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1.
Prog Neuropsychopharmacol Biol Psychiatry ; 118: 110578, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-1864636

ABSTRACT

Emerging evidence suggested that people with severe mental disorders were more vulnerable to the negative effects of the COVID-19 pandemic. However, few researches investigated the influence of global pandemics on people at clinical high risk (CHR) for psychosis. This study aimed to investigate the impact of the COVID-19 pandemic on clinical symptoms, psychological distress, and eye-tracking characteristics in CHR individuals and healthy participants. Forty-nine CHR individuals and 50 healthy controls (HC) were assessed by PTSD Checklist for DSM-5 (PCL-5), Perceived Stress Scale, 10-item version (PSS-10), and Coronavirus Impact Scale (CIS). Eye movement performances were measured by the tests of fixation stability, free-viewing, and anti-saccade. According to the mean score of CIS, participants were stratified into high-impact (n = 35) and low-impact (n = 64) subgroups. Compared with the HC group, CHR participants reported significantly higher levels of post-traumatic symptoms caused by the COVID-19 pandemic and showed abnormalities in most of the eye movement indexes. Among the altered indexes, the saccade amplitude of fixation stability test (far distractor), the scan path length of free-viewing test, and the accuracy of anti-saccade test were negatively affected by the severity of impact level in the CHR group. Moreover, the altered eye movement indexes were significantly associated with the total scores of CIS, PCL-5, and subscales of the Scale of Prodromal Syndromes (SOPS) among CHR individuals. Overall, our findings suggested the negative impact of the COVID-19 pandemic on the eye movement characteristics of CHR individuals. The present study provides valuable information on physiological distress related to the COVID-19 pandemic and sensitive neuropsychological biomarkers that interacted with social and environment stress in the CHR population.


Subject(s)
COVID-19 , Psychotic Disorders , COVID-19/epidemiology , Eye-Tracking Technology , Humans , Pandemics , Prodromal Symptoms , Psychotic Disorders/psychology
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336996

ABSTRACT

Widespread and frequent testing is critical to prevent the spread of COVID-19, and rapid antigen tests are the diagnostic tool of choice in many settings. With new viral variants continuously emerging and spreading rapidly, the effect of mutations on antigen test performance is a major concern. In response to the spread of variants the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx®) initiative created a Variant Task Force to assess the impact of emerging SARS-CoV-2 variants on in vitro diagnostic testing. To evaluate the impact of mutations on rapid antigen tests we developed a lentivirus-mediated mammalian surface-display platform for the SARS-CoV-2 Nucleocapsid protein, the target of the majority of rapid antigen tests. We employed deep mutational scanning (DMS) to directly measure the effect of all possible Nucleocapsid point mutations on antibody binding by 17 diagnostic antibodies used in 11 commercially available antigen tests with FDA emergency use authorization (EUA). The results provide a complete map of the antibodies’ epitopes and their susceptibility to mutational escape. This approach identifies linear epitopes, conformational epitopes, as well as allosteric escape mutations in any region of the Nucleocapsid protein. All 17 antibodies tested exhibit distinct escape mutation profiles, even among antibodies recognizing the same folded domain. Our data predict no vulnerabilities of rapid antigen tests for detection of mutations found in currently and previously dominant variants of concern and interest. We confirm this using the commercial tests and sequence-confirmed COVID-19 patient samples. The antibody escape mutation profiles generated here serve as a valuable resource for predicting the performance of rapid antigen tests against past, current, as well as any possible future variants of SARS-CoV-2, establishing the direct clinical and public health utility of our system. Further, our mammalian surface-display platform combined with DMS is a generalizable platform for complete mapping of protein-protein interactions.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331071

ABSTRACT

It has been suggested that COVID-19 patients have distinct tongue features, which may help to monitor the development of their condition. To determine if there was any specific tongue coating feature in COVID-19, this study investigated the difference in tongue coating between COVID-19 subjects and subjects with other acute inflammatory diseases characterized by fever. Tongue images taken with smartphones from three age-matched groups, namely, COVID group (n=92), non-COVID febrile group (n=92), and normal control group (n=92), were analyzed by two blinded raters according to a tongue coating scoring scheme, which assessed the levels of thick fur, slimy or greasy fur, discolored fur and composite index of tongue coating. Compared with control, significant increases in all coating indexes were found in the COVID group (P<0.001), as well as in the non-COVID febrile group (P<0.001). However, no difference was observed between COVID and non-COVID febrile groups for all coating indexes measured. In COVID-19 subjects, their scores of coating indexes had weak but significant correlations with certain inflammatory biomarkers, including WBC and neutrophil - lymphocyte ratio. It is concluded that COVID-19 subjects have pathological tongue coating patterns that are associated with inflammatory responses, and these coating patterns can help to indicate the direction of disease development.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323612

ABSTRACT

The analysis of the coronavirus disease 2019 (COVID-19) is of great importance to deeply understand the dynamics of this coronavirus spread. Based on the complexity of it, a modified susceptible-infected-removed (SIR) model is applied to analyze the time dependence of active and hospitalized cases in China. The time evolution of the virus spread in different provinces was adequately modeled. Changeable parameters among them have been obtained and turned to be not naively independent with each other. The non-extensive parameter was found to be strongly connected with the freedom of systems. Taken into the prevention and treatment of disease, more measures by the government lead to higher values of it.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317496

ABSTRACT

Background: More evidence in understanding the heterogeneity of COVID-19-associated acute respiratory distress syndrome (ARDS) and in improving strategy to increase the survival from the critical patients intubated is always needed. The study aimed to comprehensively explore the features of COVID-19-associated ARDS and the features and outcomes between the early and late intubation groups. Methods: : This retrospective cohort included 65 adult COVID-19 inpatients with ARDS at two hospitals in Hubei, China. The ARDS in these patients was diagnosed according to the Berlin criteria. We defined intubation within 7 days of ARDS diagnosis as ‘early’ intubation and that performed from the eighth day as ‘late’ intubation based on literatures. The outcomes were invasive mechanical ventilation and in-hospital death. The log-binomial regression models were used to explore the risk factors and the Kaplan-Meier statistic was used to estimate the risk of mortality. Results: : The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The early intubation and the late intubation had the differences in days from symptom onset/hospital admission/ARDS diagnosis to intubation (P = 0.023, P = 0.011, P < 0.001). Compared with the early-intubation group, the late-intubation group showed less severity at admission (median oxygenation index 159.0 95% CI 134.0-203.0 vs. 133.9 95% CI 98.3-183.2), but required more aggressive therapies (ICU 80% vs. 70%, CRRT 50% vs. 10%, prone-position 50% vs. 30%, and ECMO 50% vs. 10%) and had higher risk to die at hospital (RR, 3.18;95% CI 1.98-5.12). Conclusion: The ARDS caused by COVID-19 was not typical ARDS due to prolonged onset time, multiple organ injuries, and higher mortalities. The late-intubation group showed less severity at admission but higher risk of in-hospital death than the early-intubation group.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317495

ABSTRACT

Background: The reviews on the risk factors with ARDS and the worse outcomes concluded lacking robust data of risk factors to prevent COVID-19 and identified an urgent need for large sample and high-quality research in this area, as well as the features of the ARDS. Methods: : This retrospective cohort study included 333 COVID-19 inpatients at two hospitals in Hubei of China in 2020. The COVID-19-related ARDS was diagnosed according to the Berlin criteria. The outcomes were ARDS development and the intubation or in-hospital death. The cox proportional hazard ratio (HR) models were employed to determine the significant risk factors. Results: : The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The survival patients on invasive mechanical ventilation (IMV) had been intubated earlier since ARDS diagnosis than those who had not survived (5.5 median days, IQR 4.0-7.0 days versus 11.5 median days, IQR 6.0-14.0 days, P < 0.001). Males and all abnormal laboratory indices associated with the higher risk of ARDS (P<0.05) but were not linked with the risk of intubation or death (P>0.05). The sensitivity analyses found that lymphocyte count of < 1000 per mm3 at hospital admission were still significantly associated with developing ARDS when adjusting for age and male gender (HR, 4.10;95% CI, 2.40-7.10), and oxygenation index (OI) ratio < 150 were more likely to predict the intubation/death after age adjustment (HR, 2.50;95% CI, 1.17-5.30). Conclusion: The SARS-CoV-2-caused ARDS was not the typical ARDS according to Berlin criteria. The alive patients with IMV had been intubated earlier since ARDS diagnosis than those who had not survived. We identified male gender and abnormal laboratory indices associated with the ARDS but were not linked with the intubation/death. Sensitivity analysis concluded lymphocyte count of < 1000 per mm3 could predict ARDS while OI ratio less than 150 could predict intubation/death.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315710

ABSTRACT

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19.Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge.Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13;controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81;controls: 3.15±0.39, p<0.001) than the controls. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients (TICS-40: 22.98±7.12 vs. 30.46±5.53, p<0.001;IQCODE: 4.06±1.39 vs. 3.33±0.68, p<0.001) and controls (TICS-40: 22.98±7.12 vs. 30.74±5.95, p<0.001;IQCODE: 4.06±1.39 vs. 3.15±0.39, p<0.001). Severe COVID-19 patients had a higher proportion of cases with a current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients and controls. COVID-19 severity (OR: 8.142, 95% CI: 5.007-13.239) was associated with worse current cognitive function. Older age (OR: 1.024, 95% CI: 1.003 to 1.046), COVID-19 severity (OR: 2.277, 95% CI: 1.308 to 3.964), mechanical ventilation (OR: 5.388, 95% CI: 3.007 to 9.656), and hypertension (OR: 1.866, 95% CI: 1.376 to 2.531) were associated with an increased risk of longitudinal cognitive decline.Interpretation: SARS-CoV-2 infection is associated with delayed cognitive decline in elderly population. COVID-19 patients with risk factors, including severe disease, older age, mechanical ventilation, and hypertension, should be intensively monitored for delayed cognitive decline. Funding: National Natural Science Foundation of China.Conflict of Interest: We declared no conflict of interests.Ethical Approval: The study protocols were approved by the institutional review boards of the hospitals. Verbal informed consent was obtained from all participants prior to the survey.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315682

ABSTRACT

Background: In the high incidence period of COVID-19, it is very important to quickly classify and evaluate the prognosis of patients through limited clinical antibody data. Methods Chemiluminescence immunoassay was used to detect serum IgM and IgG concentrations in 1951 patients diagnosed with COVID-19, and R language was used to analyze the influence of factors such as antibody, age, gender and concomitant diseases on the prognosis of SARS-CoV-2 patients. Results The results showed that the incidence of COVID-19 was consistent with the characteristics of the elderly, and patients with hypertension, diabetes, stroke, hypoalbuminemia and anemia were at increased risk of critical illness ( p  < 0.05). The analysis of antibodies results showed that there were no significant difference in antibodies concentration between COVID-19 patients of different ages. While there were no significant difference in antibodies concentration between mild and severe patients, the expression levels of serum IgM and IgG in critically ill patients decreased ( p  = 0.000 and 0.013), and high IgM and IgG concentration could reduce the incidence of critical illness ( p  = 0.003 and 0.015). Except in the 41–60 and 91–100 age groups, the simultaneous low expression of IgM and IgG in COVID-19 patients was significantly positively correlated with the severity of illness ( p   =  0.000). Conclusions IgM and IgG were important prognostic factors for COVID-19 patients. It was hence vital to carry out special clinical classification for the management and early intervention for patients with low IgM/IgG concentrations and with concomitant diseases.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-305590

ABSTRACT

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples;pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

12.
Ther Adv Respir Dis ; 15: 17534666211049739, 2021.
Article in English | MEDLINE | ID: covidwho-1463196

ABSTRACT

AIM: The aim of this study was to investigate the predictive role of lymphocyte subsets and other laboratory measurements in patients with COVID-19. METHODS: Electronic medical records of adult patients with confirmed diagnosis of COVID-19 from the Shanghai Public Health Clinical Center were reviewed retrospectively to obtain relevant data. RESULTS: The mean age of patients was 40.98 ± 15.95 years, with 58% of the patients being males. The cutoff values at the intensive care unit (ICU) admission, mechanical ventilation, and mortality were CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, and 182), and CD4+ /CD8+ cells (1.4, 1.8, and 1.4). The cutoffs below these values indicate the higher chances of disease progression. Higher CD4+ cell count led to lesser chances for ICU admission [odds ratio (OR) (95% confidence interval (CI): 0.994 (0.991, 0.997); p = 0.0002] and mortality [OR (95% CI): 0.988 (0.979, 0.99); p = 0.001], higher CD8+ count was an independent risk factor for ICU admission. T-cell count positively correlated with total lymphocyte count and platelets, while negatively correlated with D-dimer and lactate dehydrogenase (LDH). Among patients with non-severe COVID-19, median CD8+ T cell, CD4+ T cell, total lymphocyte count, and platelets were 570, 362, 1.45, and 211, respectively, while median values decreased to 149, 106, 0.64, and 172, respectively, in patients with severe COVID-19. CONCLUSION: Lower T lymphocyte subsets were significantly associated with higher admission to ICU, mechanical ventilation, and mortality among patients with COVID-19. A cutoff value of ICU admission, mechanical ventilation, and mortality below CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, 182), and CD4+/CD8+ cells (1.4, 1.8, 1.4) may help identify patients at high risk of disease progression. The continuous evaluation of laboratory indices may help with dismal prognosis and prompt intervention to improve outcomes.


Subject(s)
COVID-19/physiopathology , Intensive Care Units/statistics & numerical data , Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/cytology , Adult , COVID-19/mortality , COVID-19/therapy , China , Disease Progression , Female , Humans , Lymphocyte Count , Male , Middle Aged , Prognosis , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , Severity of Illness Index
13.
Clin Infect Dis ; 73(2): 352-353, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1319147

Subject(s)
Methotrexate , Humans
14.
Mol Neurodegener ; 16(1): 48, 2021 07 19.
Article in English | MEDLINE | ID: covidwho-1318288

ABSTRACT

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.


Subject(s)
COVID-19/complications , Cognitive Dysfunction/virology , Aged , Aged, 80 and over , COVID-19/epidemiology , China , Cognitive Dysfunction/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , SARS-CoV-2
15.
EMBO Rep ; 22(8): e52447, 2021 08 04.
Article in English | MEDLINE | ID: covidwho-1278776

ABSTRACT

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination.


Subject(s)
COVID-19 , Influenza Vaccines , Vaccines, Virus-Like Particle , Animals , Humans , Mice , Nucleotides, Cyclic , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Virus-Like Particle/genetics
16.
Clin Infect Dis ; 72(9): 1678-1680, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1223326
17.
Sci Rep ; 11(1): 5975, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1137818

ABSTRACT

Since the emergence of SARS-CoV-2, numerous studies have been attempting to determine biomarkers, which could rapidly and efficiently predict COVID-19 severity, however there is lack of consensus on a specific one. This retrospective cohort study is a comprehensive analysis of the initial symptoms, comorbidities and laboratory evaluation of patients, diagnosed with COVID-19 in Huoshenshan Hospital, Wuhan, from 4th February to 12th March, 2020. Based on the data collected from 63 severely ill patients from the onset of symptoms till the full recovery or demise, we found not only age (average 70) but also blood indicators as significant risk factors associated with multiple organ failure. The blood indices of all patients showed hepatic, renal, cardiac and hematopoietic dysfunction with imbalanced coagulatory biomarkers. We noticed that the levels of LDH (85%, P < .001), HBDH (76%, P < .001) and CRP (65%, P < .001) were significantly elevated in deceased patients, indicating hepatic impairment. Similarly, increased CK (15%, P = .002), Cre (37%, P = 0.102) and CysC (74%, P = 0.384) indicated renal damage. Cardiac injury was obvious from the significantly elevated level of Myoglobin (52%, P < .01), Troponin-I (65%, P = 0.273) and BNP (50%, P = .787). SARS-CoV-2 disturbs the hemolymphatic system as WBC# (73%, P = .002) and NEUT# (78%, P < .001) were significantly elevated in deceased patients. Likewise, the level of D-dimer (80%, P < .171), PT (87%, P = .031) and TT (57%, P = .053) was elevated, indicating coagulatory imbalances. We identified myoglobin and CRP as specific risk factors related to mortality and highly correlated to organ failure in COVID-19 disease.


Subject(s)
C-Reactive Protein/analysis , COVID-19/pathology , Myoglobin/analysis , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Comorbidity , Female , Humans , Male , Middle Aged , Multiple Organ Failure/etiology , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Analysis , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Troponin I/blood
18.
PLoS Pathog ; 17(2): e1009352, 2021 02.
Article in English | MEDLINE | ID: covidwho-1105835

ABSTRACT

Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibody-Producing Cells/immunology , Binding Sites , Epitopes , Humans , Immunoglobulin G/immunology , Nucleocapsid/immunology , Spike Glycoprotein, Coronavirus/immunology
19.
PLoS One ; 16(1): e0245209, 2021.
Article in English | MEDLINE | ID: covidwho-1067409

ABSTRACT

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.


Subject(s)
Acute Kidney Injury/drug therapy , Acute Kidney Injury/virology , COVID-19/drug therapy , COVID-19/physiopathology , Quercetin/pharmacology , Databases, Factual , Databases, Genetic , Humans , Molecular Docking Simulation , Protein Interaction Mapping/methods , Protein Interaction Maps , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
20.
Wellcome Open Research ; 2020.
Article in English | ProQuest Central | ID: covidwho-1024793

ABSTRACT

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples;pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

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