Amount and distribution of parenchymal abnormalities at CT-scan do not predict awake prone position outcome in Covid-19

Background: Even if definitive evidence is still missing, prone position in non-intubated hypoxemic patients with Covid-19 is largely used. The aim of the present study was to investigate whether the amount and distribution of lung abnormalities evaluated by CT-scan can predict the improvement of oxygenation when Covid-19 patients undergoing non-invasive ventilation (NIV) are turned prone. Method(s): Retrospective monocentric study of severe Covid-19 patients who underwent NIV and prone position, evaluated with a basal chest CT-scan. Result(s): Forty-five severe Covid-19 patients were considered. On average 50% of the overall lung volume was involved by pneumonia at CT-scan, with ground glass, and consolidation accounting for 44, and 4%, respectively. The parenchymal abnormalities were predominantly posterior, as demonstrated by a posterior/anterior ratio of ground glass and consolidation of 1.5, and 4.4, respectively. PaO2/FiO2, whose basal value under NIV in supine position was 140 [IQR 108;169] improved on average by 67% (+98) during prone position. Once supine position was resumed, improvement in oxygenation was maintained in 28 patients (62% of the overall population, categorized as "responders"). We did not find significant difference between responders and non-responders in terms of the amount and distribution of parenchymal abnormalities. No correlation emerged between the distribution of parenchymal abnormalies and changes in oxygenation in supine position before and after prone position (R2 = 0.009, p= 0.526). Conclusion(s): the amount and distribution of lung abnormalities evaluated by CT-scan do not predict the response to awake prone position in patients with severe Covid-19 pneumonia undergoing non-invasive ventilation.

Shunt fraction in Covid-19 related Acute Respiratory Failure

Background: Failing autoregulation of pulmonary vessels and higher shunt have been described in Covid-19 related Acute respiratory failure (ARF). The aim was to investigate shunt fraction in patients with Covid-19-ARF compared to patients with other causes of ARF. Method(s): Observational study of hospitalized patients with Covid-19-ARF and other causes of ARF at Papa Giovanni XXIII Hospital, Bergamo, Italy between June 2020 and November 2021. Shunt fraction was measured by a non-invasive system during spontaneous breathing (BeaconCaresystem). Result(s): We enrolled 51 adult patients (8 female), mean age (+/-SD) 65+/-13 years and mean BMI 28,3+/-5,3 Kg/m2. Covid-19-ARF patients represented 71% (36/51). Community acquired pneumonia was the most common cause of other ARF (11/15). No differences in terms of age and BMI were described between the two groups. Pulmonary gas exchange impairment was similar, median PaO2/FIO2 ratio was 254 [IQR 162,297] in Covid-19-ARF and 269 [IQR 201,296] in other causes of ARF patients (p=0.41). Nevertheless, mean shunt fraction resulted significantly increased in Covid-19-ARF (18+/-6%) than other causes of ARF patients (12+/-9%;p=0.03) Fig. 1. Conclusion(s): Shunt fraction appears to be increased in Covid-19-ARF if compared to patients with other causes of ARF. However, this is the first study proposing this non-invasive method to measure shunt fraction in ARF and further investigations are needed to validate this technique.

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.

Long-term cardiopulmonary exercise outcomes among COVID-19 survivors: preliminary insights from an Italian study

Introduction: Early studies on the short- and medium-term cardiopulmonary sequalae of COVID-19 have shown a certain degree of exercise capacity impairment among survivors (Naeije R, Caravita S. Eur Respir J 2021;58:2101763). Whether such condition is reversible at longer follow-up is unknown. Aim(s): To assess the long-term cardiopulmonary exercise outcomes of COVID-19 in survivors who displayed a reduced exercise capacity shortly after recovery. We tested the hypothesis that physical reconditioning following hospital discharge would improve the aerobic performance and exercise capacity. Method(s): In this observational study 19 COVID-19 survivors who displayed a reduced exercise capacity 6 months after discharge (Rinaldo RF et al. Eur Respir J 2021;58:2100870) underwent reevaluation with CPET between April - May 2022. Lung function and CPET data were recorded. Result(s): At 2 year follow-up, the proportion of patients with a normal exercise capacity (12/19) was statistically significantly different from baseline (0/19), p-value 0.000 (exact McNemar's test). Among the parameters of oxygen delivery/utilization there was an overall statistically significant improvement of the anaerobic threshold (47% vs 54%). Conclusion(s): On a small group of patients, our study supports the hypothesis that exercise capacity impairment after COVID-19 is reversible at longer follow-up, with signs of an improved aerobic performance.

Where are we with the use of N-acetylcysteine as a preventive and adjuvant treatment for COVID-19?

OBJECTIVE: As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS: A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS: NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS: Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.

Severe respiratory failure in COVID19 patients was associated with higher transaminases values during the disease outbreak

Background: Sars-Cov-2 pneumonia is a pandemic disease with high morbidity and mortality In literature transaminases were frequently found abnormal but their role has not been clarified, particularly in patients with liver disease (LD). Aim of this retrospective study is to explore the role of transaminases on short-term prognosis of hospitalized COVID-19 patients Methods: patients admitted in hospital for respiratory failure due to Sars-Cov-2 were consecutively recruited Primary endpoint: evaluate role of transaminases on disease progression (DP). Secondary endpoints: find possible risk factors for (1) mortality and (2) composite outcome consisting of DP or death Results: 135 patients included Median age was 68 years (IQR 58-74), 33 3% (n=45) were female AST/ ALT at admission and after 7 days were abnormal in about two/thirds of cases CPAP patients had transaminases more frequently abnormal (p=0 01) Transaminases alterations were predictive of DP at univariate analysis In multivariate analysis CRP at day 7 was predictor of DP (OR 3 08 and 1 08) while cardiopathy and ventilation type at admission were significantly associated with death (OR 9.95 and 11.5). Conclusion: This study individuates possible prognostic factors in Sars-Cov-2 pneumonia Transaminases values do not predict DP or death, even if more severe patients have a higher prevalence of transaminases elevation CRP at day 7 is a predictor of DP, while cardiopathy and type of ventilation at admission are predictive factors of short-term mortality.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.