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1.
J Biomed Sci ; 29(1): 27, 2022 May 03.
Article in English | MEDLINE | ID: covidwho-1951231

ABSTRACT

The global pandemic of COVID-19 has caused huge causality and unquantifiable loss of social wealth. The innate immune response is the first line of defense against SARS-CoV-2 infection. However, strong inflammatory response associated with dysregulation of innate immunity causes severe acute respiratory syndrome (SARS) and death. In this review, we update the current knowledge on how SARS-CoV-2 modulates the host innate immune response for its evasion from host defense and its corresponding pathogenesis caused by cytokine storm. We emphasize Type I interferon response and the strategies of evading innate immune defense used by SARS-CoV-2. We also extensively discuss the cells and their function involved in the innate immune response and inflammatory response, as well as the promises and challenges of drugs targeting excessive inflammation for antiviral treatment. This review would help us to figure out the current challenge questions of SARS-CoV-2 infection on innate immunity and directions for future studies.


Subject(s)
COVID-19 , Antiviral Agents , COVID-19/drug therapy , Humans , Immunity, Innate , SARS-CoV-2
2.
Protein Cell ; 13(8): 602-614, 2022 08.
Article in English | MEDLINE | ID: covidwho-1777862

ABSTRACT

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.


Subject(s)
Amyotrophic Lateral Sclerosis , COVID-19 , Amyloidogenic Proteins/metabolism , Amyotrophic Lateral Sclerosis/genetics , Animals , Cytoplasmic Granules/metabolism , Mammals , SARS-CoV-2 , Stress Granules
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329931

ABSTRACT

Background: Home isolation is a generally effective strategy for coronavirus disease control during lockdown periods. This study is to determine the potential adverse consequences of home isolation to mental health among school-aged youth after lifting of major lockdown measures in central China. Methods: : This cohort study assessed the mental health of school-aged children and adolescents enrolled in Wuhan city and nearby areas in Hubei province, China, from July 1 to August 31, 2020. Post-lockdown responses to anxiety, depression, sleep disturbances and post-traumatic stress symptoms were assessed in online questionnaire-based surveys. Participants’ scores for the Zung self-rated anxiety scale, the Patient Health Questionnaire-9, the self-rating scale of sleep and the post-traumatic stress disorder self-rating scale (PTSS) were analyzed. Results: : Questionnaire responses of 730 school children were collected. Among the participants, 6.25% of them had scores above thresholds for PTSS, 5.81% had anxiety, and 48.84% had depression. All subjects reported that they experienced sleep disturbances. Subjects who had anxiety might have a high risk for developing depression [OR: 16.07, p =0.008, 95%CI (2.08-123.94)] and PTSS [OR: 12.97, p <0.001, 95%CI (5.41-31.11)]. Both depression [OR: 17.35, p =0.006, 95%CI (2.28-131.87)] and PTSS [OR: 14.18, p <0.001, 95%CI (6.00-33.47)] were risk factors for developing anxiety among participants. Interestingly, higher educational levels of primary caregivers were a risk factor for developing depression [OR: 1.62, p =0.005, 95%CI (1.16-2.28)] in the participants, but a protective factor against PTSS [OR: 0.47, p =0.048, 95%CI (0.23-0.99)]. Conclusions: : The local youth had less than expected degree of increases in their self-reported PTSS and anxiety, after exiting lockdown-related isolation. As a result of a combination of compensatory mechanisms including internet-based home-schooling and increased intra-familial interactions, home isolation did not affect the mental health of local school-aged youth to an extent as great as expected. Trial registration: The Registration number of this trial is ChiCTR2000033054.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315345

ABSTRACT

Background: Currently no satisfactory pharmaceutical intervention is available for COVID-19. This retrospective study aimed to determine the therapeutic effect of thymosin alpha1 in critical COVID-19. Results: We enrolled 109 critically ill severe acute respiratory syndrome-related coronavirus-2 RNA positive patients from 15 hospitals. The mortality rate in critical patients treated with thymosin alpha1 was 11%, compared to 56% in critical patients not treated with thymosin alpha1. With confounding factors adjusted in multivariate logistic regression, thymosin alpha1 treatment was identified as a protective factor for critical COVID-19. Conclusion: Our observation advocates the treatment of critical COVID-19 with thymosin alpha1.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323931

ABSTRACT

Background: The majority of COVID-19 patients presented persisting symptoms after discharge. We aimed to determine the long-term enteric consequences of SARS-CoV-2 infection, and to identify the risk and the protective factors for gastrointestinal sequelae.Methods: A retrospective cohort of 117 SARS-CoV-2 nucleic acid positive patients hospitalized in 12 hospitals from January 16 to March 7, 2020 were included in this study. Clinical data collected during hospitalization, from return visits and from telephone interviews in 3 months after discharge were reviewed. Multivariable logistic regression was performed to identify the risk and the protective factors for any and individual gastrointestinal sequelae.Findings: In three months after discharge, 53 patients (45%) presented at least one gastrointestinal sequelae. Common gastrointestinal sequelae included loss of appetite (28 patients, 24%), nausea (21 patients, 18%), acid reflux (21 patients, 18%), and diarrhea (17 patients, 15%). Decreased blood oxygen saturation and PPI treatment were risk factors, while enteral nutrition was a protective factor for gastrointestinal sequelae in general. For individual gastrointestinal sequelae, the decreased blood oxygen saturation was a risk factor, while male sex was a protective factor for loss of appetite after discharge. For nausea after discharge, PPI treatment was a risk factor while parenteral nutrition was a protective factor. Decreased blood oxygen saturation, BMI >25, and PPI treatment were risk factors for acid reflux after discharge. And finally, male sex was a risk factor for diarrhea after discharge.Interpretation: At three months after discharge, gastrointestinal sequelae were still common in recovering COVID-19 patients. Decreased blood oxygen saturation, PPI treatment, BMI >25, and male sex are risk factors, while nutritional support and male sex are protective factors, for gastrointestinal sequelae. Our data highlight the importance of gastrointestinal care and nutritional support for discharged COVID-19 patients.Funding: Guangdong Province “Pearl River Talent Plan” Innovation and Entrepreneurship Team Project, National Natural Science Foundation of China, and the National Key Clinical Discipline of China.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Review Boards of Sun Yat-sen University and the participating hospitals.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308343

ABSTRACT

Background: Prior studies reported that 5~32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection. Methods Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness. Results Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis >9.5 X10 9 /L, neutrophilia >6.3 X10 9 /L, lymphopenia <1.1 X10 9 /L, neutrophil-to-lymphocyte ratio >3.53, fibrinogen >4g/L, d-dimer >0.55 µg/mL, blood urea nitrogen >7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin >21 µM, and Sequential Organ Failure Assessment (SOFA) score ≥2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors. Conclusions Our findings advocate the use of risk factors SOFA score ≥2, age >60, dyspnea and leukocytosis >9.5 X10 9 /L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.

7.
Crit Care Med ; 48(5): e391-e399, 2020 05.
Article in English | MEDLINE | ID: covidwho-661181

ABSTRACT

OBJECTIVES: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. DESIGN: Prospective phase I clinical trial. SETTING: Medical center in Kaohsiung, Taiwan. PATIENTS: Moderate-to-severe acute respiratory distress syndrome with a PaO2/FIO2 ratio less than 200. INTERVENTIONS: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10 cells/kg), the next three patients with intermediate dose (5.0 × 10 cells/kg), and the final three patients with high dose (1.0 × 10 cells/kg) between December 2017 and August 2019. MEASUREMENTS AND MAIN RESULTS: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+) and mesenchymal stem cell markers (CD26+CD45-/CD29+CD45-/CD34+CD45-/CD44+CD45-/CD73+CD45-/CD90+CD45-/CD105+CD45-/CD26+CD45-) were notably progressively reduced (p for trend < 0.001), whereas the immune cell markers (Helper-T-cell/Cytotoxity-T-cell/Regulatory-T-cell) were notably increased (p for trend < 0.001) after cell infusion. CONCLUSIONS: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/physiology , Respiratory Distress Syndrome/therapy , Umbilical Cord/physiology , Adult , Aged , Drug Dosage Calculations , Female , Hospital Mortality/trends , Humans , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Mesenchymal Stem Cell Transplantation/mortality , Mesenchymal Stem Cells/classification , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/mortality , Severity of Illness Index
9.
Front Med (Lausanne) ; 8: 604263, 2021.
Article in English | MEDLINE | ID: covidwho-1106028

ABSTRACT

Corticosteroid is commonly used to reduce damage from inflammatory reactions in coronavirus disease 2019 (COVID-19). We aim to determine the outcomes of corticosteroid use in critically ill COVID-19 patients. Ninety six critically ill patients, hospitalized in 14 hospitals outside Wuhan from January 16 to March 30, 2020 were enrolled in this study. Among 96 critical patients, 68 were treated with corticosteroid (CS group), while 28 were not treated with corticosteroids (non-CS group). Multivariable logistic regression were performed to determine the possible correlation between corticosteroid use and the treatment outcomes. Forty-six (68%) patients in the CS group died compared to six (21%) of the non-CS group. Corticosteroid use was also associated with the development of ARDS, exacerbation of pulmonary fibrosis, longer hospital stay and virus clearance time. On admission, no difference in laboratory findings between the CS and the non-CS group was observed. After corticosteroid treatment, patients treated with corticosteroids were associated with higher counts of white blood cells, neutrophils, neutrophil-to-lymphocyte ratio, alanine aminotransferase level and Sequential Organ Failure Assessment score. In conclusion, corticosteroid use in critically ill COVID-19 patients was associated with a much higher case fatality rate. Frequent incidence of liver injury and multi-organ failure in corticosteroid treated patients may have contributed to the adverse outcomes. The multi-organ failure is likely caused by more persistent SARS-CoV-2 infection and higher viral load, due to the inhibition of immune surveillance by corticosteroid.

10.
Respir Res ; 21(1): 277, 2020 Oct 21.
Article in English | MEDLINE | ID: covidwho-883578

ABSTRACT

BACKGROUND: Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection. METHODS: Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness. RESULTS: Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia < 1.1 × 109/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 µg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 µM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors. CONCLUSIONS: Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.


Subject(s)
Coronavirus Infections/epidemiology , Critical Illness/epidemiology , Pneumonia, Viral/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/analysis , Blood Cell Count , COVID-19 , China/epidemiology , Cohort Studies , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Critical Care , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , ROC Curve , Regression Analysis , Risk Factors , Severity of Illness Index , Treatment Outcome
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