One-year mortality in COVID-19 is associated with patients' comorbidities rather than pneumonia severity

Background: In patients with pneumonia or ARDS who survived hospitalization, one-year mortality can affect up to one third of discharged patients. Therefore, significant long-term mortality after COVID-19 respiratory failure could be expected. The primary outcome of the present study was one-year all-cause mortality in hospitalized COVID-19 patients. Method(s): Observational study of COVID-19 patients hospitalized at Papa Giovanni XXIII Hospital (Bergamo, Italy), during the first pandemic wave. Result(s): A total of 1326 COVID-19 patients were hospitalized. Overall one-year mortality was 33.6% (N 446/1326), with the majority of deaths occurring during hospitalization (N=412, 92.4%). Thirty-four patients amongst the 914 discharged (3.7%) subsequentely died within one year. A third of these patients died for advanced cancer, while death without a cause other than COVID-19 was uncommon (8.8% of the overall post-discharge mortality). Inhospital late mortality (i.e. after 28 days of admission) interested a population with a lower age, and fewer comorbidities, more frequentely admitted in ICU. Independent predictors of post-discharge mortality were age over 65 years (HR 3.19;95% CI 1.28-7.96, p-value=0.013), presence of chronic obstructive pulmonary disease (COPD) (HR 2.52;95% CI 1.09-5.83, p-value=0.031) or proxy of cardiovascular disease (HR 4.93;95% CI 1.45-16.75, pvalue=0.010), and presence of active cancer (HR 3.64;95% CI 1.50-8.84, p-value=0.004), but not pneumonia severity. Conclusion(s): One-year post-discharge mortality depends on underlying patients' comorbidities rather than COVID19 pneumonia severity per se. Awareness among physicians of predictors of post-discharge mortality might be helpful in structuring a follow-up program for discharged patients.

LONGITUDINAL FOLLOW-UP of HUMORAL RESPONSE AGAINST SARS-COV-2 and VIRAL PERSISTENCE in 96 DMARDS-TREATED PATIENTS with PREVIOUS COVID-19 INFECTION

Background: Although it prevents severe forms of the disease, vaccination does not completely protect against the occurrence of COVID19 disease. If, DMARDs used have been associated with variable humoral response to SARS-CoV-2 vaccination, the impact of their use after SARS-CoV-2 natural infection have been poorly studied. Objectives: To characterize humoral response after SARS-CoV-2 infection and viral persistence in the nasopharyngeal sphere (NP), stools and blood of patients with rheumatic disease under DMARDs, and compared to healthy controls. Methods: Prospective monocentric longitudinal study including patients with rheumatoid arthritis or spondyloarthritis under DMARDs and with a confrmed SARS-CoV-2 infection (positive NP PCR and/or positive serology and/or pathognomonic thoracic tomography (CT)) during the frst or second wave of the COVID pandemic. Patients were followed up until one year after infection and humoral response was assessed before vaccination. Serum IgG and IgA antibodies against spike (S) and nucleocapsid (N) proteins were measured at every visit. Viral persistence was assessed at the early visit in the NP and stools using conventional RT-PCR and in the blood using a high sensitive technique (droplet digital PCR). Results: Between June 2020 and July 2021, we include 96 patients (50 SpA and 46 RA) with a mean age of 53 +/-14 years and 20 healthy controls (mean age 49 ± 16 years) corresponding to relatives of patients (spouses, children) living together and infected at the same time. The immune responses were analyzed according to 6 treatment groups: methotrexate (MTX)/salazopyrine (SLZ) monotherapy (n=17/2);anti-TNF monotherapy (n=24), anti-TNF + MTX (n=23);rituximab (RTX) (n=11);anti-IL17 or-23 (n=8);others (n=11). Visits were made at 1 month (29 ±13 days;n=18), 3 months (110 ±23 days;n=67), 6 months (231 ±35 days;n=48) and 12 months (368 ± 19 days;n=19) after infection. The anti-S and anti-N IgG Ab titers were not signifcantly different in the 6 treatment groups and the control population at 3 months. A signifcant decrease in anti-S IgA Ab titers was noted in the group treated with RTX (p=0.007) and with molecules targeting the IL17/23 pathway (p=0.007). A similar but non-signifcant trend was observed in these same treatment groups for anti-N IgA Ab (p=0.07). The titers of anti-SARS-CoV-2 antibodies at M3, was not associated with a severe COVID disease. Detection of SARS-Cov-2 RNA in stools and serum was negative for all samples taken at 1 month or 3 months. 4 patients (2 RA treated with abatacept/RTX and 2 SpA treated with anti-TNF/secukinumab) had a positive RT-PCR NP with low to very low viral load at the 1-month visit (mean Ct 36). None of these 4 patients had had a severe form of COVID19 infection. Conclusion: DMARDs-treated patients with previous proven COVID-19 did not seem to alter IgG Ab response but RTX and anti-IL17/-IL-23 might alter IgA humoral response. This lower immune response was not associated with a more severe disease. In these patients, new infection may not be considered as a full boost for the immune system. DMARDs did not induce viral persistence in the serum, the NP or in the stool.

Post-COVID-19 Lung Transplantation Italian Pivotal Protocol: Some Ethical Considerations.

SARS­CoV­2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS­CoV­2 and subsequently recovered, it has been shown that some patients with post-COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post-COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post-COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS­CoV­2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease. The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article.

Crisis Innovation: Leveraging Virtual Hackathons for Rapid Ideation

The COVID-19 crisis brought about an unprecedented wave of interest into rapid ideation and innovation. Among others, the pandemic triggered a series of collaborative innovation events-so-called hackathons-to leverage the power of the crowd for crisis response. In contrast to earlier hackathons, these events are different in their speed of mobilization, global scale, and their fully virtual nature with organizers and teams being geographically dispersed. Analyzing this new empirical phenomenon, we characterize COVID-19 hackathons against other forms of innovation crowdsourcing and describe challenges and best practices in the areas of people management, session management, technology, and knowledge management. Based on our empirical findings, we develop a conceptual framework that emphasizes the importance of managing virtual crisis hackathons as the integrated sum of its different parts. Empirical evidence is presented to demonstrate how open innovation efforts such as hackathons can be leveraged for crisis management and more generally for ideation activities in increasingly remote working environments. This article contributes to crowdsourcing research by highlighting key differences of virtual hackathons from the traditional crowdsourcing approaches and hackathons investigated by prior research. Moreover, we affirm the value of mobilizing knowledge from different sources, particularly from a broad spectrum of civil society.

Étude de la réponse humorale anti-SARS-CoV-2 et de la persistance virale dans une cohorte de 96 patients avec rhumatisme inflammatoire chronique (PR et SpA) sous immunomodulateurs, infectés par le SARS-CoV-2

Introduction L’impact des traitements immunomodulateurs utilisés dans les rhumatismes inflammatoires chroniques sur la réponse humorale anti-SARS-coV-2 et sur la persistance virale dans la sphère nasopharyngée (NP), les selles et le sang a été peu étudié à ce jour. L’objectif était de caractériser la réponse humorale anti-SARS-CoV-2 ainsi que la persistance virale NP, sérique et fécale de patients sous immunomodulateurs (DMARDs) pour un rhumatisme inflammatoire chronique, comparativement à une population témoin sans rhumatisme inflammatoire chronique et non immunodéprimée. Patients et méthodes Étude longitudinale prospective (inclusions de juin 2020 à maintenant) de patients sous DMARDs synthétiques et/ou biologiques pour une spondyloarthrite (SpA) ou une polyarthrite rhumatoïde (PR). Les titres d’Ac anti-Spike (S) et anti-Nucleocapside (N) en IgG et IgA ont été déterminés dans le sérum et sur l’écouvillonnage NP. La persistance virale NP, fécale et sérique a été déterminée par RT-PCR. L’ARNémie plasmatique du SARS-CoV-2 a été déterminée par RT-PCR numérique ultrasensible sur gouttelettes (BioRad®). Résultats Un total de 96 patients (50 SpA et 46 PR) d’âge moyen 53±14 ans ont été inclus dans l’étude COVIRIC après une infection confirmée à SARS-CoV-2 (RT-PCR et/ou sérologie positive et/ou tomodensitométrie (TDM) thoracique compatible). 20 témoins (âge moyen 49±16 ans) correspondant à des collatéraux de ces patients (conjoints, enfants majeurs) vivants sous le même toit et infectés au même moment ont été inclus comme population contrôle. Les réponses immunes ont été analysées selon 6 groupes de traitement : méthotrexate (MTX)/salazopyrine (SLZ) monothérapie (n=17/2) ;anti-TNF monothérapie (n=24), anti-TNF+MTX (n=23) ;rituximab (RTX) (n=11) ;traitements ciblant la voie IL17/23 (n=8) ;autres (n=11). Les visites étaient effectuées à 1 mois (29±13jours ;n=18), 3 mois (110±23jours ;n=67), 6 mois (231±35jours ;n=48) et 12 mois (368±19jours ;n=19) après l’infection. Aucune des visites n’était post-vaccinale. La distribution des titres d’Ac IgG anti-S et anti-N n’était pas significativement différente dans les 6 groupes de traitement et la population témoin à 3 mois. En revanche, on notait une diminution significative des IgA anti-S dans les groupes de traitement par RTX (p=0,007) et par molécules ciblant la voie IL17/23 (p=0,007). On observait une tendance similaire mais non significative dans ces mêmes groupes de traitement pour les IgA anti-N (p=0,07) dans le sérum et pour la quantification des IgA anti-S anti-SARS-CoV-2 dans les prélèvements NP du groupe RTX comparativement aux témoins (p=0,07). Les titres des Ac anti-SARS-CoV-2 à M3, quel que soit leur sous-type, ne conditionnaient pas la sévérité de l’infection COVID-19. La détection de l’ARN SARS-Cov-2 dans les selles et le sérum était négative pour l’ensemble des prélèvements réalisés à 1 mois et 3 mois. 4 patients (2 PR ;traitement par abatacept (ABA)/RTX ;2 SpA traitement par ADA/sécukinumab) avaient une RT-PCR NP positive avec charge virale faible à très faible à la visite de 1 mois (Ct moyen 36). Aucun de ces 4 patients n’avaient eu une forme sévère d’infection COVID19. Conclusion Les traitements analysés dans cette étude n’ont pas eu d’impact significatif sur les titres d’IgG anti-N et anti-S. En revanche, les traitements par RTX et ceux ciblant la voie IL17/23 semblent impacter la réponse humorale IgA mais sans lien avec la sévérité de l’infection dans la population étudiée. Les différents traitements analysés n’induisaient pas de persistance virale sérique ou dans les selles.

SARS-CoV-2 Infection among the Dental Staff from Lombardy Region, Italy

Dentists have been supposed to be among the healthcare workers at greatest risk of SARS-CoV-2 infection. However, scant data are available on the issue. The aim of this study is to quantify the SARS-CoV-2 antibody prevalence and determinants in a sample of dentists, dental hygienists, and other personnel employed among the dental staff in Lombardy region. We used an accurate rapid diagnostic test kit detecting immunoglobulins (Ig) in 504 adults. Of the 499 participants who obtained a valid antibody test, 54 (10.8%) had a SARS-CoV-2 positive test (0.4% IgM+, 1.8% both IgM+ and IgG+, and 8.6% IgG+). A statistically significant association with infection was found for geographic area (compared to Milan, adjusted odds ratio was 2.79, 95% confidence interval, CI: 1.01-7.68 for eastern and 2.82, 95% CI: 1.34-5.94, for southern Lombardy). The clinical staff did not result positive to SARS-CoV-2 more frequently than the administrative staff. This is the first study using antibody test in the dental staff personnel. It shows that the prevalence of SARS-CoV-2 infection in Lombardy region was around 10%, in line with estimates on other healthcare professionals. Despite the close physical contact with the patient, dentists have been able to scrupulously manage and effectively use protective devices.