Clinical Course Of Infection Research Articles

Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.

Relapsing bronchopneumonia due to community-associated methicillin-resistant Staphylococcus aureus: a case report

BackgroundThe emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare.Case presentationWe report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan.Discussion and conclusionsThis patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.

PECULIARITIES OF THE CORONAVIRUS INFECTION CLINICAL COURSE CAUSED BY SARS-COV2 IN CHILDREN POPULATION (LITERARY REVIEW)

The coronavirus SARS has been known since 2002. In 2019 the rapid spread of the virusSARS-CoV-2 caused a global pandemic. The article provides an analysis of informationon the origin and structure of the virus, discusses the epidemiological aspects ofcoronavirus infection and the main links of pathogenesis, describes data on the mainclinical manifestations of SARS-CoV-2 in children and the long-term consequences ofthe disease, such as multisystem inflammatory syndrome in children and adolescents(MIS-C), focused attention on diagnostic tools, methods of treatment and prevention.The purpose – to analyze and summarize information about the peculiarities of thecourse of the coronavirus infection caused by the SARS-CoV-2 virus among children, itsepidemiological characteristics and means of prevention.Conclusions. 1. Knowledge of the epidemiological and clinical features of the novelcoronavirus disease COVID-19 in the child population needs constant updating, as manyaspects of the clinical course of infection in children remain unclear. 2. CoV-2 affectschildren less frequently and less aggressively than adults, with very low mortality, whichmay be due to a rarer exposure to major sources of transmission (e. g. nosocomial) anda predisposition to significantly milder disease symptoms. 3. Laboratory and radiologicalfindings in sick children with symptoms are mostly non-specific, but they can help identifypatients in severe conditions. 4. Due to mutations of the virus, scientific studies of theclinical and pathogenetic features of the course and prevention of COVID-19 continue,because the consequences of the transferred disease require further study. 5. Vaccinationof children today is one of the important preventive measures to prevent the complicatedcourse of acute respiratory disease associated with SARS-CoV-2.

Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIVmac239 in rhesus macaques

The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates viral immune sensing, and induces cell-cycle arrest in cell culture. However, its impact invivo is controversial. Here, we show that deletion of vpr is associated with delayed viral replication kinetics, rapid innate immune activation, development and maintenance of strong B and Tcell responses, and increased neutralizing activity against SIVmac239 in rhesus macaques. All wild-type SIVmac239-infected animals maintained high viral loads, and five of six developed fatal immunodeficiency during ∼80weeks of follow-up. Lack of Vpr was associated with better preservation of CD4+ Tcells, lower viral loads, and an attenuated clinical course of infection in most animals. Our results show that Vpr contributes to efficient viral immune evasion and the full pathogenic potential of SIVmacinvivo. Inhibition of Vpr may improve humoral immune control of viral replication.

Prevalence and Associated Factors of Neonatal Sepsis among Neonates Admitted at Neonatal Intensive Care Units of Hargeisa Hospitals, Somaliland, 2023

Background: Neonatal sepsis is the main cause of neonatal death and morbidity worldwide. It is characterized by a systemic inflammatory response during the clinical course of infection which manifests within the first month of life of a newborn. Neonatal sepsis accounts for 7% of all neonatal deaths in Somalia. However, we know little about the prevalence and factors associates with neonatal sepsis in Somaliland. As a result, this study is aimed to assess the prevalence of neonatal sepsis and associated factors among neonates admitted to intensive care units at Hargeisa Hospitals in Somaliland. Methods: Institutional-based cross-sectional study was conducted among 244 medical records of neonates admitted in neonatal intensive care units of Hargeisa Hospitals from May, 2023 to June, 2023. The medical records selected at random using lottery method. Neonatal record review used to collect data using structured pretested checklist. Data entered into Epidata version 3.1 and analyzed with SPSS version 22. Bivariable and multivariable binary logistic regression used to identify associated factors at a 95% confidence interval. Significance is considered at p-value < 0.05, Multi-collinearity is examined (VIF <10) and Model fitness is evaluated using Hosmer-Lemeshow statistic test (P< 0.05). Result: The overall prevalence of neonatal sepsis in this study was 28.69% (95% CI, 22.97-34.40). Neonates whose mothers’ membranes had ruptured before giving birth (AOR=1.9; 95% CI: 1.01-3.61) and neonates delivered through assisted vaginal delivery (AOR=3.9; 95% CI: 1.19-12.64) had a positive association with neonatal sepsis than their counterparts. Recommendations: Hospitals and health professionals should enhance early detection and management of mother with PROM. Health professionals should give particular consideration to the neonate through vaginal delivery.

Vitamin D deficiency and SARS‑CoV‑2 infection: A retrospective case-Control study with big-data analysis covering March 2020 to March 2021.

Vitamin D may have immunomodulatory functions, and might therefore play a role in the pathogenesis of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no conclusive evidence exists regarding its impact on the prevalence of this infection, the associated course of disease, or prognosis. To study the association between SARS-CoV-2 infection and vitamin D deficiency in patients attending a tertiary university hospital, and to examine the clinical course of infection and prognosis for these patients. This non-interventional, retrospective study, which involved big-data analysis and employed artificial intelligence to capture data from free text in the electronic health records of patients diagnosed with SARS-CoV-2, was undertaken at a tertiary university hospital in Madrid, Spain, between March 2020 and March 2021. The variables recorded were vitamin D deficiency, sociodemographic and clinical characteristics, course of disease, and prognosis. Of the 143,157 patients analysed, 36,261 had SARS-CoV-2 infection (25.33%) during the study period, among whom 2,588 (7.14%) had a vitamin D deficiency. Among these latter patients, women (OR 1.45 [95%CI 1.33-1.57]), adults over 80 years of age (OR 2.63 [95%CI 2.38-2.91]), people living in nursing homes (OR 2.88 [95%CI 2.95-3.45]), and patients with walking dependence (OR 3.45 [95%CI 2.85-4.26]) appeared in higher proportion. After adjusting for confounding factors, a higher proportion of subjects with SARS-CoV-2 plus vitamin D deficiency required hospitalisation (OR 1.38 [95%CI 1.26-1.51]), and had a longer mean hospital stay (3.94 compared to 2.19 days in those with normal levels; P = 0.02). A low serum 25(OH) vitamin D concentration in patients with SARS-CoV-2 infection is significantly associated with a greater risk of hospitalisation and a longer hospital stay. Among such patients, higher proportions of institutionalised and dependent people over 80 years of age were detected.

Watch-and-wait approach for inactive echinococcal cysts: scoping review update since the issue of the WHO-IWGE Expert Consensus and current perspectives.

This work aims to provide an update of knowledge on the evolution of inactive cystic echinococcosis (CE) cysts (CE4-CE5) managed by 'watch-and-wait', by means of a scoping review of the literature published after the publication of the WHO-IWGE (Informal Working Group on Echinococcosis) Expert Consensus document in 2010. A total of 31 articles were included. Population ultrasound-based studies showed that spontaneously inactivated CE cysts represent 50.2% (95% confidence interval 38.7-61.8) of all detected untreated CE cysts, and that the prevalence of CE4-CE5 cysts tends to increase with age. Four longitudinal population-based studies showed that CE cysts naturally tend to evolve towards inactivation and that spontaneously inactivated cysts reactivate in a minority of cases. This was confirmed by four hospital-based studies, showing that spontaneously inactivated cysts reactivate rarely, while rate of reactivation is higher if inactivity was obtained posttreatment. It was not possible to drive conclusions on any difference in the clinical course of infection in immunocompromised or pregnant patients. CE cysts tend to evolve spontaneously to inactivation over time. The published literature supports the safety of the watch-and-wait approach for inactive cysts, sparing treatment to a substantial proportion of asymptomatic patients. A regular follow-up with ultrasound of all inactive cysts is required to detect reactivations.

SARS-CoV-2 Vaccine Breakthrough Infections of Omicron and Delta Variants in Healthcare Workers.

Understanding SARS-CoV-2 breakthrough infections in vaccinated healthcare workers is of key importance in mitigating the effects of the COVID-19 pandemic in healthcare facilities. An observational prospective cohort study was conducted in vaccinated employees with acute SARS-CoV-2 infection between October 2021 and February 2022. Serological and molecular testing was performed to determine SARS-CoV-2 viral load, lineage, antibody levels, and neutralizing antibody titers. A total of 571 (9.7%) employees experienced SARS-CoV-2 breakthrough infections during the enrolment period, of which 81 were included. The majority (n = 79, 97.5%) were symptomatic and most (n = 75, 92.6%) showed Ct values < 30 in RT-PCR assays. Twenty-four (30%) remained PCR-positive for > 15 days. Neutralizing antibody titers were strongest for the wildtype, intermediate for Delta, and lowest for Omicron variants. Omicron infections occurred at higher anti-RBD-IgG serum levels (p = 0.00001) and showed a trend for higher viral loads (p = 0.14, median Ct difference 4.3, 95% CI [-2.5-10.5]). For both variants, viral loads were significantly higher in participants with lower anti-RBD-IgG serum levels (p = 0.02). In conclusion, while the clinical course of infection with both the Omicron and Delta variants was predominantly mild to moderate in our study population, waning immune response over time and prolonged viral shedding were observed.

Impact of the COVID-19 pandemic on people in need of care or support: protocol for a SARS-CoV-2 registry

IntroductionPeople in need of care or support are severely affected by the COVID-19 pandemic. We lack valid data of long-term assessments. We present a register study to detect the physical...

First identification of multidrug-resistant Acinetobacter bereziniae isolates harboring blaNDM-1 from hospitals in South China

This study is a first report on the identification of multidrug-resistant (MDR) Acinetobacter bereziniae among non-baumannii acinetobacters that had previously escaped automated laboratory detection, and characterize their clinical courses of infection at two tertiary-care hospitals in Shenzhen city, China (2015–2017). Herein, definitive identification by PCR was performed with universal and species-specific primers targeting 16S rDNA and rpoB genes, respectively, followed by Sanger sequencing and blast analysis. Antimicrobial susceptibility of A. bereziniae isolates was assessed accordingly. Three of the five identified A. bereziniae isolates exhibited carbapenem-resistance and were subjected to a multiplex PCR assay to detect drug-resistance genes. Sequences of the rpoB amplicon were aligned with curated sequences from global databases for phylogenetic analysis on evolutionary relations. Five clinical isolates of A. bereziniae were thereby re-identified, whose infections were primarily nosocomial. Automated identification and susceptibility testing systems (Phoenix-100 and VITEK 2) proved insufficient for discriminating A. bereziniae from other acinetobacters such as Acinetobacter baumannii and Acinetobacter guillouiae. Among these isolates, three exhibited carbapenem-resistant phenotypes indistinguishable from that of carbapenem-resistant A. baumannii. The carbapenem-resistant A. bereziniae isolates were subsequently confirmed to carry a blaNDM-1 (New Delhi metallo-β-lactamase-1) gene downstream of ISAba125. Phylogenetic analysis revealed that A. bereziniae isolates evolved slowly but independently in local habitats. A. bereziniae isolates are difficult to distinguish by traditional automated detection systems. PCR-based identification via amplification and sequencing of selected house-keeping genes provides sufficient resolution for discriminating the isolates.

Network Analysis for Uncovering the Relationship between Host Response and Clinical Factors to Virus Pathogen: Lessons from SARS-CoV-2.

Analysing complex datasets while maintaining the interpretability and explainability of outcomes for clinicians and patients is challenging, not only in viral infections. These datasets often include a variety of heterogeneous clinical, demographic, laboratory, and personal data, and it is not a single factor but a combination of multiple factors that contribute to patient characterisation and host response. Therefore, multivariate approaches are needed to analyse these complex patient datasets, which are impossible to analyse with univariate comparisons (e.g., one immune cell subset versus one clinical factor). Using a SARS-CoV-2 infection as an example, we employed a patient similarity network (PSN) approach to assess the relationship between host immune factors and the clinical course of infection and performed visualisation and data interpretation. A PSN analysis of ~85 immunological (cellular and humoral) and ~70 clinical factors in 250 recruited patients with coronavirus disease (COVID-19) who were sampled four to eight weeks after a PCR-confirmed SARS-CoV-2 infection identified a minimal immune signature, as well as clinical and laboratory factors strongly associated with disease severity. Our study demonstrates the benefits of implementing multivariate network approaches to identify relevant factors and visualise their relationships in a SARS-CoV-2 infection, but the model is generally applicable to any complex dataset.

Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients.

The oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Infectious Disease 2019 (COVID-19). In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 initially enrolled patients, 50 had positive molecular testing for COVID-19+ and had symptom duration of 14 days or less. These patients were analyzed further as progression of disease could most likely be attributed to acute COVID-19 and less likely a secondary process. Of these, 38 (76%) went on to require some form of supplemental oxygen support. To identify functional patterns associated with respiratory illness requiring respiratory support, we applied an interpretable random forest classification machine learning pipeline to shotgun metagenomic sequencing data and select clinical covariates. When combined with clinical factors, both species and metabolic pathways abundance-based models were found to be highly predictive of the need for respiratory support (F1-score 0.857 for microbes and 0.821 for functional pathways). To determine biologically meaningful and highly predictive signals in the microbiome, we applied the Stable and Interpretable RUle Set to the output of the models. This analysis revealed that low abundance of two commensal organisms, Prevotella salivae or Veillonella infantium (< 4.2 and 1.7% respectively), and a low abundance of a pathway associated with LPS biosynthesis (< 0.1%) were highly predictive of developing the need for acute respiratory support (82 and 91.4% respectively). These findings suggest that the composition of the oropharyngeal microbiome in COVID-19 patients may play a role in determining who will suffer from severe disease manifestations.

On the relationship between anosmia/dysgeusia and nonspecific immunoprophylaxis COVID-19

The issues of non-specific immunoprophylaxis in the patients with new coronavirus infection have been raised since the WHO announced the COVID-19 pandemic. According to numerous studies, the new coronavirus infection is accompanied by manifestations of anosmia and dysgeusia. The purpose of this study was to perform a retrospective study of the relationships between nonspecific immunoprophylaxis of COVID-19 and conditions of anosmia/dysgeusia in the persons who underwent this infection in Sverdlovsk region over 2020.&#x0D; We have studied clinical and laboratory data of 84 employees at the general medical institution providing emergency pediatric care. All participants suffered a single infection caused by SARS-CoV-2. Etiological diagnostics included mandatory virological PCR testing of biological samples. The concentration of antibodies to the virus was determined using a set of reagents for SARS-CoV-2-IgG detection (JSC Vector-Best, Novosibirsk, Russia). A sufficient part of this group (n = 41; 48.8% of total sample) reported self-administration of non-specific immunoprophylactic therapy of COVID-19 (without consulting a doctor) since the beginning of coronavirus pandemics. To this purpose, cholecalciferol, riamilovir, human recombinant IFNa-2b, umifenovir hydrochloride monohydrate, ascorbic acid, zinc acetate were used. In 58 cases (69% of total), clinical course of infection was complicated by loss of taste and sense of smell (group No. 1), in 26 people (31.0%), no changes in taste and sense of smell were detected (group No. 2). Statistical evaluation of the data was performed using STATISTICA v.12.5.192.5 package (StatSoft, Inc., USA). Along with basic statistics, cluster analysis was performed.&#x0D; The use of cluster analysis allowed us to establish that there is a connection between the incidence of anosmia/dysgeusia and usage of distinct immunoprophylactic agents. In particular, the use of human recombinant IFNa-2b is protective in terms of reducing the number complications in COVID-19, especially, anosmia/dysgeusia caused by the new coronavirus. The use of this drug was associated with 8.5-fold decrease in the number of complications by (p = 0.03). Moreover, invasive intranasal usage of interferon, was associated with decreased hospitalization terms by 14.3% (p = 0.01); lower volume of lung tissue damage (p = 0.03), higher concentrations of IgG to SARS-CoV-2 at 2 months after reconvalescence (p = 0.001).&#x0D; For the first time, data were presented on the relationship between usage of immunoprophylactic agents and manifestations of anosmia/dysgeusia in COVID-19. The protective role of human recombinant IFNa-2b has been shown in terms of reduced incidence of the disease complications, e.g., anosmia/dysgeusia, degree of lung damage, as well as development of an antiviral humoral immune response. The data obtained could be used to substantiate clinical recommendations for prevention of new outbreaks of coronavirus infection. The limitation of the obtained results is small number of cases, thus requiring additional studies in a wider sample of respondents.

Breakthrough COVID-19 in Vaccinated Patients with Haematologic Malignancies-The First Single-Centre Experience from the Czech Republic.

Vaccination is an important tool in the fight against the COVID-19 pandemic in patients with haematologic malignancies. The paper provides an analysis of the course of breakthrough SARS-CoV-2 infection in a group of vaccinated patients with haematological malignancy and a comparison with a historical cohort of 96 non-vaccinated patients with haematologic malignancies and bone marrow failure syndromes (two patients) in the treatment of COVID-19. A severe or critical course of COVID-19 was significantly less frequent in the group of vaccinated patients (10.2% vs. 31.4%, p = 0.003). The need for hospitalisation due to COVID-19 was significantly lower in vaccinated patients (27.1% vs. 72.6%, p < 0.0001) and the duration of hospitalisation was significantly shorter (10 vs. 14 days, p = 0.045). Vaccinated patients were insignificantly less likely to require oxygen therapy during infection. COVID-19 mortality was significantly higher in non-vaccinated patients (15.6% vs. 5.1%, p = 0.047). The paper demonstrated a significant positive effect of vaccination against COVID-19 on a less severe clinical course of infection, lower need for hospitalisation and mortality. However, the results need to be evaluated even in the context of new antivirals and monoclonal antibodies against SARS-CoV-2 or virus mutations with different biological behaviour.

Does blood type have an effect on the course of COVID-19?

Introduction &#x0D; Predictive parameters that can affect the course of this infection have been the main topic of research since the beginning of the COVID-19 (Coronavirus disease 2019) pandemic. Since the discovery of blood groups, the effect of these on infectious diseases has always been of interest.&#x0D; Objectives &#x0D; To analyze the effect of ABO blood group on mortality, hospitalization duration and hematological and cytokine storm parameters in patients with COVID-19. &#x0D; Patients and methods: This retrospective study was conducted on 140 patients diagnosed with COVID-19. Demographic characteristics, laboratory parameters including ABO blood group, complete blood count (CBC) parameters, biochemical tests, cytokine storm parameters, duration of hospitalization, and final status (discharge or death) were recorded.&#x0D; Results: The 140 patients included in the analysis comprised 72 (51.4%) males and 68 (48.6%) females with a mean age of 66.3±14.0 years. . Age and gender, hospitalization duration and mortality rates were similar in all blood group types. Only D-dimer levels were found to be higher in blood group A compared with other blood groups.&#x0D; Conclusion: Although no difference in mortality was determined between groups, the D-dimer level was statistically significantly higher in COVID-19 patients with A blood group. Larger studies are needed to reflect D-dimer levels on the clinical course of infection, and thus on daily practice.

Comparison of clinical features of COVID-19 infection in children with asthma and their healthy peers.

AimWe aimed to assess the impact of COVID‐19 on asthma exacerbations and to compare the severity of symptoms of SARS‐CoV‐2 infection of asthmatic children with those of healthy children.MethodsThe clinical course of COVID‐19 was compared among 89 children with asthma and 84 healthy children with age‐ and gender‐matched. Demographic factors, severity of asthma, duration of asthma, presence of atopy, type of treatment, and compliance to treatment in asthmatic children on clinical course of infection and to determine the risk factors for severe course for asthma exacerbation during COVID‐19 were evaluated retrospectively. Demographic characteristics, clinical symptoms, duration of complaints, and hospitalization rates were statistically compared between the two groups.ResultsBoth groups had similar rates of symptomatic disease, hospitalization, and duration of fever. Among children with asthma mean age was 10.3 years, 59.6% were male, and 84.3% had mild asthma. Dyspnea was more prevalent in asthmatic children (p:0.012), but other clinical findings were not different from those of healthy controls. 12.4% (n:11) of asthmatic children had asthma exacerbation, 2.2% (n:2) of them were hospitalized; one (1.1%) of which was due to asthma exacerbation.ConclusionThe course of COVID‐19 in patients with mild to moderate asthma, who were followed up regularly and who were compliant with their treatment, was similar to their healthy peers. Since there was no severe asthma case in our study, the results could not have been generalized to all asthmatic patients. Further comprehensive and multicenter studies are required in pediatric population.

Nontuberculous mycobacterial skin and soft tissue infection in Hawai\u02bbi

BackgroundHawaiʻi has the highest nontuberculous mycobacterial (NTM) lung infection prevalence in the United States. Limited data regarding skin and soft tissue infections (SSTI) due to NTM in Hawaiʻi exists. This study describes patient demographics, clinical courses of infection, treatment patterns, and clinical outcomes of NTM SSTIs in Hawaiʻi.MethodsA retrospective chart review (n = 50) of patients diagnosed and treated at Hawaiʻi Pacific Health facilities for NTM SSTIs between January 2010 and July 2021 was conducted. Patient demographics, clinical course, and treatment data were collected from electronic medical records.ResultsHalf of the patient population consisted of females, and the average age of patients during infection was 49 years (SD = 25.6). The majority of cases (80%) were caused by rapidly growing mycobacteria (RGM), most commonly Mycobacterium abscessus. NTM SSTI by race were Asian (48%), White (28%), and Native Hawaiian and Other Pacific Islanders (16%). Almost all Asian patients with NTM SSTI were Filipino or Japanese. Diagnosis was frequently delayed. The average time to diagnosis was 116 days. Most patients achieved complete resolution (72%) following a prolonged course of antimicrobial treatment (mean = 196 days) with surgical debridement.ConclusionIncreased awareness among physicians and the community of non-mycobacterial skin infections is essential in Hawaiʻi due to the high prevalence of NTM and the high percentage of predisposed populations. Increased awareness of NTM could reduce delayed diagnosis and improve patient care. Further studies are required to inform optimal treatment and diagnostic strategies, improve patient outcomes, and aid public health surveillance efforts.

Mortality Predictive Value of the C2HEST Score in Elderly Subjects with COVID-19-A Subanalysis of the COLOS Study.

Senility has been identified among the strongest risk predictors for unfavorable COVID-19-outcome. However, even in the elderly population, the clinical course of infection in individual patients remains unpredictable. Hence, there is an urgent need for developing a simple tool predicting adverse COVID-19-outcomes. We assumed that the C2HEST-score could predict unfavorable clinical outcomes in the elderly subjects with COVID-19-subjects. Methods: We retrospectively analyzed 1047 medical records of patients at age > 65 years, hospitalized at the medical university center due to COVID-19. Subsequently, patients were divided into three categories depending on their C2HEST-score result. Results: We noticed significant differences in the in-hospital and 3-month and 6-month mortality-which was the highest in high-risk-C2HEST-stratum reaching 35.7%, 54.4%, and 65.9%, respectively. The medium-risk-stratum mortalities reached 24.1% 43.4%, and 57.6% and for low-risk-stratum 14.4%, 25.8%, and 39.2% respectively. In the C2HEST-score model, a change from the low to the medium category increased the probability of death intensity approximately two-times. Subsequently, transfer from the low-risk to the high-risk-stratum raised all-cause-death-intensity 2.7-times. Analysis of the secondary outcomes revealed that the C2HEST-score has predictive value for acute kidney injury, acute heart failure, and cardiogenic shock. Conclusions: C2HEST-score analysis on admission to the hospital may predict the mortality, acute kidney injury, and acute heart failure in elderly subjects with COVID-19.

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

SummaryThe molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.

Management of venous thromboembolism in COVID-19

Since COVID-19 was declared a pandemic in March 2020, there has been extensive human-to-human transmission, resulting in substantial respiratory pathology and manifestations outside the pulmonary parenchyma​[1,2]​. Initial observations showed that the hyper-inflammatory response induced by COVID-19 often led to systemic coagulation derangement and coagulopathy, with thrombosis an important factor in the pathology and clinical course of infection​[3–5]​. […]