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.

COVID Infection Among Kidney Transplant Recipient During the Era of COVID Vaccination: Management Outcomes

Purpose: COVID pandemic has posed a significant challenge among kidney transplant recipients (KTR) due to their immunocompromised state. There is uncertainty on immunosuppression (IS) management among those who have COVID infection. We sought to better understand the clinical course, management, and outcomes of our KTR who developed COVID infection during the period when COVID vaccine was more readily available. We also investigated the impact of vaccination status on COVID infection. Method(s): Single-center experience of COVID infected KTR. Baseline demographics, clinical data, COVID vaccination status, management, and outcomes were obtained by manual chart ion of the EMR. Result(s): 83 KTR had COVID infection. Mean age was 54 years;57% were males and 53% were African American. 47% of the patients were >3 years post-transplant. Interestingly, the proportion of COVID-infected patients who were unvaccinated and vaccinated with 2 doses were similar (42% vs 39%;p=NS) and the proportion of asymptomatic patients who were unvaccinated and vaccinated were also similar (47% vs. 53%;p=NS). Respiratory symptom was the most common manifestation (69%);49 patients (59%) required hospitalization. Mean length of stay was 15 days;19 (23%) required ICU admission and 14 (17%) required mechanical ventilation;26 developed AKI with about half requiring RRT;only 2 (18%) patients requiring RRT had renal recovery. The majority of admitted patients received dexamethasone and antibiotics. For IS management, 53% had MMF held or reduced while only 11% had CNI dose reduced;17 patients (20%) died. In multivariable modeling, only age (OR 1.1, 1.02-1.19;p=0.020) and AA race (OR 5.4, 0.73-40.2;p=0.097) were associated with risk of death. Induction, sex, BMI, and vaccination status were not significant predictors. There were no subsequent acute rejections or graft losses in those who recovered. Conclusion(s): KTR represent a vulnerable patient population for COVID infection. Due to their immunocompromised state and often more severe clinical presentation, with majority requiring hospitalization, ICU admission, and mechanical ventilation. In this single center study, COVID vaccination did not seem to have an appreciable impact on the incidence of COVID infection and presentation. It is unclear what impact immunosuppression dose reductions had on the COVID clinical course, but these reductions did not appear to increase risk of rejection or graft loss.

Comparison of Outcomes and Management of COVID Infection Among Kidney Transplant Recipients Between Pre-Vaccination Rollout Era and Post-Vaccination Rollout Era

Purpose: The COVID pandemic has posed a significant challenge among kidney transplant recipients (KTR) due to their immunocompromised states. The effects of COVID vaccination on KTRs are uncertain. We sought to better understand the clinical course, management, and outcomes of KTRs who developed COVID infection during the pre-and post-COVID vaccine rollout periods. We also compared whether there was a difference in patient outcomes or management of COVID infection between the two groups. Method(s): This was a single-center study of KTRs who were infected with COVID. Baseline demographics, clinical parameters, COVID vaccination status, management, and outcomes were obtained by manual chart ion of the electronic medical records. Result(s): We studied a total of 134 KTRs in the pre-vaccination era and 83 KTRs after vaccination rollout who had COVID infections. The mean age of the patients was 54 years in both groups, and there was a greater proportion of African American KTRs in the pre-vaccination rollout era (70% vs. 53%, P=.02). No statistically significant differences were found among sex, BMI, or induction agents. In the pre-vaccination era, KTRs were more likely to present with fever (71% vs. 51%, P<.001). No statistically significant differences were observed in the onset of COVID infection after transplant, ICU admission, the requirement of mechanical ventilation therapy, incidence of AKI (acute kidney injury), requirement of renal replacement therapy (RRT), or incidence of acute rejection. For COVID infection management, KTRs in the post-vaccination rollout era were more likely to be treated with dexamethasone (47% vs. 32%, P=.035) . No statistically significant difference was found in the proportion of patients who required reduction or discontinuation of immunosuppressive agents. In the pre-vaccination era, KTRs were more likely to recover from acute kidney injury (57% vs, 25%, P=.01). No statistically significant difference was found in mortality between groups, but the risk of death was almost twice a high in the post-vaccination rollout era (21% vs. 12%). Conclusion(s): In this single-center case-control study, COVID vaccination rollout did not seem to have an appreciable impact on the incidence of hospitalization, ICU admission, AKI, RRT requirement, or mortality. Mortality risk among KTRs in the post-vaccination rollout era was almost twice as high as it was in the pre-vaccination rollout era, although there was no statistically significant difference, which might be due to low statistical power. The lack of improved outcomes of KTRs in the postvaccination rollout remains unclear. A combination of suboptimal immunogenic response to vaccination and the Delta variant surge could be a possibility.

Trends in non-COVID-19 hospitalizations prior to and during the COVID-19 pandemic period, United States, 2017-2021.

COVID-19 pandemic-related shifts in healthcare utilization, in combination with trends in non-COVID-19 disease transmission and non-pharmaceutical intervention use, had clear impacts on rates of hospitalization for infectious and chronic diseases. Using a U.S. national healthcare billing database, we estimated the monthly incidence rate ratio of hospitalizations between March 2020 and June 2021 according to 19 ICD-10 diagnostic chapters and 189 subchapters. The majority of primary diagnoses for hospitalization showed an immediate decline in incidence during March 2020. Hospitalizations for reproductive neoplasms, hypertension, and diabetes returned to pre-pandemic levels during late 2020 and early 2021, while others, like those for infectious respiratory disease, did not return to pre-pandemic levels during this period. Our assessment of subchapter-level primary hospitalization codes offers insight into trends among less frequent causes of hospitalization during the COVID-19 pandemic in the U.S.

Modeling the Effectiveness of Healthcare Personnel Reactive Testing and Screening for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant Within Nursing Homes.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant has been hypothesized to exhibit faster clearance (time from peak viral concentration to clearance of acute infection), decreased sensitivity of antigen tests, and increased immune escape (the ability of the variant to evade immunity conferred by past infection or vaccination) compared to prior variants. These factors necessitate reevaluation of prevention and control strategies, particularly in high-risk, congregate settings like nursing homes that have been heavily impacted by other coronavirus disease 2019 (COVID-19) variants. We used a simple model representing individual-level viral shedding dynamics to estimate the optimal strategy for testing nursing home healthcare personnel and quantify potential reduction in transmission of COVID-19. This provides a framework for prospectively evaluating testing strategies in emerging variant scenarios when data are limited. We find that case-initiated testing prevents 38% of transmission within a facility if implemented within a day of an index case testing positive, and screening testing strategies could prevent 30% to 78% of transmission within a facility if implemented daily, depending on test sensitivity.

Protease-Anti-Protease Compartmentalization in SARS-CoV-2 ARDS: Therapeutic Implications

Rationale Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterised by an IL-6 driven cytokinemia, associated with a rapidly developing acute respiratory distress syndrome (ARDS). A blunted AAT response to IL-6 in SARS-CoV-2 has been associated with increased morbidity and mortality. One of the main functions of IL-6 is regulation of acute-phase proteins such as alpha-1 antitrypsin (AAT), a key lung anti-protease. We investigated the proteaseanti- protease balance in the circulation and pulmonary compartments in SARS-CoV-2 acute respiratory distress syndrome (ARDS). In addition, we investigated the effect of anti-IL-6 therapy on anti-protease defence. Methods Levels and activity of AAT and neutrophil elastase (NE) were measured in plasma (n=20), airway tissue (n=8) and tracheal secretions (n=13) of people with severe SARS-CoV-2 infection. AAT and IL-6 levels were also evaluated over time in people with moderate SARS-CoV-2 infection who received standard of care +/- tocilizumab (n=30). Results AAT plasma levels doubled in severe SARS-CoV-2 ARDS patients (329g/L +/- 08 g/L as compared to baseline levels 174g/L +/- 011 g/L, P<0001). In lung parenchyma AAT levels were increased. Despite no increase in neutrophils, an increased percentage of neutrophils involved in NET formation were observed in the alveoli. A protease-anti-protease imbalance was detected in tracheal aspirates (TA). NE was active and AAT inactivated, reflecting cleavage and complexation with NE. The major airway anti-protease, secretory leukoprotease inhibitor (SLPI) was decreased in SARS-CoV-2-infected lungs and cleaved in TAs. Induction of AAT in SARS-CoV-2 infection occurred mainly through IL-6 signalling. Tocilizumab (IL-6 receptor antagonist) down-regulated AAT during infection (13g/L+/-0225 from 2469 g/L+/-0197, P<00001) while IL-6 remained elevated (NS=0.0998) as reflected by the IL-6/AAT ratio (P=0046). Conclusion This study shows that the AAT response to SARS-CoV-2 infection is compartmentalized with an appropriate increase in plasma and alveoli but an inadequate response in airways. This underlines a significant, but potentially treatable, protease-antiprotease imbalance in SARS-CoV-2 ARDS as well as highlighting IL-6's importance in SARS-CoV-2 pathology not only as a pro-inflammatory cytokine but as an anti-inflammatory regulator. In conclusion there is unopposed NE activity in the airways of people with SARS-CoV-2 ARDS which could be amenable to AAT therapy. Our data suggest caution in the use of IL-6 blocking therapies in SARS-CoV-2-infected individuals.

The Effect of Cocooning on Patient-Reported Pulmonary Exacerbation Frequency in A ZZ Alpha-1 Antitrypsin Deficient Irish Population

Rationale: It has been suggested that individuals with ZZ alpha-1 antitrypsin deficiency (AATD) might suffer from more severe and prolonged pulmonary exacerbations compared to their MM counterparts due to the loss of immunomodulatory AAT protein. During the COVID-19 pandemic it was advised that individuals with ZZ AATD should, where practicable, cocoon to avoid contracting COVID-19. Methods: A survey of ZZ AATD individuals attending the Irish National Centre for Expertise for AATD was conducted 1 year into the COVID-19 pandemic. It evaluated the effects of cocooning on patient-reported exacerbation frequency during the 1-year COVID-19 period versus the 2 years prior to COVID-19. 184 individuals were contacted by phone, mail, or email. Results: 114 (62%) individuals successfully completed the survey. 73 (64%) cocooned during the pandemic, with men (39) and women (34) almost equally likely to cocoon. Those who cocooned tended to have a lower baseline FEV1 (% predicted). Women who cocooned had a mean FEV1 of 73.5% compared to a mean of 97.5% for women who did not cocoon. Men who cocooned had a mean FEV1 of 52.8% compared to a mean of 78.9% for men who did not cocoon. Men benefited from lower rates of exacerbation due to cocooning. They suffered an average of 0.92 exacerbations during the cocooning period versus 1.56 exacerbations per year prior to the pandemic (P = 0.0298). Women, regardless of cocooning status and non-cocooning men also demonstrated a trend towards fewer exacerbations but these were not statistically significant. In terms of hospitalisations, there were no differences observed between men or women based on cocooning status. This was likely due to the low rate of hospital admissions during the 3-year period. 14 (12%) of 114 respondents contracted COVID-19, 7 (50%) of whom were hospitalised. There was a single fatality from COVID-19. Conclusion: Further work needs to be done to establish the effects of risk reduction behaviours such as cocooning on exacerbation frequency and which groups may benefit most from this strategy. Our survey suggests that men with more advanced respiratory disease were most likely to benefit from a cocooning strategy and this may be applicable to non-COVID threats in the future.

COVID-19 Positivity Following an In-Person Surgical Society Meeting: A Cross-Sectional Survey Study.

INTRODUCTION: Many surgical societies have recently resumed in-person meetings after canceling or adopting virtual formats during the COVID-19 pandemic. These meetings implemented safety measures to limit viral exposure and ensure participant safety. While there have been anecdotal reports of COVID-19 cases after attendance, no large-scale assessments have been undertaken. The objective of this study was to evaluate COVID-19 positivity following an in-person surgical society meeting. METHODS: An online survey was administered to participants of the Society for Asian Academic Surgeons annual meeting, which was held in Chicago, Illinois in September 2021. This survey assessed vaccination status, in-person versus virtual conference attendance, and COVID-19 testing and symptoms in the 7 d immediately following the meeting. RESULTS: Among the 220 meeting participants, 173 attended in person (79%). There were 91 survey respondents (41% response rate): 67% attending physicians, 27% trainees, and 6% medical students. Nearly, all (99%) reported being fully vaccinated against COVID-19. COVID-19 testing was sought within 7 d of the meeting by 15% of in-person respondents, and all reported negative results. Among individuals who were not tested, no one reported development of symptoms (cough, shortness of breath, fever, new loss of taste/smell, etc.). CONCLUSIONS: Among in-person attendees of a recent surgical society meeting, no one reported positive COVID-19 testing after the meeting, and individuals who were not tested denied developing symptoms. While these results are encouraging, societies hosting meetings should continue to proactively assess the safety of in-person meetings to promptly identify outbreaks and opportunities for improvement.

Trends in non-COVID-19 hospitalizations prior to and during the COVID-19 pandemic period, United States, 2017-2021 (preprint)

COVID-19 pandemic-related shifts in healthcare utilization, in combination with trends in non-COVID-19 disease transmission and NPI use, had clear impacts on infectious and chronic disease hospitalization rates. Using a national healthcare billing database (C19RDB), we estimated the monthly incidence rate ratio of hospitalizations between March 2020 and June 2021 according to 19 ICD-10 diagnostic chapters and 189 subchapters. The majority of hospitalization causes showed an immediate decline in incidence during March 2020. Hospitalizations for diagnoses such as reproductive neoplasms, hypertension, and diabetes returned to pre-pandemic norms in incidence during late 2020 and early 2021, while others, like those for infectious respiratory disease, never returned to pre-pandemic norms. These results are crucial for contextualizing future research, particularly time series analyses, utilizing surveillance and hospitalization data for non-COVID-19 disease. Our assessment of subchapter level primary hospitalization codes offers new insight into trends among less frequent causes of hospitalization during the COVID-19 pandemic.

The Brain Health Champion (BHC) Study, COVID-19 sub-study: The impact of COVID-19 on behaviors adopted following interventions to promote brain-healthy activities

Background Evidence suggests that brain-healthy behaviors, such as exercise, a Mediterranean diet, and cognitive/social stimulation, help protect against the risk of cognitive decline and dementia. We have been studying two interventions (health coach vs. physician education) that promote brain-healthy behaviors in patients with mild dementia (MD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and those at-risk. When COVID-19 occurred, we became interested in determining the extent to which the pandemic may have interfered with brain-healthy behaviors that participants had adopted. We designed a sub-study to investigate the pandemic?s effects on adherence to brain-healthy behaviors in participants who completed either intervention in one of our two Brain Health Champion studies (BHC-1, BHC-2). Method Participants from BHC-1 and BHC-2 were emailed questionnaires in September 2020. Of the 25 respondents, 15 (SCD:2, MCI:8, MD:5) were from BHC-1 and 10 (At-risk:5, MCI:5) were from BHC-2. Questionnaires measured changes from the start of the pandemic (March 2020) in self-reported physical activity, diet, and social/cognitive activities, as well as current sleep quality and feelings of anxiety and depression. Result Results demonstrated that the pandemic had negatively impacted physical activity (p=.009) and social interactions (p<.001), with no significant changes in diet or cognitive activities. Additional data trends show that at-risk/SCD participants endorsed more feelings of anxiety and depression than MCI participants. At-risk/SCD participants also reported worse sleep quality than MCI participants (p=.036) across both studies and intervention arms. Conclusion Our findings suggest that the pandemic significantly impacted activities typically done outside the home (social and physical activity), while activities that are typically done at home were less affected (Mediterranean diet adherence and cognitive activity). The pandemic seemed to diminish brain-healthy behaviors that participants likely gained from the interventions, demonstrating that clinical/research programs aimed at promoting brain health are strongly influenced by changes in the environment. Trends also show that there may be a direct relationship between anxiety/depression symptoms and sleep disruption in at-risk/SCD and MCI participants. More research is necessary to determine if these disruptions of behavior and sleep are temporary and will be well-compensated when COVID-19 restrictions are lifted.

Global dissemination of knowledge through virtual platforms: Reflections and recommendations from APSA/IPEG.

BACKGROUND: The COVID-19 pandemic forced the cancelation of conventional in-person academic conferences due to the risk of virus transmission and limited ability to travel. Both the American Pediatric Surgical Association (APSA) and International Pediatric Endosurgery Group (IPEG) converted to a virtual format for their 2020 annual meetings. The purpose of this article is to review the successful implementation of the APSA and IPEG virtual meetings and reflect upon lessons learned for future virtual conferences. METHODS: Logistics, structure, and attendance statistics were reviewed. Informal interviews were conducted with key stakeholders and the number of presenters and participants were analyzed. Finally, post-meeting attendee surveys were conducted to elicit feedback after both virtual meetings. RESULTS: The meetings were organized in different ways, with APSA spreading a mix of scientific and clinical educational content over several months and IPEG keeping the meeting compressed, similar to previous in-person versions. Both meetings were free and therefore attracted a high proportion of participants (720 for APSA and 834 for IPEG). The meetings were felt to be educationally appropriate by most, although timing and lack of Continuing Medical Education (CME) opportunities were detractors. Most attendees said they would be willing to pay fees similar to in-person amounts. IPEG compressed presentations into four 2-hour sessions spread over 4 weeks, but also made material available on-line through a proprietary application. There was a broad range of international attendees. IPEG attracted a larger percentage of non-members than did APSA (3:1 nonmember to member ratio). Both societies reported net losses, largely due to lost registration revenue and non-refundable costs from having to switch from an in-person meeting. CONCLUSIONS: The main advantage of the virtual meeting was increased participation while disadvantages included the lack of networking. The key lessons learned from the meetings include methods to increase interactivity, adjustments of technical logistics, and creation of enduring material. In the future, hybrid conferences will likely become more prevalent with advantages of both platforms. LEVEL-OF-EVIDENCE: Level V - Expert Opinion.

'To prevent this disease, we have to stay at home, but if we stay at home, we die of hunger' - Livelihoods, vulnerability and coping with Covid-19 in rural Mozambique.

Non-pharmaceutical interventions (NPIs) such as social distancing and travel restrictions have been introduced to prevent the spread of the novel coronavirus (hereinafter Covid). In many countries of the Global South, NPIs are affecting rural livelihoods, but in-depth empirical data on these impacts are limited. We traced the differentiated impacts of Covid NPIs throughout the start of the pandemic May to July 2020. We conducted qualitative weekly phone interviews (n = 441) with 92 panelists from nine contrasting rural communities across Mozambique (3-7 study weeks), exploring how panelists' livelihoods changed and how the NPIs intersected with existing vulnerabilities, and created new exposures. The NPIs significantly re-shaped many livelihoods and placed greatest burdens on those with precarious incomes, women, children and the elderly, exacerbating existing vulnerabilities. Transport and trading restrictions and rising prices for consumables including food meant some respondents were concerned about dying not of Covid, but of hunger because of the disruptions caused by NPIs. No direct health impacts of the pandemic were reported in these communities during our interview period. Most market-orientated income diversification strategies largely failed to provide resilience to the NPI shocks. The exception was one specific case linked to a socially-minded value chain for baobab, where a strong duty of care helped avoid the collapse of incomes seen elsewhere. In contrast, agricultural and charcoal value chains either collapsed or saw producer prices and volumes reduced. The hyper-covariate, unprecedented nature of the shock caused significant restrictions on livelihoods through trading and transport limits and thus a region-wide decline in cash generation opportunities, which was seen as being unlike any prior shock. The scale of human-made interventions and their repercussions thus raises questions about the roles of institutional actors, diversification and socially-minded trading partners in addressing coping and vulnerability both conceptually and in policy-making.

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. METHODS: In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m2 at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change. RESULTS: Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. CONCLUSIONS: Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.