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This trial comparing treatment strategies that emphasized the use of vasopressors or intravenous fluids for early treatment of sepsis-induced hypotension showed no difference in 90-day mortality before discharge home.

To the Editor: Humoral and cellular immune responses con-tribute to overall protective immunity against SARS-CoV-2, with neutralizing antibody playing a key role in preventing viral infection. [...]a recent study has shown that booster responses to Omicron infection are affected by previous SARS-CoV-2 infec-tions (5). [...]having additional information on the types of neutralizing antibody responses induced after infection with different SARS-CoV-2 variants will be helpful in addressing this important issue. In vaccinated Delta-infected patients, neutralization titers against Delta and WA1 were similar, but again were much low-er against BA.1 (17-fold) and BA.2 (9-fold) (Figure 1B). [...]both unvaccinated and vaccinated Delta-infected patients had significantly lower neutralizing antibody responses to Omi-cron (as determined by Wilcoxons rank sum test).

Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.

To compare the outcomes of patients hospitalized with pneumonia treated with noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV). Using the HealthFacts multihospital electronic medical record database, we included patients hospitalized with a diagnosis of pneumonia and treated with NIV or IMV. We developed a propensity model for receipt of initial NIV and assessed the outcomes in a propensity-matched cohort, and in a covariate adjusted and propensity score weighted models. Among 3971 ventilated patients, 1109 (27.9%) were initially treated with NIV. Patients treated with NIV were older, had lower acuity of illness score, and were more likely to have congestive heart failure and chronic pulmonary disease. Mortality was 15.8%, 29.8% and 25.9.0% among patients treated with initial NIV, initial IMV and among those with NIV failure. In the propensity matched analysis, the risk of death was lower in patients treated with NIV (relative risk: 0.71, 95% CI: 0.59–0.85). Subgroup analysis showed that NIV was beneficial among patients with cardiopulmonary comorbidities (relative risk 0.59, 95% CI: 0.47–0.75) but not in those without (relative risk 0.96, 95% CI: 0.74–0.1.25)NIV failure was significantly (p=0.002) more common in patients without cardiopulmonary conditions (21.3%) compared to those with these conditions (13.8%). Initial NIV was associated with better survival among the subgroup of patients hospitalized with pneumonia who had COPD or heart failure. Patients who failed NIV had high in-hospital mortality, emphasizing the importance of careful patient selection monitoring when managing severe pneumonia with NIV. •One in four patients hospitalized with pneumonia and ventilated received NIV•Patients treated with NIV were older and had lower severity of illness score•NIV was associated with lower risk of death only in pneumonia patients with COPD or heart failure.•NIV failure was more common among patients without COPD and/or heart failure comorbidity

•Among 679 severely ill adults during the 2019–2020 influenza season, 38.9% were unvaccinated.•Among those unvaccinated, 51.1% reported intentionally avoiding vaccination.•Lack of insurance and being non-White or Hispanic were associated with not being vaccinated. Understanding patient factors associated with not being vaccinated is essential for successful implementation of influenza vaccination programs. We enrolled adults hospitalized with severe acute respiratory illness at 10 United States (US) hospitals during the 2019–2020 influenza season. We interviewed patients to collect data about influenza vaccination, sociodemographic characteristics, and vaccine perceptions. Among 679 participants, 264 (38.9%) reported not receiving influenza vaccination. Among those not vaccinated, 135 (51.1%) reported choosing not to receive a vaccine because of perceived ineffectiveness (36.7%) or risk (14.4%) of influenza vaccination. Sociodemographic factors associated with not being vaccinated included no medical insurance (aOR = 6.42; 95% CI: 2.52–16.38) and being non-White or Hispanic (aOR = 1.54, 95% CI: 1.02–2.32). Optimizing uptake of influenza vaccination in the US may be improved by educational programs regarding vaccine safety and effectiveness and enhancing vaccine access, particularly among non-White and Hispanic Americans and those without medical insurance.

Severe sepsis, defined as sepsis associated with acute organ dysfunction, results from a generalized inflammatory and procoagulant response to an infection. 1 The rate of death from severe sepsis ranges from 30 to 50 percent despite advances in critical care. 2 – 5 In the United States, approximately 750,000 cases of sepsis occur each year, at least 225,000 of which are fatal. 6 The inflammatory and procoagulant host responses to infection are closely related. 7 Inflammatory cytokines, including tumor necrosis factor α, interleukin-1β, and interleukin-6, are capable of activating coagulation and inhibiting fibrinolysis, whereas the procoagulant thrombin is capable of stimulating multiple inflammatory pathways. 7 – . . .

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.

Understanding similarities and differences between hesitancy for influenza and COVID-19 vaccines could facilitate strategies to improve public receptivity toward vaccination. We compared hesitancy for COVID-19 vaccines during the first 13 months of availability (January 2021–January 2022) with hesitancy for influenza vaccines in the 15 months prior to COVID-19 vaccine availability (October 2019–December 2020) among adults hospitalized with acute respiratory illness at 21 hospitals in the United States. We interviewed patients regarding vaccination status, willingness to be vaccinated, and perceptions of vaccine safety and efficacy. We used multivariate logistic regression to identify factors associated with vaccine hesitancy. Among 12,292 patients enrolled during the COVID-19 vaccine period, 5485 (44.6 %) were unvaccinated. Patient characteristics associated with not receiving the COVID-19 vaccine included younger age, female sex, higher BMI, lack of health insurance, absence of chronic comorbid medical conditions, no or rare influenza vaccination in prior years, higher CDC social vulnerability index (SVI), a measure of external stresses that may negatively impact health, living in the Midwest or southern US, lack of college or higher education, and not wearing a mask. Among 983 patients enrolled during the influenza vaccination period, 381(37.8 %) were unvaccinated. Characteristics associated with not receiving the influenza vaccine included no or one chronic comorbid medical condition, no or rare influenza vaccination in prior years, being a current smoker, and higher SVI. Discussion with healthcare providers was a reason for vaccination for 27.7 % (167) for influenza and 8.3 % (564) for COVID-19 and to decline vaccination for 0.5 % Ten great public health achievements–United States (2011) (2) for influenza and 2.2 % (118) for COVID-19. We found that higher SVI scores and lack of prior influenza vaccination were associated with hesitancy for both COVID-19 and influenza vaccines. There were regional variations in COVID-19 vaccine acceptance and discussions with HCPs significantly influenced acceptance for both vaccines. •In this cross-sectional study, prior influenza vaccination was associated with COVID-19 and influenza vaccine acceptance.•Regional variations in acceptance of the COVID-19 vaccine were observed, and social vulnerability was associated with lower acceptance of the COVID-19 vaccine.•Discussions with healthcare providers influenced both vaccine acceptance and hesitancy.

In test-negative studies of vaccine effectiveness (VE), including patients with co-circulating, vaccine-preventable, respiratory pathogens in the control group for the pathogen of interest can introduce a downward bias on VE estimates. A multicenter sentinel surveillance network in the US prospectively enrolled adults hospitalized with acute respiratory illness from September 1, 2022–March 31, 2023. We evaluated bias in estimates of VE against influenza–associated and COVID-19–associated hospitalization based on: inclusion vs exclusion of patients with a co-circulating virus among VE controls; observance of VE against the co-circulating virus (rather than the virus of interest), unadjusted and adjusted for vaccination against the virus of interest; and observance of influenza or COVID-19 against a sham outcome of respiratory syncytial virus (RSV). Overall VE against influenza–associated hospitalizations was 6 percentage points lower when patients with COVID-19 were included in the control group, and overall VE against COVID-19–associated hospitalizations was 2 percentage points lower when patients with influenza were included in the control group. Analyses of VE against the co-circulating virus and against the sham outcome of RSV showed that downward bias was largely attributable the correlation of vaccination status across pathogens, but also potentially attributable to other sources of residual confounding in VE models. Excluding cases of confounding respiratory pathogens from the control group in VE analysis for a pathogen of interest can reduce downward bias. This real-world analysis demonstrates that such exclusion is a helpful bias mitigation strategy, especially for measuring influenza VE, which included a high proportion of COVID-19 cases among controls.

The Centers for Medicare and Medicaid Services has announced reimbursement for discussing advance care planning. Conversations about previously expressed treatment preferences are important both because they may provide dispositive guidance for clinicians about what treatments the patient prefers and also because they may help surrogates make better in-the-moment judgments when the prior conversations did not address the specific clinical situation at hand. Eligible patients were aged 18 years or older, lacked decision-making capacity, required mechanical ventilation due to ARDS (3), and had a greater than or equal to 50% risk of in-hospital mortality or severe long-term functional impairment. In only 1 out of 245 conferences (0.4%) did surrogates provide information about the patient's previously expressed preferences that was dispositive for the clinical decisions at hand. The policy implication of these findings is that advance care planning should be directed at preparing surrogates for in-the-moment decision-making rather than trying to articulate an exhaustive list of treatment preferences (10). [...]it may be valuable for clinicians to reframe their expectations about how patients' previously expressed preferences will contribute to goals-of-care conversations in ICUs by moving away from expecting the information to be dispositive and toward using the information as a starting point for conversations about the patients' values. [...]we found that surrogates often had prior conversations about patients' treatment preferences; however, these preferences were rarely Washington Seattle, Washington Shannon S. Carson, M.D. University of North Carolina School of Medicine Chapel Hill, North Carolina Michael W. Peterson, M.D. University of California San Francisco Fresno...