COVID-19 in patients with Pulmonary Alveolar Proteinosis A European multicenter study

Background: Interruption of GM-CSF signaling leads to Pulmonary Alveolar Proteinosis (PAP), occasionally to lung infections and relates to the impaired ability of lung macrophages to catabolize phagocytized surfactant and handle microbes. COVID-19 is associated with worse prognosis in lung disorders. We hypothesized that PAP patients would be at increased risk for COVID-19 and poor outcome. Aim and objectives: This multi-center, retrospective, European study aimed to investigate prevalence and clinical consequences of COVID-19 in PAP and the impact of iGM-CSF treatment on hospitalization or death. Method(s): All patients with PAP and COVID-19 diagnosed and followed-up in 11 referral European centers from January 24th 2020 to August 31st 2021 were included. Prevalence, clinical course and outcome were investigated. Result(s): COVID-19 developed in 34/255 (13.3%) of patients, mostly adults (91.2%), all with autoimmune (a)PAP;all patients were infected before the preventive option of vaccination was available;11 (35.5%) were hospitalized, of whom almost half were in the ICU;3 (27%) of hospitalized patients either died or underwent lung-transplant;these three patients had worse DLCO% predicted (p=0.019) and had more often arterial hypertension (AH) (p=0.012), and a smoking history (p=0.002). All patients with mild disease treated at home survived. Among children, 3 developed COVID-19 with good outcome. Conclusion(s): PAP patients experienced similar rates of COVID-19 with the general population but increased rates of hospitalizations and deaths, underscoring the vulnerability of this population and the necessity of preventive measures to avoid infection. If infected, secondary prophylaxis with monoclonal antibodies and the impact of iGM-CSF must be considered.

Retour d'expérience sur la direction médicale de crise à l'Assistance publique–Hôpitaux de Paris pendant la crise Covid-19

Un retour d'expérience sur la direction médicale de crise (DMC) pendant la première phase de l'épidémie de Covid-19 a été effectué à l'Assistance publique–Hôpitaux de Paris (AP–HP), le plus important centre hospitalier universitaire européen. L'AP–HP s'est dotée d'un directeur médical de crise (DMC) AP–HP, de six DMC de groupes hospitaliers (GH) et d'un DMC pour chacun des 39 sites hospitaliers. Le pilotage s'est appuyé sur des réunions quotidiennes de crise AP–HP et de GH, des groupes de travail disciplinaires et des tableaux de bord quotidiens fiabilisés qui ont permis d'optimiser les actions. Des actions innovantes ont été mises en place : cellules de régulation des entrées et des sorties de réanimation, suivi des patients infectés à domicile, traçage des contacts, transferts interrégionaux de patients de réanimation. Les éléments clés de la réussite ont été les relations entre direction générale et DMC, l'articulation entre l'échelon central (AP–HP) et celui des GH, la mobilisation de tous les acteurs vers un objectif unique identifié et la mobilisation de l'ensemble des soignants, y compris les étudiants. Parmi les pistes d'amélioration soulignées, il convient de citer la généralisation des DMC hors AP–HP, conformément à la réglementation, le développement de la connaissance du mode de fonctionnement de crise, l'anticipation de la formation à la gestion de crise, la réalisation d'une information quotidienne de l'ensemble des acteurs des actions menées dans une crise de longue durée et la participation des représentants des usagers. La gestion de la recherche en temps de crise reste à inventer au niveau national, voire européen.Alternate abstract: Feedback on the medical crisis management during the first phase of the COVID-19 epidemic was provided to the Assistance publique-Hôpitaux de Paris (AP–HP), the largest university hospital center in Europe. The AP–HP has one AP–HP medical crisis director (DMC), 6 hospital group (HG) DMCs, and one DMC for each of the 39 hospital sites. Management was based on daily AP–HP and GH crisis meetings, disciplinary working groups and reliable daily dashboards, which enabled the optimization of actions. Innovative actions have been implemented: regulation units for intensive care unit entries and exits, follow-up of infected patients at home, contact tracing, and inter-regional transfers of critically-ill patients. The key elements of success were the relationship between General management, DMC, the articulation between the central level and those of the GH, the mobilization of all the actors towards a unique identified objective, and the mobilization of all the caregivers, including students. Among the highlighted avenues for improvement, it is worth mentioning the generalization of DMCs outside the AP–HP in accordance with the regulations, the development of knowledge of the crisis operating mode, the anticipation of training in crisis management, the provision of daily information to all those involved in actions carried out in a long-term crisis, and the participation of care-user representatives. The management of research in times of crisis remains to be invented at the national or even European level.

Guide for follow-up of patients with SARS-CoV-2 pneumonia. Management proposals developed by the French-language Respiratory Medicine Society. Version of 10 May 2020 / Guide pour le suivi respiratoire des patients ayant présenté une pneumonie à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de pneumologie de langue française. Version du 10 mai 2020

The French-language Respiratory Medicine Society (SPLF) proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: (1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea; (2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit; (3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome…). These proposals may evolve over time as more knowledge becomes available.

Involvement of Circulating Fibrocytes in Pathophysiology and Prognosis of COVID-19 Pneumonia

Rationale : SARS-CoV-2 infection, responsible of COVID-19, can lead to severe acute pneumonia in 15-20% of patients. Circulating fibrocytes are fibroblasts precursors involved in the repair process. Increased blood fibrocytes count is associated with a poor prognosis in fibrotic lung diseases and acute respiratory distress syndrome (ARDS). We aimed to quantify the % of circulating fibrocytes in patients hospitalized for COVID-19 and included in the French COVID cohort, in order to determine their prognosis value in this disease. Methods :SARS-CoV-2 infection was confirmed by PCR in all patients. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/Collagen-1+. Clinical and imaging data were obtained at inclusion and after 3 months. In a subgroup of patients admitted in ICU, we quantified fibrocytes in blood and broncho-alveolar lavage fluid (BALF). Serum amyloid protein (SAP), a known regulator of fibrocytes differentiation, was quantified by ELISA in serum samples. Results :We included 57 patients admitted for hypoxemic COVID-19 pneumonia (mean age 60 years [23-87]) and 15 sex- and age-matched healthy controls. Samples were taken 0 to 10 days after admission, and 14 days (4-48 days) after first symptom. The median % of circulating fibrocytes was higher in patients compared to controls (2,49% vs 1,82%, p<0,05). The % was lower in patients who died of COVID-19 (6/57) as compared to survivors (1.25% versus 2.52%, p=0.03). Fibrocyte count was lower in patients receiving corticosteroids before blood sample collection (2.28% vs 2.82%, p=0.04). Fibrocyte % did not correlate with biological severity markers (lymphocytes, LDH, ferritin, CRP). Thirty-two patients were evaluated 3 months after admission. Complete resolution of CT abnormalities was observed in 13 patients (40%). It was associated with a significantly higher initial fibrocyte count compared with patients with an incomplete resolution (2.95% vs 2.18%, p=0.03). SAP concentration in serum was higher in COVID-19 patients compared to controls (96.3 vs 65,0 mg/L, p = 0.0021);it did not correlate with fibrocyte count. We studied 7 ICU patients (mean age 62 years [50-73]). In these patients, median blood fibrocyte count was 0.94% while median BALF fibrocyte count was 5.43%, suggesting a recruitment of fibrocytes to the lung in severe cases. Conclusion : Circulating fibrocytes were increased in patients with hypoxemic COVID-19 pneumonia. Lower fibrocyte count were associated with an increased risk of in-hospital death and a slower resolution of lung CT opacities, and may be due to the recruitment of fibrocytes to the lung in the most severe cases.

Ct features of patients with COVID-19 pneumonia at three months following infection

Rationale: The long term evolution of Covid-19 pneumonia has still little been evaluated. We herein describe CT features that persist 3 months after Covid-19 symptom onset and correlate them to the extent of disease at diagnosis. Methods: Monocentric retrospective study including consecutive patients with Covid-19 confirmed by RT-PCR who presented to Bichat Hospital, Paris, France, between March and May 2020, and had a follow-up chest-CT 3 months later as part of their usual care. Chest CT analysis at 3 months evaluated ground-glass opacities (GGO, graded according to their extent and density), reticulations, bronchial distortion, honeycombing, band-like atelectasis and air trapping. The grade of persistent GGO and the presence of any sign suggestive of fibrosis were correlated to the extent of disease at presentation.Results;Any residual opacity was observed in 99/142 patients (70%). GGO, band-like atelectasis and reticulations were the most frequent findings, in 87/142 (61%), 53/142 (37%) and 40/142 (28%) patients, respectively. Signs that may suggest a fibrosing evolution, including bronchial distortion and distorted reticulations, were observed in 17/142 patients (12%), whereas no case showed honeycombing. Air trapping was present in 12 out of 80 patients (15%) who had an expiratory CT. The grade of GGO and the presence of reticulations at 3 months were highly correlated to the extent of disease at presentation (p<0.0001 and p=0.020, Kruskall Wallis) but signs suggestive of fibrosis were not (p=0.15)Conclusion: Residual opacities are frequent 3 months after Covid-19 pneumonia onset, chest CT mostly showing GGO, band-like atelectasis and reticulations. Signs that may suggest a fibrosing evolution are observed in only 12% of patients.

[Guide for management of patients with possible respiratory sequelae after a SARS-CoV-2 pneumonia. Support proposals developed by the French-speaking Respiratory Medicine Society. Version of 10 November 2020]. / Guide de prise en charge des séquelles respiratoires post infection à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de Pneumologie de Langue Française. Version du 10 novembre 2020.

The French-speaking Respiratory Medicine Society (SPLF) proposes a guide for the management of possible respiratory sequelae in patients who have presented with SARS-CoV-2 pneumonia (COVID-19). The proposals are based on known data from previous epidemics, preliminary published data on post COVID-19 follow-up and on expert opinion. The proposals were developed by a group of experts and then submitted, using the Delphi method, to a panel of 22 pulmonologists. Seventeen proposals were validated ranging from additional examinations after the minimum assessment proposed in the SPLF monitoring guide, to inhaled or systemic corticosteroid therapy and antifibrotic agents. These proposals may evolve over time as knowledge accumulates. This guide emphasizes the importance of multidisciplinary discussion.

Lung ultrasonography in patients with COVID-19: comparison with CT.

AIM: To determine whether findings from lung ultrasound and chest high-resolution computed tomography (HRCT) correlate when evaluating COVID-19 pulmonary involvement. MATERIALS AND METHODS: The present prospective single-centre study included consecutive symptomatic patients with reverse transcription polymerase chain reaction (RT-PCR)-proven COVID-19 who were not in the intensive care unit. All patients were assessed using HRCT and ultrasound of the lungs by distinct operators blinded to each other's findings. The number of areas (0-12) with B-lines and/or consolidations was evaluated using ultrasound and compared to the percentage and classification (absent or limited, <10%; moderate, 10-25%; extensive, 25-50%; severe, 50-75%; critical, >75%) of lung involvement on chest HRCT. RESULTS: Data were analysed for 21 patients with COVID-19 (median [range] age 65 [37-90] years, 76% male) and excellent correlation was found between the ultrasound score for B-lines and the classification (p<0.01) and percentage of lung involvement on chest HRCT (r=0.935, p<0.001). In addition, the ultrasound score correlated positively with supplemental oxygen therapy (r=0.45, p=0.041) and negatively with minimal oxygen saturation at ambient air (r=-0.652, p<0.01). CONCLUSION: The present study suggests that among COVID-19 patients, lung ultrasound and HRCT findings agree in quantifying lung involvement and oxygen parameters. In the context of the COVID-19 pandemic, lung ultrasound could be a relevant alternative to chest HRCT.

[Guide for follow-up of patients with SARS-CoV-2 pneumonia. Management proposals developed by the French-language Respiratory Medicine Society. Version of 10 May 2020]

The French-language Respiratory Medicine Society proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: 1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea;2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit;3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome..). These proposals may evolve over time as more knowledge becomes available.

Guide pour le suivi respiratoire des patients ayant présenté une pneumonie à SARS-CoV-2.Propositions de prise en charge élaborées par la Société de Pneumologie de Langue Française. Version du 10 mai 2020

Résumé La Société de Pneumologie de Langue Française propose un guide pour le suivi respiratoire des patients ayant présenté une pneumonie à SARS-CoV-2 à partir des données connues des précédentes épidémies, des lésions aiguës constatées chez ces patients et d’opinions d’experts. Ce guide propose une conduite à tenir selon le type de patients : 1) patient pris en charge en ville pour une infection à SARS-CoV-2 possible ou prouvée adressé par son médecin traitant pour dyspnée persistante, 2) patient hospitalisé pour pneumonie à SARS-CoV-2 en unité conventionnelle, 3) patient hospitalisé pour pneumonie à SARS-CoV-2 ayant fait un séjour en réanimation. Le suivi ultérieur sera à adapter au bilan initial. Ce guide insiste sur le fait qu’il ne faut pas méconnaitre les autres causes de dyspnée (cardiaques, thromboemboliques, syndrome d’hyperventilation, …). Ces propositions pourront évoluer dans le temps au fil des connaissances sur le sujet. The French-language Respiratory Medicine Society proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: 1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea;2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit;3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome..). These proposals may evolve over time as more knowledge becomes available.