients without reactivation, those with reactivation were significantly younger and more likely to have a lymphocyte count of <1500/µL (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.12-0.94) and two or fewer symptoms (OR: 0.20, 95% CI: 0.07-0.55) during the initial episode. CONCLUSION: Risk-stratified surveillance should be conducted among patients who have recovered from COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Real-Time Polymerase Chain Reaction , Retrospective Studies
9.
BMC Infect Dis ; 20(1): 910, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-953531

ABSTRACT

BACKGROUND: Both COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. METHODS: By retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1-4). RESULTS: We reviewed the patients' data of 94 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 37 severe influenza A. We found total lymphocytes (0.81 × 109/L vs 1.74 × 109/L, P = 0.001; 0.87 × 109/L vs 1.74 × 109/L, P < 0.0001, respectively) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of severe COVID-19 and severe influenza A patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). CONCLUSIONS: Our study suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Influenza A virus/genetics , Influenza, Human/immunology , SARS-CoV-2/genetics , Severity of Illness Index , Adult , Aged , Beijing/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Comorbidity , Cross-Sectional Studies , Disease Progression , Female , Flow Cytometry , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Lymphocyte Count , Male , Middle Aged , Prognosis , Retrospective Studies
10.
Med Sci Monit ; 26: e925974, 2020 Sep 25.
Article in English | MEDLINE | ID: covidwho-796268

ABSTRACT

BACKGROUND Coronavirus disease 2019 (COVID-19) is a new infectious disease, and acute respiratory syndrome (ARDS) plays an important role in the process of disease aggravation. The detailed clinical course and risk factors of ARDS have not been well described. MATERIAL AND METHODS We retrospectively investigated the demographic, clinical, and laboratory data of adult confirmed cases of COVID-19 in Beijing Ditan Hospital from Jan 20 to Feb 29, 2020 and compared the differences between ARDS cases and non-ARDS cases. Univariate and multivariate logistic regression methods were employed to explore the risk factors associated with ARDS. RESULTS Of the 130 adult patients enrolled in this study, the median age was 46.5 (34-62) years and 76 (58.5%) were male. ARDS developed in 26 (20.0%) and 1 (0.8%) death occurred. Fever occurred in 114 patients, with a median highest temperature of 38.5 (38-39)°C and median fever duration of 8 (3-11) days. The median time from illness onset to ARDS was 10 (6-13) days, the median time to chest CT improvement was 17 (14-21) days, and median time to negative nucleic acid test result was 27 (17-33) days. Multivariate regression analysis showed increasing odds of ARDS associated with age older than 65 years (OR=4.75, 95% CL1.26-17.89, P=0.021), lymphocyte counts [0.5-1×109/L (OR=8.80, 95% CL 2.22-34.99, P=0.002); <0.5×109/L(OR=36.23, 95% CL 4.63-2083.48, P=0.001)], and temperature peak ≥39.1°C (OR=5.35, 95% CL 1.38-20.76, P=0.015). CONCLUSIONS ARDS tended to occur in the second week of the disease course. Potential risk factors for ARDS were older age (>65 years), lymphopenia (≤1.0×109/L), and temperature peak (≥39.1°C). These findings could help clinicians to predict which patients will have a poor prognosis at an early stage.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome/etiology , Adult , Aged , Aged, 80 and over , Bacterial Infections/etiology , COVID-19 , China , Cities/epidemiology , Comorbidity , Coronavirus Infections/epidemiology , Female , Fever/etiology , Humans , Logistic Models , Lymphopenia/etiology , Male , Middle Aged , Pneumonia, Viral/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2
11.
Open Forum Infect Dis ; 7(5): ofaa169, 2020 May.
Article in English | MEDLINE | ID: covidwho-623975

ABSTRACT

BACKGROUND: There is currently a lack of nonspecific laboratory indicators as a quantitative standard to distinguish between the 2019 coronavirus disease (COVID-19) and an influenza A or B virus infection. Thus, the aim of this study was to establish a nomogram to detect COVID-19. METHODS: A nomogram was established using data collected from 457 patients (181 with COVID-19 and 276 with influenza A or B infection) in China. The nomogram used age, lymphocyte percentage, and monocyte count to differentiate COVID-19 from influenza. RESULTS: Our nomogram predicted probabilities of COVID-19 with an area under the receiver operating characteristic curve of 0.913 (95% confidence interval [CI], 0.883-0.937), greater than that of the lymphocyte:monocyte ratio (0.849; 95% CI, 0.812-0.880; P = .0007), lymphocyte percentage (0.808; 95% CI, 0.768-0.843; P < .0001), monocyte count (0.780; 95% CI, 0.739-0.817; P < .0001), or age (0.656; 95% CI, 0.610-0.699; P < .0001). The predicted probability conformed to the real observation outcomes of COVID-19, according to the calibration curves. CONCLUSIONS: We found that age, lymphocyte percentage, and monocyte count are risk factors for the early-stage prediction of patients infected with the 2019 novel coronavirus. As such, our research provides a useful test for doctors to differentiate COVID-19 from influenza.

12.
Mil Med Res ; 7(1): 28, 2020 06 07.
Article in English | MEDLINE | ID: covidwho-548559

ABSTRACT

BACKGROUND: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown. METHODS: This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined. RESULTS: 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P <  0.05). The percentage of the patients with elevated both ALT and AST was 12.7% (10/79) in mild cases vs. 46.2% (12/26) in severe cases (P = 0.001). 34.6% (9/26) severe group patients started to have abnormal ALT after admission, and 73.3% (77/105) of all patients had normal ALT before discharge. CONCLUSIONS: Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.


Subject(s)
Alanine Transaminase/blood , Betacoronavirus , Coronavirus Infections/blood , Hepatitis, Viral, Human/blood , Hepatitis, Viral, Human/virology , Liver/virology , Pneumonia, Viral/blood , Adolescent , Adult , Aged , Aged, 80 and over , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers/blood , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Female , Humans , Liver/physiopathology , Liver Function Tests , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
13.
J Transl Med ; 18(1): 206, 2020 05 20.
Article in English | MEDLINE | ID: covidwho-324357

ABSTRACT

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.


Subject(s)
Coronavirus Infections/diagnosis , Critical Illness , Lymphocytes/pathology , Neutrophils/pathology , Pneumonia, Viral/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , Child , Child, Preschool , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/pathology , Disease Progression , Female , History, 21st Century , Humans , Infant , Leukocyte Count , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Prognosis , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
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