To report a clinical case of a patient with a compatible HRCT scan and two negative SARS-CoV-2 RNA upper respiratory tract specimens but with a confirmed viral infection by BAL (19 days after symptom onset). Methods: Revision of a patient's clinical charts with COVID-19 admitted at INMI L. Spallanzani Hospital Results: Two oropharyngeal swab tests of SARS-CoV-2 by qualitative real-time reverse-transcriptasepolymerase-chain-reaction (RT-PCR) assay were performed at admission (17 days from symptoms onset) and a day apart and were found negative. BAL fluid collected 19 days after symptoms onset was positive for SARS-CoV-2. Conclusion: This case highlights importance of clinical suspicion of SARS-CoV-2 infection in diagnosis and infectivity assessment. We suggest collection of BAL fluid when consecutive nasopharyngeal swabs are negative, to confirm or exclude the diagnosis of COVID-19-associated pneumonia. Healthcare workers should perform aerosol-generating procedures in an adequately ventilated room and should wear adequate PPE.

Background: Tuberculosis (TB) can seriously affect the hematopoietic system, with involvement of both myeloid and lymphoid cell lines as well as plasma components. These hematological changes act as a marker for the diagnosis, prognosis and response to therapy. Methods: We searched PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library and WHO websites from 1950 to May 2021 for papers on the interaction between TB and common and rare hematological manifestation. Results: Hematological reactions in patients with TB are possible in both young and old women and men but seem more frequent in the elderly, and they can be predictors of both diagnosis and worse outcome for TB, regardless of whether it is pulmonary, extra pulmonary or miliary. Even anti-TB therapies can cause hematological adverse events, among which some are serious and rare and can compromise the patient’s recovery pathway to completing treatment. Conclusion: Hematological screening and follow-up, including complete blood count and coagulation, are always necessary both at the diagnosis of TB and during antitubercular treatment in order to monitor hematological parameters. Short therapy regimens for multidrug-resistant TB (MDR-TB) may also be useful for reducing hematological toxicity, especially in contexts where this cannot be monitored. Close monitoring of drug interactions and hematological adverse events is always recommended.

Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p < 0.001) had a lower chance of achieving VC. The development of moderate/severe respiratory failure (aOR = 2.65, p = 0.003), a delayed hospital admission after symptoms onset (aOR = 1.18, p < 0.001), having baseline comorbidities (aOR = 1.25, p = 0.019) and D-dimer >1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p < 0.001) and reduced the probability of death/mechanical ventilation (aHR = 0.36, p = 0.002). Conclusions In this study, severity of respiratory disease, comorbidities, delayed hospital admission and inflammatory markers negatively predicted the achievement of VC, which resulted to be associated to better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially in presence of signs of severity or comorbidities.

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate–severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate–severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate–severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate–severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate–severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

Pulmonary thromboembolism (PTE) has been associated with tuberculosis (TB), but the true incidence is unknown. The aim of our study was to retrospectively evaluate the PTE prevalence in TB patients hospitalized at the National Institute for Infectious Diseases L. Spallanzani during the January 2016–December 2021 period. Retrospective data collection and evaluation were conducted. Among 1801 TB patients, 29 (1.61%) exhibited PTE. Twenty (69%) had comorbidities; eleven (37.9%) had predisposing factors for PTE. Nineteen (65.5%) had extensive TB disease. The commonest respiratory symptoms were cough (37.9%), dyspnea (31%), chest pain (10.3%), and hemoptysis (6.9%). Twenty-five (86.2%) had elevated serum D-dimer levels. An increased prevalence of PTE from 0.6% in the pre-COVID-19 pandemic period to 4.6% in the pandemic period was found. Acute respiratory failure and extensive TB disease increased significantly in the pandemic period. The increase in PTE could be explained by the increased severity of TB in patients in the pandemic period and by increased clinical suspicion and, consequently, increased requests for D-dimer testing, including in patients with non-COVID-19 pneumonia. Patients with extensive pulmonary disease are at high risk of developing PTE. Clinicians should be aware of this potentially life-threatening complication of TB, and patients should receive a thromboembolism risk assessment.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high-resolution computed tomography pattern of "definite UIP" is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex-heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.

Idiopathic pulmonary fibrosis (IPF) is a challenging and multifactorial disease that has been thought for some time to lack effective treatments. The approval of two drugs, nintedanib and pirfenidone, has heralded a new era in its management. Areas covered: Currently, there is a growing interest on therapeutic strategies. Many studies have been designed and performed, although few of them turned out to be successful. Nowadays, nintedanib and pirfenidone are considered disease modifying drugs, recommended treatments by current evidence-based guidelines. A combined approach with more than one drug could be an effective strategy in IPF. However, data on combination therapy of the two approved drugs are still scarce, and ongoing trials are evaluating pharmacodynamic interactions and safety. The approved disease modifying drugs are also being assessed in combination with new molecules, showing promising results in preclinical models. Expert opinion: A deeper understanding of pathogenesis and key molecular mechanisms driving disease inception and progression will be key to identify novel agents to be tested both pre-clinically and clinically, possibly in combination with approved treatments. Looking at the near future, it is likely that clinical trials will adopt a phenotype-specific and pathway-specific approach, thus leading towards a personalized approach to IPF management.

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