Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2. FINDINGS: Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05]. INTERPRETATION: The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO. FUNDING: None.

Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.

Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P < 0.001) and more had a comorbidity (84% vs. 70%; P < 0.001). Of 170 discordant participants, 106 (62%) had postdischarge events captured by the TICO approach. Conclusions: Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered "recovered" using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.

Physical function and fatigue recovery at 6 months after hospitalization for COVID-19.

INTRODUCTION: There are an increasing number of individuals with long-term symptoms of coronavirus-19 disease (COVID-19); however, the prognosis for recovery of physical function and fatigue after COVID-19 is uncertain. OBJECTIVE: To report the changes in functional recovery between 1 and 6 months after hospitalization of adults hospitalized for COVID-19 and explore the baseline factors associated with physical function recovery. DESIGN: A prospective cohort study. SETTING: Tertiary care hospital. PARTICIPANTS: U.S. adult COVID-19 survivors. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Telephone interviews assessed three outcome domains: basic and instrumental activities of daily living (ADLs) performance, fatigue, and general physical function (Health Assessment Questionnaire [HAQ]). RESULTS: The age of participants (n = 92) ranged from 22 to 95 years (54.3 ± 17.2). Across outcome domains, a majority (63%-67%) of participants developed new ADL impairment, fatigue, or worsening HAQ severity by 1 month. Of those, 50%-79% partially or fully recovered by 6 months, but 21%-50% did not recover at least partially. Fifteen to 30% developed new impairment between 1 and 6 months. For those without any improvement in ADL impairments at 6 months, lower socioeconomic status was significantly more common (p = .01) and age ≥ 65 (p = .06), trending toward being more common. CONCLUSION: In this cohort, a substantial proportion of the participants who developed new ADL impairment, worsening fatigue, or HAQ severity after hospitalization for COVID-19 did not recover at least partially by 6 months after discharge. Evaluating functional status 1 month after discharge may be important in understanding functional prognosis and recovery after hospitalization for COVID-19.

Assessment of Symptom, Disability, and Financial Trajectories in Patients Hospitalized for COVID-19 at 6 Months.

Importance: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective: To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19-related hospitalization. Design, Setting, and Participants: A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure: Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures: New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results: A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P = .001) and fatigue (from 40.7% to 50.8%; P < .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P < .001) and functional limitations (from 55.3% to 47.3%; P = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance: The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.

Protection of mRNA vaccines against hospitalized COVID-19 in adults over the first year following authorization in the United States.

BACKGROUND: COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization. METHODS: Case control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states March 11 - December 15, 2021, including COVID-19 case patients and RT-PCR-negative controls. We included adults who were unvaccinated or vaccinated with two doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (<180 vs ≥180 days since dose two) and continuous time modeled using restricted cubic splines. RESULTS: 10,078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (IQR 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE <180 days was 90% (95%CI: 88-91) vs 82% (95%CI: 79-85) at ≥180 days (p < 0.001). VE declined for Pfizer-BioNTech (88% to 79%, p < 0.001) and Moderna (93% to 87%, p < 0.001) products, for younger adults (18-64 years) [91% to 87%, p = 0.005], and for adults ≥65 years of age (87% to 78%, p < 0.001). In models using restricted cubic splines, similar changes were observed. CONCLUSION: In a period largely pre-dating Omicron variant circulation, effectiveness of two mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

Differences in US Regional Healthcare Allocation Guidelines During the COVID-19 Pandemic.

BACKGROUND: Hospitals faced unprecedented scarcity of resources without parallel in modern times during the COVID-19 pandemic. This scarcity led healthcare systems and states to develop or modify scarce resource allocation guidelines that could be implemented during "crisis standards of care" (CSC). CSC describes a significant change in healthcare operations and the level of care provided during a public health emergency. OBJECTIVE: Our study provides a comprehensive examination of the latest CSC guidelines in the western region of the USA, where Alaska and Idaho declared CSC, focusing on ethical issues and health disparities. DESIGN: Mixed-methods survey study of physicians and/or ethicists and review of healthcare system and state allocation guidelines. PARTICIPANTS: Ten physicians and/or ethicists who participated in scarce resource allocation guideline development from seven healthcare systems or three state-appointed committees from the western region of the USA including Alaska, California, Idaho, Oregon, and California. RESULTS: All sites surveyed developed allocation guidelines, but only four (40%) were operationalized either statewide or for specific scarce resources. Most guidelines included comorbidities (70%), and half included adjustments for socioeconomic disadvantage (50%), while only one included specific priority groups (10%). Allocation tiebreakers included the life cycle principle and random number generators. Six guidelines evolved over time, removing restrictions such as age, severity of illness, and comorbidities. Additional palliative care (20%) and ethics (50%) resources were planned by some guidelines. CONCLUSIONS: Allocation guidelines are essential to support clinicians during public health emergencies; however, significant deficits and differences in guidelines were identified that may perpetuate structural inequities and racism. While a universal triage protocol that is equally accepted by all communities is unlikely, the lack of regional agreement on standards with justification and transparency has the potential to erode public trust and perpetuate inequity.

Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021-April 2022.

Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines. Methods: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE. Results: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary. Conclusions: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

Functional, imaging, and respiratory evaluation (FIRE) of patients post-hospitalization for COVID-19: protocol for a pilot observational study.

INTRODUCTION: We describe a protocol for FIRE CORAL, an observational cohort study that examines the recovery from COVID-19 disease following acute hospitalization with an emphasis on functional, imaging, and respiratory evaluation. METHODS AND ANALYSIS: FIRE CORAL is a multicenter prospective cohort study of participants recovering from COVID-19 disease with in-person follow-up for functional and pulmonary phenotyping conducted by the National Heart, Lung and Blood Institute (NHLBI) Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. FIRE CORAL will include a subset of participants enrolled in Biology and Longitudinal Epidemiology of PETAL COVID-19 Observational Study (BLUE CORAL), an NHLBI-funded prospective cohort study describing the clinical characteristics, treatments, biology, and outcomes of hospitalized patients with COVID-19 across the PETAL Network. FIRE CORAL consists of a battery of in-person assessments objectively measuring pulmonary function, abnormalities on lung imaging, physical functional status, and biospecimen analyses. Participants will attend and perform initial in-person testing at 3 to 9 months after hospitalization. The primary objective of the study is to determine the feasibility of longitudinal assessments investigating multiple domains of recovery from COVID-19. Secondarily, we will perform descriptive statistics, including the prevalence and characterization of abnormalities on pulmonary function, chest imaging, and functional status. We will also identify potential clinical and biologic factors that predict recovery or the occurrence of persistent impairment of pulmonary function, chest imaging, and functional status. ETHICS AND DISSEMINATION: FIRE CORAL is approved via the Vanderbilt University central institutional review board (IRB) and via reliance agreement with the site IRBs. Results will be disseminated via the writing group for the protocol committee and reviewed by the PETAL Network publications committee prior to publication. Data obtained via the study will subsequently be made publicly available via NHLBI's biorepository. STRENGTHS AND LIMITATIONS OF THE STUDY: Strengths: First US-based multicenter cohort of pulmonary and functional outcomes in patients previously hospitalized for COVID-19 infection Longitudinal biospecimen measurement allowing for biologic phenotyping of abnormalities Geographically diverse cohort allowing for a more generalizable understanding of post-COVID pulmonary sequela Limitations: Selected cohort given proximity to a participating center Small cohort which may be underpowered to identify small changes in pulmonary function.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.

BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FUNDING: NIH.

Respiratory indications for ECMO: focus on COVID-19.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with severe respiratory failure and has received particular attention during the coronavirus disease 2019 (COVID-19) pandemic. Evidence from two key randomized controlled trials, a subsequent post hoc Bayesian analysis, and meta-analyses support the interpretation of a benefit of ECMO in combination with ultra-lung-protective ventilation for select patients with very severe forms of acute respiratory distress syndrome (ARDS). During the pandemic, new evidence has emerged helping to better define the role of ECMO for patients with COVID-19. Results from large cohorts suggest outcomes during the first wave of the pandemic were similar to those in non-COVID-19 cohorts. As the pandemic continued, mortality of patients supported with ECMO has increased. However, the precise reasons for this observation are unclear. Known risk factors for mortality in COVID-19 and non-COVID-19 patients are higher patient age, concomitant extra-pulmonary organ failures or malignancies, prolonged mechanical ventilation before ECMO, less experienced treatment teams and lower ECMO caseloads in the treating center. ECMO is a high resource-dependent support option; therefore, it should be used judiciously, and its availability may need to be constrained when resources are scarce. More evidence from high-quality research is required to better define the role and limitations of ECMO in patients with severe COVID-19.

Extracorporeal Membrane Oxygenation during Respiratory Pandemics: Past, Present, and Future.

The role of extracorporeal membrane oxygenation (ECMO) in the management of severe acute respiratory failure, including acute respiratory distress syndrome, has become better defined in recent years in light of emerging high-quality evidence and technological advances. Use of ECMO has consequently increased throughout many parts of the world. The coronavirus disease (COVID-19) pandemic, however, has highlighted deficiencies in organizational capacity, research capability, knowledge sharing, and resource use. Although governments, medical societies, hospital systems, and clinicians were collectively unprepared for the scope of this pandemic, the use of ECMO, a highly resource-intensive and specialized form of life support, presented specific logistical and ethical challenges. As the pandemic has evolved, there has been greater collaboration in the use of ECMO across centers and regions, together with more robust data reporting through international registries and observational studies. Nevertheless, centralization of ECMO capacity is lacking in many regions of the world, and equitable use of ECMO resources remains uneven. There are no widely available mechanisms to conduct large-scale, rigorous clinical trials in real time. In this critical care review, we outline lessons learned during COVID-19 and prior respiratory pandemics in which ECMO was used, and we describe how we might apply these lessons going forward, both during the ongoing COVID-19 pandemic and in the future.

mRNA Vaccine Effectiveness Against Coronavirus Disease 2019 Hospitalization Among Solid Organ Transplant Recipients.

BACKGROUND: The study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. METHODS: We conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls. RESULTS: Among SOT recipients, VE was 29% (95% confidence interval [CI], -19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses. CONCLUSIONS: Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.

Associations between persistent symptoms after mild COVID-19 and long-term health status, quality of life, and psychological distress.

BACKGROUND: We sought to assess whether persistent COVID-19 symptoms beyond 6 months (Long-COVID) among patients with mild COVID-19 is associated with poorer health status, quality of life, and psychological distress. METHODS: This was a multicenter prospective cohort study that included adult outpatients with acute COVID-19 from eight sites during 2-week sampling periods from April 1 and July 28, 2020. Participants were contacted 6-11 months after their first positive SARS-CoV-2 to complete a survey, which collected information on the severity of eight COVID-19 symptoms using a 4-point scale ranging from 0 (not present) to 3 (severe) at 1 month before COVID-19 (pre-illness) and at follow-up; the difference for each was calculated as an attributable persistent symptom severity score. A total attributable persistent COVID-19 symptom burden score was calculated by summing the attributable persistent severity scores for all eight symptoms. Outcomes measured at long-term follow-up comprised overall health status (EuroQol visual analogue scale), quality of life (EQ-5D-5L), and psychological distress (Patient Health Questionnaire-4). The association between the total attributable persistent COVID-19 burden score and each outcome was analyzed using multivariable proportional odds regression. RESULTS: Of the 2092 outpatients with COVID-19, 436 (21%) responded to the survey. The median (IQR) attributable persistent COVID-19 symptom burden score was 2 (0, 4); higher scores were associated with lower overall health status (aOR 0.63; 95% CI: 0.57-0.69), lower quality of life (aOR: 0.65; 95%CI: 0.59-0.72), and higher psychological distress (aOR: 1.40; 95%CI, 1.28-1.54) after adjusting for age, race, ethnicity, education, and income. CONCLUSIONS: In participants with mild acute COVID-19, the burden of persistent symptoms was significantly associated with poorer long-term health status, poorer quality of life, and psychological distress.

Effectiveness of mRNA Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death - United States, March 2021-January 2022.

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).

Characteristics and Outcomes of US Patients Hospitalized With COVID-19.

BACKGROUND: Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. OBJECTIVE: To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. METHODS: A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. RESULTS: Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. CONCLUSIONS: In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.

Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study.

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. DESIGN: Case-control study. SETTING: 21 hospitals across the United States. PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. RESULTS: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). CONCLUSIONS: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.

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.

Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccines for Preventing Coronavirus Disease 2019 Hospitalizations in the United States.

BACKGROUND: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7-91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI, 79.3-9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8-82.6) than without immunosuppression (91.3%; 95% CI, 85.6-94.8). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.