Heterologous vaccination interventions to reduce pandemic morbidity and mortality: Modeling the US winter 2020 COVID-19 wave

COVID-19 remains a stark health threat worldwide, in part because of minimal levels of targeted vaccination outside high-income countries and highly transmissible variants causing infection in vaccinated individuals. Decades of theoretical and experimental data suggest that nonspecific effects of non–COVID-19 vaccines may help bolster population immunological resilience to new pathogens. These routine vaccinations can stimulate heterologous cross-protective effects, which modulate nontargeted infections. For example, immunization with Bacillus Calmette–Guérin, inactivated influenza vaccine, oral polio vaccine, and other vaccines have been associated with some protection from SARS-CoV-2 infection and amelioration of COVID-19 disease. If heterologous vaccine interventions (HVIs) are to be seriously considered by policy makers as bridging or boosting interventions in pandemic settings to augment nonpharmaceutical interventions and specific vaccination efforts, evidence is needed to determine their optimal implementation. Using the COVID-19 International Modeling Consortium mathematical model, we show that logistically realistic HVIs with low (5 to 15%) effectiveness could have reduced COVID-19 cases, hospitalization, and mortality in the United States fall/winter 2020 wave. Similar to other mass drug administration campaigns (e.g., for malaria), HVI impact is highly dependent on both age targeting and intervention timing in relation to incidence, with maximal benefit accruing from implementation across the widest age cohort when the pandemic reproduction number is >1.0. Optimal HVI logistics therefore differ from optimal rollout parameters for specific COVID-19 immunizations. These results may be generalizable beyond COVID-19 and the US to indicate how even minimally effective heterologous immunization campaigns could reduce the burden of future viral pandemics.

On March 16th, 2020, Imperial College London released a landmark report advocating the suppression of SARS-CoV-2 to avoid a pandemic catastrophe (1). Since then, the scientific community has been challenged to create a “bridge period” of reduced COVID-19 morbidity and mortality until safe and effective targeted vaccines are delivered globally (2). Guided by major modeling groups and international and national public health authorities, most countries quickly implemented variably stringent nonpharmaceutical interventions (NPIs) including physical distancing, self-isolation, home working, school closure, and “shielding” of vulnerable populations such as the elderly. Despite ameliorating COVID-19 incidence when applied, these “lockdowns” of regional and national economies also caused severe financial, social, and health repercussions globally (3). In the United States and other countries, resistance to and reversal of NPIs occurred in many jurisdictions, complicating pandemic control and contributing to persistently high COVID-19 incidence.The rollout of specific COVID-19 vaccines in 2021 led to a temporary reduction of pandemic caseloads in countries with effective vaccine campaigns and ample stocks, but even this has not proven to be the sought-for panacea for epidemiological, logistical, and political reasons. The emergence of virus variants—now dominated by the Omicron and Delta strains—that are more transmissible and pathogenic have reversed many gains achieved to date and have raised questions about the durability of current vaccine efficacy (4). Although a handful of mainly high-income countries have instituted vigorous campaigns that have rapidly provided high coverage, less than 5% of the world’s low-income population has received at least one COVID-19–specific vaccination (5), and even in countries with ample vaccine supply, the global phenomenon of multifactorial vaccine hesitancy has led to uneven intranational uptake that has been exploited by the Delta variant. For these reasons, the public health armamentarium against COVID-19 has ample room for adjuncts to both NPIs and COVID-19–specific vaccines.One as-yet unutilized intervention to potentially prevent SARS-CoV-2 infection and reduce COVID-19 disease is based upon heterologous or nonspecific effects (NSEs) induced by available non–SARS-CoV-2 vaccines (6). The heterologous effect of vaccination refers to the impact that vaccines can have on unrelated infections and diseases. These effects have been noted for almost a hundred years (7), and potential mechanisms include innate and adaptive immune responses. Trained immunity (8–14), increased cytokine production (15–17), viral interference (18), long-lasting type I interferons (19), the antiviral state (20), cross-reactivity (21, 22), and bystander activation (23) are some of the mechanisms proposed.Some of the best-studied heterologous vaccine actions are from “off-target effects” from the Bacillus Calmette–Guérin (BCG) vaccine (12, 24–29). Epidemiological evidence including several randomized controlled trials (RCTs) have assessed the effect of BCG vaccination on reducing neonatal mortality. In Guinea-Bissau, two RCTs of BCG given to low weight neonates showed reduction in neonatal mortality after BCG, mainly because of fewer cases of neonatal sepsis, respiratory infection, and fever (30, 31). A meta-analysis of three RCTs of BCG-Denmark showed a reduction in mortality rate of 38% at 28 d of life; marked reductions in mortality were also seen within 3 d after vaccination and at 12 mo of age (32). Interestingly, a BCG vaccination prior to an influenza vaccination can boost influenza-specific immunity (33).Because of the nonspecific benefits of BCG vaccination, a phase III trial called “ACTIVATE-2” assessed whether BCG could protect against COVID-19 in the elderly; prepublication findings suggest a 68% risk reduction for total COVID-19 clinical and microbiological diagnoses (34). A separate study showed that a history of BCG vaccination was associated with a decreased SARS-CoV-2 seroprevalence across a diverse cohort of healthcare workers, and reduced COVID-19 symptoms (35). The magnitude of protective effect against symptomatic disease was similar in both studies: a reported range of 10 to 30% reduction in all respiratory infections in the former and a 34.5% reduction in self-reported diagnosis of COVID-19 in the latter.Other epidemiological studies have shown NSE benefits from oral polio vaccine (OPV), measles-containing vaccines (MCVs), and several other common immunizations. OPV has been associated with beneficial NSE (20, 36–38) and may become pronounced with subsequent doses (39–41). A systematic review of the associations of BCG, diptheria-tetanus-pertussis, and MCVs with childhood mortality showed that BCG and MCVs reduced overall mortality by more than would be expected through their effects on the diseases they target (42). As with BCG, an RCT of MCV showed a beneficial nonspecific effect on children’s survival (43).Focusing on SARS-CoV-2 transmission, several studies have found that the administration of OPV, Hemophilus influenza type-B, measles mumps rubella (MMR), varicella, hepatitis A/B, pneumococcal conjugate, and inactivated influenza vaccines are associated with decreased SARS-CoV-2 infection rates (44–46). In addition, results from a study in a Dutch hospital showed a 37 to 49% lower risk of SARS-CoV-2 infection in healthcare workers who received the influenza vaccine in the previous flu season, and this finding was also corroborated by a preliminary in vitro study (9). Thus, there is some evidence to support an impact of routine vaccinations on SARS-CoV-2 infection rates, although these ecological studies are prone to bias, do not establish causality, and may be SARS-CoV-2 variant-specific.Vaccine-mediated heterologous effects could also extend to reducing the severity of COVID-19 disease. There are epidemiological associations between those who have had a past vaccination with BCG, MMR, inactivated influenza vaccine, and recombinant adjuvanted zoster vaccine and reduced mortality and/or reduced COVID-19 severity (35, 45, 47–57), although these additional ecological studies are similarly susceptible to bias. A recent interim analysis of an ongoing clinical trial in Brazil supports this claim, showing that vaccination with MMR reduces the risk of COVID-19 symptoms and need for treatment (58). Given that the COVID-19 pandemic is still a global health emergency (especially in undervaccinated countries) and that the premise of HVI is soundly based in the immunological and epidemiological literature, there is ample reason to consider its potential role as part of a comprehensive package of pandemic control strategies.The plethora of studies cited can help characterize the hypothetical efficacy of immune system boosting through HVIs to reduce COVID-19 morbidity and mortality. However, estimating the potential real-world effectiveness of such interventions requires their implementation in an environment that can quantify their potential population-level impact in the context of ongoing control measures on viral transmission, health care utilization, and health outcomes. This type of epidemiological projection can be achieved through the use of mathematical models of infectious disease (59–65).We used the COVID-19 International Modeling (CoMo) Consortium Model (https://comomodel.net), an open-source, age-structured, country-specific, dynamic compartmental model of SARS-CoV-2 transmission and COVID-19 illness, treatment, and mortality, to illustrate how the logistics of implementing a heterologous vaccine intervention (HVI)—in particular, the timing of initiation of such a vaccination campaign in relation to trends in disease incidence and also the age-related population targeting of such a campaign—largely determine the magnitude of their impact. In particular, we instituted an explicitly defined HVI in one of three distinct time frames during the large fall/winter wave of SARS-CoV-2 in the United States (presurge, intrasurge, and postsurge) and across the same total number of individuals in one of three distinct age-targeted population groups (20+ y old, 40+ y old, and 65+ y old).There are multiple potential applications of heterologous vaccination in this setting, e.g., as a pre–COVID-19 vaccination primer, as a simultaneously delivered or post–COVID-19 vaccination booster (i.e., replacing or delaying the use of a second COVID-specific vaccine dose), or as a solitary “bridging” intervention to reduce or delay COVID-19-related morbidity and mortality until a specific vaccine is available. Here, we explore the last use: that of a solo heterologous vaccination used as a temporizing “bridging” intervention that has only a low level of heterologous effectiveness at reducing viral transmission (here defined as reducing the likelihood of being infected by 5, 10, or 15%) and clinical severity (i.e., reducing the risk of death if infected, again by 5, 10, or 15%). Given the high levels of targeted vaccination now attained in many high-income countries, our results with respect to the prevaccinated US outbreak should be seen as general, model-informed operational guidance that could maximize the beneficial effect of efforts to use common vaccination programs to mitigate and temporize the impact of COVID-19, and possibly future viral pandemics, in the majority of countries worldwide that have not yet received sufficient quantities of COVID-19–specific vaccines to ensure population protection.     

COVID-19 vaccine uptake and hesitancy opinions from frontline health care and social care workers: Survey data from 37 countries

Background and aimsVaccine hesitancy is an ongoing major challenge. We aimed to assess the uptake and hesitancy of the COVID-19 vaccination.MethodsA short online survey was posted between April 12 to July 31, 2021 targeted at health and social care workers (HCWs) across the globe.Results275 from 37 countries responded. Most were hospital or primary care physicians or nurses, 59% women, aged 18–60 years, and 21% had chronic conditions with most prevalent being diabetes, hypertension, and asthma. We found that most HCWs (93%) had taken or willing to receive the COVID-19 vaccine. While 7% were vaccine hesitant (mainly women aged 30–39 years), respondents main concerns was the safety or potential side effects. Vaccine willing respondents raised concerns of unequal access to the COVID-19 vaccination in some countries, and highlighted that the only solution to overcoming COVID-19 infections was the vaccine booster doses given annually and free mass vaccination.ConclusionsThis study found that the majority of the frontline HCWs are willing to receive the COVID-19 vaccine. Further promotion of the COVID-19 vaccine would reassure and persuade HCWs to become vaccinated.     

Impact of the COVID-19 pandemic on the quality of diabetes care: Insights from longitudinal data in Switzerland

In this population-based cohort study on diabetes care, self-reported quality indicators measured just before (2019) and during (2021) the COVID-19 pandemic were comparable, apart from a modest increase in seasonal influenza immunization and a small decline in patient-centeredness of care in 2021.     

Sleep patterns of US healthcare workers during the first wave of the COVID-19 pandemic

Sleep and Breathing - During the first few months of the COVID-19 outbreak, healthcare workers (HCW) faced levels of personal risk, emotional distress, and professional strain not seen in their...     

Impact of the COVID-19 pandemic on percutaneous coronary interventions in Portugal

IntroductionThe COVID-19 pandemic has imposed an unprecedented burden on healthcare systems worldwide, changing the profile of interventional cardiology activity.ObjectivesTo quantify and compare the number of percutaneous coronary interventions (PCIs) performed for acute and chronic coronary syndromes during the first COVID-19 outbreak with the corresponding period in previous years.MethodsData on PCI from the prospective multicenter Portuguese Registry on Interventional Cardiology (RNCI) were used to analyze changes in PCI for ST-elevation myocardial infarction (STEMI), non-ST-elevation acute coronary syndromes (NSTE-ACS) and chronic coronary syndromes (CCS). The number of PCIs performed during the initial period of the COVID-19 outbreak in Portugal, from March 1 to May 2, 2020, was compared with the mean frequency of PCIs performed during the corresponding period in the previous three years (2017–2019).ResultsThe total number of PCIs procedures was significantly decreased during the initial COVID-19 outbreak in Portugal (?36%, p<0.001). The reduction in PCI procedures for STEMI, NSTE-ACS and CCS was, respectively, ?25% (p<0.019), ?20% (p<0.068) and ?59% (p<0.001).ConclusionsCompared with the corresponding period in the previous three years, the number of PCI procedures performed for STEMI and CCS decreased markedly during the first wave of the COVID-19 pandemic in Portugal.     

Data mining and analysis of scientific research data records on Covid-19 mortality,immunity, and vaccine development - In the first wave of the Covid-19 pandemic

Background and aimsCovid-19 is a global pandemic that requires a global and integrated response of all national medical and healthcare systems. Covid-19 exposed the need for timely response and data sharing on fast spreading global pandemics. In this study, we investigate the scientific research response from the early stages of the pandemic, and we review key findings on how the early warning systems developed in previous epidemics responded to contain the virus.MethodsWe conducted data mining of scientific literature records from the Web of Science Core Collection, using the topics Covid-19, mortality, immunity, and vaccine. The individual records are analysed in isolation, and the analysis is compared with records on all Covid-19 research topics combined. The data records are analysed with commutable statistical methods, including R Studio’s Bibliometrix package, and the Web of Science data mining tool.ResultsFrom historical analysis of scientific data records on viruses, pandemics and mortality, we identified that Chinese universities have not been leading on these topics historically. However, during the early stages of the Covid-19 pandemic, the Chinese universities are strongly dominating the research on these topics. Despite the current political and trade disputes, we found strong collaboration in Covid-19 research between the US and China. From the analysis on Covid-19 and immunity, we wanted to identify the relationship between different risk factors discussed in the news media. We identified a few clusters, containing references to exercise, inflammation, smoking, obesity and many additional factors. From the analysis on Covid-19 and vaccine, we discovered that although the USA is leading in volume of scientific research on Covid-19 vaccine, the leading 3 research institutions (Fudan, Melbourne, Oxford) are not based in the USA. Hence, it is difficult to predict which country would be first to produce a Covid-19 vaccine.ConclusionsWe analysed the conceptual structure maps with factorial analysis and multiple correspondence analysis (MCA), and identified multiple relationships between keywords, synonyms and concepts, related to Covid-19 mortality, immunity, and vaccine development. We present integrated and corelated knowledge from 276 records on Covid-19 and mortality, 71 records on Covid-19 and immunity, and 189 records on Covid-19 vaccine.     

Unexpected high frequency of early mortality in COVID‐19: a single‐centre experience during the first wave of the pandemic

We report the high frequency of early mortality in COVID‐19 patients (48.6% of 72 deaths). Early deaths were not explained by differences in age, sex and comorbidities, but they had a more severe disease at hospital admission compared with late deaths. These data highlight the importance of outpatient monitoring for the early identification of COVID‐19 patients who require hospital admission.     

Endoscopy during COVID-19 pandemic: An overview of infection control measures and practical application

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has resulted in coronavirus disease 2019(COVID-19) which has affected more than 4.5 million people in 213 countries, and has been declared a pandemic by World Health Organization on March 11, 2020. The transmission of SARS-CoV-2 has been reported to occur primarily through direct contact or droplets. There have also been reports that SARS-CoV-2 can be detected in biopsy and stool specimens, and it has been postulated that there is potential for fecal–oral transmission as well. Gastrointestinal symptoms have been reported in 17.6% of COVID-19 patients and transmission can potentially occur through gastrointestinal secretions in this group of patients. Furthermore, transmission can also occur in asymptomatic carriers or patients with viral shedding during the incubation period. Endoscopic procedures hence may pose significant risks of transmission(even for those not directly involving confirmed COVID-19 cases) as endoscopists and endoscopy staff are in close contact with patients during these aerosol generating procedures. This could result in inadvertent transmission of infection at time of endoscopy.     

Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States

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Brief Report: Dynamics of racial disparities in all-cause mortality during the COVID-19 pandemic

As research documenting disparate impacts of COVID-19 by race and ethnicity grows, little attention has been given to dynamics in mortality disparities during the pandemic and whether changes in disparities persist. We estimate age-standardized monthly all-cause mortality in the United States from January 2018 through February 2022 for seven racial/ethnic populations. Using joinpoint regression, we quantify trends in race-specific rate ratios relative to non-Hispanic White mortality to examine the magnitude of pandemic-related shifts in mortality disparities. Prepandemic disparities were stable from January 2018 through February 2020. With the start of the pandemic, relative mortality disadvantages increased for American Indian or Alaska Native (AIAN), Native Hawaiian or other Pacific Islander (NHOPI), and Black individuals, and relative mortality advantages decreased for Asian and Hispanic groups. Rate ratios generally increased during COVID-19 surges, with different patterns in the summer 2021 and winter 2021/2022 surges, when disparities approached prepandemic levels for Asian and Black individuals. However, two populations below age 65 fared worse than White individuals during these surges. For AIAN people, the observed rate ratio reached 2.25 (95% CI = 2.14, 2.37) in October 2021 vs. a prepandemic mean of 1.74 (95% CI = 1.62, 1.86), and for NHOPI people, the observed rate ratio reached 2.12 (95% CI = 1.92, 2.33) in August 2021 vs. a prepandemic mean of 1.31 (95% CI = 1.13, 1.49). Our results highlight the dynamic nature of racial/ethnic disparities in mortality and raise alarm about the exacerbation of mortality inequities for Indigenous groups due to the pandemic.     

Perceived deterioration in health status among older adults in Europe and Israel following the first wave of the COVID-19 pandemic

The COVID-19 pandemic has created challenges in providing medical care for people with health conditions other than COVID-19. The study aims to assess the prevalence of older adults’ reportage of decline in health relative to pre-pandemic and to identify its determinants.The study is based on the Survey of Health, Ageing and Retirement in Europe (SHARE) data collected during the pandemic. It comprised 51,778 people in twenty-seven European countries and Israel. Participants were asked about changes in their health status relative to pre-pandemic. Bivariate analysis and logistic regression were used to identify factors associated with worsening of health.Nine percent of people (average age 70 years) reported a worsening of health relative to pre-pandemic. A logistic regression revealed a significant relation of the probability of a downturn in health to forgoing, postponing, or being denied an appointment for medical care. Multiple chronic illnesses, developing COVID-19, having at least one form of psychosocial distress, higher age, and lower economic capacity were also found significantly related to the probability of a decline in health.Older adults’ comprehensive health needs must be addressed even when healthcare services are under strain due to pandemic outbreaks. Policymakers should attend to the healthcare needs of people whose vulnerability to the pandemic is amplified by chronic health conditions and low socioeconomic status. Public healthcare systems may experience a massive rebound of demand for health care, a challenge that should be mitigated by delivery of healthcare services and the provision of the financial resources that they need.     

Influence of the COVID-19 pandemic in the gastrointestinal oncology setting: An overview

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been impacting healthcare in various ways worldwide and cancer patients are greatly affected by the coronavirus disease 2019 (COVID-19) pandemic. The reorganization of the health facilities in order to supply the high demand resulting from the aforementioned infection as well as the social isolation measures led to impairments for the diagnosis and follow-up of patients with gastrointestinal cancers, which has had an impact on the prognosis of the oncologic patients. In that context, health authorities and organizations have elaborated new guidelines with specific recommendations for the management of individuals with gastrointestinal neoplasms during the pandemic. Of note, oncologic populations seem to be more susceptible to unfavorable outcomes when exposed to SARS-CoV-2 infection and some interactions involving virus, tumor, host immune system and anticancer therapies are probably related to the poorer prognosis observed in those COVID-19 patients. Moreover, vaccination stands out as the main prevention method against severe SARS-CoV-2 infection and some particularities have been observed regarding the seroconversion of vaccinated oncologic patients including those with gastrointestinal malignancies. In this minireview, we gather updated information regarding the influence of the pandemic in the diagnosis of gastrointestinal neoplasms, new recommendations for the management of gastrointestinal cancer patients, the occurrence of SARS-CoV-2 infection in those individuals and the scenario of the vaccination against the virus in that population.     

Significant impacts of the COVID-19 pandemic on race/ethnic differences in US mortality

The coronavirus 2019 (COVID-19) pandemic triggered global declines in life expectancy. The United States was hit particularly hard among high-income countries. Early data from the United States showed that these losses varied greatly by race/ethnicity in 2020, with Hispanic and Black Americans suffering much larger losses in life expectancy compared with White people. We add to this research by examining trends in lifespan inequality, average years of life lost, and the contribution of specific causes of death and ages to race/ethnic life-expectancy disparities in the United States from 2010 to 2020. We find that life expectancy in 2020 fell more for Hispanic and Black males (4.5 and 3.6 y, respectively) compared with White males (1.5 y). These drops nearly eliminated the previous life-expectancy advantage for the Hispanic compared with the White population, while dramatically increasing the already large gap in life expectancy between Black and White people. While the drops in life expectancy for the Hispanic population were largely attributable to official COVID-19 deaths, Black Americans saw increases in cardiovascular diseases and “deaths of despair” over this period. In 2020, lifespan inequality increased slightly for Hispanic and White populations but decreased for Black people, reflecting the younger age pattern of COVID-19 deaths for Hispanic people. Overall, the mortality burden of the COVID-19 pandemic hit race/ethnic minorities particularly hard in the United States, underscoring the importance of the social determinants of health during a public health crisis.

The coronavirus 2019 (COVID-19) pandemic has taken an unprecedented toll on mortality around the world. Most high-income countries experienced life-expectancy losses in 2020 (1–4), and many continued to experience declines in 2021 (5). The United States saw its largest drop in life expectancy (1.7 y for females and 2.1 y for males) in recent history (1), with COVID-19 deaths accounting for most of the decline for both females and males (6). Early data showed uneven impacts of the pandemic by race/ethnicity in the United States. The Center for Disease Control and Prevention estimates that between 2019 and 2020, life expectancy decreased by 3 y for the Hispanic population and by 2.9 y for the non-Hispanic Black (henceforth, Black) population, compared with a 1.2-y decline for non-Hispanic White (henceforth, White) people (6). The decrease was largest among Hispanic males (3.7 y), followed by Black males (3.3 y), and was smallest among White females (1.1 y). These findings are consistent with early studies projecting a disproportionate impact of the pandemic on life expectancy among race/ethnic minorities (7). It is important to monitor these disparities, which reflect underlying inequalities that are often magnified during a public health crisis (8). Both direct deaths from COVID-19 infection (9) as well as indirect deaths from other causes likely disproportionately affected race/ethnic minorities during the pandemic because of the social and economic disadvantages of historically marginalized populations in the United States (6, 10).This study provides a comprehensive analysis of mortality changes across racial/ethnic groups in the United States before and during the first year of the pandemic. It contributes to the evidence by 1) analyzing recent trends in life expectancy, average years of life lost (AYLL), and lifespan inequality from 2010 to 2020 separately for Black, Hispanic, and White populations; 2) identifying the ages and causes of death driving recent changes, including deaths from cardiovascular diseases (CVDs), respiratory diseases, infectious and parasitic diseases, “deaths of despair” (i.e., suicide-, drug-, and alcohol-related mortality), cancers, accidents, and COVID-19; and 3) comparing race/ethnic gaps in these outcomes before and during the pandemic.In the years before the pandemic, life expectancy in the United States followed atypical trends of stagnation that have not been observed in most high-income countries (6, 11, 12). These trends have been marked by worsening working-age mortality due to increased drug-related causes of death (13–17), as well as increased deaths from CVD at middle and later ages (18). Life expectancy is consistently higher for the White population relative to the Black population, although the gap between Black and White people narrowed from 5.7 y in 2000 to 3.8 y in 2010, (19). This convergence is partly due to relative improvements in mortality from heart diseases, HIV/AIDS, accidents, and cancer (20, 21). By contrast, the Hispanic population had higher life expectancy than the White population throughout the prepandemic period, attributable to lower mortality from cancer, CVD, diabetes, chronic respiratory diseases, perinatal conditions, as well as deaths of despair. Early evidence suggests that the pandemic has widened the White-Black gap in life expectancy, while reducing the Hispanic advantage (6). However, less is known about which ages and causes of death drove these changes (10).The COVID-19 pandemic has directly and indirectly affected multiple causes of death. For example, delays in treatment may have increased mortality from cancers (22), or avoidance of hospitals for fear of infection may have increased mortality from acute cardiovascular events (23). COVID-19 is also associated with elevated risk of cardiovascular events and diabetes in the months following infection (24, 25). Crucially, the impact of these changes likely varies across race/ethnic groups, due to differences in socioeconomic resources, rates of health insurance, and access to health care (7). Recent findings show that, while COVID-19 death rates were highest in the Hispanic population, Black people experienced exceptionally large increases in mortality from heart disease, diabetes, and external causes of death (10).So far, research on the differential impact of the pandemic on mortality across race/ethnic groups has mainly relied on estimates of overall life expectancy (6, 7, 26, 27) and standardized death rates (10). We extend these previous estimates by examining the ages and specific causes of death contributing to changes in life expectancy by race/ethnicity. While life expectancy is a widely used and important indicator for studying population health and mortality, it is an average measure that conceals population variability and inequality (28–31). Lifespan inequality captures a fundamental type of inequality: variation in length of life (32). Two populations that share the same life expectancy could experience differences in the variation around the timing of death. For instance, a high lifespan inequality measure would suggest that deaths occur within a wider age range, while a low measure of lifespan inequality would suggest a narrower age range. Hence, lifespan inequality, measured as the spread of ages at death in a population (e.g., SD), reflects how predictable length of life is at the individual level, and it underlies how uneven mortality improvements are at the population level (32, 33).Black Americans not only experience shorter life expectancy compared with Hispanic and White people but also have less predictable lifespans, with higher lifespan inequality (34, 35). The impact of the pandemic on US lifespan inequality is currently unknown. Evidence from England and Wales shows that both lifespan inequality and life expectancy decreased during 2020 because mortality was concentrated at older ages (36). However, in the United States, life-expectancy losses during the pandemic have been driven by increases in mortality at both older and working ages (1, 5, 37). Previous studies show that increased midlife death rates increase lifespan inequality (38–40).A complementary indicator to life expectancy is AYLL (41). This refers to the AYLL between birth and an upper age limit, often 95 y, from a synthetic cohort experiencing death rates in a given year throughout their lifespans. For example, if individuals between birth and age 95 live on average 80 y, then there are 15 y of life lost. While other indicators of years of life lost simply add up estimated remaining life expectancies among observed deaths (42, 43), AYLL is comparable across populations and over time, and is not affected by population age structure (44). Unlike life expectancy, this indicator enables researchers to quantify the burden of specific causes of death in a given year in a comparable way between populations (45), which is particularly important when comparing the impact of the pandemic across countries or groups with very different age structures. Conceptualized as such, AYLL represents a useful complement to life expectancy at birth, because it provides a snapshot of the contribution of different causes of death to years lost, rather than only how different causes contribute to changes in life expectancy over time. Using life expectancy, lifespan inequality, and AYLL, we comprehensively quantify the unequal impact of age- and cause-specific mortality before and during the first year of the pandemic across race/ethnic groups in the United States.     

Multisystem inflammatory syndrome in children during the COVID-19 pandemic in Turkey: first report from the Eastern Mediterranean

Objective

We aimed to describe the typical clinical and laboratory features and treatment of children diagnosed with multisystem inflammatory syndrome in children (MIS-C) and to understand the differences as compared to severe/critical pediatric cases with COVID-19 in an eastern Mediterranean country.

Methods

Children (aged <18 years) who diagnosed with MIS-C and severe/critical pediatric cases with COVID-19 and were admitted to hospital between March 26 and November 3, 2020 were enrolled in the study.

Results

A total of 52 patients, 22 patients diagnosed with COVID-19 with severe/critical disease course and 30 patients diagnosed with MIS-C, were included in the study. Although severe COVID-19 cases and cases with MIS-C share many clinical and laboratory features, MIS-C cases had longer fever duration and higher rate of the existence of rash, conjunctival injection, peripheral edema, abdominal pain, altered mental status, and myalgia than in severe cases (p<0.001 for each). Of all, 53.3% of MIS-C cases had the evidence of myocardial involvement as compared to severe cases (27.2%). Additionally, C-reactive protein (CRP) and white blood cell (WBC) are the independent predictors for the diagnosis of MIS-C, particularly in the existence of conjunctival injection and rash. Corticosteroids, intravenous immunoglobulin (IVIG), and biologic immunomodulatory treatments were mainly used in MIS-C cases rather than cases with severe disease course. There were only three deaths among 52 patients, one of whom had Burkitt lymphoma and the two cases with severe COVID-19 of late referral.

Conclusion

Differences between clinical presentations, acute phase responses, organ involvements, and management strategies indicate that MIS-C might be a distinct immunopathogenic disease as compared to pediatric COVID-19. Conjunctival injection and higher CRP and low WBC count are reliable diagnostic parameters for MIS-C cases.

Brief Report: Early assessment of the relationship between the COVID-19 pandemic and births in high-income countries

Drawing on past pandemics, scholars have suggested that the COVID-19 pandemic will bring about fertility decline. Evidence from actual birth data has so far been scarce. This brief report uses data on vital statistics from a selection of high-income countries, including the United States. The pandemic has been accompanied by a significant drop in crude birth rates beyond that predicted by past trends in 7 out of the 22 countries considered, with particularly strong declines in southern Europe: Italy (−9.1%), Spain (−8.4%), and Portugal (−6.6%). Substantial heterogeneities are, however, observed.