Increased Hospitalizations Involving Fungal Infections during COVID-19 Pandemic, United States, January 2020-December 2021.

Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019-2021. During 2020-2021, patients hospitalized with COVID-19-associated fungal infections had higher (48.5%) in-hospital mortality rates than those with non-COVID-19-associated fungal infections (12.3%). Improved fungal disease surveillance is needed, particularly during respiratory virus pandemics.

Association between thromboembolic events and COVID-19 infection within 30 days: a case-control study among a large sample of adult hospitalized patients in the United States, March 2020-June 2021.

The association between thromboembolic events (TE) and COVID-19 infection is not completely understood at the population level in the United States. We examined their association using a large US healthcare database. We analyzed data from the Premier Healthcare Database Special COVID-19 Release and conducted a case-control study. The study population consisted of men and non-pregnant women aged ≥ 18 years with (cases) or without (controls) an inpatient ICD-10-CM diagnosis of TE between 3/1/2020 and 6/30/2021. Using multivariable logistic regression, we assessed the association between TE occurrence and COVID-19 diagnosis, adjusting for demographic factors and comorbidities. Among 227,343 cases, 15.2% had a concurrent or prior COVID-19 diagnosis within 30 days of their index TE. Multivariable regression analysis showed a statistically significant association between a COVID-19 diagnosis and TE among cases when compared to controls (adjusted odds ratio [aOR] 1.75, 95% CI 1.72-1.78). The association was more substantial if a COVID-19 diagnosis occurred 1-30 days prior to index hospitalization (aOR 3.00, 95% CI 2.88-3.13) compared to the same encounter as the index hospitalization. Our findings suggest an increased risk of TE among persons within 30 days of being diagnosed COVID-19, highlighting the need for careful consideration of the thrombotic risk among COVID-19 patients, particularly during the first month following diagnosis.

Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series - 465 Health Care Facilities, United States, December 2020-October 2021.

Vaccination against SARS-CoV-2, the virus that causes COVID-19, is highly effective at preventing COVID-19-associated hospitalization and death; however, some vaccinated persons might develop COVID-19 with severe outcomes† (1,2). Using data from 465 facilities in a large U.S. health care database, this study assessed the frequency of and risk factors for developing a severe COVID-19 outcome after completing a primary COVID-19 vaccination series (primary vaccination), defined as receipt of 2 doses of an mRNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or a single dose of JNJ-78436735 [Janssen (Johnson & Johnson)] ≥14 days before illness onset. Severe COVID-19 outcomes were defined as hospitalization with a diagnosis of acute respiratory failure, need for noninvasive ventilation (NIV), admission to an intensive care unit (ICU) including all persons requiring invasive mechanical ventilation, or death (including discharge to hospice). Among 1,228,664 persons who completed primary vaccination during December 2020-October 2021, a total of 2,246 (18.0 per 10,000 vaccinated persons) developed COVID-19 and 189 (1.5 per 10,000) had a severe outcome, including 36 who died (0.3 deaths per 10,000). Risk for severe outcomes was higher among persons who were aged ≥65 years, were immunosuppressed, or had at least one of six other underlying conditions. All persons with severe outcomes had at least one of these risk factors, and 77.8% of those who died had four or more risk factors. Severe COVID-19 outcomes after primary vaccination are rare; however, vaccinated persons who are aged ≥65 years, are immunosuppressed, or have other underlying conditions might be at increased risk. These persons should receive targeted interventions including chronic disease management, precautions to reduce exposure, additional primary and booster vaccine doses, and effective pharmaceutical therapy as indicated to reduce risk for severe COVID-19 outcomes. Increasing COVID-19 vaccination coverage is a public health priority.

Mortality Risk Among Patients Hospitalized Primarily for COVID-19 During the Omicron and Delta Variant Pandemic Periods - United States, April 2020-June 2022.

The risk for COVID-19-associated mortality increases with age, disability, and underlying medical conditions (1). Early in the emergence of the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, mortality among hospitalized COVID-19 patients was lower than that during previous pandemic peaks (2-5), and some health authorities reported that a substantial proportion of COVID-19 hospitalizations were not primarily for COVID-19-related illness,* which might account for the lower mortality among hospitalized patients. Using a large hospital administrative database, CDC assessed in-hospital mortality risk overall and by demographic and clinical characteristics during the Delta (July-October 2021), early Omicron (January-March 2022), and later Omicron (April-June 2022) variant periods† among patients hospitalized primarily for COVID-19. Model-estimated adjusted mortality risk differences (aMRDs) (measures of absolute risk) and adjusted mortality risk ratios (aMRRs) (measures of relative risk) for in-hospital death were calculated comparing the early and later Omicron periods with the Delta period. Crude mortality risk (cMR) (deaths per 100 patients hospitalized primarily for COVID-19) was lower during the early Omicron (13.1) and later Omicron (4.9) periods than during the Delta (15.1) period (p<0.001). Adjusted mortality risk was lower during the Omicron periods than during the Delta period for patients aged ≥18 years, males and females, all racial and ethnic groups, persons with and without disabilities, and those with one or more underlying medical conditions, as indicated by significant aMRDs and aMRRs (p<0.05). During the later Omicron period, 81.9% of in-hospital deaths occurred among adults aged ≥65 years and 73.4% occurred among persons with three or more underlying medical conditions. Vaccination, early treatment, and appropriate nonpharmaceutical interventions remain important public health priorities for preventing COVID-19 deaths, especially among persons most at risk.

Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods - United States, December 2020-January 2022.

The B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, was first clinically identified in the United States on December 1, 2021, and spread rapidly. By late December, it became the predominant strain, and by January 15, 2022, it represented 99.5% of sequenced specimens in the United States* (1). The Omicron variant has been shown to be more transmissible and less virulent than previously circulating variants (2,3). To better understand the severity of disease and health care utilization associated with the emergence of the Omicron variant in the United States, CDC examined data from three surveillance systems and a large health care database to assess multiple indicators across three high-COVID-19 transmission periods: December 1, 2020-February 28, 2021 (winter 2020-21); July 15-October 31, 2021 (SARS-CoV-2 B.1.617.2 [Delta] predominance); and December 19, 2021-January 15, 2022 (Omicron predominance). The highest daily 7-day moving average to date of cases (798,976 daily cases during January 9-15, 2022), emergency department (ED) visits (48,238), and admissions (21,586) were reported during the Omicron period, however, the highest daily 7-day moving average of deaths (1,854) was lower than during previous periods. During the Omicron period, a maximum of 20.6% of staffed inpatient beds were in use for COVID-19 patients, 3.4 and 7.2 percentage points higher than during the winter 2020-21 and Delta periods, respectively. However, intensive care unit (ICU) bed use did not increase to the same degree: 30.4% of staffed ICU beds were in use for COVID-19 patients during the Omicron period, 0.5 percentage points lower than during the winter 2020-21 period and 1.2 percentage points higher than during the Delta period. The ratio of peak ED visits to cases (event-to-case ratios) (87 per 1,000 cases), hospital admissions (27 per 1,000 cases), and deaths (nine per 1,000 cases [lagged by 3 weeks]) during the Omicron period were lower than those observed during the winter 2020-21 (92, 68, and 16 respectively) and Delta (167, 78, and 13, respectively) periods. Further, among hospitalized COVID-19 patients from 199 U.S. hospitals, the mean length of stay and percentages who were admitted to an ICU, received invasive mechanical ventilation (IMV), and died while in the hospital were lower during the Omicron period than during previous periods. COVID-19 disease severity appears to be lower during the Omicron period than during previous periods of high transmission, likely related to higher vaccination coverage,† which reduces disease severity (4), lower virulence of the Omicron variant (3,5,6), and infection-acquired immunity (3,7). Although disease severity appears lower with the Omicron variant, the high volume of ED visits and hospitalizations can strain local health care systems in the United States, and the average daily number of deaths remains substantial.§ This underscores the importance of national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems. In addition, being up to date on vaccination and following other recommended prevention strategies are critical to preventing infections, severe illness, or death from COVID-19.

Trends in Racial and Ethnic Disparities in COVID-19 Hospitalizations, by Region - United States, March-December 2020.

Persons from racial and ethnic minority groups are disproportionately affected by COVID-19, including experiencing increased risk for infection (1), hospitalization (2,3), and death (4,5). Using administrative discharge data, CDC assessed monthly trends in the proportion of hospitalized patients with COVID-19 among racial and ethnic groups in the United States during March-December 2020 by U.S. Census region. Cumulative and monthly age-adjusted COVID-19 proportionate hospitalization ratios (aPHRs) were calculated for racial and ethnic minority patients relative to non-Hispanic White patients. Within each of the four U.S. Census regions, the cumulative aPHR was highest for Hispanic or Latino patients (range = 2.7-3.9). Racial and ethnic disparities in COVID-19 hospitalization were largest during May-July 2020; the peak monthly aPHR among Hispanic or Latino patients was >9.0 in the West and Midwest, >6.0 in the South, and >3.0 in the Northeast. The aPHRs declined for most racial and ethnic groups during July-November 2020 but increased for some racial and ethnic groups in some regions during December. Disparities in COVID-19 hospitalization by race/ethnicity varied by region and became less pronounced over the course of the pandemic, as COVID-19 hospitalizations increased among non-Hispanic White persons. Identification of specific social determinants of health that contribute to geographic and temporal differences in racial and ethnic disparities at the local level can help guide tailored public health prevention strategies and equitable allocation of resources, including COVID-19 vaccination, to address COVID-19-related health disparities and can inform approaches to achieve greater health equity during future public health threats.

The Epidemiology of Foodborne Botulism Outbreaks: A Systematic Review.

Background: We performed a systematic review of foodborne botulism outbreaks to describe their clinical aspects and descriptive epidemiology in order to inform public health response strategies. Methods: We searched seven databases for reports of foodborne botulism outbreaks published in English from database inception to May 2015. We summarized descriptive characteristics and analyzed differences in exposure and toxin types by geographic region. We performed logistic regression to assess correlations between exposure source, implicated food, and outbreak size. Results: There were 197 outbreaks reported between 1920 and 2014. The median number of cases per outbreak was 3 (range 2-97). The majority of reported outbreaks (109; 55%) occurred in the United States. Toxin types A, B, E, and F were identified as the causative agent in 34%, 16%, 17%, and 1% of outbreaks, respectively. The median duration between exposure and symptom onset was approximately 1 day. The mean percentage of cases requiring mechanical ventilation per outbreak was 34%. Seventy percent of all outbreaks and 77% of small outbreaks (≤11 cases) originated from point source exposures, while commercial foods were significantly (odds ratio, 6.9; 95% confidence interval, 2.2-21.1) associated with large outbreaks (≥12 cases). Conclusions: Toxin type A accounted for half of outbreaks, and these outbreaks had a higher proportion of patient ventilatory failure. Most outbreaks were due to point source exposures, while outbreaks due to commercial food were larger. For effective responses to foodborne botulism outbreaks, these findings demonstrate the need for timely outbreak investigation and hospital surge capacity.

Coding of odor stimulus features among secondary olfactory structures.

Sensory systems must represent stimuli in manners dependent upon a wealth of factors, including stimulus intensity and duration. One way the brain might handle these complex functions is to assign the tasks throughout distributed nodes, each contributing to information processing. We sought to explore this important aspect of sensory network function in the mammalian olfactory system, wherein the intensity and duration of odor exposure are critical contributors to odor perception. This is a quintessential model for exploring processing schemes given the distribution of odor information by olfactory bulb mitral and tufted cells into several anatomically distinct secondary processing stages, including the piriform cortex (PCX) and olfactory tubercle (OT), whose unique contributions to odor coding are unresolved. We explored the coding of PCX and OT neuron responses to odor intensity and duration. We found that both structures similarly partake in representing descending intensities of odors by reduced recruitment and modulation of neurons. Additionally, while neurons in the OT adapt to odor exposure, they display reduced capacity to adapt to either repeated presentations of odor or a single prolonged odor presentation compared with neurons in the PCX. These results provide insights into manners whereby secondary olfactory structures may, at least in some cases, uniquely represent stimulus features.

Tefillin use induces preconditioning associated changes in heart rate variability.

Short bouts of occlusion of blood flow can induce a preconditioning response that reduces subsequent damage from longer periods of ischemia. It has been shown that ischemic preconditioning (IPC) can be elicited remotely (RIPC) through limitation of blood flow and as recently described via only pain sensation. Non-obstructive banding (NOB) through the donning of tefillin (a box with sacred texts attached to a leather strap that is traditionally bound to the non-dominant arm of Jewish adults during morning prayers) has been shown to elicit an RIPC response at least partially through pain sensation. This study evaluated the effects of NOB on heart rate variability (HRV) dependent factors that are known to be affected by various RIPC stimuli. We recruited 30 healthy subjects and subjected them to NOB versus control and found various HRV markers associated with RIPC to be changed in the NOB group. This finding provides further evidence that tefillin, likely through NOB induced RIPC changes, may still be a viable clinical pathway to prevent and decrease the morbidity associated with ischemic events.

Age-dependent alterations in the number, volume, and localization of islands of Calleja within the olfactory tubercle.

The incidence of olfactory perceptual dysfunction increases substantially with aging. Putative mechanisms for olfactory sensory loss are surfacing, including neuroanatomical modifications within brain regions responsible for odor information processing. The islands of Calleja (IC) are dense cell clusters localized within the olfactory tubercle, a cortical structure receiving monosynaptic input from the olfactory bulb. The IC are hypothesized to be important for intra- and extra-olfactory tubercle information processing, and thus olfaction. However, whether the anatomy of the IC are affected throughout normal aging remains unclear. By examining the IC of C57bl/6 mice throughout adulthood and early aging (4-18 months of age), we found that the number of IC decreases significantly with aging. Stereological analysis revealed that the remaining IC in 18-month-old mice were significantly reduced in estimated volume compared with those in 4- month-old mice. We additionally found that whereas young adults (4 months of age) possess greater numbers of IC within the posterior parts of the olfactory tubercle, by 18 months of age, a greater percentage of IC are found within the anterior-most part of the olfactory tubercle, perhaps providing a substrate for the differential access of the IC to odor information throughout aging. These results show that the IC are highly plastic components of the olfactory cortex, changing in volume, localization, and even number throughout normal aging. We predict that modifications among the IC throughout aging and age-related neurodegenerative disorders might be a novel contributor to pathological changes in olfactory cortex function and olfactory perception.