Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 98
Filter
1.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1824575

ABSTRACT

Background Virtual simulation has been widely used in nursing education and nursing training. This study aims to characterize the publications in terms of countries, institutions, journals, authors, collaboration relationships, and analyze the trends of virtual simulation in nursing research. Methods Publications regarding virtual simulation in nursing were retrieved from Web of Science core collection. Microsoft Excel 2010, VOSviewer were used to characterize the contributions of the authors, journals, institutions, and countries. The trends, hot-spots and knowledge network were analyzed by Citespace and VOSviewer. Results We identified 677 papers between 1999 and 2021. The number of publications grew slowly until 2019, after that, it got a sharp increase in 2020 and 2021. The USA, Canada and Australia were three key contributors to this field. Centennial College and University of San Paulo, University of Ottawa and Ryerson University were top major institutions with a larger number of publications. Verkuyl M was the most productive and highest cited author. Clinical Simulation in Nursing, Nurse Education Today, Journal of Nursing Education were the three productive journals. The foundational themes of virtual simulation research in nursing are “virtual learning during COVID-19, clinical nursing care, education in nurse practitioners, education technology”. Conclusion Virtual simulation in nursing field has attracted considerable attention during COVID-19 pandemic. The research hotspot is gradually shifting from clinical nursing care to studies of nursing education using different virtual simulation technologies

2.
Cell Rep ; : 110864, 2022 May 08.
Article in English | MEDLINE | ID: covidwho-1821172

ABSTRACT

The pathological and immune response of individuals with COVID-19 display different dynamics in lung and intestine. Here, we depict the single-cell transcriptional atlas of longitudinally collected lung and intestinal tissue samples from SARS-CoV-2-infected monkeys at 3 to 10 dpi. We find that intestinal enterocytes are degraded at 3 days post-infection but recovered rapidly, revealing that infection has mild effects on the intestine. Crucially, we observe suppression of the inflammatory response and tissue damage related to B-cell and Paneth cell accumulation in the intestines, although T cells are activated in the SARS-CoV-2 infection. Compared with that in the lung, the expression of interferon response-related genes is inhibited, and inflammatory factor secretion is reduced in the intestines. Our findings indicate an imbalance of immune dynamic in intestinal mucosa during SARS-CoV-2 infection, which may underlie ongoing rectal viral shedding and mild tissue damage.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334362

ABSTRACT

No specific effective therapeutic drugs have been identified for COVID-19. Critically ill COVID-19 36 patients in the ICU experience high mortality. This project aims to study the effects of traditional 37 Chinese medicine (TCM) treatment on deadly outcomes caused by COVID-19. A total of 123 critically 38 ill COVID-19 patients who received close monitoring at the ICU of Vulcan Hill Hospital between 39 ICU patients received supportive management. Eighty-one patients were given additional TCM 41 treatment. Clinical characteristics during the treatment period (up to 39 days) and the clinical outcome 42 of each patient were closely monitored and analysed. We observed that patients treated with TCM had 43 lower mortality than the non-TCM treatment group (16 of 81 vs. 31 of 42;0.3 person/month vs. 2.9 44 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with 45 improved survival [multivariate HR, 0.13;95% confidence interval (CI), 0.06–0.24;P < 0.001]. 46 Furthermore, we found that TCM treatment could partially improve the inflammation status by 47 reducing the levels of proinflammatory cytokines and recovering multiple organic functions. TCM 48 treatment may decrease inflammation status by reducing the level of proinflammatory cytokines and 49 allowing the recovery of multiple organic functions, which could improve the survival rate of critically 50 ill COVID-19 patients.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334201

ABSTRACT

ABSTRACT Pre-mRNA splicing is initiated with the recognition of a single-nucleotide intronic branchpoint (BP) within a BP motif by spliceosome elements. Fifty-six rare variants in 44 human genes have been reported to alter splicing and cause disease by disrupting BP. However, until now, no computational approach has been available to efficiently detect such variants in next-generation sequencing (NGS) data. We established a comprehensive human genome-wide BP database by integrating existing BP data, and by generating new BP data from RNA-seq of lariat debranching enzyme DBR1-mutated patients and from machine-learning predictions. We in-depth characterize multiple features of BP in major and minor introns, and find that BP and BP-2 (two-nucleotides upstream of BP) positions exhibit a lower rate of variation in human populations and higher evolutionary conservation than the intronic background, whilst being comparable to the exonic background. We develop BPHunter as a genome-wide computational approach to systematically and efficiently detect intronic variants that may disrupt BP recognition in NGS data. BPHunter retrospectively identifies 48 of the 56 known pathogenic BP mutations in which we summarize a strategy for prioritizing BP mutation candidates, and the remaining 8 all create AG dinucleotides between BP and acceptor site which is probably the reason for mis-splicing. We demonstrate the utility of BPHunter prospectively by using it to identify a novel germline heterozygous BP variant of STAT2 in a patient with critical COVID-19 pneumonia, and a novel somatic intronic 59-nucleotide deletion of ITPKB in a lymphoma patient, both of which we validate experimentally. BPHunter is publicly available from https://hgidsoft.rockefeller.edu/BPHunter and https://github.com/casanova-lab/BPHunter .

6.
AIDS Care ; : 1-8, 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1751952

ABSTRACT

BACKGROUND: Although people living with HIV (PLWH) were considered to be at increased risk of SARS-CoV-2 infection, the driving force among this group of individuals is still not clear. METHODS: We investigated 1,709 PLWH through a telephone interview and identified 11 COVID-19 patients in four districts of Wuhan, China. The demographic features and major clinical characteristics of these patients were retrieved from the information management systems for COVID-19 patients of the four districts' CDC. Statistical analysis was performed to find out the driving force of COVID-19 among PLWH. RESULTS: The prevalence of COVID-19 in PLWH is 0.6% (95% CI: 0.2% - 1.0%), which is comparable to the overall population prevalence in Wuhan city (0.6%). Nine out of the 11 COVID-19 patients had relatively high CD4+ T lymphocyte count (>200/µl) and undetectable HIV viral load (<20 copies/ml), and ten of them were on antiretroviral therapy. Older PLWH with low CD4 + count, got HIV infected through homosexual activity, and had been diagnosed with HIV for a long time, were more likely to develop COVID-19. CONCLUSIONS: COVID-19 related morbidity rates were comparable between PLWH and the general population. Older age with low CD4 count, an extended period of HIV diagnosis, and treatment-naivety were potential driving forces of COVID-19 prevalence among PLWH. Strategies for preventing SARS-CoV-2 infection among PLWH with weak immune responses are required.

7.
Psychol Trauma ; 2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1751692

ABSTRACT

OBJECTIVE: As an international public health emergency panic, Corona Virus Disease-19 (COVID-19) has caused substantial impacts on economic and daily life. The public were at high risk of mental health problems and posttraumatic stress symptoms (PTSS). This study aimed to evaluate the association between objective/subjective severity of COVID-19 pandemic and PTSS, and explore the moderating role of mindfulness. METHOD: Using longitudinal and 7-day ecological momentary assessment (EMA) designs, we gathered data from 109 college students who were home-quarantined to examined study hypotheses. In the EMA phase, participants completed questionnaires measuring subjective severity, mindfulness and PTSS three times per day. Objective severity was indicated using the daily new confirmed cases. Then participants completed a follow-up measure of PTSS 2 months later, when the epidemic initially became stable. RESULTS: The results of structural equation modeling showed that state mindfulness moderated the relationship between subjectivity severity of COVID-19 and PTSS. Specifically, the association between subjective severity of COVID-19 and PTSS was positive at the low level of state mindfulness, and negative at the high level of state mindfulness. Trait mindfulness did not moderate the relationship between objectivity severity of COVID-19 and PTSS. CONCLUSION: Mindfulness-based interventions can be used as preventive mental health education to the daily lives of the general public, and to deal with unpredictable crisis events. Implications of this study are drawn for theory, practice, and research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

8.
Land ; 11(3):404, 2022.
Article in English | MDPI | ID: covidwho-1732109

ABSTRACT

We conceptualize typical rural communities in China as diversified economic clusters. In normal times, economic actors in these communities rarely cooperate with each other, but are integrated into separate commodity chains. These 'diversified clusters';, however, show resilience and flexibility when an external shock—the COVID-19 pandemic—disrupts the spatial connections throughout the existing commodity chains. In this study, we use primary field data collected from one typical rural community in Northern China to show how economic diversity, aided by social networks and space-shrinking technologies, allowed for the vertical commodity chains to be reconfigured temporarily into localized horizontal commodity networks to cope with the emergencies brought about by the pandemic. Our findings suggest that while market integration can create precarity at the individual level, it can also contribute to economic resilience at the community level if it increases economic diversity and complementarity within the community. This study sheds lights on discussions of the resilience of rural and economic clustering by a novel conceptualization of diversified clusters and also offers a nuanced understanding of the connection between market integration and community resilience.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325110

ABSTRACT

Background: Mental health is an important aspect of the management public health emergencies.While extensive research is being conducted on various aspects of the COVID-19 epidemic, one of the factors overlooked is death anxiety. Methods: A cross-sectional study based on the results of an online survey. The survey was conducted one month after the outbreak (February 18–29, 2020) and repeated at the time of resuming activity (April 8–14, 2020). The 15-item Death Anxiety Scale (T-DAS) was used to assess the degree of death anxiety, and the revised 23-item Stanford Acute Stress Response Questionnaire (SASRQ) assessed PTSD symptom clusters. Through convenient sampling, a total of 7678 cases were collected. Results: Between the first and second surveys, the number of individuals with high death anxiety rose from 48.1–53.2%, while the incidence of PTSD increased from 7–10.4%. PTSD was found to be significantly associated with living community contact history, poor health status of participants, history of life-threatening experiences, high death anxiety level, and non-medical occupation. Compared with other occupations, medical staff suffer more lasting death anxiety during the COVID-19 epidemic. Conclusions: During the COVID-19 epidemic, adverse psychological symptoms were prevalent among the general population in China.High death anxiety also was an important factor affecting PTSD.Therefore, means to address death anxiety must be included in the plan for the management of psychological effects of public health emergency and high-risk groups such as medical personnel should receive targeted intervention.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324645

ABSTRACT

Background: Novel severe acute respiratory syndrome coronavirus 2 causes the novel coronavirus disease (COVID-19) in humans, which has spread rapidly worldwide. Most critical cases of COVID-19 are accompanied by complicated chronic underlying diseases. This retrospective study aims to analyze the clinical characteristics of COVID-19 patients with chronic underlying diseases.Methods A total of 1,183 COVID-19 patients were divided into the chronic underlying disease (CUD, n = 538) group and the non-underlying disease (non-CUD, n = 645) group. The clinical characteristics and outcomes were collected and compared between the two groups.Results There were significant differences in age, weight, and SPO2 on admission between the CUD and non-CUP groups. The ratio of severe cases in the CUD group was higher than that in the non-CUD group (χ 2  = 35.58, p -value < 0.001). The white blood cell count, neutrophil count, C-reactive protein, urea nitrogen, creatinine, myoglobin, and cardiac troponin in the CUD group were significantly higher than those in the non-CUD group, while the lymphocyte count and albumin in the underlying disease group were significantly lower than those in the non-underlying disease group. No significant difference was found in the total number of tests, the number of positive or negative results in nucleic acid tests between the two groups. The negative rate for both IgG- and IgM-antibody tests in the CUD group was higher than that in the non-CUD group (χ 2  = 5.57, p -value = 0.018). No statistical difference in mortality between the CUD (n = 18) and non-CUD groups (n = 13). All surviving patients were cured and discharged. A total of 33 patients had a positive re-examination result for nucleic acid test one week after discharge, including 14 patients with underlying diseases and 19 patients without underlying diseases. Conclusion: COVID-19 patients with underlying diseases had poorer clinical conditions and had a longer hospital stay, but after active treatment, the mortality had not increased significantly.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323932

ABSTRACT

Background: Patients with severe Coronavirus Disease 2019 (COVID-19) will progress rapidly to acute respiratory failure or death. We aimed to develop a quantitative tool for early predicting mortality risk of patients with COVID-19. Methods: : 301 patients with confirmed COVID-19 admitted to Main District and Tumor Center of the Union Hospital of Huazhong University of Science and Technology (Wuhan, China) between January 1, 2020 to February 15, 2020 were enrolled in this retrospective two-centers study. Data on patient demographic characteristics, laboratory findings and clinical outcomes was analyzed. A nomogram was constructed to predict the death probability of COVID-19 patients. Results: : Age, neutrophil-to-lymphocyte ratio, D-dimer and C-reactive protein obtained on admission were identified by LASSO regression as predictors of mortality for COVID-19 patients. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.921 and 0.975 for the derivation and validation cohort, respectively. An integrated score (named ANDC) with its corresponding death probability was derived. Using ANDC cut-off values of 59 and 101, COVID-19 patients were classified into three subgroups. The death probability of low risk group (ANDC < 59) was less than 5%, moderate risk group (59 ≤ ANDC ≤ 101) was 5% to 50%, and high risk group (ANDC > 101) was more than 50%, respectively. Conclusion: The prognostic nomogram exhibited good discrimination power in early identification of COVID-19 patients with high mortality risk, and ANDC score may help physicians to optimize patient stratification management.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323743

ABSTRACT

Abstract Background: With the emergence of coronavirus disease 2019 in many places around the world, the main medical resources currently focus on the treatment of confirmed patients and the screening of suspected cases. Asymptomatic patients are difficult to detect, but they may be contagious, which makes epidemic control more difficult. We found a case of asymptomatic patient with positive urine coronavirus nucleic acid test, and we hope to attract attention of all circles.Case presentation: An asymptomatic patient with novel coronavirus infection was found in an epidemiological investigation of patients with confirmed coronavirus disease 2019. The patient was admitted to the hospital on February 24, 2020. She had no clinical manifestations such as fever, dry cough, and fatigue, and no abnormal signs. The examination showed that her throat swab was negative for nucleic acid but the urine was positive for nucleic acid. She was given antiviral and symptomatic supportive treatment. On February 26, her throat swab was checked for nucleic acid positive. On March 3 and 5, her throat swab and urine nucleic acid were negative. On March 9 and 12, her throat swab nucleic acid were negative. The patient was discharged from the hospital on March 13 and continued to be isolated and observed outside the hospital. Follow-up was conducted on March 26, the patient did not have any discomfort, the throat swab nucleic acid test was negative, and the isolation was lifted.Conclusion: There are asymptomatic patients with coronavirus disease 2019, and their urine may be one of the sources of infection.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322270

ABSTRACT

In recent years, the prevalence of several pulmonary diseases, especially the coronavirus disease 2019 (COVID-19) pandemic, has attracted worldwide attention. These diseases can be effectively diagnosed and treated with the help of lung imaging. With the development of deep learning technology and the emergence of many public medical image datasets, the diagnosis of lung diseases via medical imaging has been further improved. This article reviews pulmonary CT and X-ray image detection and classification in the last decade. It also provides an overview of the detection of lung nodules, pneumonia, and other common lung lesions based on the imaging characteristics of various lesions. Furthermore, this review introduces 26 commonly used public medical image datasets, summarizes the latest technology, and discusses current challenges and future research directions.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318623

ABSTRACT

Background: China has been severely affected by COVID-19 (Coronavirus Disease 2019) since December 2019.In the combat against COVID-19, military health workers in China suffered from many pressures. This study aimed to investigate the current psychological status and risk factors of the military health workers.Methods Using a web-based cross-sectional survey, we collected data from 194 military health workers from three inpatient wards in two COVID-19 specialized hospitals. The survey questions consisted of demographic information, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-15 (PHQ-15). Hierarchical regression analysis was used to explore potential risk factors for mental health problem.Results The overall prevalence of depressive symptoms, generalized anxiety and somatic symptoms were37.6%, 32.5% and 50%, respectively. Severe depression, generalized anxiety and somatic symptoms was 5.2%, 3.6% and 15.5%. In 22.7% of cases, comorbidities existed between depression, generalized anxiety and somatization. Junior-grade professional title was associated with depression, older age was associated with generalized anxiety and somatization, and less sleep duration and poor sleep quality were associated with all three symptoms.Conclusion The prevalence of depression, generalized anxiety and somatic symptoms were high in military health workers of COVID-19 specialized hospitals during the COVID-19 outbreak. Junior-grade professional title, older age, less sleep duration, and poor sleep quality have significant effects on the mental health of military health workers. Continuous surveillance and monitoring of the psychological consequences of the COVID-19outbreak should become routine to promote the mental health of military health workers.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311717

ABSTRACT

The Coronavirus Disease of 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health and economy. Therapeutic options such as monoclonal antibodies (mAbs) against SARS-CoV-2 are in urgent need. We have identified potent monoclonal antibodies binding to SARS-CoV-2 Spike protein from COVID-19 convalescent patients and one of these antibodies, P4A1, interacts directly and covers the majority of the Receptor Binding Motif (RBM) of Spike receptor-binding domain (RBD), shown by high-resolution complex structure analysis. We further demonstrated P4A1 binding and neutralizing activities against wild type and mutant spike proteins. P4A1 was subsequently engineered to reduce the potential risk for antibody-dependent enhancement (ADE) of infection and to extend its half-life. The engineered mAb exhibits optimized pharmacokinetic and safety profile, and results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311708

ABSTRACT

Background: Even people living with HIV/AIDS (PLWHA) were considered to be at increased risk of SARS-CoV-2 infection, the driving force among this group of individuals is still not clear. Methods: We investigated 1,701 PLWHA through a telephone interview and found 11 COVID-19 patients in four districts of Wuhan, China. The demographic features and major clinical characteristics of these patients were retrieved from the information management systems for COVID-19 patients of four districts’ CDC. Statistical analysis was performed to find out the driving force of COVID-19 among PLWHA. Results: The incidence proportion of COVID-19 in PLWHA is 0.6% (95% CI: 0.2% - 1.0%), which is comparable to the overall population incidence rate in Wuhan city (0.6%). Nine out of the 11 COVID-19/AIDS patients had relatively high CD4+ T lymphocyte count (>200/μl) and undetectable HIV viral load (<20 copies/ml), and ten of them were on antiretroviral therapy. PLWHA who were old, had low CD4+ T lymphocyte count, infected HIV through homosexual activity, and had been diagnosed for HIV for a long time, were more likely to develop COVID-19. Conclusions: : PLWHA has comparable COVID-19 morbidity rates as the general population, and older age, low CD4 count, long length since HIV diagnosis, and treatment-naive were potential driving forces of COVID-19 occurrence among PLWHA. Strategies in preventing SARS-CoV-2 infection among PLWHA with worse immune responses are needed. Article Summary Line: As COVID-19 continues to spread around the world, people living with HIV/AIDS (PLWHA) are also at risk of infection with SARS-CoV-2. We investigated the factors associated with SARS-CoV-2 infection among PLWHA in Wuhan, China.

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309716

ABSTRACT

Introduction: Cardiac injury occurs in 7-22% of patient hospitalized with COVID-19 and an elevation in troponin is associated with a 4.2-fold increase in the risk of mortality. Preliminary data showed ACEi/ARB usage might not increase mortaily in COVID-19 patients. However, it is unknown if cardiac injury in patients with severe COVID-19 can be modulated by ACEi/ARB usage during evolution of the cardiac injury. Methods: : In 154 COVID-19 patients with cardiac injury, the effect of ACEi/ARB treatment (17 patients) was compared with 137 patients without ACEi/ARB treatment. Cardiac injury was indicated by cTnI level. Results: : In ACEi/ARB treatment group and no ACEi/ARB treatment group, peak cTnI level did not show significant difference (150.5 pg/ml [31.75-1179], vs 207 pg/ml [54.65-989.4], respectively, P = 0.21). Evolution of Cardiac injury (temporal change of cTnI at day 6, 9, 12, 15, 18, 21, 24, 27, 30, and 33) showed no statistical difference. Mortality (ACEi/ARB group vs no ACEi/ARB group;52.9% vs 69.9%, P = 0.17), atrial arrhythmias (11.7% vs 24.4%, P = 0.36), requirement for invasive ventilatory support (29.4% vs 48.2%, P = 0.14) also showed no significant difference in two groups. Conclusions: : ACEi/ARB usage during the COVID-19 was not associated with exacerbation of cardiac injury. These data should be interpreted as essentially hypothesis-generating due to small sample size. Clinical Trial Registration: This retrospective study was registered in Chinese clinical trial registry (ChiCTR 2000031301).

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305004

ABSTRACT

Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.

19.
Nature ; 603(7902): 587-598, 2022 03.
Article in English | MEDLINE | ID: covidwho-1655590

ABSTRACT

SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1-5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNß and/or IFNω, which are more common in men than in women, are found in approximately 15-20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Interferon Type I/immunology , Age Distribution , Autoantibodies/immunology , COVID-19/mortality , COVID-19/pathology , Critical Illness , Dendritic Cells/immunology , Genome-Wide Association Study , Humans , Interferon Type I/genetics , Sex Distribution , Toll-Like Receptor 3/deficiency , Toll-Like Receptor 7/deficiency , Toll-Like Receptor 7/genetics
20.
J Clin Immunol ; 42(3): 471-483, 2022 04.
Article in English | MEDLINE | ID: covidwho-1653615

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. OBJECTIVES: To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. METHODS: Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. RESULTS: We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. CONCLUSIONS: Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.


Subject(s)
COVID-19 , Interferon Type I , Autoantibodies , COVID-19/complications , Child, Preschool , Cytokines , Humans , Receptor, Interferon alpha-beta/genetics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
SELECTION OF CITATIONS
SEARCH DETAIL