Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients.

Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

[Post-Covid: 2022 updates and next steps.] / Post-Covid : nouveautés 2022 et prochaines étapes.

Post-Covid is defined by persistent symptoms following a SARS-CoV-2 infection, after excluding other causes. The prevalence of post-Covid is estimated at around 30% in the general population after an infection. Some of the risk factors include female sex, the number of symptoms in the acute phase, and comorbidities. Vaccination and Omicron infection are associated with a lower prevalence. The pathophysiology of post-Covid is not known to date, with hypotheses including immune dysregulation, viral persistence, endothelial dysfunction, microthrombosis and their consequences. Current management is defined by an adaptation of daily activities, and a symptom-based approach reducing their severity, frequency and impact. Clinical trials are underway to offer potential treatments for those affected.

Le post-Covid est défini par des symptômes persistant à la suite d'une infection par le SARS-CoV-2, après avoir exclu d'autres causes. La prévalence du post-Covid est estimée à 30 % dans la population générale après une infection. Les facteurs de risque identifiés sont le sexe féminin, le nombre de symptômes dans la phase aiguë et les comorbidités. La vaccination et le variant Omicron sont associés avec une prévalence diminuée. La physiopathologie est encore à l'étude, pouvant s'agir d'un dérèglement immunitaire, d'une persistance virale, d'une dysfonction endothéliale ou de microthromboses et de leurs conséquences. La prise en charge actuelle consiste à aménager le quotidien et cibler les symptômes pour réduire leurs sévérité, fréquence et impact. Des essais cliniques sont en cours pour offrir des traitements potentiels aux personnes atteintes.

Évaluation polysomnographique des troubles du sommeil chez des patients COVID-long

Objectif Le COVID-19 est une maladie polymorphe en termes de présentation clinique, de sévérité et de durée. La HAS a établi trois critères diagnostiques de « COVID-long » : une forme symptomatique de la maladie, un ou plusieurs symptômes initiaux 4 semaines après le début de la maladie, non expliquée par un autre diagnostic. De nombreux patients COVID-long décrivent des troubles du sommeil, sur la base d’études cliniques sans polysomnographie (PSG). Notre objectif a été d’évaluer ces troubles du sommeil par un enregistrement PSG. Méthodes Vingt-deux patients COVID-long ont été adressés pour réalisation d’une PSG au centre du sommeil et de la vigilance de l’Hôtel-Dieu. Critères inclusion : critères HAS du COVID-long et critères ICSD3 de l’insomnie chronique. Critères d’exclusion : trouble du sommeil antérieur au COVID. Résultats Vingt-deux patients (13 femmes, 9 hommes), âgés de 45,9±12,8 ;IMC, 24,26±4,61. Vingt et un patients/22 présentent les critères PSG d’insomnie. Un seul patient présente un SAS avec un IAH>15. Cinquante pour cent ont un TST<6 heures temps de sommeil total (TST) 352,8±78,2min ;latence d’endormissement 28,5±23,7 minutes (norme :<30min) ;temps d’éveil intra-sommeil 77,7min 45,3±45,3 (norme :<30min). Conclusion À notre connaissance il s’agit de la première étude polysomnographique de patients COVID-long souffrant de troubles du sommeil. Nos résultats confirment la haute prévalence de troubles objectifs PSG chez ces patients.

[Patient experience, epistemic authority and health challenges: the example of long COVID]. / Expérience patient, autorité épistémique et enjeux sanitaires : l'exemple du Covid long.

Since February 2020, hundreds of thousands of patients have been left with persistant symptoms after their infection. Along with their clinicians, these patients are exposed to a high degree of uncertainty and the urgent need to produce conceptual frameworks aimed at recognising, treating and validating their experience as patients suffering from new and protracted symptoms and witnessing debates as to how these symptoms should be qualified. In this respect, long covid illustrates the need to combine the collective experiential knowledge of patients and scientific knowledge for the benefit of the patients, clinicians and research.

Interest of screening asymptomatic older adults for SARS-CoV-2 in nursing homes

Importance: Since the beginning of the pandemic, COVID-19 affected specifically elderly people aged 70 years and over in whom the mortality rate is high. We may underestimate asymptomatic people or persons with atypical COVID-19 symptoms who may spread the disease. Objective: A large screening campaign was launched all over France in several retirement homes in order to screen asymptomatic persons for SARS-CoV-2 to isolate carriers from other residents. Methods: From April 24th to 27th 2020, mobile teams of nurses from the Hôtel-Dieu Hospital were sent to five Parisian nursing homes to conduct SARS-CoV-2 RT-PCR screening tests among all asymptomatic. Results: This cross-sectional study included 297 residents: 274 asymptomatic participants (92.3%) were tested for COVID-19, mostly women (n=249/274), median age was 90 (IQR 95% [86-94]) with females being significantly older than males (90 versus 88 years, p= 0.028). A total of 35 residents (12.8%) were tested positive for COVID-19: 29 women (11.7%) and six men (24%). The proportion of PCR-positive residents was extremely variable between retirement homes and analysis of COVID-19 positive cases dispersion in each nursing home showed there was no area cluster. Conclusion: There is a real public health interest in tracking SARS-CoV-2 positive asymptomatic elderly people in nursing homes.

COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.

Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19-associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.

HIV infection and COVID-19: risk factors for severe disease.

: We performed an observational prospective monocentric study in patients living with HIV (PLWH) diagnosed with COVID-19. Fifty-four PLWH developed COVID-19 with 14 severe (25.9%) and five critical cases (9.3%), respectively. By multivariate analysis, age, male sex, ethnic origin from sub-Saharan Africa and metabolic disorder were associated with severe or critical forms of COVID-19. Prior CD4 T cell counts did not differ between groups. No protective effect of a particular antiretroviral class was observed.

Asymptomatic SARS COV-2 carriers among nursing home staff: A source of contamination for residents?

OBJECTIVES: To show that circulation of SARS-COV-2 in nursing homes in France can come from staff as well as residents' families, whether they are known or not to have had COVID-19. METHODS: This study reports a screening campaign of asymptomatic staff working in elderly nursing homes in Paris where the virus had been circulating actively in March and April 2020. RESULTS: Before the screening campaign, the rate of symptomatic COVID-19 was 23.3% among the residents and 12.1% among their home employees. Within a 72 h screening period, all employees not known to have the virus were screened by RT-PCR in nasopharyngeal swabs. Among the 241 screened employees, 32 (13.3%) tested positive for SARS-CoV-2 on RT-PCR. SARS-CoV-2 carriers and non-carriers did not differ in term of gender, age or type of staff. Staff carrying SARS-CoV-2 were strictly asymptomatic in 75% of cases while during the days following or before the test, 25% presented mild symptoms of COVID-19. Considering both symptomatic and asymptomatic cases, 66 out of 281 (23.5%) of the home employees had been carriers for COVID-19. CONCLUSION: Screening for viral carriage of asymptomatic staff in nursing homes can avoid contact and transmission to frequently severely vulnerable residents.

Efficacy of local budesonide therapy in the management of persistent hyposmia in COVID-19 patients without signs of severity: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the efficacy of local intranasal treatment with budesonide (nasal irrigation), in addition to olfactory rehabilitation, in the management of loss of smell in COVID-19 patients without signs of severity and with persistent hyposmia 30 days after the onset of symptoms. To search for an association between the presence of an obstruction on MRI and the severity of olfactory loss, at inclusion and after 30 days of treatment. TRIAL DESIGN: Two center, open-label, 2-arm (1:1 ratio) parallel group randomized controlled superiority trial. PARTICIPANTS: Inclusion criteria - Patient over 18 years of age; - Patient with a suspected SARS-CoV-2 infection, whether or not confirmed by PCR, or close contact with a PCR-confirmed case, typical chest CT scan (unsystematic frosted glass patches with predominantly sub-pleural appearance, and at a later stage, alveolar condensation without excavation or nodules or masses) or positive serology ; - Patient with isolated sudden onset hyposmia persisting 30 days after the onset of symptoms of CoV-2 SARS infection; - Affiliate or beneficiary of a social security scheme; - Written consent to participate in the study. Non-inclusion criteria - Known hypersensitivity to budesonide or any of the excipients; - Hemostasis disorder or epistaxis; - Oral-nasal and ophthalmic herpes virus infection; - Long-term corticosteroid treatment; - Treatment with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors); - Severe forms of SARS-CoV-2 with respiratory or other signs; - Hyposmia persisting for more than 90 days after the onset of symptoms - Other causes of hyposmia found on interrogation or MRI; - Patient benefiting from a legal protection measure; - Pregnant or breastfeeding women. The participants will be recruited from: Hôpital Fondation Adolphe de Rothschild and Hôpital Lariboisière in Paris, France INTERVENTION AND COMPARATOR: Intervention: Experimental group: Nasal irrigation with budesonide and physiological saline (Budesonide 1mg/2mL diluted in 250mL of physiological saline 9°/00): 3 syringes of 20mL in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. CONTROL GROUP: Nasal irrigation with physiological saline 9°/00 only: 3 syringes of 20cc in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. MAIN OUTCOMES: Percentage of patients with an improvement of more than 2 points on the ODORATEST score after 30 days of treatment. RANDOMISATION: Patients will be randomized (1:1) between the experimental and control groups, using the e-CRF. The randomization list will be stratified by centre. BLINDING (MASKING): Participants and caregivers are aware of the group assignment. People assessing the outcomes are blinded to the group assignment Numbers to be randomised (sample size) 120 patients are planned to be randomized into two groups of 60 patients. TRIAL STATUS: MDL_2020_10. Version number 2, May 22, 2020. Recruitment started on May 22, 2020. The trial will finish recruiting by August 2020. TRIAL REGISTRATION: EUDRACT number: 2020-001667-85; date of trial registration: 15 May 2020 Protocol registered on ClinicalTrial.gov, registration number: NCT04361474 ; date of trial registration: 24 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.