Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States.

BACKGROUND: Test-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls. METHODS: Adults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group. RESULTS: 5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64 years, VE was 93 % (95 % CI: 90-94) using syndrome-negative controls and 91 % (95 % CI: 88-93) using test-negative controls. CONCLUSIONS: Despite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.

A UNIQUE CASE OF SEVERE PULMONARY NOCARDIOSIS PRESENTING WITH ARDS AND CARDIOGENIC SHOCK

SESSION TITLE: Shock and Sepsis in the ICU Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Nocardiosis is a rare bacterial infection, which frequently affects immunocompromised patients. It can present as an acute, subacute, or chronic pulmonary infection with non-specific symptoms, such as fever, cough, dyspnea, weight loss, and hemoptysis. CASE PRESENTATION: A 34-year-old female with a history of chronic granulomatous disease and hidradenitis suppurativa on adalimumab presented to the ED with fever, shortness of breath, and productive cough of 2 days. Her vitals were T 101F, BP 66/48, HR 148, RR 42, and SPO2 94% on room air. On exam, she was cachectic, with bilateral crackles and rales in the right lung base. Extremities were cold, with trace pitting edema was present on bilateral lower extremities. COVID-19 PCR was negative. Despite fluid resuscitation, she remained hypotensive and was started on norepinephrine. Blood cultures were collected, and broad-spectrum antibiotics and an antifungal agent were initiated. Chest CT demonstrated bilateral multifocal consolidation with surrounding ground-glass opacities and complete consolidation of the right lower lobe. Due to worsening respiratory distress and tachypnea, and lack of improvement with non-invasive ventilation, she was intubated, placed on mechanical ventilation, and admitted to the Medical ICU. On hospital day 1, due to the patient's immunosuppression, unresolving shock, and radiographic findings, a bronchoscopy with bronchoalveolar lavage (BAL) was performed. On hospital day 2, a transthoracic echocardiogram showed LV ejection fraction of 20-25% with severe global hypokinesis of the LV. ACS workup had been unremarkable, with mildly elevated troponin and no ischemic changes on EKG. She was initiated on cardiac inotropes. On hospital day 3, BAL culture revealed Nocardia cyriacigeorgica. TMP-SMX and ceftriaxone were started for severe pulmonary nocardiosis. On hospital day 11, she was liberated from mechanical ventilation, and by hospital day 14, she was weaned off all pressors and inotropes. Approximately 4 weeks after admission, repeat TTE showed recovery of LV ejection fraction (55-60%) and she was discharged with a prolonged course of TMP-SMX and IV ceftriaxone, with duration to be determined at outpatient infectious disease follow-up. DISCUSSION: We discuss a unique case of severe pulmonary nocardiosis, presenting with ARDS and cardiogenic shock. To the best of our knowledge, this is the first case of a patient with pulmonary nocardiosis presenting with stress cardiomyopathy reported in the literature. While the pathophysiology is not well understood, theorized mechanisms include catecholamine excess, coronary artery spasm, microvascular dysfunction. CONCLUSIONS: This case highlights the need for a broad differential diagnosis in patients presenting with ARDS and cardiogenic shock and illustrates the value of clinical bronchoscopy in patients with unique presenting features. Reference #1: Lerner PI. Nocardiosis. Clin Infect Dis. 1996 Jun;22(6):891-903;quiz 904-5. doi: 10.1093/clinids/22.6.891. PMID: 8783685. Reference #2: Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005 Feb 10;352(6):539-48. doi: 10.1056/NEJMoa043046. PMID: 15703419. Reference #3: Park JH, Kang SJ, Song JK, Kim HK, Lim CM, Kang DH, Koh Y. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest. 2005 Jul;128(1):296-302. doi: 10.1378/chest.128.1.296. PMID: 16002949. DISCLOSURES: no disclosure on file for D. Clark Files;No relevant relationships by Nisha Patel No relevant relationships by Meehir Shah

Effectiveness of mRNA Vaccines Against COVID-19 Hospitalization by Age and Chronic Medical Conditions Burden Among Immunocompetent US Adults, March-August 2021.

Vaccine effectiveness (VE) against COVID-19 hospitalization was evaluated among immunocompetent adults (≥18 years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was 96% (95% confidence interval [CI], 93%-98%) among patients with no chronic medical conditions and 83% (95% CI, 76%-88%) among patients with ≥ 3 categories of conditions. VE was similar between those aged 18-64 years versus ≥65 years (P > .05). VE against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing comorbidity burden.