The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Travel from the United Kingdom to the United States by a Symptomatic Patient Infected with the SARS-CoV-2 B.1.1.7 Variant - Texas, January 2021.

In December 2020, the B.1.1.7 genetic variant of SARS-CoV-2, the virus that causes COVID-19, was first reported after emergence and rapid circulation in the United Kingdom (1). Evidence suggests that the B.1.1.7 variant is more efficiently transmitted than are other SARS-CoV-2 variants, and widespread circulation could thereby increase SARS-CoV-2 infection and hospitalization rates (1,2). The first reported SARS-CoV-2 B.1.1.7 variant case in the United States was confirmed by sequencing in Colorado on December 29, 2020.* This report describes a person who traveled from the United Kingdom to the United States after experiencing COVID-19-compatible symptoms† and was eventually confirmed to be infected with the B.1.1.7 variant.

Achromobacter xylosoxidans/denitrificans Bacteremia in a Patient With Good's Syndrome.

Good's syndrome is a rare, adult-onset immunodeficiency syndrome associated with thymomas. Here, we present a 71-year-old, previously healthy male with a history of opportunistic infections status post-thymectomy, who presented with a septic knee complicated with bacteremia without any inciting factor. Therefore, a diagnosis of Good syndrome was made. While this is a rare disease, clinicians should have a high suspicion in patients with a history of thymoma. Early diagnosis and treatment can reduce opportunistic infections and improve morbidity and mortality.

Improving death certificate completion: a trial of two training interventions.

The death certificate is an important medical document that impacts mortality statistics and health care policy. Resident physician accuracy in completing death certificates is poor. We assessed the impact of two educational interventions on the quality of death certificate completion by resident physicians. Two-hundred and nineteen internal medicine residents were asked to complete a cause of death statement using a sample case of in-hospital death. Participants were randomized into one of two educational interventions: either an interactive workshop (group I) or provided with printed instruction material (group II). A total of 200 residents completed the study, with 100 in each group. At baseline, competency in death certificate completion was poor. Only 19% of residents achieved an optimal test score. Sixty percent erroneously identified a cardiac cause of death. The death certificate score improved significantly in both group I (14+/-6 vs 24+/-5, p<0.001) and group II (14+/-5 vs 19+/-5, p<0.001) postintervention from baseline. Group I had a higher degree of improvement than group II (24+/-5 vs 19+/-5, p<0.001). Resident physicians' skills in death certificate completion can be improved with an educational intervention. An interactive workshop is a more effective intervention than a printed handout.

Mental stress provokes ischemia in coronary artery disease subjects without exercise- or adenosine-induced ischemia.

OBJECTIVES: The purpose of this study was to investigate the possibility that some patients with coronary artery disease (CAD) but negative exercise or chemical stress test results might have mental stress-induced ischemia. The study population consisted solely of those with negative test results. BACKGROUND: Mental stress-induced ischemia has been reported in 20% to 70% of CAD subjects with exercise-induced ischemia. Because mechanisms of exercise and mental stress-induced ischemia may differ, we studied whether mental stress would produce ischemia in a proportion of subjects with CAD who have no inducible ischemia with exercise or pharmacologic tests. METHODS: Twenty-one subjects (14 men, 7 women) with a mean age of 67 years and with a documented history of CAD were studied. All subjects had a recent negative nuclear stress test result (exercise or chemical). Subjects completed a speaking task involving role playing a difficult interpersonal situation. A total of 30 mCi 99mTc-sestamibi was injected at one minute into the speech, and imaging was started 40 min later. A resting image obtained within one week was compared with the stress image. Images were analyzed for number and severity of perfusion defects. The summed difference score based on the difference between summed stress and rest scores was calculated. Severity was assessed using a semiquantitative scoring method from zero to four. RESULTS: Six of 21 (29%) subjects demonstrated reversible ischemia (summed difference score > or =3) with mental stress. No subject had chest pain or electrocardiographic changes during the stressor. Mean systolic and diastolic blood pressure and heart rate all increased between resting and times of peak stress. CONCLUSIONS: Mental stress may produce ischemia in some subjects with CAD and negative exercise or chemical nuclear stress test results.

Acute and chronic psychological stress in coronary disease.

PURPOSE OF REVIEW: Coronary artery disease (CAD) is the leading cause of death in the United States and other developed countries. Along with a number of other factors thought to contribute to the high prevalence of CAD in developed societies (longer life expectancy, obesity, sedentary lifestyles), various psychological and social factors appear to promote the development or worsening of heart disease. It is well recognized that stress can be harmful to the cardiovascular system. The combination of the preexisting vulnerability and the major stressor are believed to result in cardiac arrhythmias and/or plaque rupture leading to death. RECENT FINDINGS: Recently, the epidemiologic evidence of a link between stress and CAD is very convincing, yet the biopsychosocial pathway that would explain how stress can lead to disease is less clear. Different types of psychological stress have been found to be associated with increased cardiovascular events. Evidence regarding the efficacy of psychosocial interventions is also presented. SUMMARY: It is suggested that, taken as a whole, evidence for a psychological and social impact on CAD morbidity and mortality is convincing.