Misdiagnosis of Clostridioides difficile Infections by Standard-of-Care Specimen Collection and Testing among Hospitalized Adults, Louisville, Kentucky, USA, 2019-20201.

Although Clostridioides difficile infection (CDI) incidence is high in the United States, standard-of-care (SOC) stool collection and testing practices might result in incidence overestimation or underestimation. We conducted diarrhea surveillance among inpatients >50 years of age in Louisville, Kentucky, USA, during October 14, 2019-October 13, 2020; concurrent SOC stool collection and CDI testing occurred independently. A study CDI case was nucleic acid amplification test‒/cytotoxicity neutralization assay‒positive or nucleic acid amplification test‒positive stool in a patient with pseudomembranous colitis. Study incidence was adjusted for hospitalization share and specimen collection rate and, in a sensitivity analysis, for diarrhea cases without study testing. SOC hospitalized CDI incidence was 121/100,000 population/year; study incidence was 154/100,000 population/year and, in sensitivity analysis, 202/100,000 population/year. Of 75 SOC CDI cases, 12 (16.0%) were not study diagnosed; of 109 study CDI cases, 44 (40.4%) were not SOC diagnosed. CDI incidence estimates based on SOC CDI testing are probably underestimated.

Cardiovascular complications are the primary drivers of mortality in hospitalized patients with SARS-CoV-2 community-acquired pneumonia.

BACKGROUND: Hospitalized patients with severe acute respiratory syndrome coronavirus 2 (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 co-morbidities 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 using a multistate model with 4 states: hospitalized with no cardiovascular complications, hospitalized with cardiovascular complications, discharged alive, 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% confidence intervals (CIs) were reported. RESULTS: Cardiovascular complications occurred in 18% of patients hospitalized with SARS-CoV-2 CAP. The mortality rate in this group was 45% versus 13% in patients without cardiovascular complications. Males (HR: 1.32, 95% CI: 1.03-1.68), older adults (HR: 1.34, 95% CI: 1.03-1.75), 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 less than 200 (HR: 1.46, 95% CI: 1.11-1.92) were more likely to develop cardiovascular complications after hospitalization for SARS-CoV-2 CAP; however, these factors are not associated with increased risk of death after a cardiovascular complication.

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.

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.

Impact of Hyperglycemia on Cardiovascular Events and Clinical Outcomes in Patients Hospitalized With COVID-19 Pneumonia.

OBJECTIVE: To study cardiovascular events and clinical outcomes in patients with elevated glycated hemoglobin (HbA1c) levels and/or admission hyperglycemia and those with type 2 diabetes hospitalized with SARS-CoV-2 pneumonia. METHODS: This was a multicenter retrospective study of 1645 patients hospitalized with SARS-CoV-2 pneumonia. Diagnosis of SARS-CoV-2 pneumonia required a positive reverse transcription-polymerase chain reaction result for SARS-CoV-2, presence of new or worsening pulmonary infiltrates on computed tomography scan or chest x-ray, and at least one of following: (1) new or increased cough, (2) temperature of >37.8 °C, or (3) dyspnea. Outcomes included in-hospital cardiovascular events, intensive care unit admission, and mortality. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association of elevated HbA1c levels and/or admission hyperglycemia and type 2 diabetes for individual outcomes. RESULTS: Among 1645 adults hospitalized with SARS-CoV-2 pneumonia, 18 with type 1 diabetes were excluded from the analysis. Of 1627 adults, 634 (39%) had known diagnosis of type 2 diabetes, and among 993 patients with no diabetes, 107 (10.8%) patients were identified with elevated HbA1c levels and/or admission hyperglycemia. Patients with elevated HbA1c levels and/or admission hyperglycemia had increased odds of developing acute in-hospital cardiovascular events (OR, 1.73; 95% CI, 1.07-2.80), intensive care unit admissions (OR, 1.61; 95% CI, 1.10-2.34), and mortality (OR, 1.77; 95% CI, 1.02-3.07) compared to patients with type 2 diabetes and no diabetes. CONCLUSION: Patients with elevated HbA1c levels and/or admission hyperglycemia hospitalized with SARS-CoV-2 pneumonia have increased risk of developing acute in-hospital cardiovascular complications and overall poor clinical outcomes compared with patients with type 2 diabetes and no diabetes.

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.

Association and predictive value of biomarkers with severe outcomes in hospitalized patients with SARS-CoV-2 infection.

This study analyzed the levels at admission of biomarkers for their association with and ability to predict risk of severe outcomes, including admission to the ICU, need for invasive mechanical ventilation (IMV), need for vasopressor use (VU), and in-hospital mortality (IHM) in 700 patients hospitalized with COVID-19. Biomarker data split by outcomes was compared using Mann-Whitney U tests; frequencies of biomarker values were compared using Chi-square tests and multivariable logistic regression analysis was performed to look at the impact of biomarkers by outcome. Patients that suffered IHM were more likely to have reduced platelet numbers and high blood urea nitrogen (BUN) levels among patients admitted to the ICU. Risk factors for mortality were related to hyper-coagulability (low platelet count and increased D-dimer) and decreased respiratory (PaO2/FiO2 ratio) and kidney function (BUN). Association with risks of other severe outcomes were as follows: ICU with hyper-inflammation (IL-6) and decreased respiratory function; IMV with low platelet count, abnormal neutrophil-lymphocyte ratio with reduced respiratory function, VU with inflammatory markers (IL-6), and low platelet count with respiratory function. Our studies confirmed the association of biomarkers of hematological, inflammatory, coagulation, pulmonary and kidney functions with disease severity. Whether these biomarkers have any mechanistic or causal role in the disease progress requires further investigation.

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.

Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients.

Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.

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.

Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients.

OBJECTIVE: To analyze outcomes and risk factors of cardiovascular events in a metropolitan coronavirus disease 2019 (COVID-19) database, and to perform a subgroup analysis in African American populations to determine whether outcomes and risk factors are influenced by race. DESIGN: Retrospective cohort analysis from March 9, 2020 to June 20, 2020. SETTING: Population-based study in Louisville, KY, USA. PARTICIPANTS: Seven hundred adult inpatients hospitalized with COVID-19. INTERVENTIONS: N/A. MEASUREMENTS AND MAIN RESULTS: This cohort consisted of 126 patients (18%) with cardiovascular events and 574 patients without cardiovascular events. Patients with cardiovascular events had a much higher mortality rate than those without cardiovascular events (45.2% v 8.7%, p < 0.001). There was no difference between African American and white patients regarding mortality (43.9% v 46.3%, p = 1) and length of stay for survivors (11 days v 9.5 days, p = 0.301). Multiple logistics regression analysis suggested that male, race, lower SaO2/FIO2, higher serum potassium, lower serum albumin, and number of cardiovascular comorbidities were highly associated with the occurrence of cardiovascular events in COVID-19 patients. Lower serum albumin and neoplastic and/or immune-compromised diseases were highly associated with cardiovascular events for African American COVID-19 patients. SaO2/FIO2 ratio and cardiovascular comorbidity count were significantly associated with cardiovascular events in white patients. CONCLUSIONS: Cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.