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Background: Long-COVID is a multisystem disease that can lead to significant impairments in health-related quality of life (HRQoL). Following COVID-19 infection, abnormalities on pulmonary function tests (PFT) are common. The primary aim of this study is to evaluate for any correlation between PFT abnormalities and impairment in HRQoL scores following COVID-19 infection., Methods: This is an analysis of a prospective cohort of patients in Louisville, KY who were infected with COVID-19. Data collected included demographics, past medical history, laboratory tests, PFTs, and several HRQoL questionnaires such as the EuroQol 5 Dimension HRQoL questionnaire (EQ-5D-5 L), Generalized Anxiety Disorder 7 (GAD-7), Patient Health Questionnaire (PHQ-9), and Posttraumatic stress disorder checklist for DSM-5 (PCL-5). Descriptive statistics were performed, comparing PFTs (normal vs abnormal) and time since COVID-19 infection (3- vs 6- vs ≥ 12 months)., Results: There were no significant differences in FEV1, FVC, or the percentage of patients with abnormal PFTs over time after COVID-19 infection. Following COVID-19, patients with normal PFTs had worse impairment in mobility HRQoL scores and change in GAD-7 scores over time. There were no differences over time in any of the HRQoL scores among patients with abnormal PFTs., Conclusions: Among patients with an abnormal PFT, there was no temporal association with HRQoL scores as measured by EQ-5D-5 L, GAD-7, PHQ-9, and PCL-5. Among patients with a normal PFT, mobility impairment and anxiety may be associated with COVID-19 infection. Following COVID-19 infection, impairment in HRQoL scores is not completely explained by the presence of abnormalities on spirometry., Competing Interests: Declaration of competing interest This work was supported by Gilead Sciences COMMIT COVID-19 RFP Program [grant number IN-US-983–6063]; National Center For Advancing Translational Sciences [grant number U18TR003787]; National Institute of Environmental Health Sciences [grant number P30 (P30ES030283)]; National Heart, Lung and Blood Institute 1R01HL158779–01; National Institute of Allergy and Infectious Diseases 1R01AI172873–01. Otherwise, all authors declare no other conflicts of interest in relation to this work., (Published by Elsevier Inc.)

Background: Hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) and associated comorbidities are at increased risk of cardiovascular complications. The magnitude of effect of cardiovascular complications and the role of prior comorbidities on clinical outcomes are not well defined., Research Question: What is the impact of cardiovascular complications on mortality in hospitalized patients with SARS-CoV-2 CAP? What is the impact of comorbidities and other risk factors on the risk of developing cardiovascular complications and mortality in these patients?, Study Design and Methods: This cohort study included 1,645 hospitalized patients with SARS-CoV-2 CAP. Cardiovascular complications were evaluated. The clinical course during hospitalization was described by using a multistate model with four states: (1) hospitalized with no cardiovascular complications; (2) hospitalized with cardiovascular complications; (3) discharged alive; (4) and dead. Cox proportional hazards regression was used to analyze the impact of prior comorbid conditions on transitions between these states. Hazard ratios (HRs) and 95% CIs are reported., Results: Cardiovascular complications occurred in 18% of patients hospitalized with SARS-CoV-2 CAP. The mortality rate in this group was 45% vs 13% in patients without cardiovascular complications. Male subjects (HR, 1.32; 95% CI, 1.03-1.68), older adults (HR, 1.34; 95% CI, 1.03-1.75), and patients with congestive heart failure (HR, 1.59; 95% CI, 1.18-2.15), coronary artery disease (HR, 1.34; 95% CI, 1.00-1.79), atrial fibrillation (HR, 1.43; 95% CI, 1.06-1.95), direct admissions to the ICU (HR, 1.77; 95% CI, 1.36-2.32), and Pao 2 /Fio 2  < 200 (HR, 1.46; 95% CI, 1.11-1.92) were more likely to develop cardiovascular complications following hospitalization for SARS-CoV-2 CAP; however, these factors are not associated with increased risk of death following a cardiovascular complication., Interpretation: Prior comorbidities, older age, male sex, severity of illness, and hypoxemia are associated with increased risk of cardiovascular complications. Once patients develop cardiovascular complications, the risk of death is extremely high. Cardiovascular complications are the primary drivers of mortality in hospitalized patients with SARS-CoV-2 CAP., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has caused a devastating impact on morbidity and mortality around the world. Severe acute respiratory syndrome-coronavirus-2 has a characteristic tropism for the cardiovascular system by entering the host cells and binding to angiotensin-converting enzyme 2 receptors, which are expressed in different cells, particularly endothelial cells. This endothelial injury is linked by a direct intracellular viral invasion leading to inflammation, microthrombosis, and angiogenesis. COVID-19 has been associated with acute myocarditis, cardiac arrhythmias, new onset or worsening heart failure, ischemic heart disease, stroke, and thromboembolic disease. This review summarizes key relevant literature regarding the epidemiology, diagnosis, treatment, and preventive measures related to cardiovascular complications in the setting of COVID-19., Competing Interests: None declared., (Thieme. All rights reserved.)

The spectrum of disease severity and the insidiousness of clinical presentation make it difficult to recognize patients with coronavirus disease 2019 (COVID-19) at higher risk of worse outcomes or death when they are seen in the early phases of the disease. There are now well-established risk factors for worse outcomes in patients with COVID-19. These should be factored in when assessing the prognosis of these patients. However, a more precise prognostic assessment in an individual patient may warrant the use of predictive tools. In this manuscript, we conduct a literature review on the severity of illness scores and biomarkers for the prognosis of patients with COVID-19. Several COVID-19-specific scores have been developed since the onset of the pandemic. Some of them are promising and can be integrated into the assessment of these patients. We also found that the well-known pneumonia severity index (PSI) and CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) are good predictors of mortality in hospitalized patients with COVID-19. While neither the PSI nor the CURB-65 should be used for the triage of outpatient versus inpatient treatment, they can be integrated by a clinician into the assessment of disease severity and can be used in epidemiological studies to determine the severity of illness in patient populations. Biomarkers also provide valuable prognostic information and, importantly, may depict the main physiological derangements in severe disease. We, however, do not advocate the isolated use of severity of illness scores or biomarkers for decision-making in an individual patient. Instead, we suggest the use of these tools on a case-by-case basis with the goal of enhancing clinician judgment., Competing Interests: None declared., (Thieme. All rights reserved.)

Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They are a major cause of death worldwide and often affect the most vulnerable: children, elderly and the impoverished. In this paper, we review the clinical presentation, diagnosis, severity assessment and treatment of adult outpatients with lower respiratory infections. The paper is divided into sections on specific lower respiratory infections, but we also dedicate a section to COVID-19 given the importance of the ongoing pandemic. Lower respiratory infections are heterogeneous entities, carry different risks for adverse events, and require different management strategies. For instance, while patients with acute bronchitis are rarely admitted to hospital and generally do not require antimicrobials, approximately 40% of patients seen for community-acquired pneumonia require admission. Clinicians caring for patients with lower respiratory infections face several challenges, including an increasing population of patients with immunosuppression, potential need for diagnostic tests that may not be readily available, antibiotic resistance and social aspects that place these patients at higher risk. Management principles for patients with lower respiratory infections include knowledge of local surveillance data, strategic use of diagnostic tests according to surveillance data, and judicious use of antimicrobials., Competing Interests: Conflict of interest: R. Cavallazzi has nothing to disclose. Conflict of interest: J.A. Ramirez reports grants or contracts from Pfizer (institutional payment for research); consulting fees from Dompe (personal payment); and participation on a Data Safety Monitoring Board or Advisory Board for Paratek (personal payment), all outside the submitted work., (Copyright ©The authors 2022.)

Background: The Confusion, Urea > 7 mM, Respiratory Rate ≥ 30 breaths/min, BP < 90 mm Hg (Systolic) or < 60 mm Hg (Diastolic), Age ≥ 65 Years (CURB-65) score and the Pneumonia Severity Index (PSI) are well-established clinical prediction rules for predicting mortality in patients hospitalized with community-acquired pneumonia (CAP). SARS-CoV-2 has emerged as a new etiologic agent for CAP, but the role of CURB-65 score and PSI have not been established., Research Question: How effective are CURB-65 score and PSI at predicting in-hospital mortality resulting from SARS-CoV-2 CAP compared with non-SARS-CoV-2 CAP? Can these clinical prediction rules be optimized to predict mortality in SARS-CoV-2 CAP by addition of procalcitonin and D-dimer?, Study Design and Methods: Secondary analysis of two prospective cohorts of patients with SARS-CoV-2 CAP or non-SARS-CoV-2 CAP from eight adult hospitals in Louisville, Kentucky., Results: The in-hospital mortality rate was 19% for patients with SARS-CoV-2 CAP and 6.5% for patients with non-SARS-CoV-2 CAP. For the PSI score, receiver operating characteristic (ROC) curve analysis resulted in an area under the ROC curve (AUC) of 0.82 (95% CI, 0.78-0.86) and 0.79 (95% CI, 0.77-0.80) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. For the CURB-65 score, ROC analysis resulted in an AUC of 0.79 (95% CI, 0.75-0.84) and 0.75 (95% CI, 0.73-0.77) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. In SARS-CoV-2 CAP, the addition of D-dimer (optimal cutoff, 1,813 μg/mL) and procalcitonin (optimal cutoff, 0.19 ng/mL) to PSI and CURB-65 score provided negligible improvement in prognostic performance., Interpretation: PSI and CURB-65 score can predict in-hospital mortality for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP comparatively. In patients with SARS-CoV-2 CAP, the inclusion of either D-dimer or procalcitonin to PSI or CURB-65 score did not improve the prognostic performance of either score. In patients with CAP, regardless of cause, PSI and CURB-65 score remain adequate for predicting mortality in clinical practice., (Published by Elsevier Inc.)

Background: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD., Methods: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality., Results: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death., Conclusion: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.