Insights into the lung microenvironment after severe COVID-19

The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.

Standardization of Procedures to Contain Cost and Reduce Variability of Care After the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our private and professional routine. In particular, the lockdowns have severely affected the entire healthcare system and hospital activities, forcing it to rethink the protocols in force. We suggest that this scenario, in spite of the new challenges involving so far complex healthcare providers, may lead to the unique opportunity to rethink pathways and management of patients. Indeed, having to resume institutional activity after a long interruption that has completely canceled the previously existing schemes, healthcare providers have the unique opportunity to overcome obsolete and "we have always done in this way" model on the wave of the general desire to resume a normal life. Furthermore, the pandemic has highlighted some flaws in our health system, highlighting those critical issues that most need to be addressed. This article is a review of pre-pandemic literature addressing the use of Lean Six Sigma (LSS) and standardization processes in thoracic surgery to improve efficiency. Our goal is to identify the main issues that could be successfully improved along the entire pathway of a patient from the first referral to diagnosis, hospitalization, and surgical operation up to convalescence. Furthermore, we aim to identify the standardization processes that have been implemented to achieve significant improvements in patient outcomes while reducing costs. The methods and goals that could be used in the near future to modernize our healthcare systems are drawn up from a careful reading and interpretation in light of the pandemic of the most significant review articles in the literature.

SABR-BRIDGE: Stereotactic ABlative Radiotherapy Before Resection to AvoId Delay for Early-Stage LunG Cancer or OligomEts During the COVID-19 Pandemic.

Surgical resection is the standard-of-care approach for early-stage non-small cell lung cancer (NSCLC). Surgery is also considered an acceptable standard infit patients with oligometastatic lesions in the lungs. The COVID-19 pandemic has led to worldwide issues with access to operating room time, with patients and physicians facing uncertainty as to when surgical resection will be available, with likely delays of months. Further compounding this are concerns about increased risks of respiratory complications with lung cancer surgery during active phases of the pandemic. In this setting, many thoracic oncology teams are embracing a paradigm where stereotactic ablative radiotherapy (SABR) is used as a bridge, to provide radical-intent treatment based on a combination of immediate SABR followed by planned surgery in 3-6 months. This pragmatic approach to treatment has been named SABR-BRIDGE (Stereotactic ABlative Radiotherapy Before Resection to avoId Delay for early-stage lunG cancer or oligomEts). This term has also been applied to the pragmatic study of the outcomes of this approach. In this paper, we discuss the standards of care in treatment of early-stage (NSCLC) and pulmonary oligometastases, the impetus for the SABR-BRIDGE approach, and the controversies surrounding assessment of pathological response to neo-adjuvant radiation therapy.