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1.
Front Immunol ; 13: 837524, 2022.
Article in English | MEDLINE | ID: covidwho-1731784

ABSTRACT

Effectively treating infectious diseases often requires a multi-step approach to target different components involved in disease pathogenesis. Similarly, the COVID-19 pandemic has become a global health crisis that requires a comprehensive understanding of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection to develop effective therapeutics. One potential strategy to instill greater immune protection against COVID-19 is boosting the innate immune system. This boosting, termed trained immunity, employs immune system modulators to train innate immune cells to produce an enhanced, non-specific immune response upon reactivation following exposure to pathogens, a process that has been studied in the context of in vitro and in vivo clinical studies prior to the COVID-19 pandemic. Evaluation of the underlying pathways that are essential to inducing protective trained immunity will provide insight into identifying potential therapeutic targets that may alleviate the COVID-19 crisis. Here we review multiple immune training agents, including Bacillus Calmette-Guérin (BCG), ß-glucan, and lipopolysaccharide (LPS), and the two most popular cell types involved in trained immunity, monocytes and natural killer (NK) cells, and compare the signaling pathways involved in innate immunity. Additionally, we discuss COVID-19 trained immunity clinical trials, emphasizing the potential of trained immunity to fight SARS-CoV-2 infection. Understanding the mechanisms by which training agents activate innate immune cells to reprogram immune responses may prove beneficial in developing preventive and therapeutic targets against COVID-19.


Subject(s)
COVID-19/immunology , Immunity, Innate/immunology , Humans , Killer Cells, Natural/immunology , Monocytes/immunology , SARS-CoV-2/immunology
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325235

ABSTRACT

Background: To compare the contingency modifications to the dental education between the University of Toronto Faculty of Dentistry and the Zhejiang University School of Stomatology during COVID-19 pandemic, and to share experiences in keeping the dental academic continuity, resuming practicing activities and preparing the faculty and students for a new normality. Three approaches were adopted to collect information and data: online interviews and email-contact with the instructors and the deans, a small-scale online survey of dental students, and official online announcements of various authorities. Results: : The two universities shared similarity in changing trends, while differed in details. The delivery of lectures, seminars and exams was transitioned from in-person mode to online mode and has proceeded effectively and efficiently. The pre-clinical lab training and clinical rotation were the most retarded parts and will not be resumed until the settle-down of the pandemic. Research activities have been kept on at the best possible level. Since the Zhejiang University reopened the campus in May 2020, clinical activities and research works were in recovery with a cautiously-planned and gradual phased approach. Conclusion: Both universities have been trying their best to meet the academic needs of students while protect their health, and to keep alert to the real time epidemic situation in preparation for resumption. Dental institutions could take the COVID-19 pandemic as an opportunity to armor dental students with infection control measures prior to their reengagement into clinical practice. There is a need of a new normality for global dental education that spans time and space.

4.
Virus Res ; 304: 198508, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1331289

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Pandemics , Spike Glycoprotein, Coronavirus/immunology , Adult , CD8-Positive T-Lymphocytes/cytology , COVID-19/epidemiology , Female , Humans , Immunodominant Epitopes/immunology , Male , Middle Aged , SARS-CoV-2/immunology , Young Adult
5.
J Med Internet Res ; 23(5): e26883, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1229125

ABSTRACT

BACKGROUND: The prevalence of depressive and anxiety symptoms in patients with COVID-19 is higher than usual. Previous studies have shown that there are drug-to-drug interactions between antiretroviral drugs and antidepressants. Therefore, an effective and safe treatment method was needed. Cognitive behavioral therapy (CBT) is the first-line psychological therapy in clinical treatment. Computerized CBT (cCBT) was proven to be an effective alternative to CBT and does not require face-to-face therapy between a therapist and the patient, which suited the COVID-19 pandemic response. OBJECTIVE: This study aims to evaluate the efficacy of the cCBT program we developed in improving depressive and anxiety symptoms among patients with COVID-19. METHODS: We customized a cCBT program focused on improving depressive and anxiety symptoms among patients with COVID-19, and then, we assessed its effectiveness. Screening was based on symptoms of depression or anxiety for patients who scored ≥7 on the Hamilton Depression Rating Scale (HAMD17) or the Hamilton Anxiety Scale (HAMA). A total of 252 patients with COVID-19 at five sites were randomized into two groups: cCBT + treatment as usual (TAU; n=126) and TAU without cCBT (n=126). The cCBT + TAU group received the cCBT intervention program for 1 week. The primary efficacy measures were the HAMD17 and HAMA scores. The secondary outcome measures were the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Athens Insomnia Scale (AIS). Assessments were carried out pre- and postintervention. The patients' symptoms of anxiety and depression in one of the centers were assessed again within 1 month after the postintervention assessment. RESULTS: The cCBT + TAU group displayed a significantly decreased score on the HAMD17, HAMA, SDS, SAS, and AIS after the intervention compared to the TAU group (all P<.001). A mixed-effects repeated measures model revealed significant improvement in symptoms of depression (HAMD17 and SDS scores, both P<.001), anxiety (HAMA and SAS scores, both P<.001), and insomnia (AIS score, P=.002) during the postintervention and follow-up periods in the cCBT + TAU group. Additionally, the improvement of insomnia among females (P=.14) and those with middle school education (P=.48) in the cCBT + TAU group showed no significant differences when compared to the TAU group. CONCLUSIONS: The findings of this study suggest that the cCBT program we developed was an effective nonpharmacological treatment for symptoms of anxiety, depression, and insomnia among patients with COVID-19. Further research is warranted to investigate the long-term effects of cCBT for symptoms of anxiety, depression, and insomnia in patients with COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030084; http://www.chictr.org.cn/showprojen.aspx?proj=49952.


Subject(s)
Anxiety/therapy , COVID-19/psychology , Cognitive Behavioral Therapy/methods , Depression/therapy , Adult , Female , Humans , Male , Pandemics , Prospective Studies , SARS-CoV-2/isolation & purification
6.
J Biomed Inform ; 117: 103748, 2021 05.
Article in English | MEDLINE | ID: covidwho-1152466

ABSTRACT

OBJECTIVE: Identifying symptoms and characteristics highly specific to coronavirus disease 2019 (COVID-19) would improve the clinical and public health response to this pandemic challenge. Here, we describe a high-throughput approach - Concept-Wide Association Study (ConceptWAS) - that systematically scans a disease's clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic. METHODS: We created a natural language processing pipeline to extract concepts from clinical notes in a local ER corresponding to the PCR testing date for patients who had a COVID-19 test and evaluated these concepts as predictors for developing COVID-19. We identified predictors from Firth's logistic regression adjusted by age, gender, and race. We also performed ConceptWAS using cumulative data every two weeks to identify the timeline for recognition of early COVID-19-specific symptoms. RESULTS: We processed 87,753 notes from 19,692 patients subjected to COVID-19 PCR testing between March 8, 2020, and May 27, 2020 (1,483 COVID-19-positive). We found 68 concepts significantly associated with a positive COVID-19 test. We identified symptoms associated with increasing risk of COVID-19, including "anosmia" (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 3.21-7.50), "fever" (OR = 1.43, 95% CI = 1.28-1.59), "cough with fever" (OR = 2.29, 95% CI = 1.75-2.96), and "ageusia" (OR = 5.18, 95% CI = 3.02-8.58). Using ConceptWAS, we were able to detect loss of smell and loss of taste three weeks prior to their inclusion as symptoms of the disease by the Centers for Disease Control and Prevention (CDC). CONCLUSION: ConceptWAS, a high-throughput approach for exploring specific symptoms and characteristics of a disease like COVID-19, offers a promise for enabling EHR-powered early disease manifestations identification.


Subject(s)
COVID-19/diagnosis , Natural Language Processing , Symptom Assessment/methods , Adult , Ageusia , COVID-19 Nucleic Acid Testing , Cough , Female , Fever , Humans , Male , Middle Aged , Pandemics , United States
7.
Infect Dis Poverty ; 10(1): 37, 2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1150428

ABSTRACT

BACKGROUND: The COVID-19 has caused significant toll over the globe. Pregnant women are at risk of infection. The present study examined the frequency of washing hands with soap and wearing face mask when going out, prevalence of depression and anxiety, and identified their associated factors among pregnant women during the early phase of COVID-19 outbreak in China. METHODS: A cross-sectional online survey was conducted between 24 February and 3 March 2020. A total of 15 428 pregnant women who were using maternal health care services in China completed a questionnaire which assessed their socio-demographic and pregnancy-related characteristics, contextual, cognitive and social factors related to COVID-19, frequency of washing hands and wearing face masks, and depression and anxiety. Logistics regression analyses were performed to identify the associated factors of preventive behaviours and mental health. RESULTS: The prevalence of probable anxiety and depression was 28.2% and 43.6% respectively. 19.8% reported always wearing face mask when going out, and 19.1% reported washing hands with soap for more than 10 times per day. Results from logistic regression analyses showed that older age was associated with lower levels of depression and anxiety (OR = 0.42-0.67) and higher frequency of washing hands (OR = 1.57-3.40). Higher level of education level was associated with probable depression (OR = 1.31-1.45) and higher frequency of wearing face mask (OR = 1.50-1.57). After adjusting for significant socio-demographic and pregnancy-related factors, place of residence being locked down (aOR = 1.10-1.11), being quarantined (aOR = 1.42-1.57), personally knowing someone being infected with COVID-19 (aOR = 1.80-1.92), perception that COVID-19 would pose long term physical harm to human (aOR = 1.25-1.28) were associated with higher levels of depression and anxiety, while the perception that the disease will be under control in the coming month was associated with lower levels of depression and anxiety (aOR = 0.59-0.63) and lower tendency of always wearing face mask (aOR = 0.85). Social support was associated with lower levels of depression and anxiety (aOR = 0.86-0,87) and higher frequency of washing hands (aOR = 1.06). CONCLUSIONS: The mental health and preventive behaviours of pregnant women during COVID-19 outbreak was associated with a range of socio-demographic, pregnancy-related, contextual, cognitive and social factors. Interventions to mitigate their mental health problems and to promote preventive behaviours are highly warranted.


Subject(s)
COVID-19/prevention & control , COVID-19/psychology , Health Behavior , Mental Health , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2 , Adult , Age Factors , China , Depression/epidemiology , Educational Status , Female , Hand Disinfection/trends , Humans , Logistic Models , Maternal Health Services/statistics & numerical data , Odds Ratio , Personal Protective Equipment , Pregnancy , Pregnancy Complications, Infectious/psychology , Prenatal Care , Prevalence , Risk Factors , Social Support , Surveys and Questionnaires , Young Adult
8.
Disaster Med Public Health Prep ; : 1-3, 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-1137706

ABSTRACT

OBJECTIVE: Emergent public health events, such as coronavirus disease 2019 (COVID-19), have been the focus of attention of researchers at home and abroad. In China, nurses are an important group contributing to the prevention and control of the COVID-19 pneumonia epidemic. METHODS: Using semi-structured interviews, qualitative interviews were conducted with 23 nurses who supported the novel coronavirus pneumonia epidemic, and the data were collated and analyzed using Colaizzi analysis. RESULTS: The work experience of Chinese nurses can be summarized into 4 major themes: they had different emotional experiences during aiding periods, aiding work had a double impact on the nurses, there were certain difficulties in aiding work, and there were significant age differences in aiding work experience. CONCLUSIONS: It is necessary to strengthen the psychological construction of nurses. All hospitals must coordinate and manage various safety tasks, and ensure the precise, scientific, and streamlined deployment of rescue work. Humanized management, shift adjustment, performance allocation weight, and organizational care are also the top priorities of human resource management.

9.
Sci Rep ; 11(1): 5558, 2021 03 10.
Article in English | MEDLINE | ID: covidwho-1125779

ABSTRACT

The recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell-cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell-cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Spike Glycoprotein, Coronavirus/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , Cell Fusion/methods , Female , Humans , Immunization, Passive/methods , Male , Membrane Fusion/drug effects , Middle Aged , Pandemics/prevention & control , Plasma/chemistry , Receptors, Virus/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
10.
Eur J Clin Microbiol Infect Dis ; 40(3): 565-574, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-812573

ABSTRACT

Our aim was to investigate whether SARS-CoV-2 infection raised high risks of late pregnancy complications, and posed health problems in fetuses and neonates. We analyzed the data of COVID-19 pregnant women with COVID-19 during late pregnancy and their neonates. Eleven out of 16 (69%) pregnant women with COVID-19 had ++ or +++ of ketone body in urine. The blood uric acid of pregnant patients was 334 µmol/L (IQR, 269-452). D-dimer and FDP in pregnant patients were 3.32 mg/L (IQR, 2.18-4.21) and 9.6 mg/L (IQR, 5.9-12.4). Results of blood samples collected at birth showed that 16 neonates had leukocytes (15.7 × 109/L (IQR, 13.7-17.2)), neutrophils (11.1 × 109/L (IQR, 9.2-13.2)), CK (401 U/L (IQR, 382-647)), and LDH (445 U/L (IQR, 417-559)). Twenty-four hours after birth, a neonate from COVID-19 woman had fever and positive of SARS-CoV-2 gene. Another woman had strongly positive for SARS-CoV-2 gene (+++) for 4 weeks, and delivered one neonate who had SARS-CoV-2 IgM (46 AU/mL) and IgG (140 AU/mL) on day 1 after birth. In the third trimester, COVID-19 infection in pregnant patients raised high risks of ketonuria, hypercoagulable state, and hyperfibrinolysis, which may lead to severe complications. COVID-19 increased the inflammatory responses of placenta, and fetuses and neonates had potential organ dysregulation and coagulation disorders. There was a potential intrauterine transmission while pregnant women had high titer of SARS-CoV-2, but it is necessary to detect SARS-CoV-2 in the blood cord, placenta, and amniotic fluid to further confirm intrauterine infection of fetuses.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/metabolism , Adult , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/transmission , Female , Fetal Blood/immunology , Fetal Blood/metabolism , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome/epidemiology , Pregnancy Trimester, Third , Pregnant Women , SARS-CoV-2/isolation & purification
11.
Front Immunol ; 11: 2075, 2020.
Article in English | MEDLINE | ID: covidwho-776205

ABSTRACT

To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33-59) were lymphocytes [2.5 × 109/L (IQR, 2.2-3.3)], and monocytes were 0.51 × 109/L (IQR, 0.45-0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 109/L (IQR, 0.36-0.64). Twenty-one severe patients had low PO2 [57 mmHg (IQR, 50-73)] and SO2 [90% (IQR, 86-93)] and high lactate dehydrogenase [580 U/L (IQR, 447-696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02-0.30)], and pro-BNP [498 pg/mL (IQR, 241-1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62-22.85) and 32.7 mg/L (IQR, 12.8-81.9), and a large number of RBC (46/µL (IQR, 4-242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9-10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 µmol/L (IQR, 131-256)]. In the late stage of COVID-19, severe cases had extremely low CD4+ T cells and CD8+ T cells, but unusually high neutrophils [6.5 × 109/L (IQR, 4.8-9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14-1.94)], C-reactive protein [66 mg/L (IQR, 25-114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I-III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/immunology , Coronavirus Infections/metabolism , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Adult , Aged , Blood Glucose/analysis , C-Reactive Protein/analysis , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/virology , Female , Humans , Interleukin-6/blood , Lymphocyte Count , Male , Middle Aged , Neutrophils/immunology , Pandemics , Pneumonia, Viral/virology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Uric Acid/blood
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