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1.
Clin Infect Dis ; 73(7): 1318, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-2188377
2.
Infect Control Hosp Epidemiol ; 43(5): 651-653, 2022 05.
Article in English | MEDLINE | ID: covidwho-2185117

ABSTRACT

In this retrospective cohort study of patients presenting to a national direct-to-consumer medical practice, we found that provider geographic location is a stronger driver of antibiotic prescribing than patient location. Physicians in the Northeast and South are significantly more likely than physicians in the West to prescribe antibiotics for upper respiratory infection and bronchitis.


Subject(s)
Respiratory Tract Infections , Telemedicine , Anti-Bacterial Agents/therapeutic use , Humans , Inappropriate Prescribing , Practice Patterns, Physicians' , Respiratory Tract Infections/drug therapy , Retrospective Studies
3.
PLoS One ; 17(11): e0277201, 2022.
Article in English | MEDLINE | ID: covidwho-2197029

ABSTRACT

OBJECTIVES: Respiratory tract infection (RTI) incidence varies between people, but little is known about why. The aim of this study is therefore to identify risk factors for acquiring RTIs. METHODS: We conducted a secondary analysis of 16,908 participants in the PRIMIT study, a pre-pandemic randomised trial showing handwashing reduced incidence of RTIs in the community. Data was analysed using multivariable logistic regression analyses of self-reported RTI acquisition. RESULTS: After controlling for handwashing, RTI in the previous year (1 to 2 RTIs: adjusted OR 1.96, 95% CI 1.79 to 2.13, p<0.001; 3 to 5 RTIs: aOR 3.89, 95% CI 3.49 to 4.33, p<0.001; ≥6 RTIs: OR 5.52, 95% CI 4.37 to 6.97, p<0.001); skin conditions that prevent handwashing (aOR 1.39, 95% CI 1.24 to 1.55, p<0.001); children under 16 years in the household (aOR 1.27, 95% CI 1.12, 1.43, p<0.001); chronic lung condition (aOR 1.16, 95% CI 1.02 to 1.32, p = 0.026); female sex (aOR 1.10, 95% CI 1.03 to 1.18, p = 0.005), and post-secondary education (aOR 1.09, 95% CI 1.02 to 1.17, p = 0.01) increased the likelihood of RTI. Those over the age of 65 years were less likely to develop an infection (aOR 0.89, 95% CI 0.82 to 0.97, p = 0.009). Household crowding and influenza vaccination do not influence RTI acquisition. A post-hoc exploratory analysis found no evidence these subgroups differentially benefited from handwashing. CONCLUSIONS: Previous RTIs, chronic lung conditions, skin conditions that prevent handwashing, and the presence of household children predispose to RTI acquisition. Further research is needed to understand how host and microbial factors explain the relationship between previous and future RTIs.


Subject(s)
Community-Acquired Infections , Respiratory Tract Infections , Aged , Child , Female , Humans , Community-Acquired Infections/epidemiology , Community-Acquired Infections/prevention & control , Crowding , Family Characteristics , Respiratory System , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Risk Factors
4.
PLoS One ; 17(8): e0272513, 2022.
Article in English | MEDLINE | ID: covidwho-2196972

ABSTRACT

BACKGROUND: Elderly long-term care residents (ELTCRs) face considerable burden of infection, especially evident during the COVID-19 pandemic. The nutritional status of the host can influence susceptibility to infection by altering immune system integrity, therefore, nutrition-based interventions may be a viable complement to existing infection prevention measures. OBJECTIVE: This scoping review sought to identify nutritional interventions and factors that have the strongest evidence to benefit ELTCRs, and thus best poised for rigorous clinical trial evaluation and subsequent implementation. METHODS: A database search of OVID-Medline, OVID-Embase, and Web of Science was performed from 2011 to 2021 to identify nutritional intervention studies which attribute to changes in infection in contemporary ELTCR settings. Articles were screened in duplicate and data extraction completed by a single reviewer, while a second reviewer verified the data which was fitted to identify evidence for nutritional interventions related to reducing rates of infection among ELTCRs. RESULTS: The search identified 1018 studies, of which 11 (nine clinical trials and two observational cohort studies) satisfied screening criteria. Interventions that significantly reduced risk of infection included whey protein (any infection), Black Chokeberry (urinary tract infection), and vitamin D (acute respiratory tract infection, skin and soft tissue infection). Both zinc and a dedicated meal-plan significantly improved lymphocyte parameters. Vitamin D deficiency was associated with the development of respiratory tract infections. Probiotic and soy-based protein interventions did not significantly affect risk of infection or lymphocyte parameters, respectively. CONCLUSION: The current scoping review was effective in identifying the use of nutrition-based interventions for infection prevention among ELTCRs. In this study, some nutrition-based interventions were observed to significantly influence the risk of infection among ELTCRs. Nutritional interventions such as vitamin D (preventing deficiency/insufficiency), Black Chokeberry juice, zinc gluconate, whey protein, and varied and nutrient dense meal plans may be suitable for future rigorous clinical trial evaluation.


Subject(s)
COVID-19 , Respiratory Tract Infections , Aged , COVID-19/prevention & control , Humans , Long-Term Care , Pandemics/prevention & control , Vitamin D/therapeutic use , Vitamins , Whey Proteins
5.
Curr Opin Pulm Med ; 28(3): 218-224, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-2190986

ABSTRACT

PURPOSE OF REVIEW: We aim to examine the most recent findings in the area of invasive pulmonary fungal infections to determine the appropriate/and or lack of prevention measures and treatment of upper fungal respiratory tract infections in the critically ill. RECENT FINDINGS: This will be addressed by focusing on the pathogens and prognosis over different bedridden periods in ICU patients, the occurrence of invasive fungal respiratory superinfections in patients with severe coronavirus disease 2019 which has been recently noted following the SARS-CoV-2 pandemic. Relevant reports referenced within include randomized controlled trials, meta-analyses, observational studies, systematic reviews, and international guidelines, where applicable. Of note, it is clear there is a significant gap in our knowledge regarding whether bacterial and fungal infections in coronavirus disease 2019 are directly attributable to SARS-CoV-2 or a consequence of factors such as managing high numbers of critically unwell patients, and the prolonged duration of mechanical ventilation/ICU admission duration of stay. SUMMARY: An optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, invasive aspergillosis, candidemia, and endemic mycoses continues to be limited clinically. There is a lack of standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues and suboptimal diagnostic approaches for mould blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures (i.e., the routine use of bronchoscopic examination in ICU patients with influenza-associated pulmonary aspergillosis) for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens.


Subject(s)
COVID-19 , Mycoses , Respiratory Tract Infections , Critical Illness , Humans , Mycoses/diagnosis , Mycoses/drug therapy , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/therapy , SARS-CoV-2
6.
J Allergy Clin Immunol Pract ; 10(3): 694-696, 2022 03.
Article in English | MEDLINE | ID: covidwho-2180006
7.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.22.525048

ABSTRACT

Background: Coronaviruses belong to the group of RNA family of viruses which trigger diseases in birds, humans, and mammals, which can cause respiratory tract infections. The COVID-19 pandemic has badly affected every part of the world, and the situation in the world is getting worse with the emergence of novel variants. Our study aims to explore the genome of SARS-CoV2 followed by in silico analysis of its proteins. Methods: Different nucleotide and protein variants of SARS-Cov2 were retrieved from NCBI. Contigs & consensus sequences were developed to identify variations in these variants by using SnapGene. Data of variants that significantly differ from each other was run through Predict Protein software to understand changes produced in protein structure The SOPMA web server was used to predict the secondary structure of proteins. Tertiary structure details of selected proteins were analyzed using the online web server SWISS-MODEL. Findings: Sequencing results shows numerous single nucleotide polymorphisms in surface glycoprotein, nucleocapsid, ORF1a, and ORF1ab polyprotein. While envelope, membrane, ORF3a, ORF6, ORF7a, ORF8, and ORF10 genes have no or few SNPs. Contigs were mto identifyn of variations in Alpha & Delta Variant of SARs-CoV-2 with reference strain (Wuhan). The secondary structures of SARs-CoV-2 proteins were predicted by using sopma software & were further compared with reference strain of SARS-CoV-2 (Wuhan) proteins. The tertiary structure details of only spike proteins were analyzed through the SWISS-MODEL and Ramachandran plot. By Swiss-model, a comparison of the tertiary structure model of SARS-COV-2 spike protein of Alpha & Delta Variant was made with reference strain (Wuhan). Alpha & Delta Variant of SARs-CoV-2 isolates submitted in GISAID from Pakistan with changes in structural and nonstructural proteins were compared with reference strain & 3D structure mapping of spike glycoprotein and mutations in amino acid were seen. Conclusion: The surprising increased rate of SARS-CoV-2 transmission has forced numerous countries to impose a total lockdown due to an unusual occurrence. In this research, we employed in silico computational tools to analyze SARS-CoV-2 genomes worldwide to detect vital variations in structural proteins and dynamic changes in all SARS-CoV-2 proteins, mainly spike proteins, produced due to many mutations. Our analysis revealed substantial differences in functional, immunological, physicochemical, & structural variations in SARS-CoV-2 isolates. However real impact of these SNPs can only be determined further by experiments. Our results can aid in vivo and in vitro experiments in the future.


Subject(s)
Respiratory Tract Infections , COVID-19
8.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.19.23284806

ABSTRACT

Background: Molecular multiplex assays (MPAs) for simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza and respiratory syncytial virus (RSV) in a single RT-PCR reaction reduce time and increase efficiency to identify multiple pathogens with overlapping clinical presentation but different treatments or public health implications. Methods: Clinical performance of XpertXpress SARS-CoV-2/Flu/RSV (Cepheid, GX), TaqPathTM COVID-19, FluA/B, RSV Combo kit (Thermo Fisher Scientific, TP), and PowerChekTM SARS-CoV-2/Influenza A&B/RSV Multiplex RT-PCR kit II (KogeneBiotech, PC) was compared to individual Standards of Care (SoC). Thirteen isolates of SARS-CoV-2, human seasonal influenza, and avian influenza served to assess limit of detection (LoD). Then, positive and negative residual nasopharyngeal specimens, collected under public health surveillance and pandemic response served for evaluation. Subsequently, comparison of effectiveness was assessed. Results: The three MPAs confidently detect all lineages of SARS-CoV-2 and influenza viruses. MPA-LoDs vary from 1-2 Log10 differences from SoC depending on assay and strain. Clinical evaluation resulted in overall agreement between 97% and 100%, demonstrating a high accuracy to detect all targets. Existing differences in costs, testing burden and implementation constraints influence the choice in primary or community settings. Conclusion: TP, PC and GX, reliably detect SARS-CoV-2, influenza and RSV simultaneously, with reduced time-to-results and simplified workflows. MPAs have the potential to enhancediagnostics, surveillance system, and epidemic response to drive policy on prevention and control of viral respiratory infections.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Tract Infections , Coronavirus Infections , COVID-19 , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Muscle Hypertonia
9.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.11.523616

ABSTRACT

Intranasal vaccination represents a promising approach for preventing disease caused by respiratory pathogens by eliciting a mucosal immune response in the respiratory tract that may act as an early barrier to infection and transmission. This study investigated immunogenicity and protective efficacy of intranasally administered messenger RNA (mRNA)-lipid nanoparticle (LNP) encapsulated vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Syrian golden hamsters. Intranasal mRNA-LNP vaccination systemically induced spike-specific binding (IgG and IgA) and neutralizing antibodies with similar robustness to intramuscular controls. Additionally, intranasal vaccination decreased viral loads in the respiratory tract, reduced lung pathology, and prevented weight loss after SARS-CoV-2 challenge. This is the first study to demonstrate successful immunogenicity and protection against respiratory viral infection by an intranasally administered mRNA-LNP vaccine.


Subject(s)
Coronavirus Infections , COVID-19 , Weight Loss , Respiratory Tract Infections
10.
arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2301.04754v1

ABSTRACT

In the context of continued spread of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 and the emergence of new variants, the demand for rapid, accurate, and frequent detection is increasing. Besides, the new predominant strain, Omicron variant, manifests more similar clinical features to those of other common respiratory infections. The concurrent detection of multiple potential pathogens helps distinguish SARS-CoV-2 infection from other diseases with overlapping symptoms, which is significant for patients to receive tailored treatment and containing the outbreak. Here, we report a lab-on-a-chip biosensing platform for SARS-CoV-2 detection based on subwavelength grating micro-ring resonator. The sensing surface is functionalized by specific antibody against SARS-CoV-2 spike protein, which could produce redshifts of resonant peaks by antigen-antibody combination, thus achieving quantitative detection. Additionally, the sensor chip is integrated with a microfluidic chip with an anti-backflow Y-shaped structure that enables the concurrent detection of two analytes. In this study, we realized the detection and differentiation of COVID-19 and influenza A H1N1. Experimental results show that the limit of detection of our device reaches 100 fg/mL (1.31 fM) within 15 min detecting time, and cross-reactivity tests manifest the specificity of the optical diagnostic assay. Further, the integrated packaging and streamlined workflow facilitate its use for clinical applications. Thus, the biosensing platform offers a promising solution to achieve ultrasensitive, selective, multiplexed, and quantitative point-of-care detection of COVID-19.


Subject(s)
COVID-19 , Respiratory Tract Infections
11.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2458970.v1

ABSTRACT

Background Infection is a well-known contributor to developing cardiac arrythmias such as atrial fibrillation (AF), which contributes to over 25% of all ischaemic stroke. We wanted to quantify the incidence of first-diagnosed (new) AF (nAF) during hospitalisation with COVID-19 compared to a lower respiratory tract infection (LRTI), as well as compare anticoagulation rates at discharge, reasons for non-prescription of anticoagulation and determine factors associated with developing nAF with COVID-19. Methods We analysed a comprehensive hospital coding database on patients hospitalised due to COVID-19+/-AF or LRTI +/-AF, between 1/3/2020 and 31/12/2020 at a large tertiary hospital in the UK. Incidence of nAF during COVID-19 or LRTI, and the proportions of nAF patients discharged on anticoagulation and reasons for non-prescription from both cohorts were quantified. Results 2243 patients were hospitalised with LRTI and 488 with COVID-19. nAF was diagnosed in significantly more COVID-19 patients compared to LRTI (7.0% vs 3.6%, P=0.003). However, significantly less COVID-19 patients were discharged on anticoagulation compared to LRTI (19.2% vs 55.9%, P=0.003) despite similar CHA2DS2-VASc scores, and lower ORBIT scores. 14/26 LRTI +nAF patients had documented contraindication not to be anticoagulated, whereas only 1/12 patients with COVID-19 +nAF did. Patients who developed nAF during hospitalisation with COVID-19 were older (P<0.001), had pre-existing congestive cardiac failure (P=0.004), ischaemic heart disease (IHD) or peripheral vascular disease (PVD) (P<0.001), and a higher CHA2DS2-VASc score (P=0.02). Older age (Odds ratio (OR) 1.03, P=0.007) and IHD/PVD (OR 2.87, P=0.01) increased the odds of developing nAF with COVID-19. Conclusion Higher incidence of nAF and lower anticoagulation rates in COVID-19 patients were observed, compared to LRTI. A larger proportion of COVID-19 +nAF patients did not have a clear documented reason for non-prescription of anticoagulation in their notes. Whilst we await further research and clear guidelines, a pragmatic approach would be to holistically consider anticoagulation in all patients with COVID-19+nAF and a high ischaemic stroke risk.


Subject(s)
Heart Failure , Respiratory Tract Infections , COVID-19 , Cerebral Infarction , Atrial Fibrillation , Myocardial Ischemia , Peripheral Vascular Diseases , Arrhythmias, Cardiac
12.
authorea preprints; 2023.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.167303809.92917586.v1

ABSTRACT

COVID-19, a predominantly respiratory infection, is demonstrated to cause neurologic complications even in the recovery phase. This systematic review aims to investigate the neuroimaging findings in Acute/ Subacute and Chronic or Post-COVID-19 patients. We searched the online databases of PubMed, Scopus, and Web of Science, using relevant keywords up to December, 2021. We included all observational studies reporting neuroimaging findings in confirmed COVID-19 patients, during acute/subacute or chronic phase. We included 25 studies in our study. Structural and functional neuroimaging modalities, mainly magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and computed tomography (CT), were applied in COVID patients with valuable findings to detect the neural alterations in the brain. Hypometabolism in various regions of the brain, especially the hippocampus, parahippocampus, entorhinal cortices, cingulate, and frontal cortices as well as pons and thalamus were among findings reported in post-COVID patients. In addition, anatomical alterations in different areas of the brain including the thalamus, pons, cingulate cortex, corpus callosum, and Globus pallidus were reported. Such findings can justify several post-COVID neurological symptoms or complications. Structural and functional neuroimaging in COVID and post-COVID patients potentially can show alterations which can help in follow up of patients.


Subject(s)
Nervous System Diseases , COVID-19 , Respiratory Tract Infections
13.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2433404.v1

ABSTRACT

Purpose The outbreak of coronavirus disease (COVID-19) resulted in implementation of social distancing and other public health measures to control the spread of infection and improve prevention, resulting in a decrease in respiratory syncytial virus (RSV) and pediatric respiratory tract infection rates. However, there was a rapid and large re-emergence of RSV infection in Japan. Notably, we were faced with a difficult situation wherein there was a shortage of hospital beds. This study aimed to examine the epidemiological patterns of RSV-related hospitalizations among children before and after the COVID-19 pandemic onset at two pediatric emergency referral hospitals covering the entire Tokushima Prefecture.Methods Data were extracted from electronic medical records of children hospitalized with RSV infection between January 1, 2018, and December 31, 2021. All patients meeting the eligibility criteria were included in this study. The rates of study outcomes were documented annually during 2018–2021 and compared between the 2018–2020 and 2021 periods.Results In 2020, there was no RSV infection outbreak. In contrast, in 2021, RSV infection rate peaks were observed 1–2 months earlier than those in the previous years. Hospitalizations at the peak week in 2021 were 2.2- and 2.8-fold higher than those in 2018 and 2019, respectively. Hospitalizations in 2021 were concentrated within a short period. In addition, there was a significant increase in hospitalizations among children aged 3–5 months and those older than 24 months. Hospitalizations of children with siblings at home increased. The high-flow nasal cannula (HFNC) use rate nearly doubled in 2021.Conclusions A new pandemic in the future may cause an outbreak of RSV infection that can result in an intensive increase in the number of hospitalizations of pediatric patients requiring respiratory support, especially in infants aged < 6 months. There is an urgent need to improve the preparedness of medical systems, particularly in terms of the number of inpatient beds and the immediate availability of HFNC.


Subject(s)
Coronavirus Infections , COVID-19 , Respiratory Syncytial Virus Infections , Respiratory Tract Infections
14.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2432702.v1

ABSTRACT

Background In the current era of the severe acute respiratory syndrome-coronavirus-2 epidemic, the need for respiratory care, including mechanical ventilatory (MV) management, has increased. However, there are no well-developed educational strategies for training medical personnel dealing with respiratory care in MV management.Methods A novel mixed-methods hands-on seminar for learning MV management was conducted for the residents at Chiba University Hospital in March 2022. The seminar lasted approximately 2 hours. The learning goal for the residents was to develop skills and knowledge in performing basic respiratory care, including MV, during an outbreak of a respiratory infection. The seminar with a flipped classroom consisted of e-learning, including modules on respiratory physiology and MV management, hands-on training with a low-fidelity simulator (a lung simulator), and hands-on training with a high-fidelity simulator (a human patient simulator). Each training activity was supervised by respiratory physicians, an intensivist, or a clinical engineer. The effectiveness of the seminar was evaluated using closed questions (scored on a five-point Likert scale: 1 [minimum] to 5 [maximum]) and multiple-choice questions (maximum score: 6) at the pre- and post-seminar evaluations.Results Fourteen residents at Chiba University Hospital participated in the program. The questionnaire responses revealed that the participants’ motivation for learning about MV was relatively high in the pre-seminar period (seven participants [50%] selected level 5 [very strong]), and it increased in the post-seminar period (all participants selected level 5) (p = 0.016). However, most participants (n = 12, 86%) felt the psychological burden of providing respiratory care to patients needing MV management, and the level of the psychological burden did not change significantly from the pre- to post-seminar period (p = 0.328). The responses to the multiple-choice questions revealed that the participants did not have enough knowledge to operate a mechanical ventilator, but the total score significantly improved from the pre- to post-seminar period (pre-seminar: 3.3, post-seminar: 4.6, p = 0.003).Conclusions The seminar implemented in this study helped increase the residents’ motivation to learn about respiratory care and improved knowledge of MV management in a short time. In particular, the flipped classroom may promote the efficiency of education on MV management.


Subject(s)
Coronavirus Infections , Respiratory Tract Infections
15.
BMC Public Health ; 22(1): 1167, 2022 06 11.
Article in English | MEDLINE | ID: covidwho-1885294

ABSTRACT

BACKGROUND: Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019. METHODS: We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES). RESULTS: After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for almost the half of all infections and that they exhibited the highest degree of seasonality. Coinfections of viruses are frequent; the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection. CONCLUSIONS: The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.


Subject(s)
Coinfection , Respiratory Tract Infections , Virus Diseases , Viruses , Coinfection/epidemiology , Humans , Infant , Rhinovirus , Virus Diseases/epidemiology
17.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.12.22.519205

ABSTRACT

Organisms respond to proteotoxic stress by activating a cellular defense mechanism, known as the heat shock response (HSR), that triggers the expression of cytoprotective heat shock proteins (HSP) to counteract the damaging effects of proteostasis disruption. The HSR is regulated by a family of transcription factors (heat shock factors, HSFs); among six human HSFs, HSF1 acts as a proteostasis guardian regulating acute and severe stress-driven transcriptional responses. Seasonal coronaviruses HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 (sHCoV) are globally circulating in the human population. Although sHCoV generally cause only mild upper respiratory diseases in immunocompetent hosts, severe complications may occur in specific populations. There is no effective treatment for sHCoV infections, also due to the limited knowledge on sHCoV biology. We now show that both Alpha- and Beta- sHCoV are potent inducers of HSF1, selectively promoting HSF1 phosphorylation at serine-326 residue and nuclear translocation, and triggering a powerful HSF1-driven transcriptional response in infected cells at late stages of infection. Despite the coronavirus-mediated shut-down of the host cell translational machinery, high levels of selected canonical and non-canonical HSF1-target genes products, including HSP70, HSPA6 and the zinc-finger AN1-type domain-2a gene/AIRAP, were found in HCoV-infected cells. Interestingly, silencing experiments demonstrate that HSR activation does not merely reflect a cellular defense response to viral infection, but that sHCoV activate and hijack the HSF1-pathway for their own gain. Notably, nuclear HSF1 pools depletion via Direct-Targeted HSF1 inhibitor (DTHIB) treatment was highly effective in hindering sHCoV replication in lung cells. Altogether the results open new scenarios for the search of innovative antiviral strategies in the treatment of coronavirus infections.


Subject(s)
Infections , Respiratory Tract Infections , Coronavirus Infections , Coronaviridae Infections , Fractures, Stress , Proteostasis Deficiencies , Virus Diseases
18.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.12.22.521558

ABSTRACT

As the COVID-19 pandemic continues to pose a health risk concern to humans, despite a significant increase in vaccination rates, an effective prevention and treatment of SARS-CoV- 2 infection is being sought worldwide. Herbal medicines have been used for years and played a tremendous role in several epidemics of respiratory viral infections. Thus, they are considered as a promising platform to combat SARS-CoV-2. Previously, we reported that common dandelion (Taraxacum officinale) leaf extract and its high molecular weight compounds strongly suppressed in vitro lung cell infection by SARS-CoV-2 Spike D614 and Delta variant pseudotyped lentivirus. We now here demonstrate that T. officinale extract protects against the most prominent Omicron variant using hACE2-TMPRSS2 overexpressing A549 cells as in vitro model system. Notably, compared to the original D614, and the Delta variant, we could confirm a higher efficacy. Short-term interval treatment of only 30 min was then sufficient to block the infection by 80% at 10 mg/mL extract. Further subfractionation of the extract identified compounds larger than 50 kDa as effective ACE2-Spike binding inhibitors. In summary, the evolution of SARS-CoV-2 virus to the highly transmissible Omicron variant did not lead to resistance, but rather increased sensitivity to the preventive effect of the extract.


Subject(s)
Lung Diseases , Respiratory Tract Infections , COVID-19 , Severe Acute Respiratory Syndrome
19.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2402533.v1

ABSTRACT

Introduction: COVID - 19 viruses are responsible for endemic respiratory tract infection in the wide world. Following vaccination with the nCoV-19 vaccine, however, cases of thrombosis and thrombocytopenia, to detect these cases D-dimer test should be done. Aims: this study aims to detect the relation between D- dimer and vaccination of COVID19 Methods: This study that done by vaccinated patients from the special labs in Amman the capital of Jordan between January 2022 to October 2022 using PCR tests for detecting the virus. XL-FDP level estimated by using Atlas D-Dimer Latex Kit (Atlas Medical, Cowley Rd, Cambridge) Following manufacturing instruction. Discussion/Conclusion. We conclude that the vaccinated COVID-19 patients suffer from elevated baseline D-dimer. thrombosis can occur in different organs, leading to organ failure in serious COVID-19 cases.


Subject(s)
Respiratory Tract Infections , COVID-19 , Thrombocytopenia , Thrombosis
20.
BMC Infect Dis ; 22(1): 887, 2022 Nov 26.
Article in English | MEDLINE | ID: covidwho-2139176

ABSTRACT

BACKGROUND: Persons in Pakistan have suffered from various infectious diseases over the years, each impacted by various factors including climate change, seasonality, geopolitics, and resource availability. The COVID-19 pandemic is another complicating factor, with changes in the reported incidence of endemic infectious diseases and related syndromes under surveillance. METHODS: We assessed the monthly incidence of eight important infectious diseases/syndromes: acute upper respiratory infection (AURI), viral hepatitis, malaria, pneumonia, diarrhea, typhoid fever, measles, and neonatal tetanus (NNT), before and after the onset of the COVID-19 pandemic. Administrative health data of monthly reported cases of these diseases/syndromes from all five provinces/regions of Pakistan for a 3-year interval (March 2018-February 2021) were analyzed using an interrupted time series approach. Reported monthly incidence for each infectious disease agent or syndrome and COVID-19 were subjected to time series visualization. Spearman's rank correlation coefficient between each infectious disease/syndrome and COVID-19 was calculated and median case numbers of each disease before and after the onset of the COVID-19 pandemic were compared using a Wilcoxon signed-rank test. Subsequently, a generalized linear negative binomial regression model was developed to determine the association between reported cases of each disease and COVID-19. RESULTS: In late February 2020, concurrent with the start of COVID-19, in all provinces, there were decreases in the reported incidence of the following diseases: AURI, pneumonia, hepatitis, diarrhea, typhoid, and measles. In contrast, the incidence of COVID was negatively associated with the reported incidence of NNT only in Punjab and Sindh, but not in Khyber Pakhtunkhwa (KPK), Balochistan, or Azad Jammu & Kashmir (AJK) & Gilgit Baltistan (GB). Similarly, COVID-19 was associated with a lowered incidence of malaria in Punjab, Sindh, and AJK & GB, but not in KPK and Balochistan. CONCLUSIONS: COVID-19 was associated with a decreased reported incidence of most infectious diseases/syndromes studied in most provinces of Pakistan. However, exceptions included NNT in KPK, Balochistan and AJK & GB, and malaria in KPK and Balochistan. This general trend was attributed to a combination of resource diversion, misdiagnosis, misclassification, misinformation, and seasonal patterns of each disease.


Subject(s)
COVID-19 , Communicable Diseases , Malaria , Measles , Pneumonia , Respiratory Tract Infections , Infant, Newborn , Humans , Incidence , COVID-19/epidemiology , Pakistan/epidemiology , Pandemics , Communicable Diseases/epidemiology , Syndrome , Malaria/epidemiology , Respiratory Tract Infections/epidemiology , Pneumonia/epidemiology , Measles/epidemiology , Diarrhea/epidemiology
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