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Item Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA.1 and BA.2/BA.2.12.1 Sublineages Predominated — VISION Network, 10 States, December 2021–June 2022(Center for Disease Control, 2022-07-22) Link-Gelles, Ruth; Levy, Matthew E.; Gaglani, Manjusha; Irving, Stephanie A.; Stockwell, Melissa; Dascomb, Kristin; DeSilva, Malini B.; Reese, Sarah E.; Liao, I-Chia; Ong, Toan C.; Grannis, Shaun J.; McEvoy, Charlene; Patel, Palak; Klein, Nicola P.; Hartmann, Emily; Stenehjem, Edward; Natarajan, Karthik; Naleway, Allison L.; Murthy, Kempapura; Rao, Suchitra; Dixon, Brian E.; Kharbanda, Anupam B.; Akinseye, Akintunde; Dickerson, Monica; Lewis, Ned; Grisel, Nancy; Han, Jungmi; Barron, Michelle A.; Fadel, William F.; Dunne, Margaret M.; Goddard, Kristin; Arndorfer, Julie; Konatham, Deepika; Valvi, Nimish R.; Currey, J. C.; Fireman, Bruce; Raiyani, Chandni; Zerbo, Ousseny; Sloan-Aagard, Chantel; Ball, Sarah W.; Thompson, Mark G.; Tenforde, Mark W.; Epidemiology, Richard M. Fairbanks School of Public HealthThe Omicron variant (B.1.1.529) of SARS-CoV-2, the virus that causes COVID-19, was first identified in the United States in November 2021, with the BA.1 sublineage (including BA.1.1) causing the largest surge in COVID-19 cases to date. Omicron sublineages BA.2 and BA.2.12.1 emerged later and by late April 2022, accounted for most cases.* Estimates of COVID-19 vaccine effectiveness (VE) can be reduced by newly emerging variants or sublineages that evade vaccine-induced immunity (1), protection from previous SARS-CoV-2 infection in unvaccinated persons (2), or increasing time since vaccination (3). Real-world data comparing VE during the periods when the BA.1 and BA.2/BA.2.12.1 predominated (BA.1 period and BA.2/BA.2.12.1 period, respectively) are limited. The VISION network† examined 214,487 emergency department/urgent care (ED/UC) visits and 58,782 hospitalizations with a COVID-19-like illness§ diagnosis among 10 states during December 18, 2021-June 10, 2022, to evaluate VE of 2, 3, and 4 doses of mRNA COVID-19 vaccines (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) compared with no vaccination among adults without immunocompromising conditions. VE against COVID-19-associated hospitalization 7-119 days and ≥120 days after receipt of dose 3 was 92% (95% CI = 91%-93%) and 85% (95% CI = 81%-89%), respectively, during the BA.1 period, compared with 69% (95% CI = 58%-76%) and 52% (95% CI = 44%-59%), respectively, during the BA.2/BA.2.12.1 period. Patterns were similar for ED/UC encounters. Among adults aged ≥50 years, VE against COVID-19-associated hospitalization ≥120 days after receipt of dose 3 was 55% (95% CI = 46%-62%) and ≥7 days (median = 27 days) after a fourth dose was 80% (95% CI = 71%-85%) during BA.2/BA.2.12.1 predominance. Immunocompetent persons should receive recommended COVID-19 booster doses to prevent moderate to severe COVID-19, including a first booster dose for all eligible persons and second booster dose for adults aged ≥50 years at least 4 months after an initial booster dose. Booster doses should be obtained immediately when persons become eligible.Item Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults — Nine States, January–September 2021(CDC, 2021-11) Embi, Peter J.; Levy, Matthew E.; Naleway, Allison L.; Patel, Palak; Gaglani, Manjusha; Natarajan, Karthik; Dascomb, Kristin; Ong, Toan C.; Klein, Nicola P.; Liao, I-Chia; Grannis, Shaun J.; Han, Jungmi; Stenehjem, Edward; Dunne, Margaret M.; Lewis, Ned; Irving, Stephanie A.; Rao, Suchitra; McEvoy, Charlene; Bozio, Catherine H.; Murthy, Kempapura; Dixon, Brian E.; Grisel, Nancy; Yang, Duck-Hye; Goddard, Kristin; Kharbanda, Anupam B.; Reynolds, Sue; Raiyani, Chandni; Fadel, William F.; Arndorfer, Julie; Rowley, Elizabeth A.; Fireman, Bruce; Ferdinands, Jill; Valvi, Nimish R.; Ball, Sarah W.; Zerbo, Ousseny; Griggs, Eric P.; Mitchell, Patrick K.; Porter, Rachael M.; Kiduko, Salome A.; Blanton, Lenee; Zhuang, Yan; Steffens, Andrea; Reese, Sarah E.; Olson, Natalie; Williams, Jeremiah; Dickerson, Monica; McMorrow, Meredith; Schrag, Stephanie J.; Verani, Jennifer R.; Fry, Alicia M.; Azziz-Baumgartner, Eduardo; Barron, Michelle A.; Thompson, Mark G.; DeSilva, Malini B.; Medicine, School of MedicineWhat is already known about this topic? Studies suggest that immunocompromised persons who receive COVID-19 vaccination might not develop high neutralizing antibody titers or be as protected against severe COVID-19 outcomes as are immunocompetent persons. What is added by this report? Effectiveness of mRNA vaccination against laboratory-confirmed COVID-19–associated hospitalization was lower (77%) among immunocompromised adults than among immunocompetent adults (90%). Vaccine effectiveness varied considerably among immunocompromised patient subgroups. What are the implications for public health practice? Immunocompromised persons benefit from COVID-19 mRNA vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations, practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.Item Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022(U.S. Department of Health & Human Services, 2022-01-28) Thompson, Mark G.; Natarajan, Karthik; Irving, Stephanie A.; Rowley, Elizabeth A.; Griggs, Eric P.; Gaglani, Manjusha; Klein, Nicola P.; Grannis, Shaun J.; DeSilva, Malini B.; Stenehjem, Edward; Reese, Sarah E.; Dickerson, Monica; Naleway, Allison L.; Han, Jungmi; Konatham, Deepika; McEvoy, Charlene; Rao, Suchitra; Dixon, Brian E.; Dascomb, Kristin; Lewis, Ned; Levy, Matthew E.; Patel, Palak; Liao, I-Chia; Kharbanda, Anupam B.; Barron, Michelle A.; Fadel, William F.; Grisel, Nancy; Goddard, Kristin; Yang, Duck-Hye; Wondimu, Mehiret H.; Murthy, Kempapura; Valvi, Nimish R.; Arndorfer, Julie; Fireman, Bruce; Dunne, Margaret M.; Embi, Peter; Azziz-Baumgartner, Eduardo; Zerbo, Ousseny; Bozio, Catherine H.; Reynolds, Sue; Ferdinands, Jill; Williams, Jeremiah; Link-Gelles, Ruth; Schrag, Stephanie J.; Verani, Jennifer R.; Ball, Sarah; Ong, Toan C.; Family Medicine, School of MedicineItem Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults During SARS-CoV-2 Omicron Predominance — VISION Network, 10 States, December 2021—August 2022(U.S. Department of Health & Human Services, 2022-10-21) Britton, Amadea; Embi, Peter J.; Levy, Matthew E.; Gaglani, Manjusha; DeSilva, Malini B.; Dixon, Brian E.; Dascomb, Kristin; Patel, Palak; Schrader, Kristin E.; Klein, Nicola P.; Ong, Toan C.; Natarajan, Karthik; Hartmann, Emily; Kharbanda, Anupam B.; Irving, Stephanie A.; Dickerson, Monica; Dunne, Margaret M.; Raiyani, Chandni; Grannis, Shaun J.; Stenehjem, Edward; Zerbo, Ousseny; Rao, Suchitra; Han, Jungmi; Sloan-Aagard, Chantel; Griggs, Eric P.; Weber, Zachary A.; Murthy, Kempapura; Fadel, William F.; Grisel, Nancy; McEvoy, Charlene; Lewis, Ned; Barron, Michelle A.; Nanez, Juan; Reese, Sarah E.; Mamawala, Mufaddal; Valvi, Nimish R.; Arndorfer, Julie; Goddard, Kristin; Yang, Duck-Hye; Fireman, Bruce; Ball, Sarah W.; Link-Gelles, Ruth; Naleway, Allison L.; Tenforde, Mark W.; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineeringItem Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5–17 Years — VISION Network, 10 States, April 2021–January 2022(Centers for Disease Control and Prevention, 2022-03-04) Klein, Nicola P.; Stockwell, Melissa S.; Demarco, Maria; Gaglani, Manjusha; Kharbanda, Anupam B.; Irving, Stephanie A.; Rao, Suchitra; Grannis, Shaun J.; Dascomb, Kristin; Murthy, Kempapura; Rowley, Elizabeth A.; Dalton, Alexandra F.; DeSilva, Malini B.; Dixon, Brian E.; Natarajan, Karthik; Stenehjem, Edward; Naleway, Allison L.; Lewis, Ned; Ong, Toan C.; Patel, Palak; Konatham, Deepika; Embi, Peter J.; Reese, Sarah E.; Han, Jungmi; Grisel, Nancy; Goddard, Kristin; Barron, Michelle A.; Dickerson, Monica; Liao , I-Chia; Fadel, William F.; Yang, Duck-Hye; Arndorfer, Julie; Fireman, Bruce; Griggs, Eric P.; Valvi, Nimish R.; Hallowell, Carly; Zerbo, Ousseny; Reynolds, Sue; Ferdinands, Jill; Wondimu, Mehiret H.; Williams, Jeremiah; Bozio, Catherine H.; Link-Gelles, Ruth; Azziz-Baumgartner, Eduardo; Schrag, Stephanie J.; Thompson, Mark G.; Verani, Jennifer R.; Family Medicine, School of MedicineItem Effectiveness of COVID-19 vaccines at preventing emergency department or urgent care encounters and hospitalizations among immunocompromised adults: An observational study of real-world data across 10 US states from August-December 2021(Elsevier, 2023) Embi, Peter J.; Levy, Matthew E.; Patel, Palak; DeSilva, Malini B.; Gaglani, Manjusha; Dascomb, Kristin; Dunne, Margaret M.; Klein, Nicola P.; Ong, Toan C.; Grannis, Shaun J.; Natarajan, Karthik; Yang, Duck-Hye; Stenehjem, Edward; Zerbo, Ousseny; McEvoy, Charlene; Rao, Suchitra; Thompson, Mark G.; Konatham, Deepika; Irving, Stephanie A.; Dixon, Brian E.; Han, Jungmi; Schrader, Kristin E.; Grisel, Nancy; Lewis, Ned; Kharbanda, Anupam B.; Barron, Michelle A.; Reynolds, Sue; Liao, I-Chia; Fadel, William F.; Rowley, Elizabeth A.; Arndorfer, Julie; Goddard, Kristin; Murthy, Kempapura; Valvi, Nimish R.; Weber, Zachary A.; Fireman, Bruce; Reese, Sarah E.; Ball, Sarah W.; Naleway, Allison L.; Medicine, School of MedicineBackground: Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. Methods: Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19-associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. Results: We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. Conclusions: During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19-associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.Item Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults - VISION Network, 10 States, December 2021-March 2022(Center for Disease Control, 2022-04-01) Natarajan, Karthik; Prasad, Namrata; Dascomb, Kristin; Irving, Stephanie A.; Yang, Duck-Hye; Gaglani, Manjusha; Klein, Nicola P.; DeSilva, Malini B.; Ong, Toan C.; Grannis, Shaun J.; Stenehjem, Edward; Link-Gelles, Ruth; Rowley, Elizabeth A.; Naleway, Allison L.; Han, Jungmi; Raiyani, Chandni; Vazquez Benitez, Gabriela; Rao, Suchitra; Lewis, Ned; Fadel, William F.; Grisel, Nancy; Griggs, Eric P.; Dunne, Margaret M.; Stockwell, Melissa S.; Mamawala, Mufaddal; McEvoy, Charlene; Barron, Michelle A.; Goddard, Kristin; Valvi, Nimish R.; Arndorfer, Julie; Patel, Palak; Mitchell, Patrick K.; Smith, Michael; Kharbanda, Anupam B.; Fireman, Bruce; Embi, Peter J.; Dickerson, Monica; Davis, Jonathan M.; Zerbo, Ousseny; Dalton, Alexandra F.; Wondimu, Mehiret H.; Azziz-Baumgartner, Eduardo; Bozio, Catherine H.; Reynolds, Sue; Ferdinands, Jill; Williams, Jeremiah; Schrag, Stephanie J.; Verani, Jennifer R.; Ball, Sarah; Thompson, Mark G.; Dixon, Brian E.; Community and Global Health, Richard M. Fairbanks School of Public HealthCDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome† (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.Item Estimation of COVID-19 mRNA Vaccine Effectiveness Against Medically Attended COVID-19 in Pregnancy During Periods of Delta and Omicron Variant Predominance in the United States(American Medical Association, 2022-09-01) Schrag, Stephanie J.; Verani, Jennifer R.; Dixon, Brian E.; Page, Jessica M.; Butterfield, Kristen A.; Gaglani, Manjusha; Vazquez-Benitez, Gabriela; Zerbo, Ousseny; Natarajan, Karthik; Ong, Toan C.; Lazariu, Victoria; Rao, Suchitra; Beaver, Ryan; Ellington, Sascha R.; Klein, Nicola P.; Irving, Stephanie A.; Grannis, Shaun J.; Kiduko, Salome; Barron, Michelle A.; Midturi, John; Dickerson, Monica; Lewis, Ned; Stockwell, Melissa S.; Stenehjem, Edward; Fadel, William F.; Link-Gelles, Ruth; Murthy, Kempapura; Goddard, Kristin; Grisel, Nancy; Valvi, Nimish R.; Fireman, Bruce; Arndorfer, Julie; Konatham, Deepika; Ball, Sarah; Thompson, Mark G.; Naleway, Allison L.; Epidemiology, School of Public HealthImportance: Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed. Objective: To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance. Design, setting, and participants: This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19-like illness (CLI) who underwent SARS-CoV-2 molecular testing. Exposures: Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated. Main outcomes and measures: Estimated VE against laboratory-confirmed COVID-19-associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 - aOR) × 100%. Results: Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19-associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19-associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, -49% to 37%), 42% (95% CI, -16% to 72%), 79% (95% CI, 59% to 89%), and -124% (95% CI, -414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, -102% to 93%), 86% (95% CI, 28% to 97%), and -53% (95% CI, -1254% to 83%), respectively. Conclusions and relevance: In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19-associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.Item Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study(Oxford University Press, 2024) Bergin, Stephen P.; Chemaly, Roy F.; Dadwal, Sanjeet S.; Hill, Joshua A.; Lee, Yeon Joo; Haidar, Ghady; Luk, Alfred; Drelick, Alexander; Chin-Hong, Peter V.; Benamu, Esther; Khawaja, Fareed; Nanayakkara, Deepa; Papanicolaou, Genovefa A.; Butkus Small, Catherine; Fung, Monica; Barron, Michelle A.; Davis, Thomas; McClain, Micah T.; Maziarz, Eileen K.; Madut, Deng B.; Bedoya, Armando D.; Gilstrap, Daniel L.; Todd, Jamie L.; Barkauskas, Christina E.; Bigelow, Robert; Leimberger, Jeffrey D.; Tsalik, Ephraim L.; Wolf, Olivia; Mughar, Mona; Hollemon, Desiree; Duttagupta, Radha; Lupu, Daniel S.; Bercovici, Sivan; Perkins, Bradley A.; Blauwkamp, Timothy A.; Fowler, Vance G., Jr.; Holland, Thomas L.; Pathology and Laboratory Medicine, School of MedicineBackground: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. Methods: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. Results: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). Conclusions: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing.Item Protection of Two and Three mRNA Vaccine Doses Against Severe Outcomes Among Adults Hospitalized With COVID-19-VISION Network, August 2021 to March 2022(Oxford, 2023-04-15) DeSilva, Malini B.; Mitchell, Patrick K.; Klein, Nicola P.; Dixon, Brian E.; Tenforde, Mark W.; Thompson, Mark G.; Naleway, Allison L.; Grannis, Shaun G.; Ong, Toan C.; Natarajan, Karthik; Reese, Sarah E.; Zerbo, Ousseny; Kharbanda, Anupam B.; Patel, Palak; Stenehjem, Edward; Raiyani, Chandni; Irving, Stephanie A.; Fadel, William F.; Rao, Suchitra; Han, Jungmi; Reynolds, Sue; Davis, Jonathan M.; Lewis, Ned; McEvoy, Charlene; Dickerson, Monica; Dascomb, Kristin; Valvi, Nimish R.; Barron, Michelle A.; Goddard, Kristin; Vazquez-Benitez, Gabriela; Grisel, Nancy; Mamwala, Mufaddal; Embi, Peter J.; Fireman, Bruce; Essien, Inih J.; Griggs, Eric P.; Arndorfer, Julie; Gaglani, Manjusha; Biostatistics and Health Data Science, School of MedicineBackground We assessed coronavirus disease 2019 (COVID-19) vaccination impact on illness severity among adults hospitalized with COVID-19, August 2021–March 2022. Methods We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19–like illness and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing. We calculated odds ratios (ORs) for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation. Results We included 27 149 SARS-CoV-2–positive hospitalizations. During both Delta- and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR, 0.52 [95% CI, .28–.96]; Omicron OR, 0.69 [95% CI, .54–.87]). During both periods, risk of in-hospital death was lower among vaccinated compared with unvaccinated patients but ORs overlapped across vaccination strata. We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients. Conclusions COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.