Abstract
Introduction
Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies.
Methods
Among ...adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed.
Results
Among 9825 patients, median (interquartile range IQR) age was 60 years (47–72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar–Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun–Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9–122.0) to 11.5 mg/L (2.7–42.8) and 3.1 mcg/mL (0.8–640.0) to 1.0 mcg/mL (0.5–2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period.
Conclusions
Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.
Compared to adults hospitalized with Alpha- and Delta-variant COVID-19, those hospitalized later with Omicron-variant COVID-19 were older, had more co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.
Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/changing-severity-and-epidemiology-of-adults-hospitalized-with-covid-19-in-the-united-states-after-introduction-of-covid-19-vaccines-march-2021-august-2022-f66f7f84-e1a9-4536-aa93-1e4a50d97d8f
Abstract
Background
Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), ...after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021.
Methods
We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration.
Results
On 1 November 2021, at least 3.0–5.0 million US adults, or 1.2%–1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month’s duration. Population prevalence was higher in females (1.4%–2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%–3.8%.
Conclusions
Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population.
Using household survey data and reported SARS-CoV-2 cases in the United States, we estimate at least 3.0–5.0 million adults, or 1.2%–1.9% of the US adult population, had activity-limiting post-COVID conditions of ≥1 month’s duration on 1 November 2021.
Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in individuals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg levels may provide ...important prognostic information and enable treatment stratification. We performed a laboratory-based validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) against the current gold standard CrAg tests. We assessed the diagnostic accuracy of the CrAgSQ in HIV-positive individuals undergoing CrAg screening, determined the relationship between CrAgSQ scores and dilutional CrAg titers, assessed interrater reliability, and determined the clinical correlates of CrAgSQ scores. A total of 872 plasma samples were tested using both the CrAgSQ LFA and the conventional IMMY CrAg LFA, of which 692 were sequential samples from HIV-positive individuals undergoing CrAg screening and an additional 180 were known CrAg-positive plasma samples archived from prior studies. Interrater agreement in CrAgSQ reading was excellent (98.17% agreement, Cohen's kappa 0.962,
< 0.001). Using the IMMY CrAg LFA as a reference standard, CrAgSQ was 93.0% sensitive (95% confidence interval CI 80.9% to 98.5%) and 93.8% specific (95% CI, 91.7% to 95.6%). After reclassification of discordant results using CrAg enzyme immunoassay testing, the sensitivity was 98.1% (95% CI, 90.1% to 100%) and specificity 95.8% (95% CI, 93.9% to 97.2%). The median CrAg titers for semiquantitative score categories (1+ to 4+) were 1:10 (interquartile range IQR, 1:5 to 1:20) in the CrAgSQ 1+ category, 1:40 (IQR, 1:20 to 1:80) in the CrAgSQ 2+ category, 1:640 (IQR, 1:160 to 1:2,560) in the CrAgSQ 3+ category, and 1:5,120 (IQR, 1:2,560 to 1:30,720) in the CrAgSQ 4+ category. Increasing CrAgSQ scores were strongly associated with 10-week mortality. The IMMY CrAgSQ test had high sensitivity and specificity compared to the results for the IMMY CrAg LFA and provided CrAg scores that were associated with both conventional CrAg titers and clinical outcomes.
Introduction
HIV‐associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub‐Saharan Africa (SSA). We performed a systematic review and meta‐analysis ...with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings.
Methods
We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized‐controlled trials (RCTs) or investigator‐managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short‐term (in‐hospital or two weeks), medium‐term (up to 10 weeks) and long‐term (up to six months).
Results and discussion
Seventy‐nine studies met inclusion criteria. In routine care settings, pooled short‐term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole‐based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short‐term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short‐term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized‐controlled trials. Few studies evaluated long‐term outcomes.
Conclusions
Mortality rates from HIV‐associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV‐associated meningitis in the region.
Full text
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
During the 2022–2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010–2011. Influenza A/H3N2 infections ...were predominant.
Methods
We analyzed acute respiratory illness (ARI)–associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months–17 years who had influenza molecular testing during October 2022–March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A–positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models.
Results
Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A–positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval CI, 44–52%) overall, 53% (95% CI, 47–58%) among children aged 6 months–4 years, and 38% (95% CI, 30–45%) among those aged 9–17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6–61%) overall, 56% (95% CI, 23–75%) among children ages 6 months–4 years, and 46% (95% CI, 2–70%) among those 5–17 years.
Conclusions
During the 2022–2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40–48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.
Among pediatric acute respiratory illness–associated encounters during the 2022–2023 influenza season, vaccine effectiveness was 48% (95% confidence interval CI, 44–52%) against emergency department/urgent care encounters and 40% (95% CI, 6–61%) against hospitalization.
Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/vaccine-effectiveness-against-pediatric-influenza-a-associated-urgent-care-emergency-department-andhospital-encounters-during-the-2022-2023-season-vision-network-15078ac6-f6db-43ce-9668-9524fa92cce0/
Abstract
Background
Following historically low influenza activity during the 2020–2021 season, the United States saw an increase in influenza circulating during the 2021–2022 season. Most viruses ...belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade.
Methods
We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders.
Results
In total, 86 732 ED/UC ARI-associated encounters (7696 9% cases) and 16 805 hospitalized ARI-associated encounters (649 4% cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%–29%) and 25% (95% CI, 11%–37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, −5% to 17%) or with immunocompromising conditions (4%; 95% CI, −45% to 36%).
Conclusions
During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.
During the 2021–2022 United States influenza season with predominant influenza A(H3N2) virus circulation, vaccine effectiveness against influenza-associated emergency department/urgent care encounters and hospitalizations were both 25%, with effectiveness varying by age group and presence of immunocompromising conditions.
Influenza vaccination and antiviral therapeutics may attenuate disease, decreasing severity of illness in vaccinated and treated persons. Standardized assessment tools, definitions of disease ...severity, and clinical endpoints would support characterizing the attenuating effects of influenza vaccines and antivirals. We review potential clinical parameters and endpoints that may be useful for ordinal scales evaluating attenuating effects of influenza vaccines and antivirals in hospital-based studies. In studies of influenza and community-acquired pneumonia, common physiologic parameters that predicted outcomes such as mortality, ICU admission, complications, and duration of stay included vital signs (hypotension, tachypnea, fever, hypoxia), laboratory results (blood urea nitrogen, platelets, serum sodium), and radiographic findings of infiltrates or effusions. Ordinal scales based on these parameters may be useful endpoints for evaluating attenuating effects of influenza vaccines and therapeutics. Factors such as clinical and policy relevance, reproducibility, and specificity of measurements should be considered when creating a standardized ordinal scale for assessment.
Abstract
Background
Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019–2020 ...influenza vaccine against influenza-associated hospitalization in the United States.
Methods
We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve-transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases vs test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups.
Results
A total of 3116 participants were included, including 18% (n = 553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (n = 2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval CI, 27%–52%). VE against A(H1N1)pdm09 viruses was 40% (95% CI, 24%–53%) and 33% against B viruses (95% CI, 0–56%). Of the 2 major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A + 187A,189E) was 59% (95% CI, 34%–75%) whereas no VE was observed against the other group (5A + 156K) (–1% 95% CI, –61% to 37%).
Conclusions
In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.
During the 2019-2020 United States influenza season, genetically diverse influenza A(H1N1)pdm09 and influenza B viruses of the Victoria lineage co-circulated. Overall vaccine effectiveness against influenza-associated hospitalization was 41% despite circulation of multiple antigenically drifted viruses.
Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized.
We conducted a test-negative study in an intensive care ...unit (ICU) network at 10 US hospitals to evaluate VE for preventing influenza-associated severe acute respiratory infection (SARI) during the 2019-2020 season, which was characterized by circulation of drifted A/H1N1 and B-lineage viruses. Cases were adults hospitalized in the ICU and a targeted number outside the ICU (to capture a spectrum of severity) with laboratory-confirmed, influenza-associated SARI. Test-negative controls were frequency-matched based on hospital, timing of admission, and care location (ICU vs non-ICU). Estimates were adjusted for age, comorbidities, and other confounders.
Among 638 patients, the median (interquartile) age was 57 (44-68) years; 286 (44.8%) patients were treated in the ICU and 42 (6.6%) died during hospitalization. Forty-five percent of cases and 61% of controls were vaccinated, which resulted in an overall VE of 32% (95% CI: 2-53%), including 28% (-9% to 52%) against influenza A and 52% (13-74%) against influenza B. VE was higher in adults 18-49 years old (62%; 95% CI: 27-81%) than those aged 50-64 years (20%; -48% to 57%) and ≥65 years old (-3%; 95% CI: -97% to 46%) (P = .0789 for interaction). VE was significantly higher against influenza-associated death (80%; 95% CI: 4-96%) than nonfatal influenza illness.
During a season with drifted viruses, vaccination reduced severe influenza-associated illness among adults by 32%. VE was high among young adults.
Abstract
Background
The COVID-19 pandemic was associated with historically low influenza circulation during the 2020–2021 season, followed by an increase in influenza circulation during the 2021–2022 ...US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain.
Methods
To understand the effectiveness of the 2021–2022 vaccine against hospitalized influenza illness, a multistate sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2–negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by including SARS-CoV-2–positive controls.
Results
A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2–negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2–positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95% CI: −14% to 52%) among adults aged 18–64 years, −3% (−54% to 31%) among adults aged ≥65 years, and 50% (15–71%) among adults aged 18–64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2–positive controls.
Conclusions
During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted.
During the 2021–2022 US influenza season, circulating A(H3N2) viruses were antigenically different than the vaccine. Vaccine effectiveness against hospitalized illness was 26% (95% CI: −14–52%) for adults 18–64-years and −3% (95% CI: −54–31) for adults ≥65-years.
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