Association of pulmonary function test abnormalities and quality-of-life measures after COVID-19 infection.

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.

Definition, Epidemiology, and Pathogenesis of Severe Community-Acquired Pneumonia.

The clinical presentation of community-acquired pneumonia (CAP) can vary widely among patients. While many individuals with mild symptoms can be managed as outpatients with excellent outcomes, there is a distinct subgroup of patients who present with severe CAP. In these cases, the mortality rate can reach approximately 25% within 30 days and even up to 50% within a year. It is crucial to focus attention on these patients who are at higher risk. Among the various definitions of severe CAP found in the literature, one commonly used criterion is the requirement for admission to intensive care unit. Notable epidemiological characteristics of these patients include the impact of acute cardiovascular diseases on clinical outcomes and the enduring, independent effect of pneumonia on long-term outcomes. Factors such as pathogen virulence, the presence of comorbidities, and the host response are important contributors to the pathogenesis of severe CAP. In these patients, the host response may be dysregulated and compartmentalized. Gaining a better understanding of the epidemiology and pathogenesis of severe CAP will provide a foundation for the development of new therapies for this condition. This manuscript aims to review the definition, epidemiology, and pathogenesis of severe CAP, shedding light on important aspects that can aid in the improvement of patient care and outcomes.

Influenza and Viral Pneumonia.

Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are in general nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited but there is ongoing research on the development and clinical testing of new treatment regimens and strategies.

Community-Acquired Pneumonia in the Immunocompromised Host: Epidemiology and Outcomes.

Background: The epidemiology and outcomes of community-acquired pneumonia (CAP) in immunocompromised hosts (ICHs) are not well defined. The objective of this study was to define the epidemiology and outcomes of CAP in ICHs as compared with non-ICHs. Methods: This ancillary study included a prospective cohort of hospitalized adult Louisville residents with CAP from 1 June 2014 to 31 May 2016. An ICH was defined per the criteria of the Centers for Disease Control and Prevention. Geospatial epidemiology explored associations between ICHs hospitalized with CAP and income level, race, and age. Mortality for ICHs and non-ICHs was evaluated during hospitalization and 30 days, 6 months, and 1 year after hospitalization. Results: A total of 761 (10%) ICHs were identified among 7449 patients hospitalized with CAP. The most common immunocompromising medical conditions or treatments were advanced-stage cancer (53%), cancer chemotherapy (23%), and corticosteroid use (20%). Clusters of ICHs hospitalized with CAP were found in areas associated with low-income and Black or African American populations. Mortality by time point for ICHs vs non-ICHs was as follows: hospitalization, 9% vs 5%; 30 days, 24% vs 11%; 6 months, 44% vs 21%; and 1 year, 53% vs 27%, respectively. Conclusions: Approximately 1 in 10 hospitalized patients with CAP is immunocompromised, with advanced-stage cancer being the most frequent immunocompromising condition, as seen in half of all patients who are immunocompromised. Risk for hospitalization may be influenced by socioeconomic disparities and/or race. ICHs have a 2-fold increase in mortality as compared with non-ICHs.

Epidemiology of Pneumococcal Pneumonia in Louisville, Kentucky, and Its Estimated Burden of Disease in the United States.

Streptococcus pneumoniae remains a primary pathogen in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to define the epidemiology of pneumococcal pneumonia in Louisville, Kentucky, and to estimate the burden of pneumococcal pneumonia in the United States (US). This study was nested in a prospective population-based cohort study of all adult residents in Louisville, Kentucky, who were hospitalized with CAP from 1 June 2014 to 31 May 2016. In hospitalized patients with CAP, urinary antigen detection of 24 S. pneumoniae serotypes (UAD-24) was performed. The annual population-based pneumococcal pneumonia incidence was calculated. The distribution of S. pneumoniae serotypes was characterized. Ecological associations between pneumococcal pneumonia and income level, race, and age were defined. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Among the 5402 CAP patients with a UAD-24 test performed, 708 (13%) patients had pneumococcal pneumonia. The annual cumulative incidence was 93 pneumococcal pneumonia hospitalizations per 100,000 adults (95% CI = 91-95), corresponding to an estimated 226,696 annual pneumococcal pneumonia hospitalizations in the US. The most frequent serotypes were 19A (12%), 3 (11%), and 22F (11%). Clusters of cases were found in areas with low incomes and a higher proportion of Black or African American population. Pneumococcal pneumonia mortality was 3.7% during hospitalization, 8.2% at 30 days, 17.6% at 6 months, and 25.4% at 1 year after hospitalization. The burden of pneumococcal pneumonia in the US remains significant, with an estimate of more than 225,000 adults hospitalized annually, and approximately 1 out of 4 hospitalized adult patients dies within 1 year after hospitalization.

In Patients Hospitalized for Community-Acquired Pneumonia, SARS-CoV-2 Is Associated with Worse Clinical Outcomes When Compared to Influenza.

SARS-CoV-2 and influenza are primary causes of viral community-acquired pneumonia (CAP). Both pathogens have exhibited high transmissibility and are recognized causes of pandemics. Controversy still exists regarding the clinical outcomes between patients hospitalized with CAP due to these viruses. This secondary analysis identified patients with either influenza or SARS-CoV-2 infections from three cohorts of patients hospitalized for CAP. Clinical outcomes between patients with CAP due to influenza or due to SARS-CoV-2 were evaluated. Primary outcomes included length of stay and in-hospital mortality. To account for population differences between cohorts, each case of influenza CAP was matched to two controls with SARS-CoV-2 CAP. Matching criteria included sex, age, and nursing home residency. Stratified cox-proportional hazards regression or conditional logistic regression were used where appropriate. A total of 259 patients with influenza CAP were matched to two controls with SARS-CoV-2 CAP, totaling to 518 controls. Patients with SARS-CoV-2 CAP were 2.23 times more likely to remain hospitalized at any point in time (95% confidence interval: 1.77-2.80), and had 3.84 times higher odds of dying in-hospital (95% confidence interval: 1.91-7.76) when compared to patients with influenza CAP. After matching and adjusting for confounding variables, patients admitted with SARS-CoV-2 CAP had consistently worse outcomes in comparison to their influenza CAP counterparts. This information can help clinicians decide on the level of care needed for patients with confirmed infections due to these pathogens. Additionally, estimates of disease burden can inform individuals at-risk for poor clinical outcomes, and further highlight the importance of effective preventative strategies.

Polypharmacy Interactions Impacting Methacholine Challenge Testing for Asthma Assessment in Older People.

Objective To investigate potential reasons for unusually high incidence of negative Methacholine Challenge Tests (MCT), following standardized MCT medication-hold protocol, in older people with physician-diagnosed asthma. Design An analysis of a longitudinal observational parent study of asthma. Setting Community-dwelling participants were evaluated in an outpatient clinic and at home. Participants Screening inclusion criteria for the parent study included 60 years of age or older, physician diagnosis of asthma, and a positive response to at least one of six asthma screening questions. Participants were enrolled in the study if they also demonstrate either: (1) a postbronchodilator administration response showing an increase of at least 12% and 200 mL in forced expiratory volume or an increase of at least 12% and 200 mL in forced vital capacity, or (2) an MCT result of PC20 ≤ 16 mg/mL (indicating bronchial hyper-responsiveness, MCT positive). Exclusion criteria included diagnosis of cognitive impairment or dementia, residing in a long-term care facility, more than 20 pack/ year smoking history or a history of smoking within the previous five years, inability to perform pulmonary function testing maneuvers, and a Prognostic Index score of greater than 10. Interventions Analysis of participant data for non-medication- and medication-exposure factors for association with negative MCT results. Results Anticholinergic burden and statin use were positively associated with negative MCT. Conclusion Medications not accounted for in medication-hold protocols, and concurrently in use, may impact clinical tests and outcomes.

Cardiovascular Complications in Coronavirus Disease 2019-Pathogenesis and Management.

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.

Severity of Illness Scores and Biomarkers for Prognosis of Patients with Coronavirus Disease 2019.

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.

Cardiovascular Complications Are the Primary Drivers of Mortality in Hospitalized Patients With SARS-CoV-2 Community-Acquired Pneumonia.

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 Pao2/Fio2 < 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.

How and when to manage respiratory infections out of hospital.

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.

Pneumonia Severity Index and CURB-65 Score Are Good Predictors of Mortality in Hospitalized Patients With SARS-CoV-2 Community-Acquired Pneumonia.

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.

Clinical outcomes in patients with COPD hospitalized with SARS-CoV-2 versus non- SARS-CoV-2 community-acquired pneumonia.

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.

Nutrition Therapy in Non-intubated Patients with Acute Respiratory Failure.

PURPOSE OF REVIEW: A challenging aspect of the care for patients with acute respiratory failure is their nutrition management. This manuscript consists of a literature review on nutrition therapy in non-intubated patients with acute respiratory failure receiving high-flow nasal cannula oxygenation or non-invasive positive pressure ventilation. RECENT FINDINGS: Studies show that non-intubated patients with acute respiratory failure either on non-invasive ventilation or high-flow nasal cannula are largely underfed in the initial phase of their hospitalization. Although data is limited, the available evidence suggests the feasibility of initiating oral diet in the majority of these patients in the early phase. Initial evaluation includes mental status evaluation, the Yale swallowing screening protocol, and an assessment of severity of illness. The goal should be to initiate oral diet within 24 h. If patient cannot initiate oral diet, the reason for not initiating oral diet should dictate the next step. For instance, if the reason is failure of the swallow screening, further evaluation with fiberoptic endoscopy is warranted. The inability to provide oral diet for a patient in respiratory distress may a harbinger of failure of non-invasive oxygen therapy and should prompt consideration for endotracheal intubation. We suggest placement of a small-bore feeding tube for enteral nutrition if patient is unable receive oral diet after 48 h. CONCLUSIONS: The nutrition management of these patients is better provided by a multidisciplinary team in a protocolized manner.

Acute Respiratory Distress Syndrome and Time to Weaning Off the Invasive Mechanical Ventilator among Patients with COVID-19 Pneumonia.

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) pneumonia is the main cause of the pandemic's death toll. The assessment of ARDS and time on invasive mechanical ventilation (IMV) could enhance the characterization of outcomes and management of this condition. This is a city-wide retrospective study of hospitalized patients with COVID-19 pneumonia from 5 March 2020 to 30 June 2020. Patients with critical illness were compared with those with non-critical illness. We examined the severity of ARDS and other factors associated with (i) weaning patients off IMV and (ii) mortality in a city-wide study in Louisville, KY. Of 522 patients with COVID-19 pneumonia, 219 (41.9%) were critically ill. Among critically ill patients, the median age was 60 years; 53% were male, 55% were White and 32% were African American. Of all critically ill patients, 52% had ARDS, and 38% of these had severe ARDS. Of the 25% of patients who were weaned off IMV, those with severe ARDS were weaned within eleven days versus five days for those without severe ARDS, p = 0.023. The overall mortality for critically ill patients was 22% versus 1% for those not critically ill. Furthermore, the 14-day mortality was 31% for patients with severe ARDS and 12% for patients without severe ARDS, p = 0.019. Patients with severe ARDS versus non-severe ARDS needed twice as long to wean off IMV (eleven versus five days) and had double the 14-day mortality of patients without severe ARDS.