Fatigue is one of the most commonly reported symptoms in the context of the post-COVID-19 syndrome. Notably, fatigue is characterised by overlapping physical and psychopathological symptoms, and ...questions about its trajectory over time and possible predictors remained unanswered. Thus, in the present study we aim to investigate the prevalence, the course over time, and the risk factors of post-COVID fatigue.
We included 495 patients recovered from COVID-19. For all of them we collected one month demographic, clinical and psychopathological characteristics. We evaluated fatigue severity at one, three, six, and twelve-months according to Fatigue Severity Scale (FSS). We explored the potential predictor of long-term post-COVID fatigue (six or twelve months FSS) by implementing 5000 non-parametric bootstraps enhanced elastic net penalised regression.
We found that 22%, 27%, 30%, and 34% of patients self-rated fatigue symptoms in the pathological range at one, three, six, and twelve months respectively. We detected a worsening of fatigue symptomatology over time. From the elastic net regression results, only depressive symptomatology at one month (ZSDS and BDI-13) predicted the presence of post-COVID-19 long-term fatigue. No other clinical or demographic variable was found to predict post-COVID fatigue.
We suggest that, rather independent of COVID-19 severity, depression after COVID-19 is associated with persistent fatigue. Clarifying mechanisms and risk factors of post-COVID fatigue will allow to identify the target population and to tailor specific treatment and rehabilitation interventions to foster recovery.
Abstract
Pathogenesis of endometriosis is still unclear and a role of both innate and adaptive immune system has been postulated. Some recent findings have revealed an increased risk to have ...concomitant autoimmune disease in women with endometriosis, but no study so far has investigated whether this association could affect endometriosis severity and stage. We retrospectively reviewed medical patients’ notes of women with a confirmed diagnosis of endometriosis who referred to our endometriosis outpatient clinic between January 2015 and December 2019. Cases (endometriosis and an autoimmune disease) were matched in a 1:3 ratio by age and study period with controls (endometriosis without history of autoimmunity). At univariate logistic analysis, concomitant autoimmunity (OR 2.63, 95% CI 1.64–4.21, p < 0.001) and the number of laparoscopic procedures performed (OR 2.81, 95% CI 1.45–5.43, p = 0
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002) emerged as factors significantly associated with the likelihood of stage IV endometriosis. In the multivariate logistic regression model, concomitant autoimmunity remained a significant predictor of stage IV endometriosis (OR 2.54, 95% CI 1.57–4.10, p = 0.004), whereas the association between the number of laparoscopic procedures performed and stage IV endometriosis was found to be of borderline-significance (OR 2.70, 95% 1.37–5.30, p = 0.050). Our findings suggest that endometriosis is more severe in patients who are also affected by autoimmune disturbances after controlling for relevant confounders.
A high prevalence of vitamin D (VD) deficiency in COVID-19 patients has been reported and hypothesized to increase COVID-19 severity likely because of its negative impact on immune and inflammatory ...responses. Furthermore, clear associations between hypovitaminosis D and fat body mass excess and diabetes, factors associated with COVID-19 severity, have been widely recognized.
The aim of this study was to evaluate in COVID-19 patients the relationship between VD levels and inflammatory response, body mass index (BMI), blood glucose (GLU), and disease severity.
Patients admitted to San Raffaele-Hospital for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing VD metabolism. 25-Hydroxyvitamin D levels, plasma GLU levels, BMI, and inflammatory parameters were evaluated at admission.
A total of 88 patients were included. Median VD level was 16.3 ng/mL and VD deficiency was found in 68.2% of patients. VD deficiency was found more frequently in male patients and in those affected by severe COVID-19. Regression analyses showed a positive correlation between VD and PaO2/FiO2 ratio, and negative correlations between VD and plasma GLU, BMI, neutrophil/lymphocyte ratio, C-reactive protein, and interleukin 6. Patients with both hypovitaminosis D and diabetes mellitus, as well those with hypovitaminosis D and overweight, were more frequently affected by a severe disease with worse inflammatory response and respiratory parameters, compared to those without or just one of these conditions.
We showed, for the first-time, a strict association of VD levels with blood GLU and BMI in COVID-19 patients. VD deficiency might be a novel common pathophysiological mechanism involved in the detrimental effect of hyperglycemia and adiposity on disease severity.
Drug-induced aseptic meningitis (DIAM) is an uncommon meningitis and trimethoprim with or without sulfamethoxazole is the most involved antibiotic. Although DIAM is easily treated with the ...discontinuation of the causative drug, the diagnosis is a big challenge for physicians, as it remains a diagnosis of exclusion. Here, we present a case report of trimethoprim-sulfamethoxazole induced aseptic meningitis in a woman with acute osteomyelitis.
A 52-year-old woman was admitted to the hospital for septic shock and acute osteomyelitis of the right homerus. She was started on antibiotic therapy with oxacillin and daptomycin, then oxacillin was replaced with cotrimoxazole, due to its excellent tissue penetration, including bone tissue. During cotrimoxazole therapy, the patient developed a fluent aphasia with ideomotor apraxia and muscle hypertonus.
Having excluded infectious, epileptic and vascular causes of the acute neurologic syndrome of our patient, given the improvement and full recovery after discontinuation of cotrimoxazole, we hypothesized a DIAM.
After discontinuation of cotrimoxazole, in 48 hours the patient had a full recovery.
Although DIAM can be easily managed with the withdrawal of the causative drug, it can be difficult to recognize if it is not included in the differential diagnosis. An antimicrobial stewardship program with a strict monitoring of patients by infectious disease specialists is essential, not only to optimize the appropriate use of antimicrobials, but also to improve patient outcomes and reduce the likelihood of adverse events.
SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define ...the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.
The aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19).
This was a cohort study of patients ...hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine–Gray models to assess factors associated with risk of secondary infections.
Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4–21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 109/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11–3.35), baseline PaO2/FiO2 (per 100 points lower: sdHRs 1.56, 95%CI 1.21–2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04–6.05).
Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections.
Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field ...continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold. Here, we present prevailing concepts and state of the science in NET-related research and elaborate on open questions and areas of dispute.
•COVID-19, such as other coronaviruses, is associated with psychiatric implication.•55% of the sample presented a clinical score for at least one mental disorder.•Psychiatric history, setting, and ...length of hospitalization influenced psychopathology.•Females suffered more than males, scoring higher in all the measures.•There is the need to diagnose and treat psychiatric sequelae in COVID-19 survivors.
Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors.
We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels.
A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up.
PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.
Objective
It is unclear why activated platelets and platelet‐derived microparticles (MPs) accumulate in the blood of patients with systemic sclerosis (SSc). This study was undertaken to investigate ...whether defective phagocytosis might contribute to MP accumulation in the blood of patients with SSc.
Methods
Blood samples were obtained from a total of 81 subjects, including 25 patients with SSc and 26 patients with stable coronary artery disease (CAD). Thirty sex‐ and age‐matched healthy volunteers served as controls. Studies were also conducted in NSG mice, in which the tail vein of the mice was injected with MPs, and samples of the lung parenchyma were obtained for analysis of the pulmonary microvasculature. Tissue samples from human subjects and from mice were assessed by flow cytometry and immunochemical analyses for determination of platelet–neutrophil interactions, phagocytosis, levels and distribution of P‐selectin, P‐selectin glycoprotein ligand 1 (PSGL‐1), and HMGB1 on platelets and MPs, and concentration of byproducts of neutrophil extracellular trap (NET) generation/catabolism.
Results
Activated P‐selectin+ platelets and platelet‐derived HMGB1+ MPs accumulated in the blood of SSc patients but not in the blood of healthy controls. Patients with CAD, a vasculopathy independent of systemic inflammation, had fewer P‐selectin+ platelets and a negligible number of MPs. The expression of the receptor for P‐selectin, PSGL‐1, in neutrophils from SSc patients was significantly decreased, raising the possibility that phagocytes in SSc do not recognize activated platelets, leading to a failure of phagocytosis and continued neutrophil release of MPs. As evidence of this process, activated platelets were not detected in the neutrophils from SSc patients, whereas they were consistently present in the neutrophils from patients with CAD. HMGB1+ MPs elicited generation of NETs, which were only detected in the plasma of SSc patients. In mice, P‐selectin–PSGL‐1 interaction resulted in platelet phagocytosis in vitro and influenced the ability of MPs to elicit NETs, endothelial activation, and migration of leukocytes through the pulmonary microvasculature.
Conclusion
The clearance of activated platelets via PSGL‐1 limits the undesirable effects of MP‐elicited neutrophil activation. This balance is disrupted in patients with SSc. Its reconstitution might curb vascular inflammation and prevent fibrosis.
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