Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

publishedVersio

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Prise en charge tardive de l'infection par le VIH

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Tuberculosis in the Elderly.

International audienceThe tuberculosis (TB) epidemic is most prevalent in the elderly, and there is a progressive increase in the notification rate with age. Most cases of TB in the elderly are linked to the reactivation of lesions that have remained dormant. The awakening of these lesions is attributable to changes in the immune system related to senescence. The mortality rate from tuberculosis remains higher in elderly patients. Symptoms of active TB are nonspecific and less pronounced in the elderly. Diagnostic difficulties in the elderly are common in many diseases but it is important to use all possible techniques to make a microbiological diagnosis. Recognising frailty to prevent loss of independence is a major challenge in dealing with the therapeutic aspects of elderly patients. Several studies report contrasting data about poorer tolerance of TB drugs in this population. Adherence to antituberculosis treatment is a fundamental issue for the outcome of treatment. Decreased completeness of treatment was shown in older people as well as a higher risk of treatment failure

Tuberculosis in the Elderly

The tuberculosis (TB) epidemic is most prevalent in the elderly, and there is a progressive increase in the notification rate with age. Most cases of TB in the elderly are linked to the reactivation of lesions that have remained dormant. The awakening of these lesions is attributable to changes in the immune system related to senescence. The mortality rate from tuberculosis remains higher in elderly patients. Symptoms of active TB are nonspecific and less pronounced in the elderly. Diagnostic difficulties in the elderly are common in many diseases but it is important to use all possible techniques to make a microbiological diagnosis. Recognising frailty to prevent loss of independence is a major challenge in dealing with the therapeutic aspects of elderly patients. Several studies report contrasting data about poorer tolerance of TB drugs in this population. Adherence to antituberculosis treatment is a fundamental issue for the outcome of treatment. Decreased completeness of treatment was shown in older people as well as a higher risk of treatment failure.</jats:p

Lyme borreliosis and medical wandering: what do patients think about multidisciplinary management? A qualitative study in the context of scientific and social controversy

International audienceAbstract Introduction To answer to patients’ medical wandering, often due to “unexplained symptoms” of “unexplained diseases” and to misinformation, multidisciplinary care centers for suspected Lyme borreliosis (LB), such as the 5 Tick-Borne Diseases (TBDs) Reference Centers (TBD-RC), were created a few years ago in France, the Netherlands and Denmark. Our study consisted of a comprehensive analysis of the satisfaction of the patients managed at a TBD-RC for suspected LB in the context of scientific and social controversy. Methods We included all adults who were admitted to one of the TBD-RC from 2017 to 2020. A telephone satisfaction survey was conducted 12 months after their first consultation. It consisted of 5 domains, including 2 free-text items: “What points did you enjoy?” and “What would you like us to change or to improve?”. In the current study, the 2 free-items were analyzed with a qualitative method called reflexive thematic analysis within a semantic and latent approach. Results The answer rate was 61.3% (349/569) and 97 distinctive codes from the 2-free-text items were identified and classified into five themes: (1) multidisciplinarity makes it possible to set up quality time dedicated to patients; (2) multidisciplinarity enables seamless carepaths despite the public hospital crisis compounded by the COVID-19 pandemic; (3) multidisciplinarity is defined as trust in the team’s competences; (4) an ambivalent opinion and uncertainty are barriers to acceptance of the diagnosis, reflecting the strong influence of the controversy around LB; and (5) a lack of adapted communication about TBDs, their management, and ongoing research is present. Conclusion The multidisciplinary management for suspected LB seemed an answer to medical wandering for the majority of patients and helped avoid misinformation, enabling better patient-centered shared information and satisfaction, despite the context of controversy

Perceptions, Representations, and Experiences of Patients Presenting Nonspecific Symptoms in the Context of Suspected Lyme Borreliosis

Background: Some subjective symptoms may be reported at all stages of Lyme borreliosis (LB) and may persist for several months after treatment. Nonspecific symptoms without any objective manifestation of LB are sometimes attributed by patients to a possible tick bite. The aim of our study was to explore the perceptions, representations, and experiences that these patients had of their disease and care paths. Methods: We performed a qualitative study through individual interviews (October 2017–May 2018), based on grounded theory, following the COREQ checklist. A balanced sample of patients with diverse profiles was recruited at consultations with general practitioners and infectious disease physicians. Results: Twelve patients were interviewed. Data saturation was reached at the twelfth interview. For codes, 293 were identified, and classified into 5 themes: (1) the experience of disabling nonspecific symptoms, especially pain, causing confusion and fear, (2) long and difficult care paths for the majority of the patients, experienced as an obstacle course, (3) a break with the previous state of health, causing a negative impact on every sphere of the patient’s life, (4) empowerment of the patients and the self-management of their disease, and (5) the strong expression of a desire for change, with better listening, greater recognition of the symptoms, and simpler care paths. Conclusions: This study allows for the understanding of a patient’s behaviours and the obstacles encountered, the way they are perceived, and the necessary solutions. The patients’ expectations identified here could help physicians better understand the doctor–patient relationship in these complex management situations, which would reduce the burden of the disease. The current development of specialised reference centres could help meet the patients’ demands and those of family physicians.</jats:p

Perceptions, Representations, and Experiences of Patients Presenting Nonspecific Symptoms in the Context of Suspected Lyme Borreliosis

Background: Some subjective symptoms may be reported at all stages of Lyme borreliosis (LB) and may persist for several months after treatment. Nonspecific symptoms without any objective manifestation of LB are sometimes attributed by patients to a possible tick bite. The aim of our study was to explore the perceptions, representations, and experiences that these patients had of their disease and care paths. Methods: We performed a qualitative study through individual interviews (October 2017–May 2018), based on grounded theory, following the COREQ checklist. A balanced sample of patients with diverse profiles was recruited at consultations with general practitioners and infectious disease physicians. Results: Twelve patients were interviewed. Data saturation was reached at the twelfth interview. For codes, 293 were identified, and classified into 5 themes: (1) the experience of disabling nonspecific symptoms, especially pain, causing confusion and fear, (2) long and difficult care paths for the majority of the patients, experienced as an obstacle course, (3) a break with the previous state of health, causing a negative impact on every sphere of the patient’s life, (4) empowerment of the patients and the self-management of their disease, and (5) the strong expression of a desire for change, with better listening, greater recognition of the symptoms, and simpler care paths. Conclusions: This study allows for the understanding of a patient’s behaviours and the obstacles encountered, the way they are perceived, and the necessary solutions. The patients’ expectations identified here could help physicians better understand the doctor–patient relationship in these complex management situations, which would reduce the burden of the disease. The current development of specialised reference centres could help meet the patients’ demands and those of family physicians

Abdominal Tuberculosis: Experience from Two Tertiary-Care Hospitals in the Paris Region

ABSTRACTAbdominal tuberculosis (ATB) is uncommon and not very well known by clinicians. We describe the characteristics, evolution, and treatment of patients with ATB in two large hospitals in the Paris region. We reviewed all records of patients treated for ATB, from January 01, 2010 to December 01, 2016, diagnosed by bacteriological and/or histological methods or highly suspected because of clinical/radiological features. We included 80 patients, with a median (IQR) age of 39 (29–50) years, with 56.2% being males. Among them, 63.7% had African origins, 15% Asian, and 11.2% European. Twenty-nine had a cause of immunosuppression (n = 21 HIV infection). The main abdominal localizations were lymph nodes (72.5%), peritoneum (62.5%), and solid organs (25%). Extra-abdominal localizations were recorded in 65 (81.2%) patients. Tuberculosis was proven bacteriologically in 71%, histologically in 50%, and solely clinical/radiological in 10% of cases. Patients received standard therapy for a median duration of 9 months, with a favorable outcome. Corticosteroid therapy was used in 15 cases, either for paradoxical reaction or to prevent complications. Abdominal TB was mainly represented by lymphatic and peritoneal localizations, proven bacteriologically, and associated with extra-abdominal localizations in most cases. The use of steroids remains controversial, but it does not seem systematically needed in case of abdominal involvement.</jats:p