Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

Branch retinal artery occlusion in a patient with COVID-19 infection: A case report.

We report here, a case of branch retinal artery occlusion (BRAO) in the left eye of a 76-year-old man that involved three arteries which was considered to be related to a COVID-19 infection due to high levels of blood cytokines and coagulation factors. Although the patient had hypertension and atherosclerosis, his hypertension had been well controlled for the past five years by regular antihypertensive medication. Twenty-five days after starting treatment with anti-inflammatory, anticoagulant and conservative therapy, the patient's biomarkers of inflammation and coagulation returned to normal and his vision improved. However, some visual field defects remained and were probably a consequence of low oxygen saturation.

Predictors of duodenal eosinophil counts among subjects undergoing diagnostic endoscopy.

INTRODUCTION: Duodenal eosinophilia has been implicated in the pathophysiology of functional dyspepsia. In a retrospective observational study, we previously reported that duodenal eosinophilia (as defined by a mucosal count of greater than 15 eosinophils per 5 high power fields), was associated with symptomatic erosive gastroesophageal reflux disease (GERD), concomitant co-morbidities and Chinese ethnicity but not functional dyspepsia among 289 multiracial subjects undergoing diagnostic endoscopy in 2019 before the COVID-19 pandemic. We tested the reproducibility of those findings on a larger sample that included the original cohort and another 221 subjects who underwent endoscopy in 2022 after the easing of pandemic restrictions. MATERIALS AND METHODS: Archived duodenal histology slides were assessed by a pathologist blind to demographic and clinical data gleamed retrospectively from clinical chart review. Logistic regression analysis was used to explore associations between duodenal eosinophilia and the variables age, gender, ethnicity, year of sampling (2019 vs 2022), concomitant co-morbidities, functional dyspepsia, symptomatic erosive GERD (Los Angeles Grades A to D), endoscopic oesophagitis, gallstone disease, Helicobacter pylori infection, irritable bowel syndrome and NSAID consumption. Three different thresholds for defining duodenal eosinophilia (>15, >22 and >30 eosinophils per 5 high power fields) were tested. RESULTS: Year of sampling (2019, pre-pandemic) strongly predicted duodenal eosinophilia across all thresholds (OR 11.76, 13.11 and 21.41 respectively; p = 0.000). The presence of concomitant co-morbidities was a modest predictor across all thresholds whereas Chinese ethnicity only predicted at the lowest threshold. Absolute duodenal eosinophil counts predicted symptomatic erosive GERD (OR 1.03; p = 0.015) but not functional dyspepsia (OR 1.00; p = 0.896) after adjusting for age, gender, ethnicity, concomitant comorbidities and year of endoscopy. None of the subjects reached the threshold for the diagnosis of eosinophilic duodenitis. CONCLUSION: The cumulative impact of environmental exposures on duodenal eosinophil counts may be much greater than of putative factors linked to functional dyspepsia. A signal linking duodenal eosinophil counts and symptomatic erosive GERD was detected.

[Management of HIT/anti-PF4 disorders].

Heparin-induced thrombocytopenia (HIT) was widely known as a disease characterized by development of thrombosis with thrombocytopenia after heparin exposure. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a fatal disease involving simultaneous bleeding and thrombosis after COVID-19 adenovirus vector vaccination. These were caused by HIT antibodies and anti-PF4 antibodies, respectively, but both were autoantibodies that recognized PF4, and were found to have the same pathology with different severities. In recent years, many pathologies in which anti-PF4 antibodies are produced have been reported, and a new concept of anti-PF4 disorder has been proposed. Anti-PF4 disorders are often difficult to identify due to their diverse range of causes, and the prognosis varies greatly depending on whether anti-PF4 antibodies can be measured and early treatment performed after observation of thrombocytopenia of unknown cause or thrombosis at an unusual site. To avoid overlooking anti-PF4 disorders, clinicians should become familiar with the classification of these disorders and accurately select the necessary tests.

Impact of the COVID-19 pandemic on patients with peripheral arterial disease in China: a multicenter cross-sectional study.

This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

Cytokine landscape in hospitalized children with multisystem inflammatory syndrome.

The etiology of multisystem inflammatory syndrome in children (MIS-C), frequently observed following COVID-19 infection, remains elusive. This study unveils insights derived from cytokine analysis in the sera of MIS-C patients, both before and after the administration of intravenous immunoglobulin (IVIG) and glucocorticosteroids (GCS). In this study, we employed a comprehensive 45-cytokine profile encompassing a spectrum of widely recognized proinflammatory and antiinflammatory cytokines, as well as growth factors, along with other soluble mediators. The analysis delineates three principal cytokine-concentration patterns evident in the patients' sera. Pattern no.1 predominantly features proinflammatory cytokines (IL-6, IL-15, IL-1ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), C-X-C motif chemokine ligand 10 (CXCL10/ IP-10), and IL-10) exhibiting elevated concentrations upon admission, swiftly normalizing post-hospital treatment. Pattern no. 2 includes cytokines (IL-17 A, IL-33, IFNγ, vascular endothelial growth factor (VEGF), and programmed death ligand (PD-L1)) with moderately elevated levels at admission, persisting over 7-10 days of hospitalization despite the treatment. Pattern no. 3 comprises cytokines which concentrations escalated after 7-10 days of hospitalization and therapy, including IL-1α, IL-1ß, IL-2, IL-13, platelet-derived growth factor AA/BB (PDGF AA/BB). The observed in cytokine profile of MIS-C patients showed a transition from acute inflammation to sustaining inflammation which turned into induction of humoral memory mechanisms and various defense mechanisms, contributing to recovery.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation.

BACKGROUND: An association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with acute respiratory distress syndrome (ARDS), including patients with COVID-19 (COVID-19-related acute respiratory distress syndrome (C-ARDS)) undergoing IMV, has not been rigorously evaluated. The use of emulations of a target trial in intensive care unit research remains in its infancy. To inform future, large ARDS target trials, we explored using a target trial emulation approach to analyse data from a cohort of IMV adults with C-ARDS to determine whether maintaining daily ∆p<15 cm H2O (in addition to traditional low tidal volume ventilation (LTVV) (tidal volume 5-7 cc/PBW+plateau pressure (Pplat) ≤30 cm H2O), compared with LTVV alone, affects the 28-day mortality. METHODS: To emulate a target trial, adults with C-ARDS requiring >24 hours of IMV were considered to be assigned to limited ∆P or LTVV. Lung mechanics were measured twice daily after ventilator setting adjustments were made. To evaluate the effect of each lung-protective ventilation (LPV) strategy on the 28-day mortality, we fit a stabilised inverse probability weighted marginal structural model that adjusted for baseline and time-varying confounders known to affect protection strategy use/adherence or survival. RESULTS: Among the 92 patients included, 27 (29.3%) followed limited ∆P ventilation, 23 (25.0%) the LTVV strategy and 42 (45.7%) received no LPV strategy. The adjusted estimated 28-day survival was 47.0% (95% CI 23%, 76%) in the limited ∆P group, 70.3% in the LTVV group (95% CI 37.6%, 100%) and 37.6% (95% CI 20.8%, 58.0%) in the no LPV strategy group. INTERPRETATION: Limiting ∆P may not provide additional survival benefits for patients with C-ARDS over LTVV. Our results help inform the development of future target trial emulations focused on evaluating LPV strategies, including reduced ∆P, in adults with ARDS.

Lithium Aspartate for Long COVID Fatigue and Cognitive Dysfunction: A Randomized Clinical Trial.

Importance: Neurologic post-COVID-19 condition (PCC), or long COVID, symptoms of fatigue and cognitive dysfunction continue to affect millions of people who have been infected with SARS-CoV-2. There currently are no effective evidence-based therapies available for treating neurologic PCC. Objective: To assess the effects of lithium aspartate therapy on PCC fatigue and cognitive dysfunction. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial (RCT) enrolling participants in a neurology clinic from November 28, 2022, to June 29, 2023, with 3 weeks of follow-up, was conducted. Subsequently, an open-label lithium dose-finding study with 6 weeks of follow-up was performed among the same participants enrolled in the RCT. Eligible individuals needed to report new, bothersome fatigue or cognitive dysfunction persisting for more than 4 weeks after a self-reported positive test for COVID-19, Fatigue Severity Scale-7 (FSS-7) or Brain Fog Severity Scale (BFSS) score of 28 or greater, Beck Depression Inventory-II score less than 24, and no history of a condition known to cause fatigue or cognitive dysfunction. All participants in the RCT were eligible for the dose-finding study, except for those who responded to the placebo. Intention-to-treat analysis was used. Intervention: Lithium aspartate, 10 to 15 mg/d, or identically appearing placebo for 3 weeks followed by open-label lithium aspartate, 10 to 15 mg/d, for 2 weeks. In the subsequent dose-finding study, open-label lithium aspartate dosages up to 45 mg/d for 6 weeks were given. Main Outcomes and Measures: Change in sum of FSS-7 and BFSS scores. The scores for each measure range from 7 to 49, with higher scores indicating more severe symptoms. Secondary outcomes included changes from baseline in the scores of additional questionnaires. Results: Fifty-two participants were enrolled (30 [58%] males; mean [SD] age, 58.54 [14.34] years) and 26 were randomized to treatment with lithium aspartate (10 females) and 26 to placebo (12 female). Two participants assigned to lithium aspartate were lost to follow-up and none withdrew. No adverse events were attributable to lithium therapy. There were no significant intergroup differences for the primary outcome (-3.6; 95% CI, -16.6 to 9.5; P = .59) or any secondary outcomes. Among 3 patients completing a subsequent dose-finding study, open-label lithium aspartate, 40 to 45 mg/d, was associated with numerically greater reductions in fatigue and cognitive dysfunction scores than 15 mg/d, particularly in 2 patients with serum lithium levels of 0.18 and 0.49 mEq/L compared with 1 patient with a level of 0.10 mEq/L. Conclusions and Relevance: In this RCT, therapy with lithium aspartate, 10 to 15 mg/d, was ineffective for neurologic PCC fatigue and cognitive dysfunction. Another RCT is required to assess the potential benefits of higher lithium dosages for treating neurologic PCC. Trial Registration: ClinicalTrials.gov Identifier: NCT05618587 and NCT06108297.

Baseline level of interleukin-6 is associated with the risk of acute coronary syndrome development in SARS-CoV-2 infection.

BACKGROUND: Acute coronary syndrome (ACS) is frequently reported in patients with coronavirus disease 2019 (COVID-19). Cytokine storm induced by interleukin-6 (IL-6) has been suggested to potentially cause myocardial injury in COVID-19. We investigated the association between baseline level of IL-6 and development of ACS in COVID-19 patients. METHODS: Demographic and clinical data of hospitalized COVID-19 patients from 2020 to 2022 were reviewed. Extracted data including patient characteristics, laboratory biomarkers, and systemic inflammation indexes in patients with or without ACS were reviewed and analyzed. Logistic regression models were applied to analyze predictors of ACS development and receiver-operating characteristic (ROC) curves were used to assess discriminatory power of IL-6 and other risk factors for predicting ACS development. RESULTS: Among 1,753 COVID-19 patients, 37 cases experienced ACS and 159 patients without main COVID-19 complications were randomly selected as controls. ACS patients were older (p = 0.001) and suffered from more comorbidities including diabetes (43% vs. 18%, p = 0.001), hypertension (40.5% vs. 24.5%, p = 0.050), ischemic heart disease (49% vs. 9%, p = 0.001), and hyperlipidemia (19% vs. 5%, p = 0.010). Also, decreased level of consciousness (31.6% vs. 2.5%, p = 0.001), ICU admission (65% vs. 2%, p = 0.001), and mortality events (70% vs. 0.6%, p = 0.001) were more prevalent in the ACS group. Baseline levels of IL-6 (p = 0.001), D-dimer (p = 0.026), troponin (p = 0.001), blood urea nitrogen (p = 0.002), and creatinine (p = 0.008) were higher in ACS patients but erythrocyte sedimentation rate (p = 0.013), hemoglobin (p = 0.033), and red blood cells (p = 0.028) were lower compared with controls. Also, age (OR: 1.06, p = 0.019), IL-6 (OR: 1.44, p = 0.047), and cardiovascular disease (CVD) (OR: 3.66, p = 0.043) were associated with ACS development. The area under the curve (AUC) of IL-6 and combined predictors respectively was 0.661 (p = 0.002) and 0.829 (p = 0.001). CONCLUSIONS: High IL-6 concentration at baseline is a strong predictor for ACS development in COVID-19 patients. Also, elderly and concurrent CVD are significantly associated with ACS development.

Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function.

This study aimed to assess plasma galectin-9 (Gal-9) and artemin (ARTN) concentrations as potential biomarkers to differentiate individuals with Long COVID (LC) patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) from SARS-CoV-2 recovered (R) and healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis determined a cut-off value of plasma Gal-9 and ARTN to differentiate LC patients from the R group and HCs in two independent cohorts. Positive correlations were observed between elevated plasma Gal-9 levels and inflammatory markers (e.g. SAA and IP-10), as well as sCD14 and I-FABP in LC patients. Gal-9 also exhibited a positive correlation with cognitive failure scores, suggesting its potential role in cognitive impairment in LC patients with ME/CFS. This study highlights plasma Gal-9 and/or ARTN as sensitive screening biomarkers for discriminating LC patients from controls. Notably, the elevation of LPS-binding protein in LC patients, as has been observed in HIV infected individuals, suggests microbial translocation. However, despite elevated Gal-9, we found a significant decline in ARTN levels in the plasma of people living with HIV (PLWH). Our study provides a novel and important role for Gal-9/ARTN in LC pathogenesis.

Invasive Fungal Infections in Immunocompromised Conditions: Emphasis on COVID-19.

The COVID-19 pandemic caused death of 6 million lives globally, primarily from respiratory failure, but also a significant number from invasive fungal co-infections in these patients, owing to the immune dysfunction in hospitalized patients. Such complications occurred more often in critically ill, hospitalized patients particularly those admitted in intensive care units and were reported as the major reason associated with a high mortality rate worldwide. Fungal pathogens most commonly associated with COVID-19 patients comprise members of the Mucorales (such as Rhizopus, Mucor, and Lichtheimia), as well as genera Aspergillus and Candida. In India, the prevalence rate of mucormycosis is relatively high than aspergillosis and candidiasis, and the predisposing risk factors associated with such infections included uncontrolled diabetes, underlying lung disease, leukopenia, neutropenia, malignancies and prolonged steroid therapy. However, co-infection with other fungi, including Alternaria and Scedosporium was also sporadically reported. These devastating invasive fungal infections are associated with differential mortality (high-low) and morbidity rates even after active management. The diagnosis of such infections is often challenging due to lack of sensitivity in contemporary diagnostic methods and poses an enormous challenge to healthcare experts. Thus, the role of early and accurate diagnosis, and management of such fungal infections, is vital in preventing life-threatening situations. Hence, this review focusses primarily on the epidemiology, predisposing risk factors, host environment, diagnosis and treatment of the most common medically important invasive fungal infections in immunocompromised conditions associated with COVID-19.

SSRI use during acute COVID-19 and risk of long COVID among patients with depression.

BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication. METHODS: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates. RESULTS: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)). CONCLUSIONS: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Association of self-reported periodontal disease and inequities with long haul COVID-19.

In 2000, the Surgeon General's report highlighted that the mouth is a mirror for overall health of an individual and that disparities in oral health are directly proportionate to general health inequities. Among patients hospitalized due to COVID-19, diabetes and cardiovascular disease are the most common comorbidities; several studies support the association of these conditions with periodontal disease. This study's main aim is to assess the disproportionate impact of the COVID-19 pandemic on populations from lower socioeconomic statuses. The study also aims to assess the association of self-reported periodontal disease with COVID-19 disease course and severity. A sample population of Indiana residents with positive diagnosis of SARS-CoV-2 were recruited. A validated survey tool was sent to this cohort inquiring about sociodemographic distribution; co-morbid conditions, current symptoms of "long haul COVID," course of their COVID-19 infection; history of periodontal disease, existing periodontal disease symptoms, and oral hygiene habits. 209 individuals with a history of positive COVID test were returned to the survey, and association of participant characteristics and periodontal disease-related survey items with COVID-related survey items were evaluated using chi-square tests. Lower sense of smell ratings was associated with less education (p = 0.021), being unemployed/disabled (p = 0.008), worse health status (p<0.001), more frequent bleeding gums (p = 0.031), more frequent toothache (p<0.001), lower oral health rating (p = 0.002), and vaccine status (p = 0.011). Lower sense of taste ratings were associated with older age (p = 0.018), worse health (p<0.001), more frequent bleeding gums (p<0.001), more frequent mobile or loose tooth (p = 0.010), presence of gum disease (p<0.001), more frequent loss of teeth (p = 0.013), more frequent toothache (p<0.001), worse oral health (p = 0.001), teeth lost due to gum disease (p = 0.006), and vaccine status (p = 0.001). History of hospitalization due to COVID-19 was found to be associated with a history of gum disease within the past 12 months.

Coronavirus-disease-2019-associated Stevens-Johnsons syndrome in a 15-year-old boy: a case report and review of the literature.

BACKGROUND: Stevens-Johnson syndrome (SJS) is a life-threatening condition characterized by high fever and severe mucocutaneous lesions, often triggered by drugs or infection. During the coronavirus disease 2019 pandemic, there was a marked increase in Stevens-Johnson syndrome cases, but relatively few cases were reported in children. The present article reports a pediatric case of Stevens-Johnson syndrome due to coronavirus disease 2019 infection and provides a review of the most relevant literature. CASE PRESENTATION: A previously healthy 15-year-old Han Chinese boy from China presented to the hospital with oral ulcers, conjunctival hyperemia, and widespread maculopapular rash. He had a history of fever 9 days prior and tested positive for coronavirus disease 2019 infection. Upon admission, his rash and mucosal lesions worsened, with the development of blisters on the fingertips of both hands, ocular pain, photophobia, and erosive lesions on the genital mucosa with exudation. He was diagnosed with Stevens-Johnson syndrome and received treatment with methylprednisolone, intravenous immunoglobulin, and dermatological and mucosal care. The patient's condition was managed, and the dosage of high-dose intravenous methylprednisolone was tapered down, followed by a transition to oral prednisolone. He was discharged without sequelae. CONCLUSION: We should be aware that coronavirus disease 2019 infection is associated with the development of Stevens-Johnson syndrome in children and may lead to a wide spectrum of dermatologic presentations. Although Stevens-Johnson syndrome is a relatively rare condition, given its potentially serious consequences, it is crucial to identify it as early as possible and to take appropriate preventive and therapeutic measures to reduce complications and improve the quality of life for patients.

Persistence of Coronavirus Disease 2019 Symptoms in Postacute Phase: Does Age, Sex, Comorbidities, and Severity of Infection Have an Impact?

BACKGROUND AND OBJECTIVE: Post-coronavirus disease (COVID) persistence of symptoms and the development of complications have become frequently encountered clinical problems due to multiple waves of the pandemic over the past 3 years across the world. Identifying risk factors would enable us to direct our limited resources toward the subgroups requiring long-term follow-up and treatment. With this prospective observational study, we aim to establish a statistical correlation between the persistence of symptoms and four of the most attributed risk factors for prolonged recovery: severity of acute illness, elderly age, presence of multiple comorbidities, and female gender in the Indian population. MATERIALS AND METHODS: Three hundred patients with positive COVID reverse transcription polymerase chain reaction (RTPCR) or antigen tests were enrolled over 10 months (from December 2020, after obtaining ethical clearance, to October 2021). Symptoms were recorded at baseline and followed up with a predesigned questionnaire to assess their persistence at 1-, 2-, and 4-month intervals post-COVID recovery. Appropriate statistical analysis [Pearson's correlation/analysis of variance (ANOVA) test] was used to establish the correlation between the persistence of symptoms and their severity with the presence of risk factors. RESULTS: Severity of acute illness was the single most important determining factor of persistence of symptoms as well as their severity in our study (p < 0.001) at each follow-up interval. The correlation observed between average number or severity of persistent symptoms increased with female gender, increasing age-group and presence of multiple comorbidities was not significant statistically (p > 0.05) with exception of persistent fatigue in females at 2-month interval. INTERPRETATION AND CONCLUSION: Persistent symptoms and its prevalence recorded so far represents tip of the iceberg of patients suffering with long COVID. Patients with history of severe acute illness should be followed up closely for prompt identification and rehabilitation of these cases as it had maximum bearing on the outcome of these patients.

Coronavirus Disease-19-associated Mucormycosis: A Single-center Observational Study of 69 Patients.

BACKGROUND AND OBJECTIVES: We studied the clinical presentation, risk factors, complications, and in-hospital outcomes of patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM). MATERIALS AND METHODS: A retrospective study was done on 69 COVID-19 patients with microbiologically proven mucormycosis admitted over a period of seven months from March 2021 to September 2021. RESULTS: All 69 mucormycosis patients (46 males, 23 females) had reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 infection. Their mean age was 52.8 years, with mucormycosis developing in 51 patients (73.9%) within 30 days of COVID-19 infection; 7 (10.1%) were positive on admission. Rhino-orbital-cerebral mucormycosis (ROCM) was the most common (40.3%), followed by rhino-orbital (37.3%) and sinonasal (22.4%). Diabetes mellitus was present in 98.6% of patients. Common symptoms of mucormycosis were facial pain, headache, facial swelling, and vision loss. During COVID-19, 88.4 and 52.5% received immunosuppressive treatment and zinc sulfate, respectively; 34.7% needed intensive care unit (ICU) admission. The mortality rate was 26.1%. On multivariate logistic regression analysis, the presence of chronic kidney disease, leukocytosis, ophthalmoplegia, oral/palate ulceration, current need for invasive ventilation, and past duration of oxygen therapy and zinc supplementation were significantly associated with mortality. Patients with current COVID-19 infection had severe disease with increased need for intensive care (57.1 vs 14.5%) and higher mortality (57.1 vs 22.6%) compared to mucormycosis patients with previous COVID-19 infection. INTERPRETATION AND CONCLUSION: Rhino-orbital-cerebral, rhino-orbital, and sinonasal were the most common presentations in cases of mucormycosis, with a mortality rate of 26.1%. COVID-19 coinfection predisposes patients with mucormycosis to severe disease with higher mortality.

Candidemia Following Severe COVID-19 in Hospitalised and Critical Ill Patients: A Systematic Review and Meta-Analysis.

RATIONALE: The epidemiology and clinical impact of COVID-19-associated candidemia (CAC) remained uncertain, leaving gaps in understanding its prevalence, risk factors and outcomes. METHODS: A systematic review and meta-analysis were conducted by searching PubMed, Embase and Scopus for reports of CAC prevalence, risk factors and clinical outcomes up to June 18, 2024. The generalised linear mixed model was employed to determine the prevalence and 95% confidence intervals (CIs). The risk factors and clinical outcomes were compared between patients with and without CAC using the inverse variance method. RESULTS: From 81 studies encompassing 29 countries and involving 351,268 patients, the global prevalence of CAC was 4.33% (95% Cl, 3.16%-5.90%) in intensive care unit (ICU) patients. In ICUs, the pooled prevalence of CAC in high-income countries was significantly higher than that of lower-middle-income countries (5.99% [95% Cl, 4.24%-8.40%] vs. 2.23% [95% Cl, 1.06%-4.61%], p = 0.02). Resistant Candida species, including C. auris, C. glabrata (Nakaseomyces glabratus) and C. krusei (Pichia kudriavzveii), constituted 2% of ICU cases. The mortality rate for CAC was 68.40% (95% Cl, 61.86%-74.28%) among ICU patients. Several risk factors were associated with CAC, including antibiotic use, central venous catheter placement, dialysis, mechanical ventilation, tocilizumab, extracorporeal membrane oxygenation and total parenteral nutrition. Notably, the pooled odds ratio of tocilizumab was 2.59 (95% CI, 1.44-4.65). CONCLUSIONS: The prevalence of CAC is substantial in the ICU setting, particularly in high-income countries. Several risk factors associated with CAC were identified, including several that are modifiable, offering the opportunity to mitigate the risk of CAC.

Association between thyroid function and prognosis of severe COVID-19 among patients with SARS-CoV-2 infection: a retrospective cohort study in China.

Objective: This study aims to examine the thyroid hormone profile and its association with severe coronavirus disease 2019 (COVID-19) in patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This retrospective cohort study enrolled patients admitted to a tertiary hospital due to SARS-CoV-2 infection between February 18 and May 18, 2022. Clinical data were collected retrospectively from the electronic medical record system. Based on the thyroid function, patients were divided into five groups: normal, non-thyroid illness syndrome (NTIS), hypothyroidism, thyrotoxicosis, and unclassified. The association between thyroid function and severe COVID-19 was detected using multivariable logistic regression and restricted cubic splines analysis. Results: This study included 3,161 patients, with 7.7% of them developing severe COVID-19. 44.9% of the patients had normal thyroid function, 36.5% had NTIS, 6.7% had hypothyroidism, and 1.0% had thyrotoxicosis on admission. After adjusting for age, sex, and relevant clinical characteristics, NTIS and hypothyroidism were associated with increased risks of severe COVID-19 (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.59-3.56 and OR 2.29, 95% CI 1.23-4.26, respectively), compared to normal thyroid function group. Among patients with NTIS or hypothyroidism, higher levels of total triiodothyronine (TT3) are associated with lower risks of severe COVID-19 (OR 0.73, 95% CI 0.64-0.82, for every 0.1nmol/L increase in TT3 level). Conclusion: Thyroid hormone profiles of NTIS or hypothyroidism are associated with increased risks of severe COVID-19. The decreased level of TT3 correlated with the increased risk of severe COVID-19 in patients with NTIS or hypothyroidism.

The prognostic role of Neurologic Pupil Index in COVID-19 patients: a retrospective study.

BACKGROUND: Neurological complications have been observed in approximately 30% of hospitalized COVID-19 patients. The aim of this study was to evaluate whether early assessment of the Neurological Pupil Index (NPiTM) derived from an automated pupillometry could predict mortality in critically ill COVID-19 patients. METHODS: Retrospective cohort study of adult critically ill COVID-19 patients admitted to the intensive care unit of a University Hospital; patients without NPi measurement were excluded. The worst NPi (i.e. lowest value from one eye) was collected daily and then computed over the first five days of assessment. Mortality was assessed at hospital discharge. The secondary endpoint involved assessing differences in neurological assessments between patients who developed neurological complications and those who did not. RESULTS: A total of 217 patients were included over the study period (median age 61 [50-68] years), 70% were males. A total of 97 patients (45%) died during the hospital stay. Among all patients, 35 (16%) experienced neurological complications. Non-survivors showed significantly a lower overall NPi (3.0 [2.0-4.1] vs. 3.4 [2.7-4.2]; P=0.04) than survivors. At multivariate logistic regression NPi was not significantly associated with in-hospital mortality. Moreover, no differences in different NPi measurements were observed between patients with and without neurological complications. CONCLUSIONS: In this study, NPi values were not independent predictor of mortality and neurological complications in critically ill COVID-19 patients.