Research Spotlight

Thompson, M. G., E. Stenehjem, S. Grannis, S. W. Ball, A. L. Naleway, T. C. Ong, M. B. DeSilva, K. Natarajan, C. H. Bozio, N. Lewis, K. Dascomb, B. E. Dixon, R. J. Birch, S. A. Irving, S. Rao, E. Kharbanda, J. Han, S. Reynolds, K. Goddard, N. Grisel, W. F. Fadel, M. E. Levy, J. Ferdinands, B. Fireman, J. Arndorfer, N. R. Valvi, E. A. Rowley, P. Patel, O. Zerbo, E. P. Griggs, R. M. Porter, M. Demarco, L. Blanton, A. Steffens, Y. Zhuang, N. Olson, M. Barron, P. Shifflett, S. J. Schrag, J. R. Verani, A. Fry, M. Gaglani, E. Azziz-Baumgartner and N. P. Klein (2021). “Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.” N Engl J Med 385(15): 1355-1371.

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BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

Self, W. H., M. W. Tenforde, J. P. Rhoads, M. Gaglani, A. A. Ginde, D. J. Douin, S. M. Olson, H. K. Talbot, J. D. Casey, N. M. Mohr, A. Zepeski, T. McNeal, S. Ghamande, K. W. Gibbs, D. C. Files, D. N. Hager, A. Shehu, M. E. Prekker, H. L. Erickson, M. N. Gong, A. Mohamed, D. J. Henning, J. S. Steingrub, I. D. Peltan, S. M. Brown, E. T. Martin, A. S. Monto, A. Khan, C. L. Hough, L. W. Busse, C. C. Ten Lohuis, A. Duggal, J. G. Wilson, A. J. Gordon, N. Qadir, S. Y. Chang, C. Mallow, C. Rivas, H. M. Babcock, J. H. Kwon, M. C. Exline, N. Halasa, J. D. Chappell, A. S. Lauring, C. G. Grijalva, T. W. Rice, I. D. Jones, W. B. Stubblefield, A. Baughman, K. N. Womack, C. J. Lindsell, K. W. Hart, Y. Zhu, L. Mills, S. N. Lester, M. M. Stumpf, E. A. Naioti, M. Kobayashi, J. R. Verani, N. J. Thornburg and M. M. Patel (2021). “Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions – United States, March-August 2021.” MMWR Morb Mortal Wkly Rep 70(38): 1337-1343.

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Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.

Kim, S. S., J. R. Chung, E. A. Belongia, H. Q. McLean, J. P. King, M. P. Nowalk, R. K. Zimmerman, G. K. Balasubramani, E. T. Martin, A. S. Monto, L. E. Lamerato, M. Gaglani, M. E. Smith, K. M. Dunnigan, M. L. Jackson, L. A. Jackson, M. W. Tenforde, J. R. Verani, M. Kobayashi, S. Schrag, M. M. Patel and B. Flannery (2021). “mRNA Vaccine Effectiveness against COVID-19 among Symptomatic Outpatients Aged ≥16 Years in the United States, February – May 2021.” J Infect Dis.

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Evaluations of vaccine effectiveness (VE) are important to monitor as COVID-19 vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or SARS-CoV-2 testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, VE of mRNA vaccines against COVID-19 was 91% (95% CI: 83-95) for full vaccination and 75% (95% CI: 55-87) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Jeffery, A. D., J. A. Werthman, V. Danesh, M. S. Dietrich, L. C. Mion and L. M. Boehm (2021). “Assess, Prevent, and Manage Pain; Both Spontaneous Awakening and Breathing Trials; Choice of Analgesia/Sedation; Delirium: Assess, Prevent, and Manage; Early Mobility; Family Engagement and Empowerment Bundle Implementation: Quantifying the Association of Access to Bundle-Enhancing Supplies and Equipment.” Crit Care Explor 3(9): e0525.

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Describe the physical environment factors (i.e., availability, accessibility) of bundle-enhancing items and the association of physical environment with bundle adherence. DESIGN: This multicenter, exploratory, cross-sectional study used data from two ICU-based randomized controlled trials that measured daily bundle adherence. Unit- and patient-level data collection occurred between 2011 and 2016. We developed hierarchical logistic regression models using Frequentist and Bayesian frameworks. SETTING: The study included 10 medical and surgical ICUs in six academic medical centers in the United States. PATIENTS: Adults with qualifying respiratory failure and/or septic shock (e.g., mechanical ventilation, vasopressor use) were included in the randomized controlled trials. INTERVENTIONS: The Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility bundle was recommended standard of care for randomized controlled trial patients and adherence tracked daily. MEASUREMENTS AND MAIN RESULTS: The primary outcome was adherence to the full bundle and the early mobility bundle component as identified from daily adherence documentation (n = 751 patient observations). Models included unit-level measures such as minimum and maximum distances to bundle-enhancing items and patient-level age, body mass index, and daily mechanical ventilation status. Some models suggested the following variables were influential: unit size (larger associated with decreased adherence), a standard walker (presence associated with increased adherence), and age (older associated with decreased adherence). In all cases, mechanical ventilation was associated with decreased bundle adherence. CONCLUSIONS: Both unit- and patient-level factors were associated with full bundle and early mobility adherence. There is potential benefit of physical proximity to essential items for Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility bundle and early mobility adherence. Future studies with larger sample sizes should explore how equipment location and availability influence practice.

Cox, M., J. Thatcher, D. Graybeal and J. Hise (2021). “Intrasinus tPA for Successful Treatment of Extensive Dural Sinus Thrombosis in a Young Patient With COVID-19: Rationale and Protocol.” Neurohospitalist 11(4): 382-384.

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A 34-year-old with a recent diagnosis of COVID-19 with mild symptoms (fever, cough, mild dyspnea on exertion), presented to an outside hospital with severe headaches and nausea. Other than COVID-19, her only other notable history was the use of oral contraceptives. Her initial non-contrast CT scan was reportedly normal. She was discharged home with anti-emetics and medications for pain control. Her symptoms persisted, and she presented to our emergency department for repeat evaluation. [No abstract; excerpt from article].