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1.
iScience ; : 105701, 2022.
Article in English | ScienceDirect | ID: covidwho-2131224

ABSTRACT

Summary Influenza A virus (IAV) and SARS-CoV-2 virus are both acute respiratory viruses currently circulating in the human population. This study aims to determine the impact of IAV infection on SARS-CoV-2 pathogenesis and cardiomyocyte function. Infection of human bronchial epithelial cells (HBEC), A549 cells, lung fibroblasts (HLF), monocyte derived macrophages (MDMs), cardiac fibroblasts (HCF) and hiPSC-derived cardiomyocytes with IAV enhanced the expression of ACE2, the SARS-CoV-2 receptor. Similarly, IAV infection increased levels of ACE2 in the lungs of mice and humans. Interestingly, we detected heavily glycosylated form of ACE2 in hiPSC-CMs and poorly glycosylated ACE2 in other cell types. Also, prior IAV infection enhances SARS-CoV-2 spike protein binding and viral entry in all cell types. However, efficient SARS-CoV-2 replication was uniquely inhibited in cardiomyocytes. Glycosylation of ACE2 correlated with enzymatic conversion of its substrate Ang II, induction of eNOS and nitric oxide production, may provide a potential mechanism for the restricted SARS-CoV-2 replication in cardiomyocytes.

2.
Journal of the Academy of Consultation-Liaison Psychiatry ; 2022.
Article in English | ScienceDirect | ID: covidwho-2122553

ABSTRACT

Background Several studies report incidence of psychiatric symptoms and disorders among patients who recovered from COVID-19;however, little is known about the emotional impact of acute COVID-19 illness and recovery on these survivors. Qualitative methods are ideal for understanding the psychological impact of a novel illness. Objective To describe the emotional experience of acute COVID-19 illness and recovery in patients who contracted the virus during the early months of the pandemic. Methods Semi-structured interviews conducted by consultation-liaison (C-L) psychiatrists were used to elicit participant responses about the emotional impact of the acute and recovery phases of COVID-19 illness. Participants recruited from the Maryland, District of Columbia, and Virginia area were interviewed and audio recorded between June 2020 and December 2020. The research team extracted qualitative themes from the recordings using the principles of thematic analysis. Results One hundred and one COVID-19 survivors (54 women;mean [SD] age, 50 [14.7] years) were interviewed a mean of 5.16 months after their acute illness, and their responses were audio recorded. Most participants were White (77%), non-Hispanic/Latino (86.1%), and not hospitalized for COVID-19 (87.1%). Coders identified 26 themes from participant responses. The most frequently coded themes included Anxiety/Worry (49), Uncertainty (37), Support from Others (35), Alone/Isolation (32), Positive Reframe/Positive Emotions (32). Conclusions and Relevance Survivors who contracted SARS-CoV-2 during the early months of the pandemic described both negative and positive valence emotions. They experienced emotional distress and psychosocial stressors associated with acute illness and recovery but also drew upon personal resiliency to cope. This report highlights the utility of qualitative research methods in identifying emotional responses to a novel illness that may otherwise go unnoted. C-L psychiatrists may be uniquely positioned to work in collaboration with medical colleagues in developing a multidimensional approach to evaluating an emerging illness.

3.
J Neurosurg ; : 1-9, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2109667

ABSTRACT

A cancer diagnosis is life altering and frequently associated with both acute and long-lasting psychosocial and behavioral distress for patients. The impact of a diffuse glioma diagnosis on mental health is an important aspect of the patient experience with their disease. This needs to be understood by neurosurgeons so these concerns can be appropriately addressed in a timely fashion and integrated into the multidisciplinary care of neuro-oncology patients. The relatively grave prognosis associated with diffuse gliomas, the morbidity associated with treatment, and the constant threat of developing a new neurological deficit all can negatively affect a patient's mental ability to cope and ultimately manifest in mental health disorders such as anxiety and depression. The objective of this systematic review was to describe the variety of behavioral health disorders patients may experience following a glioma diagnosis and discuss possible treatment options. The PubMed, Web of Science, Embase, and PsycINFO databases were searched through July 1, 2022, using broad search terms, which resulted in 5028 studies that were uploaded to Covidence systematic review software. Duplicates, non-English-language studies, and studies with irrelevant outcomes or incorrect design were removed (n = 3167). A total of 92 articles reporting behavioral health outcomes in brain tumor patients were categorized and extracted for associations with overall mental health, anxiety, depression, distress, stress, pharmacology, interventions, and mental health in caregivers. The authors identified numerous studies reporting the prevalence of mental health disorders and their negative influence in this population. However, there is a paucity of literature on therapeutic options for patients. Given the strong correlation between patient quality of life and mental well-being, there is a considerable need for early recognition and treatment of these behavioral health disorders to optimize everyday functioning for patients.

4.
Int J Methods Psychiatr Res ; : e1953, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2094222

ABSTRACT

OBJECTIVES: The DSM-5 Level 1 Cross-Cutting Symptom Measure (DSM-XC) was developed by the American Psychiatric Association as a transdiagnostic mental health symptom survey. Despite its promise as a screening tool, few studies have assessed its latent dimensionality or provided guidance on interpreting responses. We examined the factor structure of the DSM-XC in a convenience sample of participants with varying degrees of psychopathology. METHODS: Participants (n = 3533) were enrolled in an online study on the mental health impact of COVID-19 (NCT04339790). We used a factor analytic framework with exploratory and confirmatory analyses to evaluate candidate factor solutions. Convergent validity analysis with concurrent study measures was also performed. RESULTS: Six-factor and bifactor candidate solutions both had good fit and full measurement invariance across age, sex, and enrollment date. The six-factor solution resulted in constructs labeled as: mood, worry, activation, somatic, thought, and substance use. A general psychopathology factor and two residual factors (mood and anxiety constructs) explained the variance of the bifactor solution. CONCLUSIONS: Our analysis supports that the DSM-XC is a multidimensional instrument spanning many mental health symptoms. We provide scoring solutions for two factor structures that capture broader constructs of psychopathology. Use of a convenience sample may limit generalizability of findings.

5.
J Am Coll Health ; : 1-4, 2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2082231

ABSTRACT

Objective: To examine the associations between coping methods and college adjustment among a sample of U.S. undergraduate students during the COVID-19 pandemic. Participants: We used a sample of 117 undergraduate students between the age of 18-25 years old. Approximately 76% of the sample identified as women and 58% identified as White. Methods: Participants completed online questionnaires that assessed the use of forward-focused coping, trauma-focused coping, and several domains of college adjustment (i.e., academic adjustment, social adjustment, personal-emotional adjustment, and attachment). We used multiple regression to identify the association between coping methods and college adjustment, using race and gender as control variables. Results: Forward-focused coping methods were significantly and positively related to academic adjustment, social adjustment, and attachment, while and trauma-focused coping methods were significantly and negatively related to personal-emotional adjustment. Conclusions: The use of forward-focused coping methods may be beneficial for undergraduate students during the COVID-19 pandemic.

6.
J Clin Invest ; 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2079145

ABSTRACT

SARS-CoV-2 infection in immunocompromised individuals is associated with prolonged virus shedding and evolution of viral variants. Rapamycin and its analogs (rapalogs, including everolimus, temsirolimus, and ridaforolimus) are FDA-approved as mTOR inhibitors for the treatment of human diseases, including cancer and autoimmunity. Rapalog use is commonly associated with increased susceptibility to infection, which has been traditionally explained by impaired adaptive immunity. Here, we show that exposure to rapalogs increases susceptibility to SARS-CoV-2 infection in tissue culture and in immunologically naive rodents by antagonizing the cell-intrinsic immune response. By identifying one rapalog (ridaforolimus) that is less potent in this regard, we demonstrate that rapalogs promote Spike-mediated entry into cells by triggering the degradation of antiviral proteins IFITM2 and IFITM3 via an endolysosomal remodeling program called microautophagy. Rapalogs that increase virus entry inhibit the mTOR-mediated phosphorylation of the transcription factor TFEB, which facilitates its nuclear translocation and triggers microautophagy. In rodent models of infection, injection of rapamycin prior to and after virus exposure resulted in elevated SARS-CoV-2 replication and exacerbated viral disease, while ridaforolimus had milder effects. Overall, our findings indicate that preexisting use of certain rapalogs may elevate host susceptibility to SARS-CoV-2 infection and disease by activating lysosome-mediated suppression of intrinsic immunity.

7.
Chest ; 162(4):A87-A88, 2022.
Article in English | EMBASE | ID: covidwho-2060538

ABSTRACT

SESSION TITLE: Rare Cases in Cardiothoracic Surgery SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Membranous dehiscence after tracheal resection is an uncommon but deadly complication. It may present acutely with loss of airway, insidiously with progressive stridor, infection or subcutaneous emphysema, or asymptomatically. Treatment may be conservative if the separation is minimal but may require re-exploration if the defect is more severe. The extent of dehiscence amenable to conservative treatment is not well described in the literature. This case report describes the conservative treatment of a posterior membrane dehiscence. CASE PRESENTATION: A 50-year-old woman suffered from stridor due to tracheal stenosis after prolonged intubation from COVID-19. Endobronchial treatments were unsuccessful because of a malacic segment of airway. Via a cervical approach, approximately 2cm of malacic trachea was resected. Reconstruction was performed with a running suture of the posterior membrane and interrupted, figure-of-eight sutures of the anterior trachea. On postoperative day 5, the patient developed subcutaneous emphysema. A CT scan was obtained (Figure 1A), demonstrating disruption of the membranous portion of the anastomosis. As the patient's breathing was not affected, conservative treatment was preferred. She was encouraged to maintain her neck in a flexed position while continuously monitored with a pulse oximeter and treated with intravenous and aerosolized antibiotics. A repeat CT scan was obtained one week after (Figure 1B), showing no residual tracheal wall defect. Postoperative bronchoscopy showed that the posterior membrane had healed entirely. She remains asymptomatic on follow-up visits. DISCUSSION: Wound dehiscence after tracheal resection and reconstruction occurs in about 1-4% of the cases (1, 2), and it is associated with a significant morbidity and a 0.6% chance of mortality (1). We believe the membranous anastomosis failed because the posterior membrane was inflamed and adhered to the esophagus during the index operation. We did not want to perform a bronchoscopy in this situation, as positioning and coughing could exacerbate the dehiscence. As her breathing was unaffected at this point, we debated between a conservative or invasive approach. Conservative management is preferred for small defects and mild symptoms (3), but there is sparse further elaboration in the literature. Because the cartilaginous anastomosis appeared intact and she was breathing spontaneously, we decided to treat conservatively with expectant management. This included aggressive treatment with antibiotics to avoid infection and further anastomotic breakdown. More examples are needed to establish the likelihood of success with conservative treatment versus revisional surgery for partial dehiscence. CONCLUSIONS: Dehiscence after tracheal resection increases morbidity and mortality significantly. This is an example of a posterior membrane dehiscence that resolved spontaneously with conservative measures. Reference #1: Stock C, Gukasyan N, Muniappan A, Wright C, Mathisen D. Hyperbaric oxygen therapy for the treatment of anastomotic complications after tracheal resection and reconstruction. J Thorac Cardiovasc Surg. 2014;147(3):1030-5. Reference #2: Young A, Bigcas JLM. Tracheal Resection. [Updated 2022 Feb 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563234/. Reference #3: Auchincloss HG, Wright CD. Complications after tracheal resection and reconstruction: prevention and treatment. J Thorac Dis. 2016;8(Suppl 2):S160-7. DISCLOSURES: No relevant relationships by Rocio Castillo-Larios No relevant relationships by Magdy El-Sayed Ahmed No relevant relationships by Sebastian Fernandez-Bussy No relevant relationships by daniel hernandez No relevant relationships by Samuel Jacob No relevant relationships by Ian Makey No relevant relationships by Sai Priyanka Pulipaka No relevant relationships b Mathew Thomas No relevant relationships by Alejandra Yu Lee-Mateus

8.
University of Illinois Law Review ; 2022(1):357-410, 2022.
Article in English | Scopus | ID: covidwho-2058457

ABSTRACT

Recently, administrative agencies around the world have engaged in a grand experiment to regulate new technologies: regulatory sandboxes. Regulatory sandboxes allow developers, in cooperation with an agency, to conduct limited tests of new technologies in real-world settings for the purpose of generating and sharing information about them. Thus far, however, "regulatory sandboxes" as named appear almost exclusively in the context of financial technologies, or FinTech. Whether regulatory sandboxes, in fact, exist elsewhere in administrative law would be a significant finding for both regulators and scholars;it would blunt criticisms that agencies are slow to respond to new technologies, provide regulators with an additional tool for governing new technologies, and suggest that lessons learned from current regulatory sandboxes are applicable elsewhere. This Article is the first to explore this broader view of regulatory sandboxes and develop a synoptic theory of them. To do so, it uses one of the most radical programs to introduce new technologies in U.S. history: The U.S. Food and Drug Administration s ("FDA") s Emergency Use Authorization ("EUA") program for COVID-19 treatments and vaccines. EUAs like regulatory sandboxes but in stark contrast to typical FDA approval processes focus on real-world deployment as a means for information gathering. EUAs are also technologically flexible and crafted with close input from the developer, among other features. Generalizing FDA s experience with EUAs also provides lessons about the intersection of regulatory sandboxes with public trust in the agency, political interference, and the maintenance of regulatory standards. At the same time, FDA s COVID-19 EUAs are exceptional in two senses: They touch upon the public health, widely considered to be exceptional subject matter in administrative law. © 2022 University of Illinois College of Law. All rights reserved.

9.
Front Immunol ; 13: 1007089, 2022.
Article in English | MEDLINE | ID: covidwho-2055023

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), which is known to regulate NF-κB signaling. We confirmed the Nsp14-IMPDH2 protein interaction and identified that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14- mediated NF-κB activation and cytokine induction. Furthermore, IMPDH2 inhibitors (RIB, MPA) or NF-κB inhibitors (bortezomib, BAY 11-7082) restricted SARS-CoV-2 infection, indicating that IMPDH2-mediated activation of NF-κB signaling is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in inducing NF-κB activation through IMPDH2 to promote viral infection.


Subject(s)
COVID-19 , Exoribonucleases , IMP Dehydrogenase , NF-kappa B , Viral Nonstructural Proteins , Bortezomib , Cytokines/metabolism , Exoribonucleases/metabolism , Humans , IMP Dehydrogenase/metabolism , Inosine , Interleukin-6 , Interleukin-8 , Mycophenolic Acid , NF-kappa B/metabolism , Oxidoreductases , Proteomics , Ribavirin , SARS-CoV-2 , Viral Nonstructural Proteins/metabolism
10.
International Journal of Mental Health Nursing ; 31:31-31, 2022.
Article in English | Web of Science | ID: covidwho-2030762
11.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2105822.v1

ABSTRACT

Background: The pandemic of COVID-19 has led to an upsurge of critically ill patients requiring advanced life support. Bacteria and fungi have been isolated as etiological agents for co-infections among COVID-19 patients in the intensive care unit (ICU). Co-infection has been associated with worse outcomes among COVID-19 patients in ICUs. The aim of this study was to determine the prevalence of co-infections and their antimicrobial susceptibility patterns among COVID-19 patients admitted to intensive care units in Uganda.    Materials and Methods: A multi-center cross-sectional retrospective survey was carried out in Intensive Care Units (ICUs) in Mulago national referral hospital, UMC Victoria and TMR international hospital in Uganda. The records of 216 hospitalized ICU COVID-19 patients were purposively sampled using a standardized data abstraction tool. The collected data were double entered in Epi-data version 3.1 and exported to Stata version 17.0 for statistical analysis. Results: The prevalence of co-infections (bacterial and fungal) was 111(51.39%) with respiratory tract infections 57(51.35%) being the most prevalent. Staphylococcus aureus 23(28.75%), Citrobacter freudii 19(23.75%), Pseudomonas aureginosa 15(18.75%) and Klebsiella pneumoniae 10(12.50%) were the most frequently isolated bacterial species. The prevalence of multidrug resistant bacterial species was 75.95%. About 07/8(8.75%) of the bacterial species were extended spectrum beta lactamase or AmpC beta lactamase producers. Some of ESBL producers demonstrated susceptibility to Augmentin, Amikacin and trimethoprim.  Augmentin 33/54(61.11%) and ceftriaxone 4/44(9.09%) had the highest and lowest overall antibiotic susceptibility respectively.  About 31/111(27.93%) of the organisms were Candida albicans. The fungal species isolated had good overall susceptibility to most commonly used antifungal agents in the study setting. Conclusion: This study found a high prevalence of co-infections (bacterial and fungal). Respiratory tract infection was the most prevalent. There was an overwhelming burden of multidrug resistant infections with some extended spectrum drug resistant organisms isolated among COVID-19 patients admitted in the Ugandan ICUs. There is need for establishment of stronger policy measures in regards to antibiotic stewardship, antimicrobial surveillance and infection control to inform empirical antibiotic therapy and mitigate the spread MDR bacteria and antibiotic drug resistance among COVID-19 patients.

12.
Proc Natl Acad Sci U S A ; 119(35): e2110105119, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-2000999

ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main target for neutralizing antibodies (NAbs). The S protein trimer is anchored in the virion membrane in its prefusion (preS) but metastable form. The preS protein has been stabilized by introducing two or six proline substitutions, to generate stabilized, soluble 2P or HexaPro (6P) preS proteins. Currently, it is not known which form is the most immunogenic. Here, we generated recombinant vesicular stomatitis virus (rVSV) expressing preS-2P, preS-HexaPro, and native full-length S, and compared their immunogenicity in mice and hamsters. The rVSV-preS-HexaPro produced and secreted significantly more preS protein compared to rVSV-preS-2P. Importantly, rVSV-preS-HexaPro triggered significantly more preS-specific serum IgG antibody than rVSV-preS-2P in both mice and hamsters. Antibodies induced by preS-HexaPro neutralized the B.1.1.7, B.1.351, P.1, B.1.427, and B.1.617.2 variants approximately two to four times better than those induced by preS-2P. Furthermore, preS-HexaPro induced a more robust Th1-biased cellular immune response than preS-2P. A single dose (104 pfu) immunization with rVSV-preS-HexaPro and rVSV-preS-2P provided complete protection against challenge with mouse-adapted SARS-CoV-2 and B.1.617.2 variant, whereas rVSV-S only conferred partial protection. When the immunization dose was lowered to 103 pfu, rVSV-preS-HexaPro induced two- to sixfold higher antibody responses than rVSV-preS-2P in hamsters. In addition, rVSV-preS-HexaPro conferred 70% protection against lung infection whereas only 30% protection was observed in the rVSV-preS-2P. Collectively, our data demonstrate that both preS-2P and preS-HexaPro are highly efficacious but preS-HexaPro is more immunogenic and protective, highlighting the advantages of using preS-HexaPro in the next generation of SARS-CoV-2 vaccines.


Subject(s)
Proline , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccine Development , Vesicular Stomatitis , Viral Vaccines , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Humans , Mice , Proline/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vesicular Stomatitis/immunology , Vesicular Stomatitis/prevention & control , Vesicular Stomatitis/virology , Vesiculovirus/immunology , Viral Proteins/immunology , Viral Vaccines/immunology
13.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.09.01.22279488

ABSTRACT

BackgroundCOVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. ObjectiveWe aim to describe the impact of the COVID-19 pandemic on AMR across healthcare settings. Data SourceA search was conducted in December 2021 in World Health Organizations COVID-19 Research Database with forward citation searching up to June 2022. Study EligibilityStudies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. MethodsPooling was done separately for Gram-negative and Gram-positive organisms. Random effects meta-analysis was performed. ResultsOf 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n=25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (IRR 0.99, 95% CI: 0.67 to 1.47) or proportion (RR 0.91, 95% CI: 0.55 to 1.49) of MRSA or VRE cases. A non-statistically significant increase was noted for resistant Gram-negatives (i.e., ESBL, CRE, MDR or carbapenem-resistant Pseudomonas or Acinetobacter species, IRR 1.64, 95% CI: 0.92 to 2.92; RR 1.08, 95% CI: 0.91 to 1.29). The absence of enhanced IPAC and/or ASP initiatives was associated with an increase in Gram-negative AMR (RR 1.11, 95%CI: 1.03 to 1.20), while studies that did report implementation of these initiatives noted no change in Gram-negative AMR (RR 0.80, 95%CI: 0.38 to 1.70). However, a test for subgroup differences showed no statistically significant difference between these groups (P=0.40) ConclusionThe COVID-19 pandemic could play an important role in the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. There is considerable heterogeneity in both the AMR metrics utilized and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic. PROSPERO registration: CRD42022325831This research was carried out as part of routine work, no funding was received Data collection template, data, and analytic code are available upon request.

14.
Proc Natl Acad Sci U S A ; 119(33): e2201616119, 2022 08 16.
Article in English | MEDLINE | ID: covidwho-1960617

ABSTRACT

With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P-M or F-SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P-M gene junction was more efficient than from the F-SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1-/- mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.


Subject(s)
COVID-19 Vaccines , COVID-19 , Measles-Mumps-Rubella Vaccine , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccine Efficacy , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine , Measles-Mumps-Rubella Vaccine/genetics , Measles-Mumps-Rubella Vaccine/immunology , Mesocricetus , Mice , Mumps virus/genetics , Mumps virus/immunology , Proline/genetics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology
15.
Pandemics and Global Health ; : 31-71, 2021.
Article in English | Scopus | ID: covidwho-1918705

ABSTRACT

The human diaspora started from the beginning of civilization but its intensity and speed were enhanced or induced by the advancement in the travel sector. Pandemics during human history indicated that diaspora is the main vector/tool of spreading among the millions. In this context, this chapter is focused to understand the perspective and conscious level of nations in the following four questions. 1. Is there any satisfactory technological advancement to identify the pandemic diseases of international travelers in the context of the developed stage of diaspora? 2. How the advanced technological development catalyzed the intensity and speed of dispersal mechanism of pandemic disease outbreaks like COVID-19? 3. Is there any apt security against pandemics among nations and how will it be formed? It was observed that, during the COVID-19 period, the immediate response of science and technology was not sufficient to ensure the security of the people in the context of diaspora. Even though nations had successfully developed bio-weapons through technological advancement, they had failed to guarantee security consciousness to their people. The diaspora of the present century is facing the extreme challenge of pandemic diseases because of the poor predictive mechanism on the evolution of microbes in the climatic changing scenario. © 2022 by Nova Science Publishers, Inc.

16.
ssrn; 2022.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4149035
17.
Pediatric Blood and Cancer ; 69(SUPPL 2):S31, 2022.
Article in English | EMBASE | ID: covidwho-1885447

ABSTRACT

Background: Approximately 60% of children with Sickle Cell Disease (SCD) have at least one vaso-occlusive pain episode (VOE) per year. VOE can sometimes require hospitalization, but often needs continued patient-specific management at home following discharge. Despite the recognized utility of personalized treatment plans for patients with SCD, use and communication regarding these pain plans can vary. The COVID-19 pandemic saw widespread use of telemedicine to improve healthcare access for patients needing medical care. Little is known about its potential usability to improve post-hospitalization pain management in SCD. Objectives: The objective of this study was to determine if hospital follow-up telemedicine visits allowed for improved caregiver-provider communication regarding home pain management, improved scheduling of outpatient sickle cell follow-up, and decreased readmissions. Design/Method: Data for telemedicine visits conducted between August 2021 through December 2021 are presented here. All patients with SCD admitted to the hematology/oncology unit at Riley Hospital for Children were eligible for a telemedicine visit within 48 to 72 hours of discharge. Visits were requested by the inpatient nurse navigator and included in the patient's discharge education handout. Telemedicine visits were performed by Hematology/Oncology Advanced Practice Providers (APPs). During the visits, all patients/caregivers were asked: 1) If they had any difficulty obtaining their medications after discharge, 2) If their home pain plan was reviewed with them prior to discharge, 3) If they had any questions about their regimen, 4) If their pain control was adequate, and 5) If they had a follow-up scheduled with the SCD clinic. Results: Forty-seven patients with SCD were hospitalized during this timeframe. Average age was 12.75 years (+/-5.82). Most (70%) had Hemoglobin SS, and most were hospitalized for pain (83%). Eight patients were readmitted within 30 days. Of those hospitalized, 4 did not attend their telemedicine visit (1 due to wrong number, 1 refused the visit, and 2 readmitted prior to scheduled visit). Only 48% of patients were given a copy of their home pain plan. Eighteen patients/caregivers had questions about their home pain plan and dosing, needed augmentation of their plan, and/or had difficulty in obtaining their prescriptions after discharge. Five patients did not have a follow-up appointment with the sickle cell clinic scheduled by the time of their telemedicine visit. Conclusion: Hospital follow-up telemedicine visits allowed for improved communication regarding home management and scheduling of follow-up. The findings from this work demonstrate the usability of telemedicine to improve transition of care from the inpatient to the outpatient setting.

18.
Ann Intern Med ; 175(7): 969-979, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1863261

ABSTRACT

BACKGROUND: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. DESIGN: Cohort study. (ClinicalTrials.gov: NCT04411147). SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. MEASUREMENTS: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. RESULTS: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. LIMITATIONS: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. CONCLUSION: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. PRIMARY FUNDING SOURCE: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.


Subject(s)
COVID-19 , Acute Disease , Adult , COVID-19/complications , Cohort Studies , Female , Humans , Longitudinal Studies , Quality of Life , SARS-CoV-2
19.
Proc Natl Acad Sci U S A ; 119(21): e2202012119, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1852638

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV-2) is a worldwide health concern, and new treatment strategies are needed. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4) and its mouse homolog, caspase-11 (CASP11), are up-regulated in SARS­CoV-2 infections and that CASP4 expression correlates with severity of SARS­CoV-2 infection in humans. SARS­CoV-2­infected Casp11−/− mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) mice and mice lacking the caspase downstream effector gasdermin-D (Gsdmd−/−). Notably, viral titers were similar regardless of CASP11 knockout. Global transcriptomics of SARS­CoV-2­infected WT, Casp11−/−, and Gsdmd−/− lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp11−/− mice. We confirmed that protein levels of inflammatory mediators interleukin (IL)-1ß, IL-6, and CXCL1, as well as neutrophil functions, were reduced in Casp11−/− lungs. Additionally, Casp11−/− lungs accumulated less von Willebrand factor, a marker for endothelial damage, but expressed more Kruppel-Like Factor 2, a transcription factor that maintains vascular integrity. Overall, our results demonstrate that CASP4/11 promotes detrimental SARS­CoV-2­induced inflammation and coagulopathy, largely independently of GSDMD, identifying CASP4/11 as a promising drug target for treatment and prevention of severe COVID-19.


Subject(s)
COVID-19 , Caspases, Initiator/metabolism , SARS-CoV-2 , Thromboinflammation , Animals , COVID-19/enzymology , COVID-19/pathology , Caspases, Initiator/genetics , Disease Progression , Humans , Lung/pathology , Mice , Mice, Knockout , Severity of Illness Index , Thromboinflammation/enzymology , Thromboinflammation/genetics
20.
Vaccine ; 40(25): 3455-3460, 2022 05 31.
Article in English | MEDLINE | ID: covidwho-1821520

ABSTRACT

OBJECTIVE: To determine pertussis and influenza vaccination coverage during pregnancy among women delivering in all the maternities of Geneva (Switzerland), during the COVID-19 pandemic. METHODS: All women delivering in all the maternity centres of the canton of Geneva from 1st November 2020 to 30th November 2020 (beginning of the flu vaccination season) and from 8th March 2021 to 7th April 2021 (end of the flu vaccination season) had their records checked upon admission to the labour ward regarding pertussis and influenza vaccination during pregnancy. Reasons for non-vaccination were recorded. Univariate and multivariate analyses were done to identify predictors of vaccine uptake. RESULTS: 951 women delivered in Geneva during the two study periods, of which 950 were included in the study. 86.2% were vaccinated against pertussis, with no significant difference between the study periods (87.5% vs 85% at the beginning and end of the flu vaccination season respectively). 49.8% were vaccinated against influenza, with no significant difference between the study periods (48.8% vs 50.7% beginning and end of the flu vaccination season respectively). The influenza vaccine was 5 times more likely not to be proposed (8.9% vs. 1.7%) and 3 times more likely to be refused (26.6% vs. 8%) than the pertussis vaccine. Main reason for refusal was a lack of maternal desire for both vaccines, but not vaccine fear. Maternal parity ≥ 1 was significantly associated with pertussis vaccine uptake at univariate analysis. Women were significantly more likely to accept the influenza vaccine if they had a university degree or if they did not deliver in a midwife-only run delivery unit in both univariate and multivariate analysis. CONCLUSIONS: In Geneva, most gynaecologists offer pertussis immunization during antenatal care and uptake is high, but more efforts must be done to increase influenza vaccination coverage. Education level impacts maternal flu vaccination uptake, but other social disparities did not.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Pregnancy Complications, Infectious , Whooping Cough , COVID-19/epidemiology , COVID-19/prevention & control , Female , Humans , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Pandemics/prevention & control , Pertussis Vaccine , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Prospective Studies , Vaccination , Whooping Cough/epidemiology , Whooping Cough/prevention & control
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