Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.

Among the secondary fungal infections in Coronavirus-19 (COVID-19) infection, Aspergillosis has been reported more often than Mucormycosis. Disseminated mucormycosis is almost always a disease of severely immunosuppressed hosts. We report a young obese Asian male who was admitted with an acute anterior cerebral artery (ACA) territory infarct and severe COVID-19 pneumonitis to the intensive care unit (ICU). He had a complicated stay with recurrent episodes of vasoplegic shock and multi-organ dysfunction. At autopsy, he was confirmed to have disseminated mucormycosis. We believe this to be the first documented case of disseminated mucormycosis in an immunocompetent host with COVID-19 infection. The lack of sensitive non-invasive modalities and biomarkers to diagnose mucormycosis, along with the extremely high mortality in untreated cases, present a unique challenge to clinicians dealing with critically ill patients with COVID-19.

Pulmonary vein thrombosis represents a potentially fatal disease. This syndrome may clinically mimic pulmonary embolism but has a different investigation strategy and prognosis. Pulmonary vein thrombosis is difficult to diagnose clinically and usually requires a combination of conventionally used diagnostic modalities. The authors report a case of a 78-year-old previously healthy female presenting with collapse and shortness of breath. Serum biochemistry revealed acute kidney injury, positive D-dimmer's and increased C reactive protein. Chest radiography demonstrated volume loss in the right lung. The patient was started on antibiotics and also therapeutic doses of low molecular weight heparin. The working diagnosis included community acquired pneumonia & pulmonary embolism. A computed tomography pulmonary angiogram was performed to confirm the clinical suspicions of pulmonary embolism. This demonstrated a thrombus in the pulmonary vein, with associated fibrosis and volume loss of the right lower lobe. A subsequent thrombophilia screen revealed a positive lupus anticoagulant antibody and rheumatoid factor and also decreased anti thrombin III and protein C levels. The urine protein/creatinine ratio was found to be 553 mg/mmol. The diagnosis of this patient was therefore of idiopathic pulmonary fibrosis associated with pulmonary vein thrombosis. Whether or not the pulmonary vein thrombosis was a primary cause of the fibrosis or a consequence of it was unclear. There are few data on the management of pulmonary vein thrombosis, but anticoagulation, antibiotics, and, in cases of large pulmonary vein thrombosis, thrombectomy or pulmonary resection have been used.

Non-invasive ventilation (NIV) is a clinically proven, cost-effective intervention for acidotic exacerbations of COPD that is recommended by UK national guidelines. This study examines the extent to which these recommendations are being followed in the UK. Between August and October 2003 a national audit of COPD exacerbations was conducted by the Royal College of Physicians and the British Thoracic Society. 233 (94%) UK hospitals submitted data for 7,529 prospectively recruited acute COPD admissions, documenting process of care and outcomes from a retrospective case note audit. They also completed a resources and organisation of care proforma. Nineteen hospitals (8%) reported they did not offer NIV. There was no access to NIV in 92 (39%) intensive care units in 88 (36%), high-dependency units or on general wards of 85 (34%) hospitals. In 74 (30%) NIV was available on all 3 sites. A low pH (<7.35) was noted at some time during admission for 26% (1714/6544) of patients and NIV was administered to 31%. Patients receiving NIV were more often admitted under a respiratory physician, or seen at some stage by a respiratory specialist and had more severe disease (higher PaCO2 (median 9.8 v 7.8 kPa), lower oxygen tension (median 8.8 v 9.8 kPa), higher incidence of peripheral oedema (48% v 39%), of pneumonia (27% v 16%), higher in-hospital mortality (26% v 14%) and at 90 days (37% v 24%) and longer hospital stays (median 9 v 7 days) than those not receiving NIV. Hospitals with least usage of NIV had similar mortality rates to those using NIV more often. A comprehensive NIV service is not available in many hospitals admitting patients with acute respiratory failure secondary to COPD. Access to acute NIV is inadequate and does not conform with NICE and BTS guidelines. These observational audit data do not demonstrate benefits of NIV on survival when compared to conventional management, contrary to results from randomised trials. Reasons for this are unclear but unmeasured confounding factors and poor patient selection for NIV are likely explanations.

Both acute and advanced heart failure are an increasing threat in term of survival, quality of life and socio-economical burdens. Paradoxically, the use of successful treatments for chronic heart failure can prolong life but—per definition—causes the rise in age of patients experiencing acute decompensations, since nothing at the moment helps avoiding an acute or final stage in the elderly population. To complicate the picture, acute heart failure syndromes are a collection of symptoms, signs and markers, with different aetiologies and different courses, also due to overlapping morbidities and to the plethora of chronic medications. The palette of cardio- and vasoactive drugs used in the hospitalization phase to stabilize the patient’s hemodynamic is scarce and even scarcer is the evidence for the agents commonly used in the practice (e.g., catecholamines). The pipeline in this field is poor and the clinical development chronically unsuccessful. Recent set backs in expected clinical trials for new agents in acute heart failure (AHF) (omecamtiv, serelaxine, ularitide) left a field desolately empty, where only few drugs have been approved for clinical use, for example, levosimendan and nesiritide. In this consensus opinion paper, experts from 26 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Israel, Italy, The Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, U.K. and Ukraine) analyse the situation in details also by help of artificial intelligence applied to bibliographic searches, try to distil some lesson-learned to avoid that future projects would make the same mistakes as in the past and recommend how to lead a successful development project in this field in dire need of new agents.

Antibacterial-resistant gram-negative hospital-acquired infections result in significant morbidity and mortality. In clinical trials, ceftolozane/tazobactam (C/T) has been effective against these infections; however, real-world findings are limited. SPECTRA was a global, retrospective, observational inpatient study of adults treated with C/T for ≥48 hours, conducted between 2016 and 2020. The primary objective was to describe real-world utilisation of C/T: socio-demographic, clinical characteristics, prescribing patterns, clinical outcomes, and healthcare resource utilisation in hospitalized patients treated with C/T. In total, 617 patients from 7 countries met inclusion criteria. Most (82.7%) had ≥1 comorbidity. The most common medical conditions where C/T was used were pneumonia (29.5%), sepsis (20.4%), complicated intra-abdominal infection (15.1%), and complicated urinary tract infection (14.4%). The most common pathogens were Pseudomonas aeruginosa (87.4%) and Escherichia coli (8.2%). Median C/T treatment duration was 11 days. Clinical success occurred in 67.3% of patients (including those with 'unknown' status in the denominator). In a separate analysis that excluded those with 'unknown' status, clinical success ranged from 94.1% in patients with bacteraemia to 58.9% with sepsis. Overall, 18.8% of patients had documented microbiologic response. All-cause in-hospital mortality was 21.2%; infection-related mortality was 7.6%. Median hospital length of stay was 42 days (30 days for those who received early C/T therapy [before pathogen identification] vs. 48 days for definitive therapy [after identification]). These data elucidate real-world utilisation and prescribing patterns of C/T in a diverse patient population with complex medical conditions and various profiles of pathogen resistance between 2016 and 2020.