Michael Whitaker's research while affiliated with Marietta College and other places

Background Since the COVID-19 pandemic began in 2020, > 1 million persons have died in the US due to COVID-19. While various research illustrated in-hospital mortality in detail, post-discharge mortality has not been well described. Data from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were used to describe in-hospital and post-discharge mortality among adults hospitalized with COVID-19 in the US during the first year of the pandemic. Methods COVID-NET is a population-based surveillance system in 14 states that captures laboratory-confirmed COVID-19-associated hospitalizations, defined as any patient residing in the catchment areas with a positive SARS-CoV-2 test during hospitalization or ≤ 14 days prior to admission. Detailed chart reviews were conducted by trained surveillance officers on a representative sample stratified by age group, state, and month. Cases were linked to death certificate data to identify those who died ≤ 60 days after hospital discharge. Data were restricted to adults ages ≥ 18 years admitted from March 2020–April 2021. Proportions of mortality and hospitalization rate (per 100,000) were calculated by month to investigate trends in adults aged ≥ 75 years. Results 176,044 hospitalized adults met the COVID-NET case definition during the study period; 26,149 underwent full chart review. Overall, 9.7% died in-hospital and 6% died post-discharge; among those ≥ 75 years, these proportions were 18.1% and 16.2%, respectively (Figure 1). Among adults who died post-discharge, 47.5%, 33.1% and 28.3 were discharged to another facility, hospice, and private residence +/- services, respectively. Post-discharge mortality among those ≥ 75 years exceeded in-hospital mortality during October 2020 and December 2020 – February 2021. Hospitalization rates among those ≥ 75 years peaked in December 2020; the following month, January 2021, had the highest proportion of post-discharge mortality (22.6%) in this age group (Figure 2). Mortality among hospitalized adults ages ≥18 years with laboratory-confirmed COVID-19, COVID-19-Associated Hospitalization Surveillance Network, March 2020–April 2021 Figure 1 Hospitalization Rate and Mortality among laboratory-confirmed COVID-19 among adults ages ≥75 years, COVID-19 Associated Hospitalization Surveillance Network, March 2020–April 2021 Figure 2 Conclusion Among all deaths in adults with a COVID-19-associated hospitalization, two-thirds occurred in-hospital and one-third occurred ≤ 60 days post-discharge. Increases in post-discharge mortality followed a period of high COVID-19-associated hospitalization rates among ≥ 75 years. Disclosures All Authors: No reported disclosures

Background During the COVID-19 pandemic, hospitals performed widespread screening for SARS-CoV-2, resulting in identification of asymptomatic or mildly ill persons with SARS-CoV-2 who were admitted for other reasons. We examined trends in reasons for admission to identify hospitalized adults with a positive SARS-CoV-2 test likely admitted for COVID-19-related illness. Methods From June 2020–January 2023, hospitalized patients aged ≥ 18 years with a positive screening or clinician-directed SARS-CoV-2 test ≤ 14 days prior to or during hospitalization were identified from > 300 hospitals across 14 states in the population-based COVID-19-Associated Hospitalization Surveillance Network. Trained staff abstracted charts for a representative sample of patients. COVID-19-related admissions were indicated if 1) COVID-19 or 2) COVID-19-associated symptoms or clinical presentations were listed as chief complaint or reason for admission in the history of present illness. Percentages for sampled cases were weighted to account for probability of selection. Results Among 424,047 adults hospitalized with SARS-CoV-2 infection, the proportion aged ≥ 75 years increased over time to > 40% by October 2022 (Figure 1). The proportion of patients among 34,644 sampled hospitalizations admitted with likely COVID-19-related illness declined from 88.0% (June 1, 2020–June 19, 2021) to 72.4% (June 19, 2022–January 31, 2023) (Figure 2). The greatest decline in COVID-19-related admissions occurred in adults aged 18–49 years; the smallest decline occurred in adults aged ≥75 years: > 80% of these admissions in all periods were likely COVID-19-related. Among adults hospitalized from June 2022–January 2023, 27.1% had non-COVID-19 reasons for admission, including planned procedures (2.4%), obstetrics labor and delivery (5.0%), psychiatric admission requiring acute medical care (2.5%), trauma (2.6%), and other reasons likely unrelated to COVID-19 (14.6%).Figure 1.Proportion of laboratory-confirmed SARS-CoV-2 infection-associated hospitalizations by adult age group, June 2020 – January 2023Figure 2.Proportions of hospitalized adults with laboratory-confirmed SARS-CoV-2 infection who had COVID-19 as a likely reason for admission, by age group and variant predominance period — COVID-NET, June 2020 – January 2023 Conclusion While the proportion of COVID-19-related admissions decreased over time among patients hospitalized with laboratory-confirmed SARS-CoV-2, most adults with a positive SARS-CoV-2 test were likely admitted for reasons related to COVID-19. Misclassification of admission reason may occur. Disclosures Art Reingold, MD, GSK: Advisor/Consultant|Takeda: Advisor/Consultant|VBI: Advisor/Consultant

Background Respiratory syncytial virus (RSV) is an important cause of respiratory illness and hospitalization in older adults and adults with certain underlying medical conditions. With novel RSV vaccines in development, it is critical to identify adults at increased risk of severe illness. Methods Population-based surveillance was conducted through the RSV Hospitalization Surveillance Network (RSV-NET) over 8 seasons (2014–2022) across 75 counties in 12 states. We included non-pregnant adults (≥ 18 years) residing in the RSV-NET catchment area who were hospitalized with laboratory-confirmed RSV infection (clinician-directed testing) during each season (October–April, except 2020–2021, which spanned October 2020–September 2021). Demographic and outcomes data (all seasons) and underlying medical conditions (October 2014–April 2018) were abstracted from medical records. We calculated percentages of adults with intensive care unit (ICU) admission, mechanical ventilation (MV), and in-hospital death, stratified by demographic characteristics. We calculated age-adjusted percentages with these outcomes, stratified by underlying conditions. Results We identified 13,080 RSV-associated hospitalizations among adults; 61.9% were aged ≥ 65 years (Table 1). ICU admission was recorded in 18.6%, MV in 7.2%, and in-hospital death in 4.2%. Most in-hospital deaths (54.1%) occurred among adults aged ≥ 75 years. Among adults 18–49 years, immune compromise (34.8%) and asthma (29.8%) were the most frequent underlying conditions (Figure). Adults with non-asthma chronic lung disease (CLD) and with cardiovascular diseases had the highest age-adjusted percentages of in-hospital death (Table 2). Adults with non-asthma CLD had the highest age-adjusted percentages of ICU admission and MV. Conclusion Among adults with RSV-associated hospitalization, older age and cardiopulmonary conditions were associated with severe illness. Hospitalized young adults more likely had immune compromise or asthma. This study was limited by clinician-driven testing, which likely under-detected RSV-associated hospitalizations. Older adults and adults with cardiopulmonary and immune compromising conditions may benefit from RSV vaccination when licensed products become available. Disclosures All Authors: No reported disclosures

Background Pregnant persons are at increased risk for adverse outcomes from COVID-19 infection. We describe trends and clinical outcomes among pregnant patients hospitalized with a positive SARS-CoV-2 test. Methods From January 2021–January 2023, hospitalized pregnant patients aged 15–49 years with a positive screening or clinician-directed SARS-CoV-2 test ≤ 14 days prior to or during hospitalization were identified from > 300 hospitals across 99 counties in 14 states in the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET). Trained staff conducted chart abstractions on a representative sample of patients. We examined trends in the proportion of pregnant patients with COVID-19 respiratory symptoms and, among those with respiratory symptoms, trends in demographics and clinical outcomes from January–November 2021 (pre-Omicron), December 2021–June 2022 (early Omicron) and July 2022–January 2023 (later Omicron). Percentages presented were weighted to account for the probability of selection for sampled cases. Results Out of 1,637 hospitalized pregnant patients with SARS-CoV-2 infection, respiratory symptoms were recorded for 359 (21.9%). The proportion without respiratory symptoms increased from 73.4% (pre-Omicron) to 82.1% (later Omicron). Over the study period, among those with respiratory symptoms, the proportion with ≥1 underlying medical condition increased from 32.7% to 61.5% (Table 1), while the proportion requiring intensive care unit admission or mechanical ventilation decreased from 17.3% to 7.0% and from 7.2% to 0.0%, respectively (Table 2). During the later Omicron period, among patients with respiratory symptoms, 37.8% were unvaccinated, 35.7% had received a primary vaccination series only and 18.7% had received ≥1 booster doses (Table 2); a higher proportion (29.3%) of asymptomatic patients had received ≥1 boosters in the same period (Figure).Table 1.Characteristics of hospitalized pregnant patients (aged 15–49 years) with respiratory symptoms and a positive SARS-CoV-2 test, by pandemic period—COVID-NET, 14 U.S. States, January 2021–January 2023Table 2.Clinical characteristics among hospitalized pregnant patients (15–49 years) with respiratory symptoms and a positive SARS-CoV-2 test—COVID-NET, 14 U.S. States, January 2021–January 2023 Conclusion The proportion of symptomatic pregnant patients hospitalized with COVID-19 who had severe clinical outcomes decreased over time, although adverse clinical outcomes continue to occur. Most symptomatic hospitalized pregnant patients were not up to date with COVID-19 vaccination during a period when COVID-19 booster doses were available. Disclosures All Authors: No reported disclosures

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years.

Background Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population especially when the population affected is undefined. Methods We evaluated the utility of CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), COVID-19 Case Surveillance System (CCSS), and 2020 U.S. Census data to determine demographic representation in the four stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at U.S. ACTT sites, with the respective 95% confidence intervals, to the reference data in forest plots. Results U.S. ACTT sites enrolled 3,509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic or Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with U.S. Census and CCSS. The proportion of participants ages 65 years was either similar or lower than COVID-NET and higher than CCSS and U.S. Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions While surveillance data of hospitalized cases may not be available early in an outbreak, it is a better comparator than U.S. Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Fungal respiratory illnesses caused by endemic mycoses can be nonspecific and are often mistaken for viral or bacterial infections. We performed fungal testing on serum specimens from patients hospitalized with acute respiratory illness (ARI) to assess the possible role of endemic fungi as etiologic agents. Patients hospitalized with ARI at a Veterans Affairs hospital in Houston, Texas, during November 2016–August 2017 were enrolled. Epidemiologic and clinical data, nasopharyngeal and oropharyngeal samples for viral testing (PCR), and serum specimens were collected at admission. We retrospectively tested remnant sera from a subset of patients with negative initial viral testing using immunoassays for the detection of Coccidioides and Histoplasma antibodies (Ab) and Cryptococcus, Aspergillus, and Histoplasma antigens (Ag). Of 224 patient serum specimens tested, 49 (22%) had positive results for fungal pathogens, including 30 (13%) by Coccidioides immunodiagnostic assays, 19 (8%) by Histoplasma immunodiagnostic assays, 2 (1%) by Aspergillus Ag, and none by Cryptococcus Ag testing. A high proportion of veterans hospitalized with ARI had positive serological results for fungal pathogens, primarily endemic mycoses, which cause fungal pneumonia. The high proportion of Coccidioides positivity is unexpected as this fungus is not thought to be common in southeastern Texas or metropolitan Houston, though is known to be endemic in southwestern Texas. Although serological testing suffers from low specificity, these results suggest that these fungi may be more common causes of ARI in southeast Texas than commonly appreciated and more increased clinical evaluation may be warranted.

Background: COVID-19 is associated with cardiac complications. Objectives: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults. Methods: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes. Results: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not. Conclusions: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization.