Evolution of the Clinical Profile and Outcomes of Unvaccinated Patients Affected by Critical COVID-19 Pneumonia from the Pre-Vaccination to the Post-Vaccination Waves in Italy.

The vaccination campaign and the new SARS-CoV-2 variants may have changed the clinical profile and outcomes of patients admitted to sub-intensive unit care. We conducted a retrospective study aimed to compare the clinical and radiological features of unvaccinated critical COVID-19 patients hospitalized during the last pandemic wave (December 2021-February 2022, No-Vax group) and before starting the vaccination campaign (March-December 2020, Pre-Vax group). The No-Vax group was also compared with vaccinated patients of the same pandemic wave (Vax group). With respect to the Pre-Vax group, the No-Vax group contained a higher percentage of smokers (p = 0.0007) and a lower prevalence of males (p = 0.0003). At admission, the No-Vax patients showed both a higher CT score of pneumonia and a worse severe respiratory failure (p < 0.0001). In the No-Vax group, a higher percentage of deaths occurred, though this was not significant. In comparison with the No-Vax group, the Vax patients were older (p = 0.0097), with a higher Charlson comorbidity index (p < 0.0001) and a significantly lower HRCT score (p = 0.0015). The percentage of deaths was not different between the two groups. The No-Vax patients showed a more severe disease in comparison with the Pre-Vax patients, and were younger and had fewer comorbidities than the Vax patients.

Biologicals decrease psychological distress, anxiety and depression in severe asthma, despite Covid-19 pandemic.

Patients with respiratory diseases suffer more from problems of severe psychiatric comorbidity than the general population. Asthma might cause psychiatric disorders and affect patients' quality of life negatively. Previous studies reported that mental disorders prevail in asthmatic patients, causing anxiety, depression, and suicidal risk. The aim of this study is to evaluate in real life the prevalence of psychological comorbidities in asthmatics with severe asthma treated by biologicals (Benralizumab, Mepolizumab, Omalizumab). This study starts with the hypothesis that psychological distress, anxiety, depression and suicidal risk in severe asthma patients decreases if treated by biologicals. This study involves a sample of 90 patients (32 males, 58 females and aged 53.92 ± 15.92) suffering from severe asthma and treated with the biological drugs of Benralizumab, Mepolizumab, Omalizumab during Covid-19 pandemic. At the beginning of the treatment (T0) and after 16 weeks (T1), there have been reported results from both clinical disease control, assessed using the ACT, and psychological disorders, assessed with the PSS, HADS and C-SSRS. In the sample of these patients treated with biologicals for severe asthma, the study reported a significant change in all observed parameters, including asthma control (ACT), stress (PSS), anxiety (HADS-A) and depressive symptoms (HADS-D, despite Covid-19 pandemic. In addition, there was a significant improvement in disease management, perceived stress, anxiety and depressive symptoms after a 16 week treatment for severe asthma, independent from the type of biologic drugs used during the pandemic.

New Onset of Eosinophilic Granulomatosis with Polyangiitis Following mRNA-Based COVID-19 Vaccine.

Anti-SARS-CoV-2 vaccines are safe and effective, also in individuals with allergic and immune-mediated diseases (IMDs). There are reports suggesting that vaccines may be able to trigger de-novo or exacerbate pre-existing IMDs in predisposed individuals. Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis characterized by asthma, eosinophilia, and eosinophil-rich granulomatous inflammation in various tissues. We describe the case of a 63-year-old man who experienced cardiac, pulmonary, and neurological involvement one day after the administration of the booster dose of anti-SARS-CoV-2 vaccine (mRNA-1273). A diagnosis of EGPA was made and the patient was treated with high-dose steroids and cyclophosphamide, with a good clinical response. Interestingly, our patient had experienced a significant worsening of his pre-existing asthma six months earlier, just after the first two vaccine shots with the ChAdOx1 anti-SARS-CoV-2 vaccine. It is impossible to know whether our patient would have had developed EGPA following natural SARS-CoV-2 infection or at some point in his life regardless of infectious stimuli. Nevertheless, our report may suggest that caution should be paid during the administration of additional vaccine doses in individuals who experienced an increase in IMD severity that persisted over time following previous vaccine shots.

Switch from Omalizumab to Benralizumab in Allergic Patients with Severe Eosinophilic Asthma: A Real-Life Experience from Southern Italy.

BACKGROUND: The wide availability of monoclonal antibodies for the add-on therapy of severe asthma currently allows for the personalization of biologic treatment by selecting the most appropriate drug for each patient. However, subjects with overlapping allergic and eosinophilic phenotypes can be often eligible to more than one biologic, so that the first pharmacologic choice can be quite challenging for clinicians. Within such a context, the aim of our real-life investigation was to verify whether allergic patients with severe eosinophilic asthma, not adequately controlled by an initial biologic treatment with omalizumab, could experience better therapeutic results from a pharmacologic shift to benralizumab. PATIENTS AND METHODS: Twenty allergic patients with severe eosinophilic asthma, unsuccessfully treated with omalizumab and then switched to benralizumab, were assessed for at least 1 year in order to detect eventual changes in disease exacerbations, symptom control, oral corticosteroid intake, lung function, and blood eosinophils. RESULTS: In comparison to the previous omalizumab therapy, after 1 year of treatment with benralizumab our patients experienced significant improvements in asthma exacerbation rate (p < 0.01), rescue medication need (p < 0.001), asthma control test (ACT) score (p < 0.05), forced expiratory volume in the first second (FEV1) (p < 0.05), and blood eosinophil count (p < 0.0001). Furthermore, with respect to the end of omalizumab treatment, the score of sino-nasal outcome test-22 (SNOT-22) significantly decreased after therapy with benralizumab (p < 0.05). CONCLUSION: The results of this real-life study suggest that the pharmacologic shift from omalizumab to benralizumab can be a valuable therapeutic approach for allergic patients with severe eosinophilic asthma, not adequately controlled by anti-IgE treatment.

Asthma Control during COVID-19 Lockdown in Patients with Severe Asthma under Biological Drug Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has deeply affected the management of patients with severe asthma, treated with add-on biological therapies. Objective: In this study, severe asthmatic patients on treatment with one of three different biologics (omalizumab, mepolizumab, benralizumab) underwent a survey to evaluate the effects of COVID-19 on the management of their clinical condition, with regard to the changes caused by the limited access to health facilities during the pandemic period. Methods: In this prospective observational study, 28 severe asthmatic outpatients referring to the Respiratory Unit of Magna Graecia University Hospital, Catanzaro (Italy), were asked to answer a telephone survey from May to July 2021. This survey included the evaluation of demographic and clinical data, as well as the number of lung function tests performed, exacerbations, biologic doses administered at hospital, or at general practitioner office, or through self-administration. Adherence to biological therapies before and during the pandemic period was also assessed. Moreover, the most recent asthma control test (ACT) score and the last forced expiratory volume in the first second (FEV1) measurement, recorded during the pandemic phase, were compared to the pre-pandemic (baseline) period. Results: When comparing the pre-pandemic data with the pandemic observations, the mean ACT score and the exacerbation rate did not significantly change [ACT, 21.5 ±2.8 to 23.0 ±3.9 (p = 0.1);exacerbation rate, 0.3 ±0.6 and 0.5 ±1.5 (p = 0.3)]. When considering some variables related to disease management in the same periods, a statistically significant difference was detected with regard to the mean number of outpatient visits (5.2 ±3.8 vs. 0.9 ±2.5, p < 0.0001), as well as to the mean number of accesses to health facilities for the administration of biological drugs (from 7.0 ±3.4 to 2.5 ±3.9, p < 0.0001). None of the patients reported to have been infected with the SARS-CoV-2 virus and no adverse drug reactions (ADR) occurred during the study. Conclusions: The above results suggest that COVID-19 pandemic did not induce any significant change related to severe asthma control. Indeed, add-on treatment with biological drugs was regularly continued, despite the obvious limited access to health facilities.

MALDI MS-Based Investigations for SARS-CoV-2 Detection

The urgent need to fight the COVID-19 pandemic has impressively stimulated the efforts of the international scientific community, providing an extraordinary wealth of studies. After the sequence of the virus became available in early January 2020, safe and effective vaccines were developed in a time frame much shorter than everybody expected. However, additional studies are required since viral mutations have the potential of facilitating viral transmission, thus reducing the efficacy of developed vaccines. Therefore, improving the current laboratory testing methods and developing new rapid and reliable diagnostic approaches might be useful in managing contact tracing in the fight against both the original SARS-CoV-2 strain and the new, potentially fast-spreading CoV-2 variants. Mass Spectrometry (MS)-based testing methods are being explored, with the challenging promise to overcome the many limitations arising from currently used laboratory testing assays. More specifically, MALDI-MS, since its advent in the mid 1980s, has demonstrated without any doubt the great potential to overcome many unresolved analytical challenges, becoming an effective proteomic tool in several applications, including pathogen identification. With the aim of highlighting the challenges and opportunities that derive from MALDI-based approaches for the detection of SARS-CoV-2 and its variants, we extensively examined the most promising proofs of concept for MALDI studies related to the COVID-19 outbreak.

Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence.

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab's therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

Mapping the SARS-CoV-2-Host Protein-Protein Interactome by Affinity Purification Mass Spectrometry and Proximity-Dependent Biotin Labeling: A Rational and Straightforward Route to Discover Host-Directed Anti-SARS-CoV-2 Therapeutics.

Protein-protein interactions (PPIs) are the vital engine of cellular machinery. After virus entry in host cells the global organization of the viral life cycle is strongly regulated by the formation of virus-host protein interactions. With the advent of high-throughput -omics platforms, the mirage to obtain a "high resolution" view of virus-host interactions has come true. In fact, the rapidly expanding approaches of mass spectrometry (MS)-based proteomics in the study of PPIs provide efficient tools to identify a significant number of potential drug targets. Generation of PPIs maps by affinity purification-MS and by the more recent proximity labeling-MS may help to uncover cellular processes hijacked and/or altered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing promising therapeutic targets. The possibility to further validate putative key targets from high-confidence interactions between viral bait and host protein through follow-up MS-based multi-omics experiments offers an unprecedented opportunity in the drug discovery pipeline. In particular, drug repurposing, making use of already existing approved drugs directly targeting these identified and validated host interactors, might shorten the time and reduce the costs in comparison to the traditional drug discovery process. This route might be promising for finding effective antiviral therapeutic options providing a turning point in the fight against the coronavirus disease-2019 (COVID-19) outbreak.

Oxygen therapy via high flow nasal cannula in severe respiratory failure caused by Sars-Cov-2 infection: a real-life observational study.

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death.In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man-machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS.The reviews of this paper are available via the supplemental material section.

Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications.

The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.

Allergy clinics in times of the SARS-CoV-2 pandemic: an integrated model.

BACKGROUND: Almost the entire World is experiencing the Coronavirus-Disease-2019 (COVID-19) pandemic, responsible, at the end of May 2020, of more than five million people infected worldwide and about 350,000 deaths. In this context, a deep reorganization of allergy clinics, in order to ensure proper diagnosis and care despite of social distancing measures expose, is needed. MAIN TEXT: The reorganization of allergy clinics should include programmed checks for severe and poorly controlled patients, application of digital medicine service for mild-to-moderate disease in well-controlled ones, postponement of non urgent diagnostic work-ups and domiciliation of therapies, whenever possible. As far as therapies, allergen immunotherapy (AIT) should not be stopped and sublingual immunotherapy (SLIT) fits perfectly for this purpose, since a drug home-delivery service can be activated for the entire pandemic duration. Moreover, biologic agents for severe asthma, chronic spontaneous urticaria and atopic dermatitis should be particularly encouraged to achieve best control possible of severe disease in times of COVID-19 and, whenever possible, home-delivery and self-administration should be the preferred choice. CONCLUSION: During COVID-19 pandemic, allergists have the responsibility of balancing individual patients' needs with public health issues, and innovative tools, such as telemedicine and digital medicine services, can be helpful to reduce the risk of viral spreading while delivering up-to-date personalized care.