Background In the United States, laboratory confirmed coronavirus disease 2019 (COVID-19) is nationally notifiable. However, reported case counts are recognized to be less than the true number of cases because detection and reporting are incomplete and can vary by disease severity, geography, and over time. Methods To estimate the cumulative incidence SARS-CoV-2 infections, symptomatic illnesses, and hospitalizations, we adapted a simple probabilistic multiplier model. Laboratory-confirmed case counts that were reported nationally were adjusted for sources of under-detection based on testing practices in inpatient and outpatient settings and assay sensitivity. Results We estimated that through the end of September, 1 of every 2.5 (95% Uncertainty Interval (UI): 2.0–3.1) hospitalized infections and 1 of every 7.1 (95% UI: 5.8–9.0) non-hospitalized illnesses may have been nationally reported. Applying these multipliers to reported SARS-CoV-2 cases along with data on the prevalence of asymptomatic infection from published systematic reviews, we estimate that 2.4 million hospitalizations, 44.8 million symptomatic illnesses, and 52.9 million total infections may have occurred in the U.S. population from February 27–September 30, 2020. Conclusions These preliminary estimates help demonstrate the societal and healthcare burdens of the COVID-19 pandemic and can help inform resource allocation and mitigation planning.

Background Several underlying conditions have been associated with severe acute respiratory syndrome coronavirus 2 illness, but it remains unclear whether underlying asthma is associated with worse coronavirus disease 2019 (COVID-19) outcomes. Objective Given the high prevalence of asthma in the New York City area, our objective was to determine whether underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 compared with patients without asthma. Methods Electronic heath records were reviewed for 1298 sequential patients 65 years or younger without chronic obstructive pulmonary disease who were admitted to our hospital system with a confirmed positive severe acute respiratory syndrome coronavirus 2 test result. Results The overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6%, yet a higher prevalence (23.6%) was observed in the subset of 55 patients younger than 21 years. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission, or mortality between patients with and without asthma. Observations between patients with and without asthma were similar when stratified by obesity, other comorbid conditions (ie, hypertension, hyperlipidemia, and diabetes), use of controller asthma medication, and absolute eosinophil count. Conclusions Among hospitalized patients 65 years or younger with severe COVID-19, asthma diagnosis was not associated with worse outcomes, regardless of age, obesity, or other high-risk comorbidities. Future population-based studies are needed to investigate the risk of developing COVID-19 among patients with asthma once universal testing becomes readily available.

Although gap junctions are not known to be important in mediating cell‐cell interactions amongst migratory cells, our studies showed that the connexin 43 (Cx43) gap junction gene is widely expressed in mouse neural crest cell lineages. Using in situ hybridization analysis, Cx43 expression was detected in presumptive neural crest cells emerging from the neural folds of the early postimplantation embryo. Neural crest expression of the Cx43 gap junction gene was also indicated by the analysis of transgenic mice containing a lacZ reporter construct driven by the Cx43 promoter. In neural tube explant cultures of these transgenic mice, lacZ expression was observed in the emerging neural crest outgrowths. Whole mount X‐gal staining of these transgenic embryos at various stages of development showed lacZ expression in neural crest cells distributed along the entire craniocaudal axis, with expression found in both cranial and trunk neural crest cells contributing to a wide range of embryonic tissues. This included presumptive cardiac neural crest cells localized in the heart. In light of the widespread expression of Cx43 in neural crest cell lineages, dye injection studies were carried out to determine if neural crest cells are functionally coupled via gap junctions. Such studies revealed extensive dye coupling among presumptive neural crest cells, thus demonstrating that these migratory cells are indeed gap junctional communication competent. In total, these observations suggest that gap junctions may play a role in mouse neural crest development. This possibility is particularly intriguing given the recent finding that the Cx43 knockout mice die of defects associated with the outflow tract [Reaume et al., 1995], a region of the heart in which neural crest cells are required for normal development. Dev. Genet. 20: 119–132, 1997. © 1997 Wiley‐Liss, Inc.

Background In the United States, Coronavirus Disease 2019 (COVID-19) deaths are captured through the National Notifiable Disease Surveillance System and death certificates reported to the National Vital Statistics System (NVSS). However, not all COVID-19 deaths are recognized and reported because of limitations in testing, exacerbation of chronic health conditions that are listed as the cause of death, or delays in reporting. Estimating deaths may provide a more comprehensive understanding of total COVID-19–attributable deaths. Methods We estimated COVID-19 unrecognized attributable deaths, from March 2020—April 2021, using all-cause deaths reported to NVSS by week and six age groups (0–17, 18–49, 50–64, 65–74, 75–84, and ≥85 years) for 50 states, New York City, and the District of Columbia using a linear time series regression model. Reported COVID-19 deaths were subtracted from all-cause deaths before applying the model. Weekly expected deaths, assuming no SARS-CoV-2 circulation and predicted all-cause deaths using SARS-CoV-2 weekly percent positive as a covariate were modelled by age group and including state as a random intercept. COVID-19–attributable unrecognized deaths were calculated for each state and age group by subtracting the expected all-cause deaths from the predicted deaths. Findings We estimated that 766,611 deaths attributable to COVID-19 occurred in the United States from March 8, 2020—May 29, 2021. Of these, 184,477 (24%) deaths were not documented on death certificates. Eighty-two percent of unrecognized deaths were among persons aged ≥65 years; the proportion of unrecognized deaths were 0•24–0•31 times lower among those 0–17 years relative to all other age groups. More COVID-19–attributable deaths were not captured during the early months of the pandemic (March–May 2020) and during increases in SARS-CoV-2 activity (July 2020, November 2020—February 2021). Discussion Estimating COVID-19–attributable unrecognized deaths provides a better understanding of the COVID-19 mortality burden and may better quantify the severity of the COVID-19 pandemic. Funding None