Coronavirus Disease 2019 Patients Research Articles

COVID-19 and the risk of acute cardiovascular diseases: a two-sample Mendelian randomization study

BackgroundEvidence suggests that coronavirus disease 2019 (COVID-19) is associated with the risk of cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between COVID-19 and CVDs by using two-sample Mendelian randomization (MR) analysis.MethodsSummary‐level data for COVID-19 and CVDs including myocarditis, heart failure (HF), acute myocardial infarction (AMI), arrhythmia and venous thromboembolism (VTE) were obtained from the IEU OpenGWAS project, a public genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) were used as instrumental variables. Five complementary MR methods were performed, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode and simple mode methods. IVW method was considered as the primary approach. Besides, sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis, were performed to evaluate the robustness of the results.ResultsAccording to the IVW results, our MR study indicated that genetically predicted COVID-19 was not causally connected with the risk of CVDs [myocarditis: odds ratio (OR) = 1.407, 95% confidence interval (CI) = 0.761-2.602, p-value = 0.277; HF: OR = 1.180, 95% CI = 0.980-1.420, p-value = 0.080; AMI: OR = 1.002, 95% CI = 0.998-1.005, p-value = 0.241; arrhythmia: OR = 0.865, 95% CI = 0.717-1.044, p-value = 0.132; VTE: OR = 1.013, 95% CI = 0.997-1.028, p-value = 0.115]. The supplementary MR methods showed similar results. Sensitivity analyses suggested that the causal estimates were robust.ConclusionThis two-sample MR analysis did not provide sufficient evidence for a causal relationship between COVID-19 and the risk of acute CVDs, which may provide new insights into the prevention of acute CVDs in COVID-19 patients.

Association of ACE2 and TMPRSS2 towards COVID-19 susceptibility

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) is pneumonia like viral disease which was originated from Wuhan China in 2019. Besides its high morbidity and mortality, a lot of physiological, enzymatic, hormonal and genetic imbalances had also been observed among Corona Virus Disease-19 (COVID-19) patients. The purpose of the present study was the assessment of comorbidities and association of single nucleotide polymorphisms (SNPs) in Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine (TMPRSS) gene among COVID-19 patients. A total of 300 (healthy control n = 150 COVID-19 n = 150) individuals were sampled and genotyped for ACE2 rs2285666 and TMPRSS rs2070788 SNPs respectively. A total of 92/150 (61.3%) were male infected population, among the various age groups (age group 1: 1–15 yrs; age group 2: 16–30 yrs; age group 3: 31–45; age group 4: 46 and above) where most of the patients were from age group 4 (46 and above) 79/150 (52.7%) followed by age group 3 (31–45) 44/150 (29.3%). Logistic regression analysis showed that among clinical features cough (90%) was observed to be highest followed by fever (80%), sore throat (76%) and shortness of breath (75%). Hypertension (51%), type II diabetes (48.4%), ischemic heart disease (43.3%) history was found to prevalent highly associated with infected individuals. For ACE2 rs2285666, we found disease risk association for both allele and genotype while TMPRSS did not reveal genotype association. It is concluded from the current study that COVID-19 infects majority of male population. ACE2 rs2285666 allele and genotype association was observed with COVID-19 infection and protective association of TMPRSS2 rs2070788 allele towards COVID-19 infection.

Prognostic Nutritional Index (PNI) and Systemic Immune-Inflammatory Index (SII) as markers of severity among patients having COVID-19 infection.

Prognostic nutritional index (PNI) and systemic immune-inflammatory index (SII) are two novel markers that have emerged as potential candidates as an early indication of the severity of the disease in coronavirus disease 2019 (COVID-19) patients. The objective of the study is to assess the utility of the prognostic nutritional index (PNI) and systemic immune-inflammatory index (SII) as markers of severity among patients with COVID-19 infection. This is a retrospective study conducted in a tertiary care centre in South India. A total of 80 patients diagnosed with COVID-19 were included in the study. The patients were divided into mild, moderate, and severe groups based on the clinical parameters as per Indian Council of Medical Research guidelines. Lab values taken at admission were obtained from patient records, using which the PNI and SII were calculated using standard formulae. These markers were correlated with the severity of the COVID-19 illness. PNI and SII were significantly elevated in the patients with severe COVID-19 illness as compared with mild COVID-19 illness. The mean PNI among subjects with mild COVID-19 and severe COVID-19 being 46.62 ± 6.51 and 34.09 ± 5.81, respectively. The mean SII among subjects with mild COVID-19 was 9,52,287.2 ± 1,42,113, and among subjects with severe COVID-19 was 15,39,461 ± 8,04,285. The cut-off value for PNI and SII for predicting severity of COVID-19 illness was 35.93 and 5,82,400, respectively. The sensitivity for PNI was 87.5, and the SII was 95. The present study showed a significant correlation between the SII and PNI as markers used to determine the severity of COVID-19. Based on these findings, it can be effectively used independently of other markers to predict critical illness among COVID-19 patients.

Alterations in hematologic, coagulation, and inflammatory markers based on fever status in hospitalized COVID-19 patients: A retrospective study.

Laboratory markers like lymphopenia, thrombocytopenia, elevated D-dimer, and C-reactive protein (CRP) predict worse outcomes in coronavirus disease 2019 (COVID-19). However, a comprehensive analysis of hematologic and coagulation parameter alterations based on fever status is lacking. This retrospective study analyzed 300 COVID-19 patients hospitalized from March to December 2020. Demographic, clinical, and laboratory data were extracted from electronic medical records. Patients were stratified into fever (n = 200) and no fever (n = 100) groups. Hematologic, coagulation, and inflammatory markers were compared between groups using appropriate statistical tests. Multivariate regression identified independent predictors of fever. Fever was associated with leukocytosis, neutrophilia, lymphopenia, thrombocytopenia, elevated CRP, D-dimer, procalcitonin, interleukin-6, neutrophil to lymphocyte ratio (NLR), and ferritin compared to no fever (all P < 0.05). D-dimer (r = 0.42), CRP (r = 0.52), NLR (r = 0.48), and interleukin-6 (r = 0.46) demonstrated the strongest correlation with fever (P < 0.001). High D-dimer >1000 ng/mL (adjusted odds ratio 2.7), CRP >100 mg/L (3.1), lymphopenia <1.0 × 109/L (2.8), NLR >4 (2.9), and thrombocytopenia <150 × 109/L (2.7) were significant independent predictors of fever status (P < 0.005). These parameters had moderate sensitivity (40-60%) and high specificity (74-88%) for discriminating febrile patients with AUC of 0.85. Marked alterations in hematologic, coagulation, and inflammatory markers occur in COVID-19 based on fever. Routine laboratory parameters can facilitate diagnosis and risk stratification.

Parameters Predictive of Propofol-Associated Acute Pancreatitis in Critically Ill Patients with COVID-19 Pneumonia: A Retrospective Cohort Study.

Propofol, a commonly used agent for short- and long-term sedation, is associated with acute pancreatitis. The main indirect mechanism of propofol-associated acute pancreatitis is by inducing hypertriglyceridemia. Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often require prolonged mechanical ventilation and sedation. We examined the incidence rate of acute pancreatitis among critically ill adults with COVID-19 pneumonia on mechanical ventilation receiving propofol. In addition, we attempted to determine cutoff levels of serum triglycerides and doses of propofol that are predictive of propofol-associated acute pancreatitis. This was a multicenter retrospective cohort study using a large dataset of hospitalized patients with COVID-19. The collected data included the number of days on propofol, cumulative doses of propofol, peak levels of serum triglycerides, serum lipase levels, and abdominal imaging findings. We used receiver-operating characteristic analysis in conjunction with Youden's index to identify the optimal thresholds for propofol administration parameters and levels of triglycerides that would provide maximal sensitivity and specificity for predicting acute pancreatitis. Out of 499 critically ill patients with COVID-19 pneumonia, 154 met the inclusion criteria. Six (4%) patients had suspected acute pancreatitis based on elevated serum lipase levels. Cutoff values greater than 688 mg/dL for peak level of triglycerides, 4.5 days on propofol, 3007 mg/day for average daily propofol dose, and 24 113 mg for cumulative propofol dose were associated with high risk of suspected acute pancreatitis. The negative predictive values for suspected acute pancreatitis using these cutoffs ranged from 98% to 100%. Propofol use in critically ill COVID-19 patients is associated with a low incidence rate of acute pancreatitis. We identified cutoff values for serum triglycerides and cumulative propofol dose that are linked to higher risk of propofol-associated pancreatitis. More research is needed to examine the true incidence of propofol-associated pancreatitis and help develop optimal cutoff values for certain parameters to help guide safe propofol administration.

An ex vivo human precision-cut lung slice platform provides insight into SARS-CoV-2 pathogenesis and antiviral drug efficacy.

Here, established an ex vivo human precision-cut lung slice platform for assessing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral replication kinetics, innate immune response, disease progression, and antiviral drugs. Using this platform, we identified early induction of specific cytokines, especially IP-10 and IL-8, as potential predictors for severe coronavirus disease 2019 (COVID-19), and uncovered a hitherto unrecognized phenomenon that while infectious virus disappears at late times of infection, viral RNA persists and lung histopathology commences. This finding may have important clinical implications for both acute and post-acute sequelae of COVID-19. This platform recapitulates some of the characteristics of lung disease observed in severe COVID-19 patients and is therefore a useful platform for understanding mechanisms of SARS-CoV-2 pathogenesis and for evaluating the efficacy of antiviral drugs.

The Status of Intima-Media Thickness of Bilateral Carotid Arteries in the Postinfection Phase of SARS-CoV-2

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the cardiovascular system by activating systemic inflammatory responses that cause vascular dysfunction. However, the long-term effects of SARS-CoV-2 on the cardiovascular system remain unclear. Therefore, this study aimed to compare the carotid intima-media thickness (cIMT) between patients who have recovered from Coronavirus disease-2019 (COVID-19) and healthy individuals to evaluate the feasibility of vascular complications in the postinfection phase of COVID-19. Materials and Methods: In this cross-sectional study, the cIMT was compared between 47 recovered patients with severe COVID-19 and 42 healthy individuals without a history of COVID-19 (controls) using Doppler sonography. Demographic and sonographic data were analyzed using SPSS version 26 statistical software. Results: A total of 47 young adults (30.8 ± 5.78 years, 7 men and 40 women) were evaluated 3 to 6 months after hospitalization for severe COVID-19, and were compared with 42 young healthy individuals (26.5 ± 5.85 years, 5 men and 37 women). The mean right and left cIMT were significantly lower in recovered COVID-19 patients than in healthy individuals (right cIMT: case group, 0.38 ± 05 mm vs control group, 0.40 ± 0.02 mm, P &lt; .01; left cIMT: case group, 0.38 ± 0.05 mm vs control group, 0.40 ± 0.02, P &lt; .01). Conclusion: A history of positive SARS-CoV-2 was associated with lower cIMT compared with controls. In this cohort, endothelial dysfunction may not have been the main driver of COVID-19 complications in recovered patients. However, more studies should be conducted on the relationship between cIMT and vascular complications.

CXCL12/CXCR4 as a potential axis in diagnosis and predicting disease severity in COVID-19 patients: a new perspective

Abstract Objectives Coronavirus disease 2019 (COVID-19) exhibits variations in terms of patients’ clinical symptoms and levels of routinely employed biochemical markers. The aim of the current study was to determine the correlation between serum levels of the C-X-C chemokine ligand type 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4), one of its specific receptors, and disease severity in COVID-19 patients. Methods Sixty-nine patients were diagnosed with COVID-19 from February to July 2021, and a healthy control group of 39 individuals were enrolled in the study. Patients were divided into subgroups: mild-moderate and severe. Serum CXCL12 and CXCR4 levels were measured using the enzyme-linked immunosorbent assay method. Results CXCL12 and CXCR4 concentrations were both significantly higher in the clinically severe disease group compared to the mild-moderate disease group (p&lt;0.05 in both groups). CXCL12 and CXCR4 levels were also significantly higher in the patients with clinically mild-moderate disease compared to the control group (p&lt;0.001 and p&lt;0.05, respectively). Both CXCL12 and CXCR4 levels were correlated with clinical severity. Serum CXCL12 and CXCR4 levels were significantly positively correlated. Assuming a cut-off value of 1.44 ng/mL, serum CXCL12 levels showed 98 % sensitivity and 84 % specificity to distinguish between COVID-19 patients and healthy individuals (AUC=0.98, p&lt;0.001, 95 % CI=0.95–1.0). Serum CXCR4 levels distinguished individuals with COVID-19 from healthy controls with 88 % sensitivity and 72 % specificity at a cut-off value of 69.7 pg/mL (AUC=0.82, p&lt;0.001, 95 % CI=0.74–0.9). Conclusions Serum CXCL12 and CXCR4 levels may be included among the biomarkers used to differentiate patients with COVID-19 and determine the clinical severity of the disease.

The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody

BackgroundThe global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection.MethodsThis retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression.ResultsForty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10–20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19–38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding.ConclusionsAmong 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.

Prevalence and prognostic role of thoracic lymphadenopathy inCovid-19.

The prevalent coronavirus disease 2019 (COVID-19) pandemic has spread throughout the world and is considered a serious threat to global health. The prognostic role of thoracic lymphadenopathy in COVID-19 is unclear. The aimof the present meta-analysis was to analyze the prognostic role of thoracic lymphadenopathy for the prediction of 30-day mortality in patients with COVID-19. The MEDLINE library, Cochrane, and SCOPUS databases were screened for associations between CT-defined features and mortality in COVID-19 patients up to June 2021. In total, 21 studies were included in the present analysis. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The meta-analysis was performed using RevMan 5.3. Heterogeneity was calculated by means of the inconsistency index I2. DerSimonian and Laird random-effect models with inverse variance weights were performed without any further correction. The included studies comprised 4621 patients. The prevalence of thoracic lymphadenopathy varied between 1 % and 73.4 %. The pooled prevalence was 16.7 %, 95 % CI = (15.6 %; 17.8 %). The hospital mortality was higher in patients with thoracic lymphadenopathy (34.7 %) than in patients without (20.0 %). The pooled odds ratio for the influence of thoracic lymphadenopathy on mortality was 2.13 (95 % CI = [1.80-2.52], p < 0.001). The prevalence of thoracic lymphadenopathy in COVID-19 is 16.7 %. The presence of thoracic lymphadenopathy is associated with an approximately twofold increase in the risk for hospital mortality in COVID-19. · The prevalence of lymphadenopathy in COVID-19 is 16.7 %.. · Patients with lymphadenopathy in COVID-19 have a higher risk of mortality during hospitalization.. · Lymphadenopathy nearly doubles mortality and plays an important prognostic role.. · Bucher AM, Sieren M, Meinel F et al. Prevalence and prognostic role of thoracic lymphadenopathy in Covid-19. Fortschr Röntgenstr 2024; DOI: 10.1055/a-2293-8132.

Retrospective evaluation of acute kidney injury in paediatric COVID-19 patients: a tertiary referral hospital experience.

Coronavirus disease 2019 (COVID-19) has been recognised as a risk factor for acute kidney injury (AKI). Our aim was to investigate the risk factors contributing to hospitalised and outpatient paediatric COVID-19-associated AKI. A retrospective observational study was conducted on patients aged 1month to 18years with diagnosed COVID-19-associated AKI applied to a tertiary paediatric referral hospital between March 1, 2020 and March 1, 2022. A total of 6683 patients were evaluated and 486 patients were included in the study. Acute kidney injury was observed in 3.7% of outpatients and 23.9% of hospitalised patients. Multivariate logistic regression analysis showed that, on admission, a history of contact with a COVID-19 positive person (p < 0.001), age below 12months (p = 0.004), presence of comorbidities (p < 0.001), abdominal pain (p = 0.008), anorexia (p = 0.003), dyspnoea (p = 0.005), higher lactate dehydrogenase values (p = 0.004), neutrophilia (p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (p = 0.003), higher white blood cell counts (p = 0.006), elevated C-reactive protein (CRP) levels (p = 0.002), anaemia (p = 0.015), hypoalbuminaemia (p < 0.001), hyperglycaemia (p = 0.006), and presence of proteinuria (p = 0.003) were independent predictors of AKI. Higher rates of hospitalisation (p < 0.001) and admission to the paediatric intensive care unit (PICU) (p < 0.001), longer length of hospitalisation (p < 0.001), and greater need for mechanical ventilation (p < 0.001) were associated with AKI. This study reveals that not only hospitalised children, but also paediatric patients are at risk for AKI. The presence of comorbidities, abdominal pain, anorexia, dyspnoea, anaemia, inflammation, hypoalbuminaemia, proteinuria and history of contact with a COVID-19 positive person were the main risk factors for AKI. COVID-19-associated AKI was associated with worse outcomes.

The effect of early versus late remdesivir treatment in hospitalized mild to moderate COVID-19 patients in the Omicron era: A retrospective study.

Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, P = .03). Delaying remdesivir treatment ≥ 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; P = .03) and Charlson comorbidity index ≥ 3 (aOR, 9.62; 95% CI, 1.65-56.10; P = .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.

Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections.

Brain effects of mild COVID-19 in healthy young adults: A pilot study

Rationale and objectivesThis study examined the brain effects of mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which are incompletely understood. Our objective was to ascertain within-person changes associated with mild coronavirus disease 2019 (COVID-19) in otherwise healthy adults. Materials and methodsWe leveraged existing pre-pandemic baseline neuroimaging and neurocognitive data, and collected follow-up data from uninfected controls and individuals with prior mild COVID-19, during December 2020 and January 2021, when vaccines were not yet available. We compared change during follow-up in patients (n = 5) versus controls (n = 15). ResultsWe identified a decrease of intracellular volume fraction (ICVF), decrease of isotropic volume fraction (ISO) and decrease of orientation dispersion index (ODI) in multiple inferior frontal regions of interest in COVID-19 patients; this longitudinal change was significantly different from the control group which demonstrated increases in equivalent measures. This pattern suggests injury with neuronal loss and/or inflammation as underlying mechanisms. Neurocognitive studies identified a pattern of cognitive decline (processing speed, executive function, verbal learning, working memory) in patients, that did not reach significance. ConclusionOur pilot data suggests that mild COVID-19 may result in brain pathology and impact neurocognitive function in younger adults in a manner parallel to prior findings in older individuals. Though findings may not generalize to other SARS-CoV-2 variants, larger longitudinal studies of mild COVID-19 should be undertaken to understand the potential clinical implications of these findings over the longer term.

Pulmonary herpes simplex virus and cytomegalovirus in patients with acute respiratory distress syndrome related to COVID-19

PurposeHuman herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging and there is ongoing debate about its association with mortality and benefit of antiviral medication. We aimed to quantify the incidence and pathogenicity of pulmonary CMV and HSV reactivations in critically ill COVID-19 patients.MethodsMechanically ventilated COVID-19 patients seropositive for CMV or HSV were included in this observational cohort study. Diagnostic bronchoscopy with bronchoalveolar lavage was performed routinely and analyzed for alveolar viral loads and inflammatory biomarkers. Utilizing joint modeling, we explored the dynamic association between viral load trajectories over time and mortality. We explored alveolar inflammatory biomarker dynamics between reactivated and non-reactivated patients.ResultsPulmonary reactivation (> 104 copies/ml) of CMV occurred in 6% of CMV-seropositive patients (9/156), and pulmonary reactivation of HSV in 37% of HSV-seropositive patients (63/172). HSV viral load dynamics prior to or without antiviral treatment were associated with increased 90-day mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.04–1.47). The alveolar concentration of several inflammatory biomarkers increased with HSV reactivation, including interleukin (IL)-6, IL-1β, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF).ConclusionIn mechanically ventilated COVID-19 patients, HSV reactivations are common, while CMV reactivations were rare. HSV viral load dynamics prior to or without antiviral treatment are associated with mortality. Alveolar inflammation is elevated after HSV reactivation.

Predicting the Need for Advanced Respiratory Support in COVID-19 Patients During the Initial Pandemic Phase: A Retrospective Analysis.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to high morbidity and mortality rates worldwide. It is known that some patients, initially hospitalized in general wards, deteriorate over time and require advanced respiratory support (ARS). This study aimed to identify key risk factors predicting the need for ARS in patients during the pandemic's early months. In this retrospective study, we included patients admitted within the first three months of the pandemic who were diagnosed with COVID-19 via reverse transcription polymerase chain reaction (RT-PCR). The patients who required ARS or invasive mechanical ventilation at admission were excluded. Data on demographics, comorbidities, symptoms, vital signs, and laboratory parameters were collected. Statistical analyses, including multivariate logistic regression and receiver operating characteristic(ROC) curve analysis, were performed to identify independent predictors of ARS and determine the cut-off point. Among 162 patients, 32.1% required ARS. Key differences between ARS and non-ARS groups included age, body mass index (BMI), coronary artery disease prevalence, neutrophil count,C-reactive protein (CRP), ferritin, D-dimer, troponin T levels, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation response index (SIRI), and symptom-to-admission time. Multivariate analysis revealed that age, elevated CRP levels, elevated ferritin levels, and SIRI were significant predictors for ARS. The ROC curve for SIRI showed an area under the curve (AUC) of 0.785, with a cut-off value of 1.915. Age, CRP levels, ferritin levels, and SIRI are crucial predictors of the need for ARS in COVID-19 patients. The early identification of high-risk patients is essential for timely interventions and resource optimization, particularly during the early stages of pandemics. These insights may assist in optimizing strategies for future respiratory health crisis management.

Thyroid dysfunction in the wake of Omicron: understanding its role in COVID-19 severity and mortality.

SARS-CoV-2 can invade the thyroid gland. This study was to delineate the risk of thyroid dysfunction amidst the prevalence of the Omicron variant, and to investigate the correlation between thyroid function and Coronavirus disease 2019 (COVID-19) outcomes. The study also aimed to ascertain whether thyroid dysfunction persisted during COVID-19 recovery phase. This was a retrospective cohort study. COVID-19 patients from the Renmin Hospital of Wuhan University, China during the epidemic of Omicron variants were included, and their thyroid function were analyzed in groups. A history of thyroid disease was not associated with COVID-19 outcomes. COVID-19 can lead to a bimodal distribution of thyroid dysfunction. The severity of COVID-19 was inversely proportional to the levels of thyroid- stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4), leading to a higher prevalence of thyroid dysfunction. Severe COVID-19 was a risk factor for euthyroid sick syndrome (ESS) (OR=22.5, 95% CI, 12.1 - 45.6). Neutrophil to lymphocyte ratio mediated the association between severe COVID-19 and ESS (mediation effect ratio = 41.3%, p < 0.001). ESS and decreased indicators of thyroid function were associated with COVID-19 mortality, while high levels of FT3 and FT4 exhibited a protective effect against death. This effect was more significant in women (p < 0.05). During the recovery period, hyperthyroidism was quite uncommon, while a small percentage of individuals (7.7%) continued to exhibit hypothyroidism. COVID-19 severity was linked to thyroid dysfunction. Severe COVID-19 increased the risk of ESS, which was associated with COVID-19 mortality. Post-recovery, hyperthyroidism was rare, but some individuals continued to have hypothyroidism.

The relationship between spiritual health and COVID-19 anxiety among nurses: a national online cross-sectional study

The Coronavirus disease 2019 (COVID-19) outbreak has created many concerns in most countries. Nurses are among healthcare workers who are largely engaged in providing care to COVID-19 patients, which makes nurses prone to disease-related worries and stresses. Thus, it is essential to identify the factors which may alleviate their stress and anxiety. This study aimed to determine the relationship between COVID-19 anxiety and spiritual health among Iranian nurses. This cross-sectional online survey was conducted between March 2020 and January 2021 on 919 Iranian nurses who worked in healthcare centers in Iran during the COVID-19 outbreak. The participants were recruited by convenience sampling Method. The data were collected using a demographic questionnaire, Ellison’s standard Spiritual Well-Being (SWB) Scale, and the standard scale of Corona Disease Anxiety. Data were analyzed using SPSS software and p-value less than 0.05 was considered significant. Of the participants, 47.0% (95% confidence interval (CI) 43.7–50.2%) had moderate to severe anxiety. The mean score of spiritual health was 73.3 ± 12.5. The multiple linear model indicated a significant negative correlation with a medium effect size between SWB and COVID-19 anxiety levels in a way that for 10 units increase in the SWB was associated with 2.72 units decrease in anxiety score (Adjusted partial r = − 0.320, p < 0.001). The findings revealed a reverse significant relationship between spiritual health and COVID-19 anxiety. On the other hand, nurses with better spiritual health experienced a lower level of COVID-19 anxiety. Therefore, improving spiritual health could help decrease nurses’ anxiety during COVID-19.

The relationship between Nuclear Factor-Kappa B and Inhibitor-Kappa B parameters with clinical course in COVID-19 patients.

We aimed to investigate the serum Nuclear Factor Kappa B (NF-κB) p105, NF-κB p65 and Inhibitor Kappa B Alpha (IκBα) levels in patients with mild/moderate Coronavirus Disease 2019 (COVID-19) and their association with the course of the disease. Blood was drawn from 35 COVID-19 patients who applied to the Department of Emergency Medicine of Istanbul University-Cerrahpasa at the time of diagnosis and from 35 healthy individuals. The patients were evaluated to have mild/moderate degree of disease according to National Early Warning Score 2 (NEWS2) scoring and computed tomography (CT) findings. The markers were studied in the obtained serum samples, using enzyme-linked immunoassay (ELISA). Receiver Operating Characteristic (ROC) analysis was performed. Statistical significance was evaluated to be p < 0.05. NF-κB p105 levels were significantly higher in the COVID-19 group compared to the control group. C-reactive protein (CRP), D-dimer, ferritin levels of the patients were significantly higher (p < 0.001) compared to the control group, while the lymphocyte count was found lower (p = 0.001). IκBα and NF-κB p65 levels are similar in both groups. Threshold value for NF-κB p105 was above 0.78 ng/mL, sensitivity was 71.4% and specificity was 97.1% (p < 0.05). NF-κB p105 levels at the time of diagnosis of the patients who required supplemental oxygen (O2), were significantly higher (p < 0.01). The rise in serum NF-κB p105 levels during the early stages of infection holds diagnostic value. Besides its relation with severity might have a prognostic feature to foresee the requirement for supplemental O2 that occurs during hospitalization.

Lower or higher oxygenation targets in the intensive care unit: an individual patient data meta-analysis

PurposeOptimal oxygenation targets for patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are not clearly defined due to substantial variability in design of previous trials. This study aimed to perform a pre-specified individual patient data meta-analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) and the Handling Oxygenation Targets in coronavirus disease 2019 (COVID-19) (HOT-COVID) trials to compare targeting a partial pressure of arterial oxygen (PaO2) of 8–12 kPa in adult ICU patients, assessing both benefits and harms.MethodsWe assessed 90-day all-cause mortality and days alive without life support in 90 days using a generalised mixed model. Heterogeneity of treatment effects (HTE) was evaluated in 14 subgroups, and results graded using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN).ResultsAt 90 days, mortality was 40.4% (724/1792) in the 8 kPa group and 40.9% (733/1793) in the 12 kPa group (risk ratio, 0.99; 95% confidence interval [CI] 0.92–1.07; P = 0.80). No difference was observed in number of days alive without life support. Subgroup analyses indicated more days alive without life support in COVID-19 patients targeting 8 kPa (P = 0.04) (moderate credibility), and lower mortality (P = 0.03) and more days alive without life support (P = 0.02) in cancer-patients targeting 12 kPa (low credibility).ConclusionThis study reported no overall differences comparing a PaO2 target of 8–12 kPa on mortality or days alive without life support in 90 days. Subgroup analyses suggested HTE in patients with COVID-19 (moderate credibility) and cancer (low credibility).