Presence Of Preexisting Conditions Research Articles

Gene expression changes in COVID-19 patients impact pathways related to circadian rhythm, phosphatidylinositol signaling, cytokine storm, and platelet aggregation

The emergence of SARS-CoV-2 and the resulting COVID-19 disease pandemic had a grave impact on human society causing severely ill patients were to be placed on mechanical ventilators. The severity of the disease depended on such factors as age and the presence of pre-existing conditions. Although with the earnest effort, vaccines have been developed against the disease, there is still a long way to go to completely eradicate COVID-19. Currently, there are concerns about the complications associated with COVID-19 patients and associated conditions. This research aimed to find correlation between gene expression profiles of COVID-19 patients and factors such as age, severity, and mechanical ventilators. To do this, we probe COVID-19 patient data for dysregulated genes and pathways in severe disease. The relevant data was selected from the Gene Expression Omnibus (GEO) datasets GSE152418, GSE171110 and GSE157103. We identified differentially expressed genes (DEGs) between defined groups: COVID-19 patients and control individuals, severe ill and moderately ill COVID-19 patients, young (<40 years) and old (>70 years), and patients who require versus do not require mechanical ventilation. Analyses of over-represented pathways among DEGs and identification of enriched gene sets among cohorts provided further etiological insights. The impact of DEGs on protein-protein interactions (PPIs) between products of these genes were evaluated. The results highlight pathways related to immune response as well as inflammation, cancer, circadian clock, and PI signaling in COVID-19 patients. Key genes regulating circadian clock and PI signaling were downregulated, however, various genes and proteins regulating inflammation and cancer were upregulated in the COVID-19 patients. The product of the up-regulated gene, FLT3, which promotes phosphorylation of STAT5A/STAT5β, resulting in increased cytokine production is connected to VAV1 and TET proteins which play a role in cytokine production. Among old patients, besides pathways related to inflammation and the immune system, pathways such as platelet activation, signaling and aggregation as well as extracellular matrix organization were affected by gene expression dysregulation. In patients requiring mechanical ventilation, pathways impacted include PD-1 signaling, TCR signaling, translocation of ZAP-70 to immunological synapse, and phosphorylation of CD3 and TCR zeta chains. These observations shed insights into relevant genes and pathways impacting COVID-19 patients.

Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.

Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.

Work and Mental Distress among Nurses in the Amazon Region of Brazil during the COVID-19 Pandemic.

To assess the relationship between psychopathological symptoms and the social, clinical, and occupational profile of nurses in the Amazon region of Brazil during the COVID-19 pandemic. A descriptive cross-sectional online study was conducted in 2020 with 261 nurses. The Symptom Assessment Scale-40 was utilized. The presence of pre-existing conditions before the pandemic was associated with psychotism (p=0.044). Experiencing constraints and/or violence at work during the pandemic was associated with somatization (p=0.025), and working hours were associated with anxiety (p=0.025). Nurses predominantly exhibited symptoms related to fear (33.7%), tension (34.5%), and a sense that something is wrong in the mind (22.6%). A significant association was observed between working hours and anxiety symptoms, the experience of constraints and/or violence at work during the COVID-19 pandemic and somatization symptoms, as well as between pre-existing conditions and psychotism symptoms related to COVID-19.

Erectile Dysfunction: Key Role of Cavernous Smooth Muscle Cells.

Erectile dysfunction is increasingly affecting men, from the elderly to young adults, being a sexual disorder related to the inability to generate or maintain a penile erection. This disorder is related to psychosocial factors such as anxiety, depression, and low self-esteem, to organic factors such as the presence of preexisting conditions like hypertension, diabetes and dyslipidemia. The pathophysiology of the disease is related to changes in the neurotransmission of the autonomic or the non-cholinergic non-adrenergic nervous system, as well as the release of local mediators, such as thromboxane A2 and endothelin, and hormonal action. These changes lead to impaired relaxation of cavernous smooth muscle, which reduces local blood flow and impairs penile erection. Currently, therapy is based on oral vasodilation, such as sildenafil, tadalafil, vardenafil and iodenafil, or by direct administration of these agents into the corpus cavernosum or by intraurethral route, such as alprostadil and papaverine. Despite this, studies that consolidate the understanding of its pathophysiological process contribute to the discovery of new more efficient drugs for the treatment of erectile dysfunction. In this sense, in the present work an extensive survey was carried out of the mechanisms already consolidated and the most recent ones related to the development of erectile dysfunction.

Extra-Pulmonary Complications in SARS-CoV-2 Infection: A Comprehensive Multi Organ-System Review.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is typically presented with acute symptoms affecting upper and lower respiratory systems. As the current pandemic progresses, COVID-19 patients are experiencing a series of nonspecific or atypical extra-pulmonary complications such as systemic inflammation, hypercoagulability state, and dysregulation of the renin–angiotensin–aldosterone system (RAAS). These manifestations often delay testing, diagnosis, and the urge to seek effective treatment. Although the pathophysiology of these complications is not clearly understood, the incidence of COVID-19 increases with age and the presence of pre-existing conditions. This review article outlines the pathophysiology and clinical impact of SARS-CoV-2 infection on extra-pulmonary systems. Understanding the broad spectrum of atypical extra-pulmonary manifestations of COVID-19 should increase disease surveillance, restrict transmission, and most importantly prevent multiple organ-system complications.

Mental Health Symptomatology and Posttraumatic Growth among Those with Multimorbidity in COVID Pandemic: Cross-Sectional Findings from the STRONG Study in Greece

Background: Individuals with physical or mental health conditions represent a vulnerable population, especially during the COVID-19 pandemic. However, limited information is available concerning posttraumatic growth and common mental health symptoms of this vulnerable health group during COVID-19. Methods: An online cross-sectional study (STRONG study; psychological changes and effects after COVID-19 quarantine in Greece) was conducted from 28 September 2020 (no lockdown restrictions) to 2 November 2020, just before the second lockdown in Greece. Main outcomes were depressive and anxiety symptoms as well as posttraumatic growth. Results: A total of 860 adults participated in the study. A high proportion of participants did not report any pre-existing health condition (61%), while 334 individuals reported one or more physical or mental health conditions. Overall, 20.2% of the participants reported significant depressive symptoms, and 27.9% reported moderate to high posttraumatic growth. The presence of physical and mental health conditions, either as single diagnosis or as a multimorbidity, was significantly associated with the development of depressive symptomatology (either physical or mental health conditions: OR = 1.12; 95% CI, 1.07–1.17, p &lt; 0.001; both physical and mental health conditions: OR = 1.23; 95% CI, 1.14–1.33, p &lt; 0.001). Posttraumatic growth did not differ between those with or without any pre-existing health issue. Conclusions: Although having a physical or/and a mental health condition predicted the development of depressive symptomatology in a post-lockdown period, the presence of pre-existing conditions was not associated with posttraumatic growth development. Clinicians should be aware of depressive symptoms among their multimorbid patients, even after exiting lockdown.

The Perfect Storm: Rapid Progression of Diabetic Ketoacidosis in Pediatric Diabetes in the Setting of COVID-19

Introduction: The COVID-19 pandemic has introduced countless challenges to the medical field and has brought increased attention to pediatric patients with pre-existing diagnoses such as diabetes. While pediatric patients have lower rates of COVID-19 mortality, the presence of pre-existing conditions can heighten the severity of their clinical presentation. Here we discuss how COVID-19 may contribute to the pathophysiology of DKA.Case Presentation: Our patient is a 6-year old female with known type 1 diabetes for 6 months, with positive GAD 0.25 nmol/L, c-peptide 0.3 ng/ml, blood glucose 555 mg/dl, HbA1c 10.9, beta hydroxybutyrate (βOHB) 3.21mmol/l, pH 7.35, HCO3 21 mEq/L at her initial presentation, and insulin requirement <0.5 IU/kg/day (in honeymoon). She presented to an outside hospital due to acute onset of abnormal breathing and altered mental status. The day prior, she had one episode of emesis, diarrhea, and abdominal pain, but no fever. She was reported to be agonal breathing with a GCS of 8 and unresponsive to physical or verbal stimuli. She was intubated shortly after arrival and given mannitol. Initial labs included a glucose 486 mg/dL, pH 6.88, bicarbonate 4 mEq/L, lactate 5.8 mmol/L, βOHB 11.9 mmol/L, and anion gap 29 mEq/L, all consistent with severe DKA. With a known family member with COVID-19, she was tested and found to be COVID-19 positive. She was transferred via flight to a higher level of care. Remarkably, she was appropriate for extubation the following day with return to her baseline mental status with improved acidosis. On day three of hospitalization, she developed further COVID-19 symptoms which included sore throat, productive cough, fatigue, headache, and high fever. These symptoms persisted four more days until she was afebrile and discharged home in good condition.Conclusion: Our patient’s rapid progression and severity of illness, including the need for intubation, requires the discussion of how COVID-19 might affect diabetes and suggests opportunities for improvement in clinical practice in children with preexisting diabetes. 1) COVID-19 might change the underlying pathophysiology and cause severe metabolic complications. Possible mechanisms might include a) binding to angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, leading to insulin resistance and islet cell destruction b) enabling a proinflammatory “cytokine storm” in the setting of higher basal proinflammatory state from diabetes. Additionally, ketoacidosis and altered mental status have been discovered in patients with COVID-19 without diabetes, which could potentiate the symptoms of DKA. 2) Prompt recognition and treatment of DKA is warranted as caregivers may attribute the symptoms to COVID-19 rather than DKA and recognition could be too late if symptoms are as acute as described in this case report.

Population with an increased risk of severe COVID-19 in Germany. Analyses from GEDA 2019/2020-EHIS.

Only a minority of people who test positive for COVID-19 develop a severe or critical form of the disease. Many of these have risk factors such as old age or pre-existing conditions and, therefore, are at the focus of protective measures. This article determines the number of people at risk in Germany and differentiates them according to age, sex, education, household type and federal state. The analyses presented here are based on data from the German Health Update (GEDA) 2019/2020-EHIS, which was carried out as a nationwide cross-sectional telephone-based survey between April 2019 and October 2020. The definition of being at increased risk of severe COVID-19 is primarily based on a respondent’s age and the presence of pre-existing conditions. Around 36.5 million people in Germany are at an increased risk of developing severe COVID-19. Of these, 21.6 million belong to the high-risk group. An above-average number of people at risk live alone. The prevalence of an increased risk is higher among middle-aged men than among women of the same age, and significantly higher among people with a low level of education than among people with a high level of education. The highest proportion of people with an increased risk live in Saarland and in the eastern German federal states. When fighting the pandemic, it is important to account for the fact that more than half of the population aged 15 or over is at increased risk of severe illness. Moreover, the regional differences in risk burden should be taken into account when planning interventions.

Toxicity risk from glucocorticoids in sarcoidosis patients.

Glucocorticoids (GC) are considered first-line therapy for treating sarcoidosis, but there are few data about the adverse consequences of GC. Although there are several steroid-sparing medications available for treatment, a large proportion of patients are treated with prolonged courses of GC. The toxicities of GC in sarcoidosis populations have not been carefully evaluated. We performed a retrospective cohort study of all newly diagnosed sarcoidosis patients who had the entirety of their medical care in a single health system. We analyzed the time to development of a composite toxicity end-point, including diabetes, hypertension, weight gain, hyperlipidemia, low bone density and ocular complications of GC using Cox proportional hazards analysis. One hundred and five patients were ever treated with GC, whereas 49 were not treated during a median follow-up of 101 months. GC-treated patients developed 1.3±1.1 toxicities during therapy, versus 0.6±1.0 in the non-treated group. After adjustment for age, gender, race and preexisting conditions, the hazard ratio for ever-treated patients was 2.37 (1.34-4.17) for the composite end-point. Age and the presence of preexisting conditions also were associated with reaching the end-point. Similar effects were seen when analyzed for cumulative GC dose and for duration of GC use. For individual end-points, weight gain (HR 2.04) and new hypertension (HR 3.36) were associated with any use of GC. Our data suggest that GC are associated with clinically important toxicities in sarcoidosis patients, associated with both the cumulative dose and duration of treatment.

Antibiotic use for Vibrio infections: important insights from surveillance data

BackgroundThere is a paucity of data on the in vivo efficacy of antibiotics for lethal Vibrio species. Analyses of long-term surveillance datasets may provide insights into use of antibiotics to decrease mortality.MethodsThe United States Centers for Disease Control and Prevention (CDC) Cholera and Other Vibrio Illness Surveillance (COVIS) dataset from 1990 to 2010, with 8056 records, was analysed to ascertain trends in antibiotics use and mortality.ResultsTwo-thirds of patients (5243) were prescribed antibiotics - quinolones (56.1 %), cephalosporins (24.1 %), tetracyclines (23.5 %), and penicillins (15.4 %). Considering all Vibrio species, the only class of antibiotic associated with reduced odds of mortality was quinolone (odds ratio 0.56, 95 % CI 0.46-0.67). Patients with V. vulnificus treated according to CDC recommendations had lower mortality (quinolone alone: 16.7 %, 95 % CI 10.2-26.1; tetracycline plus cephalosporin: 21.7 %, 16.8-27.5; no antibiotic: 51.1 %, 45.6-56.7; each p < 0.001). Cephalosporin alone was associated with higher mortality (36.8 %, 28.2-46.3). For V. cholerae non-O1, non-O139, mortality rates were lower for quinolone (0 %, 0–2.0) or tetracycline (4.3 %, 1.2-14.5) compared to no antibiotic (9.3 %, 6.4-13.3). For all Vibrio species, mortality rates increased with number of antibiotics in the treatment regimen (p < 0.001). Treatment regimens that included quinolone were associated with lower mortality rates regardless of the number of antibiotics used. The main clinical syndromes of patients with V. vulnificus infection were septicaemia (53.1 %) and wound infections (30.6 %). Mortality among V. vulnificus patients with septicaemia was significantly higher than for other clinical syndromes (p < 0.001). In a multivariate regression model, mortality in cases with V. vulnificus was associated with presence of pre-existing conditions (ORs ranged from 4.52 to 10.30), septicaemia (OR 2.64, 95 % CI 1.92-3.63) and no antibiotic treatment (OR 7.89, 95 % CI 3.94-15.80).ConclusionIn view of the lack of randomized control trials, surveillance data may inform treatment decisions for potentially lethal Vibriosis. Considering all Vibrio species, use of quinolones is associated with lower mortality and penicillin alone is not particularly effective. For the most lethal species, V. vulnificus, treatment that includes either quinolone or tetracycline is associated with lower mortality than cephalosporin alone. We recommend treating patients who present with a clinical syndrome suggestive of V. vulnificus infection with a treatment regimen that includes a quinolone.

Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection

PurposeThe purpose of this article is to describe the clinical and epidemiologic features and outcomes among children hospitalized with pandemic influenza A/H1N1 2009 infection.MethodsWe retrospectively reviewed the charts of hospitalized pediatric patients (<18 years) diagnosed with pandemic influenza A/H1N1 2009 infection by reverse-transcriptase polymerase chain reaction at a tertiary hospital in Seoul, Korea, between September 2009 and February 2010.ResultsA total of 72 children were hospitalized with pandemic influenza A/H1N1 2009 infection (median age, 6.0 years; range, 2 months to 18 years). A total of 40% had at least 1 underlying medical condition, including asthma (17%), malignancies (19%), and heart diseases (17%). Of the 72 patients, 54 (76%) children admitted with H1N1 infection showed radiographic alterations compatible with pneumonia. There was no significant difference in pre-existing conditions between pandemic influenza A/H1N1 infected patients with or without pneumonia. Children with pandemic influenza A/H1N1 pneumonia were more likely to have a lower lymphocyte ratio (P=0.02), higher platelet count (P=0.02), and higher level of serum glucose (P=0.003), and more commonly presented with dyspnea than did those without pneumonia (P=0.04).ConclusionNo significant differences in age, sex, or presence of preexisting conditions were found between children hospitalized with pandemic influenza A/H1N1 H1N1 influenza infection with pneumonia and those without pneumonia. Higher leukocyte count, higher glucose level, and a lower lymphocyte ratio were associated with the development of pandemic A/H1N1 2009 influenza pneumonia.

890 Pandemic Influenza a (H1N1) Infection in Pediatric Population: A Multicentric Study in North-Eastern Italy

The rapid increase of new cases of pandemic influenza A (H1N1) in Italy in the autumn 2009 was alarming and limited data were available on disease characteristics and outcomes of children who required hospital admission.Objective: To describe clinical characteristics, treatment and outcome of children hospitalized for H1N1 pandemic influenza in the nineteen Pediatric Units of the Veneto Region (North-Eastern Italy, ∼800.000 inhabitants 0-17 years).Methods: Retrospective study including children consecutively admitted from November 2009 to February 2010 for H1N1 influenza confirmed on reverse-transcriptase polymerase-chain-reaction assay.Results: Clinical, laboratory, and radiographic data of 200 children were reviewed. The median age was 4.15 years (range 0-17.5). At least one underlying medical condition was found in 43.5% of patients. Fever and cough were the most frequent symptoms (92.5% and 64.5% respectively). In 81% of patients chest radiograph findings were consistent with pneumonia. Eleven (5.5 %) were admitted to an intensive care unit (ICU) and 5 (2.5%) required mechanical ventilation. Only 1 patient admitted to ICU was previously healthy. Antiviral therapy was administered in 103 patients (51.5%) after a median of 2 days from onset of symptoms. Secondary bacterial infection was identified in 8/200 (4%). The median length of hospital stay was 4 days (range 1-72). Death occurred in 2 patients (1%), who both had severe prior medical conditions.Conclusion: Pandemic H1N1 influenza rarely requires hospitalization and, in hospitalized children, it mainly appears to cause a mild disease. The presence of pre-existing conditions is the most significant risk factor for severe disease.

Efficacy of Tonsillectomy in Treatment of Recurrent Group A β‐Hemolytic Streptococcal Pharyngitis

The objective of this study was to determine whether children with tonsillectomies experienced fewer recurrent group A beta-hemolytic streptococcal (GABHS) infections after surgery compared with children who did not receive tonsillectomies. The authors conducted a retrospective cohort study of 290 children 4 to <16 years who experienced three or more episodes of group A beta-hemolytic streptococcal pharyngitis at least 1 month apart in 12 months. Children without tonsillectomy were 3.1 times (95% confidence interval, 1.9-4.9; P < .001) more likely to develop a subsequent group A beta-hemolytic streptococcal pharyngitis infection during follow up than children who underwent tonsillectomy after adjusting for the number of group A beta-hemolytic streptococcal pharyngitis infections per patient within the previous year and the presence of preexisting conditions. Among the children who developed a subsequent group A beta-hemolytic streptococcal pharyngitis infection, the children without a tonsillectomy developed a group A beta-hemolytic streptococcal pharyngeal infection sooner (median, 0.6 vs. 1.1 years). Tonsillectomy is associated with a decrease in the number of group A beta-hemolytic streptococcal pharyngitis infections in children with a history of recurrent groups A beta-hemolytic streptococcal pharyngitis infection. Tonsillectomy also increased the amount of time before development of further GABHS pharyngitis.