Search

Background COVID-19 has disproportionately affected older people. Objective The objective of this paper to investigate whether frailty is associated with all-cause mortality in older hospital inpatients, with COVID-19. Design Cohort study. Setting Secondary care acute hospital. Participants Participants included are 677 consecutive inpatients aged 65 years and over. Methods Cox proportional hazards models were used to examine the association of frailty with mortality. Frailty was assessed at baseline, according to the Clinical Frailty Scale (CFS), where higher categories indicate worse frailty. Analyses were adjusted for age, sex, deprivation, ethnicity, previous admissions and acute illness severity. Results Six hundred and sixty-four patients were classified according to CFS. Two hundred and seventy-one died, during a mean follow-up of 34.3 days. Worse frailty at baseline was associated with increased mortality risk, even after full adjustment (P  = 0.004). Patients with CFS 4 and CFS 5 had non-significant increased mortality risks, compared to those with CFS 1–3. Patients with CFS 6 had a 2.13-fold (95% CI 1.34–3.38) and those with CFS 7–9 had a 1.79-fold (95% CI 1.12–2.88) increased mortality risk, compared to those with CFS 1–3 (P  = 0.001 and 0.016, respectively). Older age, male sex and acute illness severity were also associated with increased mortality risk. Conclusions Frailty is associated with all-cause mortality risk in older inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

Background This study aimed to describe the mortality excess during the three first epidemic periods of COVID-19 in all regions of France. Methods Two complementary approaches were implemented. First, we described the number of death of patients infected with or diagnosed with COVID-19 in health care (HC) and medico-social (MS) institutions. Then, we estimated general all-cause mortality excess (all ages) by comparing the mortality observed with the expected mortality. We used a daily number of death model according to a negative binomial distribution, as a function of the long-term trend in mortality (penalized spline function of time) and its seasonal variation (cyclic spline function). The model provided expected mortality during epidemic periods with a 95% credibility interval. Each region defined three epidemic periods, including the overseas territories. Results The two approaches were consistent in the most affected regions but there are major regional disparities that vary according to the epidemic period. There is an east–west gradient in the relative excess of deaths from all-causes during each epidemic period. The deaths observed in HC and MS institutions alone do not explain the excess (or deficit) of mortality in each region and epidemic period. Conclusion An analysis by age group according to the two approaches and a comparison of death specific causes could provide a better understanding of these differences. Electronic death registration system (mortality by medical causes) would allow a rapid mortality related estimation to an emerging pathology like Coronavirus Disease-2019 (COVID-19) but is still insufficient for real-time medical causes of death monitoring. [ABSTRACT FROM AUTHOR]

Background There are still many unknowns about COVID-19. We do not know its exact mortality rate nor the speed through which it spreads across communities. This lack of evidence complicates the design of appropriate response policies. Methods We source daily death registry data for 4100 municipalities in Italy's north and match them to Census data. We augment the dataset with municipality-level data on a host of co-factors of COVID-19 mortality, which we exploit in a differences-in-differences regression model to analyze COVID-19-induced mortality. Results We find that COVID-19 killed more than 0.15% of the local population during the first wave of the epidemic. We also show that official statistics vastly underreport this death toll, by about 60%. Next, we uncover the dramatic effects of the epidemic on nursing home residents in the outbreak epicenter: in municipalities with a high share of the elderly living in nursing homes, COVID-19 mortality was about twice as high as in those with no nursing home intown. Conclusions A pro-active approach in managing the epidemic is key to reduce COVID-19 mortality. Authorities should ramp-up testing capacity and increase contact-tracing abilities. Adequate protective equipment should be provided to nursing home residents and staff. [ABSTRACT FROM AUTHOR]

The author comments on a research paper on the prevalence, incidence and mortality of delirium in the COVID-19 disease, which references a study by S. C. Shao et al., published in a 2021 issue of "Age Ageing". Topics discussed include the characteristics of delirium, the challenges facing health professionals in managing delirium in patients with COVID-19, findings on its prevalence on admission and during hospitalization, and the study's implications for care for patients with delirium.

Mortality of candidemia in coronavirus disease 2019 (COVID-19) patients has not been deeply studied despite evidence suggesting an increased occurrence. We performed a systematic review and meta-analysis to summarize the available evidence about these patients' mortality and length of stay. Data about the in-hospital, all-cause and 30-day mortality, and length of stay were pooled. Subgroup analyses were performed to assess sources of heterogeneity. Twenty-six articles out of the 1915 records retrieved during the search were included in this review. The pooled in-hospital mortality was 62.62% (95% CI, 54.77% to 69.86%), while the mortality in intensive care unit (ICU) was 66.77% (95% CI, 57.70% to 74.75%). The pooled median in-hospital length of stay was 30.41 (95% CI, 12.28 to 48.55) days, while the pooled median length of stay in the ICU was 28.28 (95% CI, 20.84 to 35.73) days. The subgroup analyses did not identify the sources of heterogeneity in any of the analyses. Our results showed high mortality in patients with candidemia and COVID-19, suggesting the need to consider screening measures to prevent this life-threatening condition. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does exogenous estrogen use affect COVID-19-related mortality in women? SUMMARY ANSWER Menopausal hormone therapy (MHT) was associated with a lower likelihood of all-cause fatality related to COVID-19 in postmenopausal women (odds ratio (OR) 0.28, 95% CI 0.18, 0.44; 4 studies, 21 517 women) but the combined oral contraceptive pill in premenopausal women did not have a significant effect (OR 1.00, 95% CI 0.42–2.41; 2 studies, 5099 women). WHAT IS KNOWN ALREADY Men are much more likely to die from COVID-19 than women. STUDY DESIGN, SIZE, DURATION In this systematic meta-analysis, a literature search was conducted using the following search terms related toCOVID-19 and estrogen, sex hormones, hormonal replacement, menopause, or contraception. The PubMed, Scopus, Cochrane Library, and EMBASE databases were searched to identify relevant studies published between December 2019 and December 2021. We also searched MedRxiv as a preprint database and reviewed the reference lists of all included studies and clinical trial registries for ongoing clinical studies until December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS All comparative studies that compared the rates mortality and morbidity (hospitalization, intensive care unit (ICU) admission, and ventilation support) due to COVID-19 in women using exogenous estrogen to a control group of women (nonusers) were included. A review of the studies for inclusion, extraction of data, and assessment of the risk of bias was performed independently by two reviewers. The ROBINS-I tool and the RoB 2 tool were used for bias assessment of the included studies. Pooled odds ratios (ORs) with 95% CIs were calculated using Review Manager V5.4.1. The I 2 statistic was used to quantify heterogeneity. The quality of the evidence was assessed using GRADE criteria. MAIN RESULTS AND THE ROLE OF CHANCE After searching the databases, we identified a total of 5310 studies. After removing duplicate records, ineligible studies, and ongoing studies, a total of four cohort studies and one randomized controlled trial comprising 177 809 participants were included in this review. There was a moderate certainty of evidence that MHT was associated with a lower likelihood of all-cause fatality related to COVID-19 (OR 0.28, 95% CI 0.18, 0.44; I 2 = 0%; 4 studies, 21 517 women). The review indicated a low certainty of evidence for other outcomes. The mortality rate of premenopausal women in the combined oral contraceptive pill group did not differ significantly from the control group (OR 1.00, 95% CI 0.42–2.41; 2 studies, 5099 women). MHT marginally increased the rate of hospitalization and ICU admission (OR 1.37, 95% CI 1.18–1.61; 3 studies, 151 485 women), but there was no significant difference in the need for respiratory support between MHT users and nonusers (OR 0.91, 95% CI 0.52–1.59; 3 studies, 151 485 women). Overall, the tendency and magnitude of the effects of MHT in postmenopausal women with COVID-19 were consistent across the included studies. LIMITATIONS, REASONS FOR CAUTION The certainty of the evidence for other outcomes of this review may be limited, as all included studies were cohort studies. In addition, the dosages and durations of exogenous estrogen used by postmenopausal women varied from study to study, and combined progestogen administration may have had some effect on the outcomes. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study can aid in counseling postmenopausal women taking MHT when they are diagnosed with COVID, as they have a lower chance of death than those not taking MHT. STUDY FUNDING/COMPETING INTEREST(s) Khon Kaen University provided financial support for this review and had no involvement at any stage of the study. The authors have no conflicts of interest to declare. REGISTRATION NUMBER PROSPERO, CRD42021271882. [ABSTRACT FROM AUTHOR]

Background To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. Methods Total, sex- and age-specific weekly all-cause mortality for 2015–2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015–2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. Results Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. Conclusions This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies. [ABSTRACT FROM AUTHOR]

Background and objective To investigate the effect of the COVID-19 pandemic on non-COVID-19 deaths in Mexico. Methods This study analyzes monthly administrative data on 15 different causes of death in Mexico from 2017 to 2020. The effects of the COVID-19 pandemic on non-COVID-19 deaths are conducted using a difference-in-differences methodology and an event study. Results The evidence shows mixed results. There is an increase in six causes of death: diabetes (36.8%), hypertension (25.8%), heart attacks (40.9%), bronchitis- asthma (24.2%), anemia (28.6%) and prostate cancer (21.4%). There is a decrease in two causes of death: traffic accidents (8.8%) and HIV (13.8%). There are null effects for seven causes of death: breast cancer, cerebrovascular disease, malnutrition, alcohol-related liver disease, renal insufficiency, homicides and suicides. Conclusions The COVID-19 pandemic affected non-COVID-19 deaths caused by diseases that require intensive healthcare services. Conversely, this pandemic reduced social interactions, which contributed to a decrease on deaths such as traffic accidents. [ABSTRACT FROM AUTHOR]

Aims Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. Methods and results This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71–0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90–1.42) and 0.86 (95% CI: 0.70–1.05; p interaction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73–2.98; 3.85, 95% CI: 3.21–4.63; and 3.95, 95% CI: 3.04–5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94–1.67 vs. 0.83; 95% CI: 0.59–1.16, p interaction = 0.04). Conclusions Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications. [ABSTRACT FROM AUTHOR]

Background Concerns have been raised that angiotensin-converting enzyme-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) might facilitate transmission of severe acute respiratory syndrome coronavirus 2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association between ACE-I/ARB treatment and risk of death amongst people with COVID-19 in the first 6 months of the pandemic. Methods We identified a cohort of adults diagnosed with either confirmed or probable COVID-19 (from 1 January to 21 June 2020) using computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. This comprised 465 general practices in England, United Kingdom with a nationally representative population of 3.7 million people. We constructed mixed-effects logistic regression models to quantify the association between ACE-I/ARBs and all-cause mortality among people with COVID-19, adjusted for sociodemographic factors, comorbidities, concurrent medication, smoking status, practice clustering, and household number. Results There were 9,586 COVID-19 cases in the sample and 1,463 (15.3%) died during the study period between 1 January 2020 and 21 June 2020. In adjusted analysis ACE-I and ARBs were not associated with all-cause mortality (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.85–1.21 and OR 0.84, 95% CI 0.67–1.07, respectively). Conclusion Use of ACE-I/ARB, which are commonly used drugs, did not alter the odds of all-cause mortality amongst people diagnosed with COVID-19. Our findings should inform patient and prescriber decisions concerning continued use of these medications during the pandemic. [ABSTRACT FROM AUTHOR]

Background Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a coronavirus disease 2019 (COVID-19) infection subpopulation. Methods A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland during 2010–21. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan–Meier and Cox proportional hazards analyses were used to assess mortality associations. Results In 1720 haemodialysis patients over a median of 21.9 (interquartile range 9.1–42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥8.23) versus quartile 1 (NLR <3.12) 1.63, 95% confidence interval (CI) 1.32–2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53–6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34–2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48–14.92 and PLR: aHR 3.40, 95% CI 1.02–11.36; for highest vs lowest quartiles). Conclusions NLR is strongly associated with mortality in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients. [ABSTRACT FROM AUTHOR]

Background and objectives It is well documented that college student populations are vulnerable to food insecurity and other adverse environmental conditions. Additionally, exposure to environmental adversity can have deleterious, long-term effects on physical and mental health. This study applies evolutionary life history theory to examine the relationship between environmental adversity, mental distress and diet among resource insecure university students during the COVID-19 pandemic. Methodology Structured and semi-structured surveys were used to assess perceptions of environmental adversity (including mortality risk, food insecurity and resource availability; and changes in these factors over the course of COVID-19), mental distress, diet and use of campus support services. Participants included 51 college students recruited through an economic crisis center located at a large public university in southern California. Results Most students were experiencing mental distress and food insecurity, and food insecurity and other components of adversity increased during COVID-19. Food insecurity was significantly associated with both perceived extrinsic mortality risk and mental distress, whereas mental distress was significantly associated with reduced dietary quality and caloric intake. Use of two or more campus support resources and/or living with family or rent free disrupted the associations of food insecurity with extrinsic mortality risk and mental distress. Conclusion and Implication This study contributes to a growing body of applied evolutionary frameworks concerned with the health and wellbeing of economically vulnerable populations. It also provides novel insights informed by life history theory into interventions and recommendations for improving support services for financially insecure college students. [ABSTRACT FROM AUTHOR]

Objective To establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) compared with a propensity-matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK. Methods This is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a predesigned standardized case record form. Adult patients (≥18 years) admitted between 1 April 2020 and 31 July 2020 were included. Results Overall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with SLE, RA or aPL syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia [240 (60.91%) vs 206 (52.28%), P  = 0.015], elevated LDH [150 (38.08%) vs 43 (10.92%), P  < 0.001] and raised creatinine [122 (30.96%) vs 86 (21.83%), P  = 0.01], respectively. A significantly higher proportion of patients with severe rheumatologic AD had elevated CRP [77 (96.25%) vs 70 (87.5%), P  = 0.044] and LDH [20 (25%) vs 6 (7.5%), P  = 0.021]. Patients with severe rheumatologic AD had significantly higher mortality [32/80 (40%)] compared with propensity matched cohort of patients without AD [20/80 (25%), P  = 0.043]. However, there was no difference in 180-day mortality between propensity-matched cohorts of patients with or without AD in general (P  = 0.47). Conclusions Patients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and elevated LDH were more frequent in patients with any AD while elevated CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Limited recent observational data have suggested that there may be a protective effect of oestrogen on the severity of COVID-19 disease. Our aim was to investigate the association between hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP) use and the likelihood of death in women with COVID-19.Methods: We undertook a retrospective cohort study using routinely collected computerized medical records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. We identified a cohort of 1,863,478 women over 18 years of age from 465 general practices in England. Mixed-effects logistic regression models were used to quantify the association between HRT or COCP use and all-cause mortality among women diagnosed with confirmed or suspected COVID-19 in unadjusted and adjusted models.Results: There were 5,451 COVID-19 cases within the cohort. HRT was associated with a reduction in all-cause mortality in COVID-19 (adjusted OR 0.22, 95% CI 0.05 to 0.94). There were no reported events for all-cause mortality in women prescribed COCPs. This prevented further examination of the impact of COCP.Conclusions: We found that HRT prescription within 6 months of a recorded diagnosis of COVID-19 infection was associated with a reduction in all-cause mortality. Further work is needed in larger cohorts to examine the association of COCP in COVID-19, and to further investigate the hypothesis that oestrogens may contribute a protective effect against COVID-19 severity. [ABSTRACT FROM AUTHOR]

Background: Excess mortality during the COVID-19 pandemic is of major scientific and political interest.Methods: We critically reviewed different estimates of all-cause excess mortality for the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), which have been much studied during the COVID-19 pandemic, using the latest register data to discuss uncertainties and implications.Results: We show using back-calculation of expected deaths from Nordic all-cause deaths that the Institute for Health Metrics and Evaluation model is a clear outlier in the compared estimates and likely substantially overestimates excess mortality of Finland and Denmark, and probably Sweden. Our review suggests a range of total Nordic excess deaths of perhaps 15 000-20 000, but results are sensitive to assumptions in the models as shown.Conclusions: We document substantial heterogeneity and uncertainty in estimates of excess mortality. All estimates should be taken with caution in their interpretation as they miss detailed account of demographics, such as changes in the age group populations over the study period. [ABSTRACT FROM AUTHOR]

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n  = 1,141; C statistic: C  = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission. [ABSTRACT FROM AUTHOR]

Background Unlike other countries, South Korea did not implement a large-scale lockdown or closure of businesses to manage the coronavirus disease 2019 (COVID-19) pandemic, but relied on changes in population behaviours and early isolation and treatment of patients. It is important to evaluate the effectiveness of such alternative strategies on the mortality of the general population. Methods Mortality and monthly population data from 2013 to 2020 were obtained. A quasi-Poisson regression model adjusting for age structure, seasonality and time was used to evaluate whether underlying trends for monthly mortality rate have changed with the pandemic. Stratification analyses based on sex and location of deaths (inside vs outside of medical facilities) were conducted. Results The risk estimates showed no changes in non-accidental mortality during the COVID-19 pandemic [relative risk (RR) (95% confidence interval, 95% CI), slope change: 1.00 (1.00, 1.01), step change: 0.99 (0.97, 1.01)] compared with those before the pandemic. In cause-specific analysis, there was an abrupt and sustained decrease in the mortality rate of respiratory diseases [RR (95% CI), step change: 0.81 (0.77, 0.84)]. In the analysis of deaths by location, an increase in non-accidental mortality [RR (95% CI), slope change: 1.01 (1.01, 1.02), step change: 1.16 (1.11, 1.22)] and several cause-specific mortalities was observed outside of medical facilities. Conclusions The non-accidental mortality rate in South Korea for the first year of the pandemic followed the historical trends. However, there was a decrease in mortality associated with respiratory diseases, and an increase in mortality occurring outside of medical facilities. The findings may be attributed to changes in public behaviours, and availability of medical resources during the pandemic. [ABSTRACT FROM AUTHOR]

Objective People with inflammatory arthritis have an increased incidence of serious illness and mortality, placing them at risk of poor outcomes from coronavirus disease 2019 (COVID-19). This study explored patients' perceptions of risk from COVID-19 over a longitudinal period of the pandemic. Methods Fifteen adults with inflammatory arthritis attending a National Health Service rheumatology service each took part in three semi-structured telephone interviews conducted between 16 September 2020 and 29 July 2021. Interpretive phenomenological analysis was undertaken by two researchers and two public contributors. Results Four main themes relating to perceptions of risk from COVID-19 were identified: inflammatory arthritis; medications and co-morbidities; immediate social environment; health policy communication; and media influence. Participants recognized that having inflammatory arthritis increased their individual risk. Perceptions of risk and associated fear increased during the pandemic, influenced by family/friends who had had COVID-19 and health policy communications. The perceived constant use of negative messages led to many participants disengaging with the media. At the final interviews, when the vaccination programme was well established, participants continued to assess the risk and benefits of engaging in activities. Conclusion This study demonstrates the breadth of factors that influenced perceptions of risk in people with an inflammatory arthritis. As health professionals, we have only a small sphere of influence over some of these factors, namely health-care communications. People with inflammatory arthritis appropriately knew that their condition increased their infection risk, but more could be done to consider how and to what extent we involve patients in explaining risk at times of crisis. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic causes an overwhelming number of hospitalization and deaths with a significant socioeconomic impact. The vast majority of studies indicate that asthma and allergic diseases do not represent a risk factor for COVID-19 susceptibility nor cause a more severe course of disease. This raises the opportunity to investigate the underlying mechanisms of the interaction between an allergic background and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The majority of patients with asthma, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies and drug allergies exhibit an over-expression of type 2 immune and inflammatory pathways with the contribution of epithelial cells, innate lymphoid cells, dendritic cells, T cells, eosinophils, mast cells, basophils, and the type 2 cytokines interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31. The potential impact of type 2 inflammation-related allergic diseases on susceptibility to COVID-19 and severity of its course have been reported. In this review, the prevalence of asthma and other common allergic diseases in COVID-19 patients is addressed. Moreover, the impact of allergic and non-allergic asthma with different severity and control status, currently available asthma treatments such as inhaled and oral corticosteroids, short- and long-acting β2 agonists, leukotriene receptor antagonists and biologicals on the outcome of COVID-19 patients is reviewed. In addition, possible protective mechanisms of asthma and type 2 inflammation on COVID-19 infection, such as the expression of SARS-CoV-2 entry receptors, antiviral activity of eosinophils and cross-reactive T-cell epitopes, are discussed. Potential interactions of other allergic diseases with COVID-19 are postulated, including recommendations for their management. [ABSTRACT FROM AUTHOR]

Background: Preliminary studies have suggested a link between socio-economic characteristics and COVID-19 mortality. Such studies have been carried out on particular geographies within the USA or selective data that do not represent the complete experience for 2020.Methods: We estimated COVID-19 mortality rates, number of years of life lost to SARS-CoV-2 and reduction in life expectancy during each of the three pandemic waves in 2020 for 3144 US counties grouped into five socio-economic status categories, using daily death data from the Johns Hopkins University of Medicine and weekly mortality age structure from the Centers for Disease Control.Results: During March-May 2020, COVID-19 mortality was highest in the most socio-economically advantaged quintile of counties and lowest in the two most-disadvantaged quintiles. The pattern reversed during June-August and widened by September-December, such that COVID-19 mortality rates were 2.58 times higher in the bottom than in the top quintile of counties. Differences in the number of years of life lost followed a similar pattern, ultimately resulting in 1.002 (1.000, 1.004) million years in the middle quintile to 1.381 (1.378, 1.384) million years of life lost in the first (most-disadvantaged) quintile during the whole year.Conclusions: Diverging trajectories of COVID-19 mortality among the poor and affluent counties indicated a progressively higher rate of loss of life among socio-economically disadvantaged communities. Accounting for socio-economic disparities when allocating resources to control the spread of the infection and to reinforce local public health infrastructure would reduce inequities in the mortality burden of the disease. [ABSTRACT FROM AUTHOR]

Background Mortality is a critical measure of disease impact. The European Union (EU) countries share the same regulatory framework but different implementation policies. Methods We extracted cumulative COVID-19 mortality data across the EU countries. We evaluated the 27 member states using the location quotient (LQ) to adjust for the expected mortality in the whole EU region, where an LQ <1 signifies a more and an LQ >1 a less favorable outcome. We categorized EU members into 3 distinct profiles based on their LQ estimates: favorable profile, LQ ≤0.9; unfavorable profile, LQ >1.10; and average profile, LQ between 0.9 and 1.10. We compared LQ estimates and profiles with the prevaccination era that ended in December 2020 with the COVID-19 vaccine rollout. Results Twelve member states had a favorable profile, 4 had an average profile, and 11 had an unfavorable profile. In quantitative analysis, an improvement (negative LQ difference) was noted across countries with higher vaccination coverage (median, 71% fully vaccinated vs 57% for countries with positive LQ differences). There was a significant negative association between the share of fully vaccinated and LQ changes (ρ = –0.62, P  < .001) and a significant 4-month lag effect. After COVID-19 vaccines became available, 4 countries improved their profile and 5 moved to a worse profile. Conclusions There is significant variability in mortality and impact of COVID-19 between countries, even if they share the same regulatory framework. Extending immunization coverage may lead the transition to a more favorable profile, and alter the trajectory of COVID-19 mortality. [ABSTRACT FROM AUTHOR]

Background Years of Life Lost (YLLs) measure the shortfall in life expectancy due to a medical condition and have been used in multiple contexts. Previously it was estimated that there were 1.2 million YLLs associated with coronavirus disease 2019 (COVID-19) deaths in the USA through 11 July 2020. The aim of this study is to update YLL estimates for the first full year of the pandemic. Methods We employed data regarding COVID-19 deaths in the USA through 31 January 2021 by jurisdiction, gender and age group. We used actuarial life expectancy tables by gender and age to estimate YLLs. Results We estimated roughly 3.9 million YLLs due to COVID-19 deaths, which correspond to roughly 9.2 YLLs per death. We observed a large range across states in YLLs per 10 000 capita, with New York City at 298 and Vermont at 12. Nationally, the YLLs per 10 000 capita were greater for males than females (136.3 versus 102.3), but there was significant variation in the differences across states. Conclusions Our estimates provide further insight into the mortality effects of COVID-19. The observed differences across states and genders demonstrate the need for disaggregated analyses of the pandemic's effects. [ABSTRACT FROM AUTHOR]

In this brief communication, we discuss the confusion of mortality with fatality in the interpretation of evidence in the coronavirus disease 2019 (COVID-19) pandemic, and how this confusion affects the translation of science into policy and practice. We discuss how this confusion has influenced COVID-19 policy in France, Sweden, and the United Kingdom and discuss the implications for decision-making about COVID-19 vaccine distribution. We also discuss how this confusion is an example of a more general statistical fallacy we term the "Missing Link Fallacy." [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group.Methods: Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level.Results: In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years.Conclusions: All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted. [ABSTRACT FROM AUTHOR]

Background: Variations in the age patterns and magnitudes of excess deaths, as well as differences in population sizes and age structures, make cross-national comparisons of the cumulative mortality impacts of the COVID-19 pandemic challenging. Life expectancy is a widely used indicator that provides a clear and cross-nationally comparable picture of the population-level impacts of the pandemic on mortality.Methods: Life tables by sex were calculated for 29 countries, including most European countries, Chile and the USA, for 2015-2020. Life expectancy at birth and at age 60 years for 2020 were contextualized against recent trends between 2015 and 2019. Using decomposition techniques, we examined which specific age groups contributed to reductions in life expectancy in 2020 and to what extent reductions were attributable to official COVID-19 deaths.Results: Life expectancy at birth declined from 2019 to 2020 in 27 out of 29 countries. Males in the USA and Lithuania experienced the largest losses in life expectancy at birth during 2020 (2.2 and 1.7 years, respectively), but reductions of more than an entire year were documented in 11 countries for males and 8 among females. Reductions were mostly attributable to increased mortality above age 60 years and to official COVID-19 deaths.Conclusions: The COVID-19 pandemic triggered significant mortality increases in 2020 of a magnitude not witnessed since World War II in Western Europe or the breakup of the Soviet Union in Eastern Europe. Females from 15 countries and males from 10 ended up with lower life expectancy at birth in 2020 than in 2015. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries.Methods: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths.Results: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality.Conclusions: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes. [ABSTRACT FROM AUTHOR]

Objective Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. Methods A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017–18 were included. Outcomes were death and complications within 30 days of hospitalization. Results We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5–93.2%), chronic kidney disease (14.0–52.7%) and heart disease (29.0–83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2–4.3% vs 6.32–24.6%). Conclusion Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. [ABSTRACT FROM AUTHOR]

Background Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). Aim To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. Design A systematic review and meta-analysis. Methods Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28–30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. Results Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28–30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82–0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74–1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35–0.93). Conclusion The treatment with TCZ reduces 28–30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19. [ABSTRACT FROM AUTHOR]

Background COVID-19 deaths are commoner among care-home residents, but the mortality burden has not been quantified. Methods Care-home residency was identified via a national primary care registration database linked to mortality data. Life expectancy was estimated using Makeham–Gompertz models to (i) describe yearly life expectancy from November 2015 to October 2020 (ii) compare life expectancy (during 2016–18) between care-home residents and the wider population and (iii) apply care-home life expectancy estimates to COVID-19 death counts to estimate years of life lost (YLL). Results Among care-home residents, life expectancy in 2015/16 to 2019/20 ranged from 2.7 to 2.3 years for women and 2.3 to 1.8 years for men. Age–sex-specific life expectancy in 2016–18 in care-home residents was lower than in the Scottish population (10 and 2.5 years in those aged 70 and 90, respectively). Applying care home-specific life expectancies to COVID-19 deaths yield mean YLLs for care-home residents of 2.6 and 2.2 for women and men, respectively. In total YLL care-home residents have lost 3,560 years in women and 2,046 years in men. Approximately half of deaths and a quarter of YLL attributed to COVID-19 were accounted for by the 5% of over-70s who were care-home residents. Conclusion COVID-19 infection has led to the loss of substantial years of life in care-home residents aged 70 years and over in Scotland. Prioritising the 5% of older adults who are care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of YLL. [ABSTRACT FROM AUTHOR]

Background epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic. Methods cohort study of 179 UK care homes with 9,339 residents and 11,604 staff. We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality and estimate attributable mortality. Results 2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff, respectively. Sixty-eight percent (121/179) of care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection. Out of 607 residents with confirmed infection, 217 died (case fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was twofold higher in care homes with outbreaks versus those without (adjusted hazard ratio: 2.2 [1.8; 2.6]). Conclusions findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy. [ABSTRACT FROM AUTHOR]

Background Monoclonal antibody treatment may prevent complications of coronavirus disease 2019 (COVID-19). We sought to quantify the impact of bamlanivimab monoclonal antibody monotherapy on hospitalization and mortality among outpatients at high risk of COVID-19 complications. Methods In this observational study we compared outpatients who received bamlanivimab monoclonal antibody from December 9, 2020 to March 3, 2021 to nontreated patients with a positive polymerase chain reaction or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the same period who were eligible for monoclonal antibody treatment. The primary outcome was 28-day hospitalization or all-cause mortality, and the secondary outcome was hospitalization or emergency department visit without hospitalization. The risk-adjusted odds of study outcomes comparing bamlanivimab treated and untreated patients was determined using 1:5 propensity matching and multivariable logistic regression. Results Among 232 patients receiving bamlanivimab matched with 1160 comparator patients, the mean age was 67 years, 56% were female, and 196 (14%) of patients experienced hospitalization or mortality. After adjustment for propensity to receive treatment, bamlanivimab treatment was associated with a significantly reduced risk-adjusted odds of hospitalization or mortality within 28 days (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.24–0.69; P <.001). Bamlanivimab treatment was also associated with a significantly lower risk adjusted odds of hospitalization or emergency department visit without hospitalization (OR, 0.54; 95% CI, 0.35–0.82; P =.004). The results were most strongly associated with patients age 65 years and older. Conclusions Bamlanivimab monoclonal antibody monotherapy was associated with reduced hospitalizations and mortality within 28 days among outpatients with mild to moderate COVID-19. Use of bamlanivimab monotherapy for outpatients with mild to moderate COVID-19 infection was associated with reductions in hospitalizations and mortality within 28 days. Benefit was strongest in those age 65 years or older [ABSTRACT FROM AUTHOR]

Background Our objective was to characterize young adult patients hospitalized with coronavirus disease 2019 (COVID-19) and identify predictors of survival at 30 days. Methods This retrospective cohort study took place at 12 acute care hospitals in the New York City area. Patients aged 18–39 hospitalized with confirmed COVID-19 between March 1 and April 27, 2020 were included in the study. Demographic, clinical, and outcome data were extracted from electronic health record reports. Results A total of 1013 patients were included in the study (median age, 33 years; interquartile range [IQR], 28–36; 52% female). At the study end point, 940 (92.8%) patients were discharged alive, 18 (1.8%) remained hospitalized, 5 (0.5%) were transferred to another acute care facility, and 50 (4.9%) died. The most common comorbidities in hospitalized young adult patients were obesity (51.2%), diabetes mellitus (14.8%), and hypertension (13%). Multivariable analysis revealed that obesity (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.28–5.73; P =.002) and Charlson comorbidity index score (aHR, 1.20; 95% CI, 1.07–1.35; P =.002) were independent predictors of in-hospital 30-day mortality. Conclusions Obesity was identified as the strongest negative predictor of 30-day in-hospital survival in young adults with COVID-19. [ABSTRACT FROM AUTHOR]

Background Disparities in cross-regional coronavirus disease 2019 (Covid-19) mortality remain poorly understood. The association between pre-epidemic health and epidemic mortality can inform a policy response to future outbreaks. Method We conducted an ecological study of the association between the cumulative deaths attributed to Covid-19 epidemic in the 20 Italian regions and nine determinants of population health derived from a systematic review of the literature. We used a multiple least square regression to predict the cross-regional variation in mortality observed from the onset of the epidemic to 23 September 2020. Results Four independent variables best explained the cross-regional differences in the number of deaths attributed to Covid-19: the force of infection, population density, number of elderly living in assisted facilities and the standard rate of diabetes. The semi-partial correlation coefficients suggest that the force of infection and the number of elderly residents in nursing homes were the dominant predictors of the number of deaths attributed to Covid-19. Statistical controls and validation confirmed the generalizability of the predictive model. Conclusions Our findings indicate that a significant reduction of social contacts in main metropolitan areas and the timely isolation of elderly and diabetic residents could significantly reduce the death toll of the next wave of Covid-19 infection in Italy. [ABSTRACT FROM AUTHOR]

Introduction Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality.Methods: Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell's C statistic and Akaike information criterion (AIC)].Results: The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable).Conclusions: The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning. [ABSTRACT FROM AUTHOR]

Reported outcomes, such as incidence rates of mortality and intensive care unit admission, vary widely across epidemiological coronavirus disease 2019 (COVID-19) studies, including in the nephrology field. This variation can in part be explained by differences in patient characteristics, but also methodological aspects must be considered. In this review, we reflect on the methodological factors that contribute to the observed variation in COVID-19-related outcomes and their risk factors that are identified in the various studies. We focus on issues that arose during the design and analysis phase of the European Renal Association COVID-19 Database (ERACODA), and use examples from recently published reports on COVID-19 to illustrate these issues. [ABSTRACT FROM AUTHOR]

Background Older adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. Methods Using data from the Premier Healthcare Database on 181 813 hospitalized adults diagnosed with COVID-19 during March–September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity. Results Overall, 84 497 (47%) patients were admitted to the ICU, 29 078 (16%) received IMV, and 27 864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92–0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09–1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09–1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06–1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups. Conclusions These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes. [ABSTRACT FROM AUTHOR]

During the coronavirus disease 2019 (COVID-19) pandemic, hemodialysis patients constitute one of the most vulnerable patient populations as they have more significant comorbidities and need to visit healthcare settings frequently even under pandemic conditions. It was also largely demonstrated that hemodialysis patients have high mortality rates with severe to fatal disease due to COVID-19 during their initial hospitalization. Even though the functional decline and fatigue after severe infections are not a novel entity, some long-term effects of COVID-19 have drawn attention with their prolonged effects even after discharge. A recent prospective, observational study by Carriazo et al. provided the first evidence to compare long-term mortality rates of hemodialysis patients with and without COVID-19. Carriazo et al. stated a hazard ratio of 3.00 for the mortality rates of hemodialysis patients over a 1-year follow-up period after their COVID-19 diagnosis. They emphasized that the high mortality rates of hemodialysis patients with COVID-19 are not limited to the initial hospitalization period but also continue after discharge, especially in the first 3 months. In light of this study, it can be recommended that hemodialysis patients with COVID-19 should be monitored closely and continuously, and hemodialysis patients should be prioritized for vaccination against COVID-19 with close follow-up for their antibody levels. [ABSTRACT FROM AUTHOR]

Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19. [ABSTRACT FROM AUTHOR]

The high mortality rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a critical concern of the coronavirus disease 2019 (COVID-19) pandemic. Strikingly, men account for the majority of COVID-19 deaths, with current figures ranging from 59% to 75% of total mortality. However, despite clear implications in relation to COVID-19 mortality, most research has not considered sex as a critical factor in data analysis. Here, we highlight fundamental biological differences that exist between males and females, and how these may make significant contributions to the male-biased COVID-19 mortality. We present preclinical evidence identifying the influence of biological sex on the expression and regulation of angiotensin-converting enzyme 2 (ACE2), which is the main receptor used by SARS-CoV-2 to enter cells. However, we note that there is a lack of reports showing that sexual dimorphism of ACE2 expression exists and is of functional relevance in humans. In contrast, there is strong evidence, especially in the context of viral infections, that sexual dimorphism plays a central role in the genetic and hormonal regulation of immune responses, both of the innate and the adaptive immune system. We review evidence supporting that ineffective anti-SARS-CoV-2 responses, coupled with a predisposition for inappropriate hyperinflammatory responses, could provide a biological explanation for the male bias in COVID-19 mortality. A prominent finding in COVID-19 is the increased risk of death with pre-existing cardiovascular comorbidities, such as hypertension, obesity, and age. We contextualize how important features of sexual dimorphism and inflammation in COVID-19 may exhibit a reciprocal relationship with comorbidities, and explain their increased mortality risk. Ultimately, we demonstrate that biological sex is a fundamental variable of critical relevance to our mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) and immunosuppression, such as in renal transplantation (RT), stand as one of the established potential risk factors for severe coronavirus disease 2019 (COVID-19). Case morbidity and mortality rates for any type of infection have always been much higher in CKD, haemodialysis (HD) and RT patients than in the general population. A large study comparing COVID-19 outcome in moderate to advanced CKD (Stages 3–5), HD and RT patients with a control group of patients is still lacking. Methods We conducted a multicentre, retrospective, observational study, involving hospitalized adult patients with COVID-19 from 47 centres in Turkey. Patients with CKD Stages 3–5, chronic HD and RT were compared with patients who had COVID-19 but no kidney disease. Demographics, comorbidities, medications, laboratory tests, COVID-19 treatments and outcome [in-hospital mortality and combined in-hospital outcome mortality or admission to the intensive care unit (ICU)] were compared. Results A total of 1210 patients were included [median age, 61 (quartile 1–quartile 3 48–71) years, female 551 (45.5%)] composed of four groups: control (n = 450), HD (n = 390), RT (n = 81) and CKD (n = 289). The ICU admission rate was 266/1210 (22.0%). A total of 172/1210 (14.2%) patients died. The ICU admission and in-hospital mortality rates in the CKD group [114/289 (39.4%); 95% confidence interval (CI) 33.9–45.2; and 82/289 (28.4%); 95% CI 23.9–34.5)] were significantly higher than the other groups: HD = 99/390 (25.4%; 95% CI 21.3–29.9; P < 0.001) and 63/390 (16.2%; 95% CI 13.0–20.4; P < 0.001); RT = 17/81 (21.0%; 95% CI 13.2–30.8; P = 0.002) and 9/81 (11.1%; 95% CI 5.7–19.5; P = 0.001); and control = 36/450 (8.0%; 95% CI 5.8–10.8; P < 0.001) and 18/450 (4%; 95% CI 2.5–6.2; P < 0.001). Adjusted mortality and adjusted combined outcomes in CKD group and HD groups were significantly higher than the control group [hazard ratio (HR) (95% CI) CKD: 2.88 (1.52–5.44); P = 0.001; 2.44 (1.35–4.40); P = 0.003; HD: 2.32 (1.21–4.46); P = 0.011; 2.25 (1.23–4.12); P = 0.008), respectively], but these were not significantly different in the RT from in the control group [HR (95% CI) 1.89 (0.76–4.72); P = 0.169; 1.87 (0.81–4.28); P = 0.138, respectively]. Conclusions Hospitalized COVID-19 patients with CKDs, including Stages 3–5 CKD, HD and RT, have significantly higher mortality than patients without kidney disease. Stages 3–5 CKD patients have an in-hospital mortality rate as much as HD patients, which may be in part because of similar age and comorbidity burden. We were unable to assess if RT patients were or were not at increased risk for in-hospital mortality because of the relatively small sample size of the RT patients in this study. [ABSTRACT FROM AUTHOR]

As of 15 August 2020, Coronavirus disease 2019 (COVID-19) has been reported in >21 million people world-wide and is responsible for more than 750,000 deaths. The occurrence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be as high as 43%. This is comparable to AKI in other forms of pneumonia requiring hospitalization, as well as in non-infectious conditions like cardiac surgery. The impact of AKI on COVID-19 outcomes is difficult to assess at present but, similar to other forms of sepsis, AKI is strongly associated with hospital mortality. Indeed, mortality is reported to be very low in COVID-19 patients without AKI. Given that AKI contributes to fluid and acid–base imbalances, compromises immune response and may impair resolution of inflammation, it seems likely that AKI contributes to mortality in these patients. The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2. Mitochondria play a central role in the metabolic deregulation in the adaptive response to the systemic inflammation and are also found to be vital in response to both direct viral damage and tissue reperfusion. These stress conditions are associated with increased glycolysis and reduced fatty acid oxidation. Thus, there is a strong rationale to target AKI for therapy in COVID-19. Furthermore, many approaches that have been developed for other etiologies of AKI such as sepsis, inflammation and ischemia–reperfusion, have relevance in the treatment of COVID-19 AKI and could be rapidly pivoted to this new disease. [ABSTRACT FROM AUTHOR]

Background While the COVID-19 outbreak in China now appears suppressed, Europe and the USA have become the epicentres, both reporting many more deaths than China. Responding to the pandemic, Sweden has taken a different approach aiming to mitigate, not suppress, community transmission, by using physical distancing without lockdowns. Here we contrast the consequences of different responses to COVID-19 within Sweden, the resulting demand for care, intensive care, the death tolls and the associated direct healthcare related costs. Methods We used an age-stratified health-care demand extended SEIR (susceptible, exposed, infectious, recovered) compartmental model for all municipalities in Sweden, and a radiation model for describing inter-municipality mobility. The model was calibrated against data from municipalities in the Stockholm healthcare region. Results Our scenario with moderate to strong physical distancing describes well the observed health demand and deaths in Sweden up to the end of May 2020. In this scenario, the intensive care unit (ICU) demand reaches the pre-pandemic maximum capacity just above 500 beds. In the counterfactual scenario, the ICU demand is estimated to reach ∼20 times higher than the pre-pandemic ICU capacity. The different scenarios show quite different death tolls up to 1 September, ranging from 5000 to 41 000, excluding deaths potentially caused by ICU shortage. Additionally, our statistical analysis of all causes excess mortality indicates that the number of deaths attributable to COVID-19 could be increased by 40% (95% confidence interval: 0.24, 0.57). Conclusion The results of this study highlight the impact of different combinations of non-pharmaceutical interventions, especially moderate physical distancing in combination with more effective isolation of infectious individuals, on reducing deaths, health demands and lowering healthcare costs. In less effective mitigation scenarios, the demand on ICU beds would rapidly exceed capacity, showing the tight interconnection between the healthcare demand and physical distancing in the society. These findings have relevance for Swedish policy and response to the COVID-19 pandemic and illustrate the importance of maintaining the level of physical distancing for a longer period beyond the study period to suppress or mitigate the impacts from the pandemic. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. Aims We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. Methods On 15 April 2020, a Google internet search was performed using the keywords 'doctor', 'physician', 'death', 'COVID' and 'coronavirus' in English and Farsi, and Chinese using the Baidu search engine. The age, sex and medical speciality of physicians who died from COVID-19 in the line of duty were recorded. Individuals greater than 90 years of age were excluded. Results We found 278 physicians who died with COVID-19 infection, but complete details were missing for 108 individuals. The average age of the physicians was 63.7 years with a median age of 66 years, and 90% were male (235/261). General practitioners and emergency room doctors (108/254), respirologists (5/254), internal medicine specialists (13/254) and anaesthesiologists (6/254) comprised 52% of those dying. Two per cent of the deceased were epidemiologists (5/254), 2% were infectious disease specialists (4/254), 6% were dentists (16/254), 4% were ENT (9/254) and 3% were ophthalmologists (8/254). The countries with the most reported physician deaths were Italy (121/278; 44%), Iran (43/278; 15%), Philippines (21/278; 8%), Indonesia (17/278; 6%), China (16/278; 6%), Spain (12/278; 4%), USA (12/278; 4%) and UK (11/278;4%). Conclusions Physicians from all specialities may die from COVID. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work. [ABSTRACT FROM AUTHOR]

Background Various types of pulmonary diseases are associated with iron deficiency. However, information on iron status in coronavirus disease 2019 (COVID-19) is scarce. Methods This study included 50 hospitalized patients with confirmed COVID-19. The role of serum iron in predicting severity and mortality of COVID-19 was evaluated. Results The most common symptoms of COVID-19 patients in this study were cough (82%), fever (64%), and chest distress (42%). Of the 50 patients, 45 (90%) patients had abnormally low serum iron levels (<7.8 μmol/L). The severity of COVID-19 was negatively correlated with serum iron levels before and after treatment and was positively correlated with C-reactive protein, serum amyloid A, D-dimer, lactate dehydrogenase, urea nitrogen, and myoglobin levels. Decreased serum iron level could predict the transition of COVID-19 from mild to severe and critical illness. Seven (53.8%) patients with a lower serum iron level after treatment in the critical group had died. There was a significant difference in posttreatment serum iron levels between COVID-19 survivors and nonsurvivors. Conclusions Serum iron deficiency was detected in the patients with COVID-19. The severity and mortality of the disease was closely correlated with serum iron levels. Low serum iron concentration was an independent risk factor for death in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The novel virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the associated Coronavirus Disease 2019 (COVID-19) represent a pathogen to which human beings have limited to no evolved immune response. The most severe symptoms are associated with overactive inflammatory immune responses, leading to a cytokine storm, tissue damage, and death, if not balanced and controlled. Hypotheses within Evolutionary Medicine, including the Hygiene/Old Friends Hypothesis, provide an important lens through which to understand and possibly control this overactive immune response. In this article, we explore the role that infection with soil-transmitted helminths (STHs; i.e. intestinal parasitic worms) may play in dampening SARS-CoV-2 symptoms and mitigating the worst COVID-19 outcomes. Specifically, STHs stimulate the immunosuppressive and regulatory T-helper 2 (TH2) branch of the immune system, which decreases ACE2-receptor expression (i.e. receptors SARS-CoV-2 uses to infect host cells), balances the inflammatory TH1/TH17 branches of the immune system triggered by SARS-CoV-2 infection, and reduces inflammation through the release of anti-inflammatory/regulatory cytokines. Because STHs are common and affect the most vulnerable and marginalized members of society, it is especially important to consider how these parasites may impact COVID-19 outcomes. Areas experiencing endemic STH infections are often characterized by a lack of preventative infrastructure and medical care, which may further exacerbate risk of SARS-CoV-2 infection and COVID-19 development. For this reason, we also explore biocultural factors that contribute to disease outcomes for both SARS-CoV-2 and STH infections. Biocultural and Evolutionary Medicine perspectives on COVID-19 are crucial for understanding the global impact of the disease. Lay summary: An evolutionary perspective is required to understand the global impact and various presentations of COVID-19. We consider how coinfection with soil-transmitted helminths (common parasitic worms that coevolved with humans) may suppress inflammatory immune activity, thereby potentially reducing COVID-19 disease severity. Structural and lifestyle factors shaping coinfection patterns are also discussed. [ABSTRACT FROM AUTHOR]

We reviewed publicly available data from major US health jurisdictions to compare severe acute respiratory syndrome coronavirus 2 case fatality rates in people experiencing homelessness with the general population. The case fatality rate among people experiencing homelessness was 1.3 times (95% CI, 1.1–1.5) that of the general population, suggesting that people experiencing homelessness should be prioritized for vaccination. [ABSTRACT FROM AUTHOR]

Background More than 100 US physicians have died from COVID-19. I considered the number of US physician deaths in comparison to the expected COVID death rate in the general population. Aims To estimate the whether US physicians are at increased risk of death from COVID-19 due to occupational exposures. Methods COVID-related physician deaths were identified through searches using Medscape In Memoriam , and multiple internet searches using Google and Facebook. An obituary or death notice was obtained in all but one case. Death rates among physicians were compared to the expected rate based on COVID deaths in the US population. Results Up to 7 October 2020, there were 108 deaths among US physicians. Physicians make up about 0.33% of the US population. By 1 October 2020, there were 210 000 COVID deaths in the US population with 693 expected physician deaths. Observed deaths were 16% of expected. Seventy-five per cent of the deaths occurred among physicians older than age 60 and about half appeared to be among those retired from clinical practice. Conclusions Observed physician deaths were significantly below expected based on deaths the general population. Prudent use of personal protective equipment may explain the lower-than-expected death rates. [ABSTRACT FROM AUTHOR]