The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

Beyond the lung involvement in COVID-19 patients.

Since COVID-19 spread all over the world becoming a pandemic illness, researchers have better characterized route of virus transmissibility and clinical signs and symptoms of the disease. Since viral transmission occurs through the droplets emitted during coughing or sneezing, the lungs are primarily affected. However, SARS-CoV-2 can affect several human organs due to high expressions of ACE2 receptor which is the main viral target, and the virus may affect not only higher and lower respiratory tracts, but also heart, kidney, gastro enteric tract, liver, pancreas, nervous system and skin. This review focuses on extra pulmonary involvement underlying atypical presentation of COVID-19. There is a great body of evidence concerning several human organ abnormalities associated to the SARS-CoV-2, enough to consider COVID-19 as a multisystemic and polyhedral disease.

Coronavirus Disease 2019: COSeSco - A Risk Assessment Score to Predict the Risk of Pulmonary Sequelae in COVID-19 Patients.

BACKGROUND: The presence of interstitial pneumonia in coronavirus disease 2019 (COVID-19) patients, as diagnosed through laboratory, functional, and radiological data, provides potential predicting factors of pulmonary sequelae. OBJECTIVES: The objectives were the creation of a risk assessment score for pulmonary sequelae at high-resolution computed tomography (HRCT) through the assessment of laboratory data, lung function, and radiological changes in patients after the onset of COVID-19 interstitial pneumonia and the identification of predictive factors. METHODS: We enrolled 121 subjects hospitalized due to COVID-19 pneumonia in our study. Clinical features, Charlson Comorbidity Index (CCI) score, HRCT score, and blood chemistry data at hospital admission, as well as HRCT score, pulmonary function testing values, exercise capacity by means of a 6-Minute Walk Test (6MWT), and dyspnea perception by the modified Medical Research Council (mMRC) at 4-month follow-up, were all recorded. The variables were elaborated in order to create a predictive model to identify patients at high risk of pulmonary sequelae at HRCT. RESULTS: At the time of follow-up visit, 63% of patients had functional abnormality (diffusion lung capacity and/or total lung capacity <80% of predicted). Age, BMI, CCI, D-dimer, 6MWT, and mMRC were included in the COVID-19 Sequelae Score (COSeSco, ranging 0-15), which was able to individuate COVID-19 patients with radiologic sequelae (HRCT score >10%) at follow-up. The most revelatory COSeSco value that was found to intercept the highest sensitivity (100%) and specificity (77%) was 2. CONCLUSION: The COSeSco - comprising age, BMI, comorbidities, D-dimer, walking distance, and dyspnea perception - makes it possible to identify particularly at-risk COVID-19 patients who are likely to develop pulmonary sequelae assessed by HRCT.

Sex-Related Differences in Long-COVID-19 Syndrome.

Background: Sex differences have been demonstrated in the acute phase of coronavirus disease 2019 (COVID-19). Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance. Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex. Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.

Platypnea-Orthodeoxia Syndrome after SARS-CoV-2 interstitial pneumonia: an overview and an update on our patient.

Platypnea-Orthodeoxia Syndrome (POS) is a clinical entity defined as positional dyspnoea (platypnea) and arterial desaturation (orthodeoxia) that occurs when sitting or standing up and usually resolves by lying down. Up to April 25th 2021, eleven cases of POS after SARS-CoV-2 pneumonia have been reported on Pubmed. Accordingly, SARS-CoV-2 infection may be considered as an emergent cause of POS due to an increase in ventilation/perfusion (V/Q) mismatch. In this article we provide an update on the patient with POS after fibrotic evolution of SARS-CoV-2 interstitial pneumonia, which we previously reported and we discuss the case reports of POS due to SARS-CoV-2 infection.

Sex-related differences in long COVID-19 syndrome

Aims Sex-differences have been demonstrated in the acute phase of COVID-19 infection;females (f) were found to be less prone to develop a severe disease than males (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods and results The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection from a sex-perspective. For this purpose, we enrolled 223 patients (89 F and 134 M) who experienced a SARS-CoV-2 infection. In the acute phase of the illness, females reported more frequently than males: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhoea, and myalgia without significant differences in breathlessness, cough, and sleep disturbance. After a mean follow-up time of 5 months after the acute phase, females were significantly more likely than males to report weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnoea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough and sleep disturbance were not influenced by sex. Conclusions We demonstrated that females were more symptomatic than males not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID syndrome because it is a significant predictor of persistent symptoms in females, such as dyspnoea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex-perspective in order to implement early preventive and personalized therapeutic strategies.

Dexamethasone in Patients Hospitalized with COVID-19: Whether, When and to Whom.

A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9-65.1, p < 0.05) in all patients, 8.3 (95%CI 6.0-13.1, p < 0.05) in patients receiving invasive mechanical ventilation, and 34.6 (95%CI 22.1-79.0, p < 0.05) in patients receiving oxygen only (with or without noninvasive ventilation). Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 (95%CI 18.1-50.9, p < 0.05). NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9-20.6) in subjects <70 years, 27.0 (95%CI 18.5-49.8) in men, and 16.2 (95%CI 13.2-20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support.

Long-Term Cardiac Sequelae in Patients Referred into a Diagnostic Post-COVID-19 Pathway: The Different Impacts on the Right and Left Ventricles.

Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 consecutive patients who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow-up visit. Clinical features' data about the acute phase along with information about the follow-up visit, including ECG and Echocardiographic parameters, were recorded. At an average follow-up of 5 months, echocardiography showed morpho-functional characteristics of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and bi-ventricular systolic-diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated with chest High-Resolution computed tomography score and hemodynamic Instability (HI), and with C-reactive protein, respectively. Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies.

What happens to people's lungs when they get coronavirus disease 2019?

The novel coronavirus SARS-CoV-2 was first identified in Wuhan in December 2019 as cause of the consequent novel coronavirus disease 2019 (COVID-19). The virus has since spread worldwide. The clinical presentation following human infection ranges from a mild upper respiratory tract infection to severe acute respiratory distress syndrome and sepsis. We reviewed literature using Pubmed to identify relevant English-language articles published until April 15, 2020. Search terms include novel coronavirus pneumonia, severe acute respiratory syndrome coronavirus 2, coronavirus and ventilation. We summarized what SARS-CoV-2 infection means for the lungs.