[Post-COVID-19 syndrome]. / Syndrome post-COVID-19.

In the aftermath of acute infection with the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a large number of symptoms persist or appear, constituting a real syndrome called "long COVID-19" or "post-COVID- 19" or "post-acute COVID-19 syndrome". Its incidence is very high, half of patients showing at least one symptom at 4-6 months after Coronarovirus infectious disease 2019 (COVID-19). They can affect many organs. The most common symptom is persistent fatigue, similar to that seen after other viral infections. Radiological pulmonary sequelae are relatively rare and not extensive. On the other hand, functional respiratory symptoms, primarily dyspnoea, are much more frequent. Dysfunctional breathing is a significant cause of dyspnoea. Cognitive disorders and psychological symptoms are also very common, with anxiety, depression and post-traumatic stress symptoms being widely described. On the other hand, cardiac, endocrine, cutaneous, digestive or renal sequelae are rarer. The symptoms generally improve after several months, even if their prevalence at two years remains significant. Most of the symptoms are favored by the severity of the initial illness, and the psychic symptoms by the female sex. The pathophysiology of most symptoms is poorly understood. The influence of the treatments used in the acute phase is also important. Vaccination, on the other hand, seems to reduce their incidence. The sheer number of affected patients makes long-term COVID-19 syndrome a public health challenge.

Syndrome post-COVID-19☆ Post-COVID-19 syndrome

Dans les suites de l'infection aiguë par le severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), de très nombreux symptômes persistent ou apparaissent, constituant un véritable syndrome appelé « COVID-19 long » ou « syndrome post-COVID-19 » ou « syndrome de COVID-19 post-aigu ». Son incidence est très élevée, la moitié des patients présentant au moins un symptôme à 4–6 mois après le Coronarovirus infectious disease 2019 (COVID-19). Ils peuvent toucher de très nombreux organes. Le symptôme le plus fréquent est une fatigue persistante, semblable à celle rencontrée après d'autres infections virales. Les séquelles pulmonaires radiologiques sont relativement rares et peu étendues. En revanche, les symptômes respiratoires fonctionnels, en premier lieu la dyspnée, sont beaucoup plus fréquents. La respiration dysfonctionnelle est une cause de dyspnée non négligeable. Des troubles cognitifs et des symptômes psychiques sont aussi très fréquents, les symptômes anxieux, dépressifs et de stress post-traumatique étant largement décrits. Les séquelles cardiaques, endocriniennes, cutanées, digestives ou rénales sont en revanche plus rares. Les symptômes vont globalement en s'améliorant au terme de plusieurs mois, même si leur prévalence à deux ans reste non négligeable. La plupart des symptômes sont favorisés par la gravité de la maladie initiale, et les symptômes psychiques par le sexe féminin. La physiopathologie de la plupart des symptômes est mal connue. L'influence des traitements utilisés à la phase aiguë l'est aussi. La vaccination semble en revanche réduire leur incidence. Le nombre total de patients touchés fait du syndrome de COVID-19 long un défi pour la santé publique.

Functional respiratory complaints among COVID-19 survivors: a prospective cohort study

Background Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear. Methods We assessed the proportion and characteristics of patients with "functional respiratory complaints” (FRCs) (as defined by Nijmegen Questionnaire>22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (i.e., symptomatic and/or ICU survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardio-pulmonary exercise testing (CPET). Findings In the COMEBAC cohort, 37 had significant FRCs (20.9%, IC95: 14.9–26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-minute walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, 7/21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12/21 patients, 5/21 had normal CPET, 3/21 had deconditioning and 1/21 had evidence of uncontrolled cardiovascular disease. Interpretation FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases. Funding Assistance Publique-Hôpitaux de Paris.

Characteristics and outcomes of asthmatic outpatients with COVID-19 who receive home telesurveillance.

Background: The prognosis of asthmatic outpatients with COVID-19 needs to be clarified. The objectives of this study were: 1) to investigate the characteristics and outcomes of asthmatic patients receiving initial ambulatory care and home monitoring for COVID-19 with Covidom, a telesurveillance solution; and 2) to compare the characteristics and outcomes between asthmatic and non-asthmatic patients. Methods: Inclusion criteria were age ≥18 years, suspected or confirmed COVID-19 diagnosis allowing initial ambulatory care, registration in Covidom between March 2020 and April 2021 and completion of the initial medical questionnaire. We compared clinical characteristics and outcomes between asthmatic and non-asthmatic patients, and we evaluated whether asthma was independently associated with clinical worsening (hospitalisation or death) within 30 days follow-up using a multivariate logistic regression model. Results: 33 815 patients met the inclusion criteria. Asthma was reported in 4276 (12.6%). The main comorbidities among asthmatic patients were obesity (23.1%), hypertension (12.7%) and diabetes (4.5%). As compared with non-asthmatic patients, asthmatic patients were more often female (70.0 versus 62.1%, p<0.001), of younger age (42.2 versus 43.8 years, p<0.001) and obese (23.1 versus 17.6%, p<0.001). The rate of hospitalisation did not differ significantly (4.7 versus 4.2%, p=0.203) and no asthmatic patient died during follow-up (versus 25 non-asthmatic patients, 0.1%; p=0.109). In multivariate analysis, asthma was independently associated with higher risk of clinical worsening (OR 1.23, 95% CI 1.04-1.44, p=0.013). Conclusion: In a large French cohort of patients receiving initial ambulatory care and home monitoring for COVID-19, asthma was independently associated with higher risk of clinical worsening although no asthmatic patient died within the 30 days follow-up.

Perceptions on Home-Administration of Biologics in the Context of Severe Asthma: An International Qualitative Study.

BACKGROUND: Biologics are an effective therapy for severe asthma. Home administration of biologics by patients is likely to facilitate their accessibility. Yet little is known about patients' and health care providers' (HCPs) perceptions regarding home administration of biologics. OBJECTIVE: The aim of this study is to create more insight into the perceptions and experiences of patients and HCPs regarding home administration of biologics in the context of the treatment of severe asthma. METHODS: A qualitative international study was performed in the Netherlands, United States, Australia, and United Kingdom. In each country, 2 focus groups were held with potential/recent and long-term users of biologics at home. Prior to the focus groups, patients were prompted with themes on online forums. For triangulation purposes, interviews were held with HCPs to discuss salient findings from forums and focus groups. Data were analyzed with qualitative content analysis. RESULTS: In total, 75 patients participated in the forums, of which 40 participated in the focus groups. Furthermore, 12 HCPs were interviewed. The following overarching themes were identified: living with severe asthma; practical aspects of using biologics; the role of HCPs regarding biologics; social support from family, friends, and others; effectiveness of biologics and other treatments; side effects of biologics. CONCLUSIONS: This study showed that, for those using biologics for severe asthma, the benefits of home administration of biologics usually outweigh inconvenience and side effects. Guided practice, accessible support contact, and monitoring including social support should be central in the transition from hospital to home administration of asthma biologics.

Post-acute COVID-19 syndrome.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has resulted in millions of deaths and a major strain on health systems worldwide. Medical treatments for COVID-19 (anticoagulants, corticosteroids, anti-inflammatory drugs, oxygenation therapy and ventilation) and vaccination have improved patient outcomes. The majority of patients will recover spontaneously or after acute-phase management, but clinicians are now faced with long-term complications of COVID-19 including a large variety of symptoms, defined as "post-acute COVID-19 syndrome". Most studies have focused on patients hospitalised for severe COVID-19, but acute COVID-19 syndrome is not restricted to these patients and exists in outpatients. Given the diversity of symptoms and the high prevalence of persistent symptoms, the management of these patients requires a multidisciplinary team approach, which will result in the consumption of large amounts of health resources in the coming months. In this review, we discuss the presentation, prevalence, pathophysiology and evolution of respiratory complications and other organ-related injuries associated with post-acute COVID-19 syndrome.

Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group.

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

COVID-19 in Patients with Pulmonary Hypertension: A National Prospective Cohort Study.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients (n = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Respiratory symptoms and radiological findings in post-acute COVID-19 syndrome.

Rationale: The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for coronavirus disease 2019 (COVID-19) are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. Methods: In the COMEBAC (Consultation Multi-Expertise de Bicêtre Après COVID-19) cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests and high-resolution computed tomography of the chest were collected. Results: Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent <25% in 97% of the patients. The patients with fibrotic lesions were older (61±11 versus 56±14 years, p=0.03), more frequently managed in an ICU (87.9 versus 47.4%, p<0.001), had lower total lung capacity (74.1±13.7 versus 84.9±14.8% pred, p<0.001) and diffusing capacity of the lung for carbon monoxide (D LCO) (73.3±17.9 versus 89.7±22.8% pred, p<0.001). The combination of new-onset dyspnoea, fibrotic lesions and D LCO <70% pred was observed in eight out of 478 patients. Conclusions: New-onset dyspnoea and mild fibrotic lesions were frequent at 4 months, but the association of new-onset dyspnoea, fibrotic lesions and low D LCO was rare.

Respiratory symptoms and radiologic findings in post-acute COVID-19 syndrome

Rationale The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for COVID-19 are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. Methods In the COMEBAC cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests, high-resolution computed tomography of the chest were collected. Results Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent <25% in 97% of the patients. The patients with fibrotic lesions were older (61±11 versus 56±14 years, p=0.03), more frequently managed in ICU (87.9 versus 47.4%, p<0.001), had lower total lung capacity (74.1±13.7 versus 84.9±14.8%pred, p<0.001) and diffusing lung capacity for carbon monoxide (DLCO) (73.3±17.9 versus 89.7±22.8%pred, p<0.001). The combination of new-onset dyspnoea, fibrotic lesions and DLCO <70%pred was observed in 8/478 patients. Conclusions New-onset dyspnoea and mild fibrotic lesions were frequent at 4 months, but the association of new-onset dyspnoea, fibrotic lesions and low DLCO was rare.

Asthma and COVID-19: an update.

As the world faces the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, concerns have been raised that asthma patients could be at increased risk of SARS-CoV-2 infection and disease severity. However, it appears that asthma is not an independent risk factor for both. Furthermore, asthma is not over-represented in hospitalised patients with severe pneumonia due to SARS-CoV-2 infection and there was no increased risk of asthma exacerbations triggered by SARS-CoV-2. There is accumulating evidence that asthma phenotypes and comorbidities are important factors in evaluating the risk for SARS-CoV-2 infection and disease severity, as findings suggest that Th2-high inflammation may reduce the risk of SARS-Cov-2 infection and disease severity in contrast to increased risk in patients with Th2-low asthma. The use of inhaled corticosteroids (ICS) is safe in asthma patients with SARS-CoV-2 infection. Furthermore, it has been proposed that ICS may confer some degree of protection against SARS-CoV-2 infection and the development of severe disease by reducing the expression of angiotensin converting enzyme-2 and transmembrane protease serine in the lung. In contrast, chronic or recurrent use of systemic corticosteroids before SARS-CoV-2 infection is a major risk factor of poor outcomes and worst survival in asthma patients. Conversely, biological therapy for severe allergic and eosinophilic asthma does not increase the risk of being infected with SARS-CoV-2 or having worse COVID-19 severity. In the present review we will summarise the current literature regarding asthma and COVID-19.

The Role of Prior Warnings When Cheating Is Easy and Punishment Is Credible

During the COVID-19 sanitary crisis, many exams were hastily moved to online mode. This revived a much needed debate over the privacy issues associated with online proctoring of exams, while the validity and fairness of unproctored exams were increasingly questioned. With a randomized control trial, we estimate the effectiveness of prior warnings as a means of discouraging academic dishonesty in exams. We use original, non-intrusive technologies to surreptitiously identify cheating in a series of unproctored assignments and send a targeted warning to half of the students who were identified as cheaters. We then compare their cheating behavior on the final exam with the behavior of the group of unwarned cheaters. The warning proves effective but does not completely eliminate cheating, as some students’ cheating strategies become more sophisticated following issuance of the warnings. We conclude that switching traditional exams to online mode should be accompanied by proctoring. When proctoring is not possible, credible and effective anti-cheating technologies should be deployed together with adequate warnings.

COVID-19 risk and outcomes in adult asthmatic patients treated with biologics or systemic corticosteroids: Nationwide real-world evidence.

BACKGROUND: Managing severe asthma during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging, particularly due to safety concerns regarding the use of systemic corticosteroids and biologics. OBJECTIVES: We sought to determine the association between biologics or systemic corticosteroids use and PCR positivity for SARS-CoV-2 and coronavirus disease 2019 (COVID-19) outcomes among asthmatic patients. METHODS: We used the computerized database of Clalit Health Services, the largest health care provider in Israel, to identify all asthmatic adult patients who underwent PCR testing for SARS-CoV-2, between March 1, 2020, and December 7, 2020. A cohort approach was used to assess the association between biologics use and steroids treatment and COVID-19 severity and 90-day mortality. RESULTS: Overall, 8,242 of 80,602 tested asthmatic patients had positive PCR testing result for SARS-CoV-2. Both biologics and systemic corticosteroids were not associated with increased risk of SARS-CoV-2 infection. Multivariate analyses revealed that biologics were not associated with a significantly increased risk of moderate to severe COVID-19, nor with the composite end point of moderate to severe COVID-19 or all-cause mortality within 90 days. Chronic systemic corticosteroid use was associated with significantly increased risk of all tested outcome. Recent (within the previous 120 days) systemic corticosteroid use, but not former use, was significantly associated with increased risk of both moderate to severe COVID-19 and the composite of moderate to severe COVID-19 or all-cause mortality. CONCLUSIONS: Biologics approved for asthma and systemic corticosteroids are not associated with increased risk of SARS-CoV-2 infection. In contrast, systemic corticosteroids are an independent risk factor for worst COVID-19 severity and all-cause mortality. Our findings underscore the risk of recent or current exposure to systemic corticosteroids in asthmatic patients infected with SARS-CoV-2.