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 (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab 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 Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

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

Distributed control approach for Community Energy Management Systems in presence of storage

In this paper we present a suitable control methodology of an ICT platform for the management and control of Distributed Generation (DG) units and active energy consumers, which act together as an Energy Community (EC). The exploitation of local storage facility is included. Within this platform the proposed control methodologiy allows to adapt unit generation profiles and active loads to ensure economic benefits to each EC actor. The key aspect is the organization in two levels of control: at residential level a Smart Home Controller (SHC) monitors and control a subset of appliances, while at higher level a Community energy Management System (CEMS) efficiently coordinate generation units, storage units and power grid energy withdrawals. Proposed control methodologies involve the distributed solution of a dynamic programming problem

Distributed control approach for Community Energy Management Systems

In this paper we present a system architecture and suitable control methodologies of an ICT platform for the management and control of Distributed Generation (DG) units and active energy consumers, which act together as an Energy Community (EC). Within this platform the proposed control methodologies allow to adapt unit generation profiles and active loads to ensure economic benefits to each EC actor. The key aspect is the organization in two levels of control: at residential level a Smart Home Controller (SHC) monitors and control a subset of appliances, while at higher level a Community energy Management System (CEMS) efficiently coordinate generation units and power grid energy withdrawals. Proposed control methodologies involve the design of a distributed algorithm

An event driven Smart Home Controller enabling cost effective use of electric energy and automated Demand Side Management

This paper proposes the design of a Smart Home Controller strategy providing efficient management of electric energy in a domestic environment. The problem is formalized as a binary linear programming problem, the output of which specifies the best time to run of Smart Household Appliances, under a Virtual Power Threshold constraint, taking into account the real power threshold and the forecast of consumption from not plannable loads. This problem formulation allows to analyze relevant scenarios from consumer and energy retailer point of view: here optimization of economic saving in case of multi-tariff contract and Demand Side Management have been discussed and simulated. Simulations have been performed on relevant test cases, based on real load profiles provided by the smart appliance manifacturer Electrolux S.p.A. and on energy tariffs suggested by the energy retailer Edison. Results provide a proof of concept about the consumers benefits coming from the use of local energy management systems and the relevance of automated Demand Side Management for the general target of efficient and cost effective operation of electric networks. © 2011 IEEE

High frequency of type I interferon auto-antibodies in a group of middle-aged HIV-infected patients: A cross-sectional exploratory study

Background: Auto-antibodies neutralizing the activity of type I interferons have been recently described in patients infected by SARS-CoV-2. They can be present even before the onset of the infection. Since type I interferons exert a dichotomous role in the pathogenesis of acute versus chronic HIV infection and auto-antibodies are often found in untreated and anti-retroviral treated HIV+ patients, we investigated whether auto-antibodies anti-type I interferons are present at high prevalence in those HIV+ patients with concomitant opportunistic infections (OIs).Methods: The analysis of auto-antibodies against two types of type I interferons (IFN-alpha 2 and IFN-omega) was performed using the ELISA test in 60 patients chronically infected by HIV who showed concomitant infections caused by mycobacterium tuberculosis or nontuberculosis mycobacterium or with active cytomegalovirus infections. Results were compared with those of 283 SARS-CoV-2 swab positive patients showing mild to severe pneumonia. A chi-square (chi(2)) test or the Wilcoxon-Mann-Whitney test were used to compare the HIV+ patient categorical or continuous variables, respectively.Results: A high prevalence of auto-antibodies to type I interferons was found in middle-aged HIV-infected patients with concomitant OIs (11.6% vs. 5.3% in COVID-19 subjects; p < .05). No statistically differences were found for viro/immunological characteristics (CD4 and CD8 cell counts and viral load) between patients with and without type I interferons auto-antibodies.Conclusions: This study, which is the first searching auto-antibodies against type I interferons in HIV-infected patients, demonstrated that their prevalence was higher than that expected by the age of these patients. Furthermore, it indicated that these auto-antibodies are nonspecifically increased in critical SARS-CoV-2 infection but can be found also in other infections

Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves

none9Coronavirus disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical, and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.noneQuaresima, Virginia; Scarpazza, Cristina; Sottini, Alessandra; Fiorini, Chiara; Signorini, Simona; Delmonte, Ottavia Maria; Signorini, Liana; Quiros-Roldan, Eugenia; Imberti, LuisaQuaresima, Virginia; Scarpazza, Cristina; Sottini, Alessandra; Fiorini, Chiara; Signorini, Simona; Delmonte, Ottavia Maria; Signorini, Liana; Quiros-Roldan, Eugenia; Imberti, Luis

Chronic productive cough in young adults is very often due to chronic rhino-sinusitis

BACKGROUND: Chronic productive cough is a common clinical problem; often potential causes outside the lower respiratory tract are forgotten or ignored. The aim of this study was to make a precise etiopathogenetic diagnosis of chronic productive cough in young adults. METHODS: In a clinical setting, 212 subjects (mean age 41+/-5 years) who had reported chronic productive cough in a previous postal survey of a young adult population underwent within two years clinical and functional investigations following a rational diagnostic approach. Two pulmonologists independently established the diagnosis using a clinically structured interview on nasal and respiratory symptoms, spirometry and other tests when appropriate (bronchodilator test or methacholine bronchial challenge, chest radiography); if rhino-sinusitis was suspected, subjects underwent an ENT examination with nasal endoscopy and/or sinus computed tomography. RESULTS: At the end of the diagnostic procedure, 87 subjects (41%) no longer had chronic productive cough and had normal function. Fifty-eight subjects (27%) had chronic rhino-sinusitis; seventeen subjects (8%) had asthma, and of these fourteen also had chronic rhino-sinusitis; 50 subjects (24%) had COPD stage 0+, of these seven also had chronic rhino-sinusitis. Chronic rhino-sinusitis was more frequent in females than in males (p<0.05). CONCLUSIONS: Both in clinical practice and in epidemiological studies, it is important to consider that the origin of chronic productive cough could be frequently outside the lower respiratory tract; a consistent percentage of young adults with persistent productive cough has indeed chronic rhino-sinusitis