Changes in all-cause and cause-specific mortality during the first year of the COVID-19 pandemic in Minnesota: population-based study.

BACKGROUND: The COVID-19 pandemic resulted in unprecedented increases in mortality in the U.S. and worldwide. To better understand the impact of the COVID-19 pandemic on mortality in the state of Minnesota, U.S.A., we characterize the changes in the causes of death during 2020 (COVID-19 period), compared to 2018-2019 (baseline period), assessing for differences across ages, races, ethnicities, sexes, and geographic characteristics. METHODS: Longitudinal population-based study using Minnesota death certificate data, 2018-2020. Using Poisson regression models adjusted for age and sex, we calculated all-cause and cause-specific (by underlying causes of death) mortality rates per 100,000 Minnesotans, the demographics of the deceased, and years of life lost (YLL) using the Chiang's life table method in 2020 relative to 2018-2019. RESULTS: We identified 89,910 deaths in 2018-2019 and 52,030 deaths in 2020. The mean daily mortality rate increased from 123.1 (SD 11.7) in 2018-2019 to 144.2 (SD 22.1) in 2020. COVID-19 comprised 9.9% of deaths in 2020. Other categories of causes of death with significant increases in 2020 compared to 2018-2019 included assault by firearms (RR 1.68, 95% CI 1.34-2.11), accidental poisonings (RR 1.49, 95% CI 1.37-1.61), malnutrition (RR 1.48, 95% CI 1.17-1.87), alcoholic liver disease (RR, 95% CI 1.14-1.40), and cirrhosis and other chronic liver diseases (RR 1.28, 95% CI 1.09-1.50). Mortality rates due to COVID-19 and non-COVID-19 causes were higher among racial and ethnic minority groups, older adults, and non-rural residents. CONCLUSIONS: The COVID-19 pandemic was associated with a 17% increase in the death rate in Minnesota relative to 2018-2019, driven by both COVID-19 and non-COVID-19 causes. As the COVID-19 pandemic enters its third year, it is imperative to examine and address the factors contributing to excess mortality in the short-term and monitor for additional morbidity and mortality in the years to come.

A Case-Control Autopsy Series of Liver Pathology Associated with Novel Coronavirus Disease (COVID-19)

Background: COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a global health emergency. Although well-known for pulmonary injury, COVID-19 is a systemic process. Previous autopsy case series have speculated about, although not clearly defined, patterns of hepatic injury, with steatosis being reported in many patients. This retrospective study is the first case-control study investigating hepatic pathology in a large cohort of deceased COVID-19 patients. Design: Consented autopsy cases at two institutions, between 4/2020 and 2/2021, were retrospectively searched for documentation of COVID-19 as a contributing cause of death. A control group of 40 consecutive consented COVID-19(-) autopsy cases during the same period was identified. The autopsy report and electronic medical records were reviewed for clinical information. H&E-stained liver sections were examined for selected histologic features. Results: 54 COVID-19(+) (mean age 72, M:F=3.2:1) were included in the study. The 40 control cases had a mean age of 64 years and a M:F=1.4:1. The study group was significantly older (p=0.0095) but there was no significant difference in sex. The control group had a higher rate of chronic alcoholism and underlying malignancy, with no difference noted in BMI or other comorbidities. The study group was more likely to have received steroid (72.2% vs. 30%, p<0.0001) and anticoagulation therapy (75.9% vs. 47.5%, p=0.009). Histologically, the study group showed a higher incidence of clinically insignificant steatosis (≤5%), (33.3% vs 12.5%;P = 0.03). Presence of clinically relevant (>5%) steatosis or zonal distribution of steatosis was not significantly different between the groups. Mild nonspecific lobular inflammation and acidophil bodies were also more common in COVID-19 cases (51.9% vs 30.0%;P = 0.04). No significant difference was noted among other histologic features, including vascular changes (Table 1). Conclusions: Mild nonspecific lobular necroinflammatory activity is a common finding in deceased COVID-19 patients, suggestive of COVID-19 hepatitis. COVID-19 is unlikely a cause of clinically significant steatosis. However, patients with COVID-19 are more likely to have low levels of steatosis (≤5%) compared to controls. The high rate of steroid therapy in this population may be a possible source of this minor component of steatosis.

4 Impact of the SARS-CoV-2 Pandemic on Emergency Department Presentations in an Integrated Health System

Study Objectives: We aimed to quantify the impact of the SARS-CoV-2 pandemic on emergency department (ED) volumes and patient presentations, and to evaluate changes in community mortality for the purpose of characterizing new patterns of emergency care utilization. Methods: This is an observational cross-sectional study using electronic health records for ED visits in an integrated, multi-hospital system with academic and community practices across four states for visits between March 17 to April 21, 2019, and February 9 to April 21, 2020. We compared quantity and proportion of common and critical chief complaints and diagnoses, triage assessments, trauma activations, throughput, disposition, and hospital lengths-of-stay for selected diagnoses, and out-of-hospital deaths. Academic and community hospitals were evaluated separately and in combination for an overall picture of emergency department utilization. Results: Compared to both the preceding four weeks (n=37,670), and the prior year (n=35,037), ED visits from March 17 to April 21, 2020 (n=18,646) decreased 49% and 53.2% respectively. The total numbers of patients diagnosed with myocardial infarctions (STEMI and Non-STEMI), stroke, appendicitis and cholecystitis all decreased by a similar percentage. While there were fewer visits for mental health (n=1104 in preceding weeks, n=1032 for year-prior, n=752 during pandemic), they made up a larger proportion of ED visits - 2.9% for both baselines and 4% during period of interest (p<.001 for both). Compared to both baselines, the percentages of traumas were similar;however, the absolute number of red (n= 35 during COVID;n=72, p<.001 peri-COVID;n=67, p=.002 pre-COVID) and yellow (p=.002 peri-COVID;p=.004 pre-COVID) declined overall, driven by a drop at academic centers by nearly 60% for red traumas and 50% for yellow. Mortality was considered a surrogate for delayed/deferred emergency care. Southern Minnesota Regional Medical Examiner’s Office data showed an increase in natural deaths during the COVID period (n=250) versus pre-COVID (n=204) baseline (p=.037). Out-of-hospital mortality for natural (non-COVID-related) and non-natural deaths increased from 73 pre-COVID to 128 during the COVID period (p<.001). The significant increase in out-of-hospital mortality drives the overall mortality increase. There was an increase in deaths, driven by out-of-hospital mortality. Conclusion: Fewer patients presenting with acute and time-sensitive diagnoses suggests that patients are deferring care, this may be further supported by an increase in out-of-hospital mortality as well as a lower number of patients presenting with complaints and diagnoses that would be expected to remain stable for a given population during the periods studied. Understanding which patients are deferring care and why will allow us to develop outreach strategies and ensure that those in need of rapid assessment and treatment will continue to seek it, preventing downstream morbidity and mortality.

Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology.

We report the neuropathological findings of a patient who died from complications of COVID-19. The decedent was initially hospitalized for surgical management of underlying coronary artery disease. He developed post-operative complications and was evaluated with chest imaging studies. The chest computed tomography (CT) imaging results were indicative of COVID-19 and he was subsequently tested for SARS-CoV-2, which was positive. His condition worsened and he died after more than 2 weeks of hospitalization and aggressive treatment. The autopsy revealed a range of neuropathological lesions, with features resembling both vascular and demyelinating etiologies. Hemorrhagic white matter lesions were present throughout the cerebral hemispheres with surrounding axonal injury and macrophages. The subcortical white matter had scattered clusters of macrophages, a range of associated axonal injury, and a perivascular acute disseminated encephalomyelitis (ADEM)-like appearance. Additional white matter lesions included focal microscopic areas of necrosis with central loss of white matter and marked axonal injury. Rare neocortical organizing microscopic infarcts were also identified. Imaging and clinical reports have demonstrated central nervous system complications in patients' with COVID-19, but there is a gap in our understanding of the neuropathology. The lesions described in this case provide insight into the potential parainfectious processes affecting COVID-19 patients, which may direct clinical management and ongoing research into the disease. The clinical course of the patient also illustrates that during prolonged hospitalizations neurological complications of COVID may develop, which are particularly difficult to evaluate and appreciate in the critically ill.