Resting-state EEG rhythms are abnormal in post COVID-19 patients with brain fog without cognitive and affective disorders.

OBJECTIVES: Several persons experiencing post-covid-19 (post-COVID) with "brain fog" (e.g., fatigue, cognitive and psychiatric disorders, etc.) show abnormal resting-state electroencephalographic (rsEEG) rhythms reflecting a vigilance dysfunction. Here, we tested the hypothesis that in those post-COVID persons, abnormal rsEEG rhythms may occur even when cognitive and psychiatric disorders are absent. METHODS: The experiments were performed on post-COVID participants about one year after hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inclusion criteria included a "brain fog" claim, no pre-infection, and actual organic chronic disease. Matched controls (no COVID) were also enrolled. All participants underwent clinical/neuropsychological assessment (including fatigue assessment) and rsEEG recordings. The eLORETA freeware estimated regional rsEEG cortical sources at individual delta (<4 Hz), theta (4-7 Hz), and alpha (8-13 Hz) bands. Beta (14-30 Hz) and gamma (30-40 Hz) bands were pre-fixed. RESULTS: More than 90% of all post-COVID participants showed no cognitive or psychiatric disorders, and 75% showed ≥ 2 fatigue symptoms. The post-COVID group globally presented lower posterior rsEEG alpha source activities than the Control group. This effect was more significant in the long COVID-19 patients with ≥ 2 fatigue symptoms. CONCLUSIONS: In post-COVID patients with no chronic diseases and cognitive/psychiatric disorders, "brain fog" can be associated with abnormal posterior rsEEG alpha rhythms and subjective fatigue. SIGNIFICANCE: These abnormalities may be related to vigilance and allostatic dysfunctions.

Health-related quality of life in survivors of severe COVID-19 infection.

BACKGROUND: Long-term effects of Coronavirus Disease 2019 (COVID-19) are increasingly recognized as having a significant impact on Health-Related Quality of Life (HRQoL). Understanding HRQoL status for each patient affected by long COVID-19 and its determinants may have a key role to prevent and treat this condition. METHODS: In this prospective observational study conducted in a large academic COVID-19 hospital in Rome, participants were contacted 2 years after hospital admission for severe COVID-19. To assess HRQoL, EQ-5D-5L and Visual analog scale (EQ VAS) standard questionnaires were administered by interview. Logistic regression model was used to the five health dimensions as dependent variables (0 = no problem, 1 = some/extreme problem). KEY RESULTS: In 137 enrolled patients, the mean pre-COVID and post-COVID EQ-5D-5L index and EQ-VAS score were 0.97 (SD 0.06), 0.79 (SD 0.26) and 72.38 (SD 15.18), respectively. After subdivision of the participants for clinical and social variables, the EQ-5D-5L index resulted significantly lower than in the pre-COVID-19 period. Female gender, unemployed status, and chronic comorbidities were the most common predictors for having any problems in each EQ-5D-5L domain, while also older age and higher Body Mass Index (BMI) showed to be related to a lower EQ-VAS score. CONCLUSION: HRQoL showed to be still low in patients 2 years after acute severe COVID-19. Given the significant impact of SARS-CoV-2 on long-term chronic symptoms, predictors of poor outcomes must be considered during the acute phase of illness to plan a tailored follow-up path for each patient.

Exploiting Bacteria for Improving Hypoxemia of COVID-19 Patients.

BACKGROUND: Although useful in the time-race against COVID-19, CPAP cannot provide oxygen over the physiological limits imposed by severe pulmonary impairments. In previous studies, we reported that the administration of the SLAB51 probiotics reduced risk of developing respiratory failure in severe COVID-19 patients through the activation of oxygen sparing mechanisms providing additional oxygen to organs critical for survival. METHODS: This "real life" study is a retrospective analysis of SARS-CoV-2 infected patients with hypoxaemic acute respiratory failure secondary to COVID-19 pneumonia undergoing CPAP treatment. A group of patients managed with ad interim routinely used therapy (RUT) were compared to a second group treated with RUT associated with SLAB51 oral bacteriotherapy (OB). RESULTS: At baseline, patients receiving SLAB51 showed significantly lower blood oxygenation than controls. An opposite condition was observed after 3 days of treatment, despite the significantly reduced amount of oxygen received by patients taking SLAB51. At 7 days, a lower prevalence of COVID-19 patients needing CPAP in the group taking probiotics was observed. The administration of SLAB51 is a complementary approach for ameliorating oxygenation conditions at the systemic level. CONCLUSION: This study proves that probiotic administration results in an additional boost in alleviating hypoxic conditions, permitting to limit on the use of CPAP and its contraindications.

Post-Traumatic Stress Disorder Trajectories the Year after COVID-19 Hospitalization.

Background: Coronavirus disease (COVID-19) hospitalization has been related to Post-Traumatic Stress Disorder (PTSD). Available information is limited by insufficient follow-up and lack of longitudinal studies. Baseline factors (e.g., sex; obesity) have been related to PTSD, but post-hospitalization factors have not been studied. Objective: This study aimed to analyse prevalence, baseline, post-discharge factors and possible clinical courses of PTSD after hospitalization for COVID-19. Method: 109 patients (94.7% of the original sample) completed a programme of three follow-up telephone assessments during the year following hospitalization. Data included clinical and sociodemographic factors as well as psychometric tools assessing PTSD, social support, and perception of threat to life (PTL). Mixture model analysis was performed to study the longitudinal course of PTSD symptoms. Chronic (>6 months) PTSD predictors were also analysed. Results: 1-year PTSD period prevalence was 23.9%, peaking at six months; 11% of the patients suffered chronic PTSD. Pre- and post-hospitalization factors influenced the onset and course of PTSD over time. These included working status, PTL, and lack of social support. Interestingly, obesity, pulmonary diseases and family cluster infection seem specifically related to PTSD following COVID-19. Inversely, clinical interventions, older age and male gender were protective. Conclusions: PTSD following COVID-19 hospitalization is common. The analysed demographic, social, clinical, and psychological factors predict PTSD symptomatology over time and can modify odds of a chronic course. Clinicians could better identify cases at risk of a chronic PTSD course. Finally, treatment as usual appeared related to a better outcome and should be proposed to patients with PTSD.

SARS-CoV-2 Among Migrants Recently Arrived in Europe From Low- and Middle-Income Countries: Containment Strategies and Special Features of Management in Reception Centers.

Despite the "migrants and COVID-19" topic has been neglected since felt marginal concerning other aspects of the SARS-CoV-2 pandemic, it represents a relevant public health issue in the European countries. This report describes COVID-19 containment strategies adopted in a large Italian reception center hosting recently arrived asylum-seeker migrants. Risk assessment and prevention measures adopted were described. Geo-spatial epidemiological analysis of the outbreak was reported. Significant gaps in the knowledge of self-protection measures from contagious diseases and in the perception of the pandemic risk were observed in migrants; health promotion activities, targeted to remove cultural barriers and improve behaviors appropriate to individual protection, were able to fulfill this gap. In low-resource settings, especially in closed communities, the implementation of social distancing strategies, the systematic use of individual protection devices, and active syndromic surveillance are essential tools to limit the risk of outbreaks. In the event of an outbreak, it is relevant to rapidly activate containment procedures based on systematic screening, isolation, and quarantine, taking into consideration the limits of tracing contacts within a closed community. Not being able to trace certain contacts, the geo-spatial epidemiological analysis of cases distribution could be key in the management of the outbreak. Interestingly, positive cases identified in our facility were all clinically pauci-symptomatic or asymptomatic. Dedicated strategies are needed to minimize the chance of SARS-CoV-2 transmission in a limited space such as reception centers and a vulnerable population such as migrants.

Depressive Symptoms among Individuals Hospitalized with COVID-19: Three-Month Follow-Up.

Individuals affected by Coronavirus Disease 2019 (COVID-19) may experience psychiatric symptoms, including depression and suicidal ideation, that could lead to chronic impairment and a reduction in quality of life. Specifically, depressive disorder shows high incidence and may lead to chronic impairment and a reduction in the quality of life. To date, no studies on the presence of suicidality and quantitative analysis of depressive symptoms and their risk factors have yet been published. In this study, we aim to assess the prevalence of depressive symptoms and related risk factors at 3 months after discharge to home care following hospitalization for COVID-19 infection. METHODS: Participants were contacted three months after hospital discharge from one of the five COVID-19 hospitals in Rome, as part of a larger project on health outcomes in COVID-19 inpatients (Long Term Neuropsychiatric Disorder in COVID-19 Project), and the Patient Health Questionnaire-9 (PHQ-9) was administered by telephone interview. RESULTS: Of 115 participants, 14.8% (N = 17) received a PHQ-9-based diagnosis of depression, and n = 7 of them scored 1 or more on the item on suicidality. A linear regression model showed the predictive role of female sex, pulmonary chronic condition and previous mental disorder in the development of depressive disorder; the latter was confirmed also by binary logistic regression. Severity indexes of disease (length of hospitalization and intensive care treatment) were found not to be associated with the development of depressive symptoms. CONCLUSIONS: A small but clinically meaningful number of participants in the current study reported that they experienced symptoms of depression and suicidal ideation 3 months post-discharge from their COVID-19 hospitalization. In particular, given the findings that a history of prior psychiatric disorders was predictive of the development of depression symptoms, clinicians should carefully monitor for the presence of all psychiatric symptoms at follow-up visits.

Antiretroviral Therapy Dampens Mucosal CD4+ T Lamina Propria Lymphocytes Immune Activation in Long-Term Treated People Living with HIV-1.

HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.

Alteration of type I interferon response is associated with subclinical atherosclerosis in virologically suppressed HIV-1-infected male patients.

Given human immunodeficiency virus-1 (HIV-1)-infected patients have alterations in the type I interferon (IFN-I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN-I response and subclinical cardiovascular disease (CVD) association in HIV-1-infected patients. Transcript levels of IFN-α/ß and IFN-stimulated gene 56 (ISG56) were evaluated by RT/real-time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV-1-positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or <50%), calcium volume score, calcium Agatston score, and myocardial extracellular volume were examined by coronary computerized tomography scan. Carotid intima-media thickness (cIMT), Framingham risk score, atherosclerotic cardiovascular disease (ASCVD) score, and risk score developed by data collection on adverse effects of anti-HIV drugs (D:A:D) were also measured. Increased IFN-α, IFN-ß, and ISG56 levels were observed in all HIV-1-infected males compared to healthy controls (p < .001 for all genes analyzed). HIV-1-infected patients with a stenosis degree ≥50% showed a higher Framingham risk score (p = .019), which was correlated with IFN-ß and ISG56 levels. HIV-1-infected males with enhanced IFN-I levels and stenosis displayed a higher ASCVD calculated risk (p = .011) and D:A:D score (p = .004). Also, there was a trend toward higher IFN-α and ISG56 mRNA levels in HIV-1-positive patients with an increased cIMT (p > .05). Dysregulation of IFN-I response might participate in the pathogenesis of HIV-1-associated CVD.

Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection.

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.

Post-traumatic Stress Disorder Among COVID-19 Survivors at 3-Month Follow-up After Hospital Discharge.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe but treatable mental disorder that develops after a life-threatening traumatic event. Coronavirus disease 19 (COVID-19) hospitalisation is a potentially traumatic experience, especially in severe cases. Furthermore, the unprecedented context of the severe acute respiratory syndrome coronavirus 2 pandemic, with daily media bombardment about COVID-19 mortality, may have amplified life-threatening perception also in patients with moderate infection. The aim of this study was to assess the prevalence and risk factors of PTSD at 3-month follow-up in patients hospitalised for COVID-19 infection. DESIGN: In this cohort follow-up study conducted in a large Italian academic COVID-19 hospital, 115 recruited survivors were contacted by telephone 3 months after discharge to home care. The Posttraumatic Stress Disorder Checklist for DSM-5 was administered. Multivariate logistic regression models were used to analyse risk factors for the development of PTSD. KEY RESULTS: A total of 10.4% of the sample received a PCL-5-based diagnosis of PTSD. Other 8.6% of the sample received a diagnosis of subthreshold PTSD, which leads to significant levels of distress and impairment. Multivariate regression analysis indicated that previous psychiatric diagnosis (odds ratio (OR) = 6.3, 95% confidence interval (CI): 3.7-78.6, p < 0.001) and obesity (OR = 3.51, 95% CI: 1.4-857.9, p = 0.03) were risk factors for developing PTSD. Chronic pulmonary diseases approached significance as a risk factor (OR = 6.03, 95% CI: 1.0-37.1, p = 0.053). Male sex was a protective factor (OR=0.04, 95% CI: 0.0-0.041, p = 0.007). CONCLUSIONS: PTSD and subthreshold PTSD rates in patients hospitalised for COVID-19 are worrying. Female sex and pre-existing mental disorders are established risk factors for PTSD, while the prospective association with obesity needs further investigation. Clinicians treating COVID-19 should consider screening for PTSD at follow-up assessments in patients discharged from the hospital.

Post-Traumatic Stress Symptoms in Healthcare Workers Dealing with the COVID-19 Pandemic: A Systematic Review.

Prevention of post-traumatic stress symptoms (PTSS) in healthcare workers (HCWs) facing the current COVID-19 pandemic is a challenge worldwide as HCWs are likely to experience acute and chronic, often unpredictable, occupational stressors leading to PTSS. This review aims to analyze the literature to discover which topics have been focused on and what the latest developments are in managing the occupational risk of PTSS in HCWs during the current pandemic. For the purpose of this review, we searched for publications in MEDLINE/Pubmed using selected keywords. The articles were reviewed and categorized into one or more of the following categories based on their subject matter: risk assessment, risk management, occurrence rates. A total of 16 publications matched our inclusion criteria. The topics discussed were: "Risk Assessment", "Occurrence Rates", and "Risk Management". Young age, low work experience, female gender, heavy workload, working in unsafe settings, and lack of training and social support were found to be predictors of PTSS. This review's findings showed the need for urgent interventions aimed at protecting HCWs from the psychological impact of traumatic events related to the pandemic and leading to PTSS; healthcare policies need to consider preventive and management strategies toward PTSS, and the related psychic sequelae, in HCWs.

Oral Bacteriotherapy Reduces the Occurrence of Chronic Fatigue in COVID-19 Patients.

Long COVID refers to patients with symptoms as fatigue, "brain fog," pain, suggesting the chronic involvement of the central nervous system (CNS) in COVID-19. The supplementation with probiotic (OB) would have a positive effect on metabolic homeostasis, negatively impacting the occurrence of symptoms related to the CNS after hospital discharge. On a total of 58 patients hospitalized for COVID-19, 24 (41.4%) received OB during hospitalization (OB+) while 34 (58.6%) taken only the standard treatment (OB-). Serum metabolomic profiling of patients has been performed at both hospital acceptance (T0) and discharge (T1). Six months after discharge, fatigue perceived by participants was assessed by administrating the Fatigue Assessment Scale. 70.7% of participants reported fatigue while 29.3% were negative for such condition. The OB+ group showed a significantly lower proportion of subjects reporting fatigue than the OB- one (p < 0.01). Furthermore, OB+ subjects were characterized by significantly increased concentrations of serum Arginine, Asparagine, Lactate opposite to lower levels of 3-Hydroxyisobutirate than those not treated with probiotics. Our results strongly suggest that in COVID-19, the administration of probiotics during hospitalization may prevent the development of chronic fatigue by impacting key metabolites involved in the utilization of glucose as well as in energy pathways.

Hepatitis B and HIV coinfection in Northern Uganda: Is a decline in HBV prevalence on the horizon?

BACKGROUND: The available data concerning hepatitis B virus (HBV) infection in Uganda are limited, particularly in the case of people living with HIV/AIDS (PLWH). HBV is not routinely tested when starting antiretroviral therapy (ART). We aimed to determine the prevalence, the correlates of the risk of HBV infection, and the association with outcomes of ART among PLWH attending a busy HIV clinic in a referral hospital in Northern Uganda. PATIENTS AND METHODS: From April to June 2016, a random sample of 1000 PLWH attending the outpatients' clinic of St. Mary's Hospital, Gulu, Uganda were systematically selected to undergo a rapid hepatitis B surface antigen (HBsAg) test after administering a questionnaire in this cross-sectional study. HIV care parameters were obtained from client files. Multivariate logistic regression and general linear model were used for the analysis. RESULTS: 950 of the 985 evaluable patients (77% females; mean age 42.8 years) were receiving ART. The overall prevalence of HBsAg was 7.9% (95% confidence interval [CI] 6.2-9.6%), and was significantly lower among the females (6.8% vs 11.7%; p = 0.020). The factors independently associated with higher HBV infection were having lived in an internally displaced persons' camp (adjusted odds ratio [aOR] 1.76, 95% CI 1.03-2.98; p = 0.036) and having shared housing with HBV-infected people during childhood (aOR 3.30, 95% CI 1.49-7.32; p = 0.003). CD4+ T cell counts were significantly lower in HBV patients (p = 0.025), and co-infection was associated with a poorer CD4+ T cell response to ART (AOR 0.88; 95% CI 0.79-0.98; p = 0.030). CONCLUSIONS: The observed prevalence of HBV among the PLWH may be underestimated or a signal of HBV decline in the region. The factors favouring horizontal HBV transmission identified suggest extending HBV screening and vaccine prophylaxis among PLWH.

Infected chronic ischemic wound topically treated with a multi-strain probiotic formulation: a novel tailored treatment strategy.

BACKGROUND: A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor. AIM: CLINICAL REPORT: An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria. METHODS: Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy. RESULTS: During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy. CONCLUSION: The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings.

Aseptic meningitis induced by intravenous immunoglobulins in a child with acute Epstein-Barr virus infection and thrombocytopenia.

Drug-induced aseptic meningitis (DIAM) represents a diagnostic challenge since clinical and cerebrospinal fluid (CSF) findings may be indistinguishable from a bacterial meningitis. Intravenous immunoglobulin (IVIg) are commonly used in a variety of diseases, including inflammatory and autoimmune disorders. Although usually well-tolerated, various adverse effects have been reported. DIAM is a serious neurological side effect of IVIg therapy: albeit rare (0.067% of all IVIg infusions), the condition represents an important diagnostic challenge and should be considered by physicians. Here we report a case of an aseptic meningitis induced by IVIg therapy in a child with acute Epstein-Barr virus (EBV) infection and thrombocytopenia.

Effect of Legal Status on the Early Treatment Outcomes of Migrants Beginning Combined Antiretroviral Therapy at an Outpatient Clinic in Milan, Italy.

OBJECTIVE: In a setting of free access to HIV care, we compared the early treatment outcomes of HIV-infected undocumented migrants (UMs), documented migrants (DMs), and Italian subjects. METHODS: The clinical data of 640 Italians and 245 migrants who started combined antiretroviral therapy (cART) at an HIV clinic in Milan, Italy, were reviewed. The migrants were mainly Latin Americans (83 DMs and 56 UMs) or sub-Saharan Africans (52 DMs and 11 UMs), but a minority were of other origin (33 DMs and 10 UMs). Retention in follow-up and HIV suppression were compared between UMs, DMs, and natives 12 months ± 90 days after start of cART. RESULTS: There were no significant between-group differences in the stage of HIV infection at the start of cART or the type of regimen received. The Latin American DMs and UMs included a higher proportion of transgender women than the other ethnic groups (P < 0.001). The UMs were less frequently followed up after 12 months than the DMs and natives (P = 0.004) and were more frequently permanently lost to follow-up (P < 0.001). UM status was an independent predictor of lost to follow-up (adjusted odds ratio 8.05, P < 0.001). The DMs and UMs were less frequently HIV suppressed after 12 months than the natives (78% and 80.7% vs 90.5%, P = 0.001), and Latin American migrants were significantly less likely to be virologically suppressed than the natives (adjusted odds ratio 0.30, P = 0.001). CONCLUSIONS: Despite their free access to cART, subgroups of migrants facing multiple levels of vulnerability still have difficulties in gaining optimal HIV care.