MEDICC Review

Implications of Low-grade Inflammation in SARS-CoV-2 Immunopathology
April 2021, Vol 23, No 2

INTRODUCTION Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19’s immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment.

OBJECTIVE Describe the main immunopathogenic alterations of COVID-19 in patients of advanced age or with chronic non-communicable diseases. DATA

ACQUISITION We carried out a bibliographic search of primary references in PubMed, Elsevier, Science Direct and SciELO. A total of 270 articles met our initial search criteria. Duplicate articles or those unrelated to at least one chronic comorbidity, senescence or inflammation and those that studied only patient clinical characteristics, laboratory tests or treatments were excluded. Finally, our selection included 124 articles for analysis: 10 meta-analyses, 24 original research articles, 67 review articles, 9 editorials, 9 comments, 3 books and 2 websites.

DEVELOPMENT Hypertension and diabetes mellitus are the most common comorbidities in COVID-19 patients. Risk of developing severe manifestations of the disease, including death, is increased insenescent and obese patients and those with cardiovascular disease, cancer or chronic obstructive pulmonary disease. Low-grade chronic inflammation is characteristic of all these conditions, reflected in a pro-inflammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, inflammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute inflammation overlap with the patient’s pro-inflammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifies already-existing alterations, causing failures in the immune system’s control mechanisms. The resulting cytokine storm causes an uncontrolled systemic inflammatory response marked by high serum levels of inflammatory biomarkers and a pro-inflammatory cytokine profile with decompensation of underlying diseases. In asthma, chronic eosinophilic inflammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors.

CONCLUSIONS Low-grade chronic inflammation present in advanced age and chronic diseases—but not in bronchial asthma—produces a pro-inflammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.

KEYWORDS SARS-CoV-2, COVID-19, inflammation, aging, chronic disease, immune system

Cuba’s public health outcomes are rooted in political and social phenomena that have favored achievement of health indicators well above expectations for an economy of its size. A less studied causal component of Cuba’s development in health is the creation, from early in the 1960s, of scientific research capacity throughout the health system, including use of science to launch a domestic industry for manufacturing high-tech products. This component should play an even greater role in meeting Cuba’s 21st century health challenges, especially the demographic and epidemiological transitions, increasing prevalence of chronic diseases, rapid emergence of a complex-product biotechnology pharmacopoeia, greater molecular stratification of diseases, rising health costs, and the need to maintain communicable diseases under control in a global context of climate change and more population mobility.

Tackling these challenges will demand greater scientific influence in the health system, application of a scientific approach in all activities and at all levels, and integration with scientific endeavors of other sectors such as agriculture, industry and education.

KEYWORDS Public health, science, health care costs, health workforce, chronic disease, biotechnology, immunology, aging, Cuba

INTRODUCTION Many clinical settings lack the necessary resources to complete angiographic studies, which are commonly used to predict complications and death following acute coronary syndrome. Corrected QT-interval dispersion can be useful for assessing risk of myocardial infarction recurrence.

OBJECTIVE Evaluate the relationship between corrected QT-interval dispersion and recurrence of myocardial infarction in patients with ST-segment elevation.

METHODS We conducted a prospective observational study of 522 patients with ST-segment elevation myocardial infarction admitted consecutively to the Camilo Cienfuegos General Provincial Hospital in Sancti Spiritus, Cuba, from January 2014 through June 2017. Of these, 476 were studied and 46 were excluded because they had other disorders. Demographic variables and classic cardiovascular risk factors were included. Blood pressure, heart rate, blood glucose, and corrected and uncorrected QT-interval duration and dispersion were measured. Patients were categorized according to the Killip-Kimball classification. Association between dispersion of the corrected QT-interval and recurrence of infarction was analyzed using a binary logistic regression model, a regression tree and receiver operator characteristic curves.

RESULTS Patients with recurrent infarction (56; 11.8%) had higher average initial blood glucose values than those who did not have recurrence; the opposite occurred for systolic and diastolic blood pressure and for left ventricular ejection fraction. Dispersion of the corrected QT-interval was a good predictor of infarction recurrence according to a multivariate analysis (OR = 3.09; 95% CI = 1.105–8.641; p = 0.032). Cardiac arrest is the variable that best predicts recurrence. No recurrence of infarction occurred in 97% of patients without cardiac arrest, left ventricular ejection fraction >45% and corrected QT-interval dispersion <80 ms.

CONCLUSIONS Risk of infarction recurrence is low in patients without cardiac arrest, with left ventricular ejection fraction >45% and with dispersion of corrected QT-interval <80 ms. Patients with corrected QT-interval dispersion ≥80 ms have greater risk of recurrence of infarction, which suggests that this variable could be used for stratification of risk following ST-segment elevation myocardial infarction.

KEYWORDS ST-elevation myocardial infarction, myocardial infarction, electrocardiography, chronic disease, risk assessment, Cuba

The Panama Aging Research Initiative is a cohort study of 423 adults aged ≥65 years recruited from an outpatient geriatric department of Panama’s largest public hospital, the Social Security Fund’s Dr Arnulfo Arias Madrid Hospital Complex (Complejo Hospitalario Dr Arnulfo Arias Madrid de la Caja de Seguro Social). The study provides the first reports of modifiable and non-modifiable risk factors of cognitive impairment and dementia, as well as various health conditions common among older adults in Panama, including chronic illnesses, polypharmacy and rates of comorbidity. The initial study, conducted September 2012–May 2016, included a clinical interview; physical assessments of body mass index and handgrip strength; and cognitive testing, plus non-fasting blood draws for measurements of genetic (Apolipoprotein E genotype) and blood-based biological markers.

Information was collected regarding limitations in activities of daily living, symptoms of depression and fall incidents. A subsample of participants provided cerebrospinal fluid to measure proteins related to Alzheimer’s disease; another subsample underwent ultrasonography and electroencephalography.

This report describes the general study design and highlights lessons learned and future directions. In particular, drawing on lessons learned from this clinical research, a community-based prospective cohort study is currently under way among older adults in Panama to validate a blood-based biomarker profile for detecting mild cognitive impairment and Alzheimer’s disease, as well as risk factors for cognitive decline.

KEYWORDS: Dementia, biomarkers, Latin America, aging, cognition, chronic disease, Panama

Aging and Alzheimer is a prospective, longitudinal cohort study involving 2944 adults aged ≥65 years from selected areas in Cuba’s Havana and Matanzas Provinces. This door-to-door study, which began in 2003, includes periodic assessments of the cohort based on an interview; physical exam; anthropometric measurements; and diagnosis of dementia and its subtypes, other mental disorders, and other chronic non-communicable diseases and their risk factors. Information was gathered on sociodemographic characteristics; disability, dependency and frailty; use of health services; and characteristics of care and caregiver burden. The first assessment also included blood tests: complete blood count, blood glucose, kidney and liver function, lipid profile and ApoE4 genotype (a susceptibility marker). In 2007–2011, the second assessment was done of 2010 study subjects aged ≥65 years who were still alive. The study provides data on prevalence and incidence of dementia and its risk factors, and of related conditions that affect the health of older adults. It also contributes valuable experiences from field work and interactions with older adults and their families. Building on lessons learned, a third assessment to be done in 2016–2018 will incorporate a community intervention strategy to respond to diseases and conditions that predispose to dementia, frailty and dependency in older adults.

KEYWORDS Dementia, Alzheimer disease, chronic disease, aging, chronic illness, frailty, dependency, cohort studies, Cuba

INTRODUCTION Systematic measurement of population physical activity levels is an important component of public health surveillance.

OBJECTIVES Describe patterns of physical activity in the Cuban population aged 15–69 years and identify factors associated with regular physical activity.

METHODS A descriptive cross-sectional study was conducted using a complex sampling design, representative of urban and rural areas, sex and age groups, including 7915 individuals. The International Physical Activity Questionnaire (short format) was applied. The population was classified as active, irregularly active and sedentary, according to sex, age, marital status, education, skin color, employment and perception of health risk related to physical inactivity or overweight. Percentages, odds ratios (OR) and 95% confidence intervals (CI) were calculated and a multinomial regression model was fitted with active persons as the reference category.

RESULTS Approximately 71% of the population self-classified as active, 23% as sedentary and 5.9% as irregularly active. Women had a higher probability of being sedentary (OR 2.51, CI 2.12–2.98) and irregularly active (OR 2.56, CI 95% 1.87–3.49). The probability of being sedentary increased with age (OR 1.19, CI 1.12–1.26), and also with the condition of being a homemaker, retired, or unemployed. Perceiving overweight as a high risk to health reduced likelihood of inactivity (OR 0.49, CI 0.29–0.83).

CONCLUSIONS Some 7 of 10 Cubans are physically active. The groups with the highest probability of inactivity and irregular activity and associated factors have been identified through national application (for the first time) of the International Physical Activity Questionnaire. The results should be taken into account for implementation of specialized strategies to promote systematic physical activity.

KEYWORDS Physical activity, physical exercise, sedentary lifestyle, health behavior, risk factors, chronic disease, women’s health, surveillance, Cuba

INTRODUCTION Population aging translates into more people with chronic non-communicable diseases, disability, frailty and dependency. The study of frailty—a clinical syndrome associated with an increased risk of falls, disability, hospitalization, institutionalization and death—is important to improve clinical practice and population health indicators. OBJECTIVES In a cohort of older adults in Havana and Matanzas provinces, Cuba, estimate prevalence of frailty and its risk factors; determine incidence of dependency; estimate mortality risk and identify mortality predictors. METHODS A prospective longitudinal study was conducted door to door, from June 2003 through July 2011, in a cohort of 2813 adults aged ≥65 years living in selected municipalities of Havana and Matanzas provinces; mean followup time was 4.1 years. Independent variables included demographics, behavioral risk factors and socioeconomic indicators, chronic non-communicable diseases (hypertension, stroke, dementia, depression, diabetes, anemia), number of comorbidities, and APOE ε4 genotype. Dependent variables were frailty, dependency and mortality. Criteria for frailty were slow walking speed, exhaustion, weight loss, low physical activity and cognitive decline. Prevalence and frailty risk were estimated by Poisson regression, while dependency and mortality risks and their predictors were determined using Cox regression. RESULTS Frailty syndrome prevalence was 21.6% (CI 17.9%–23.8%) at baseline; it was positively associated with advanced age, anemia and presence of comorbidities (stroke, dementia, depression, three or more physically debilitating diseases). Male sex, higher educational level, married or partnered status, and more household amenities were inversely associated with frailty prevalence. In followup, dependency incidence was 33.1 per 1000 person-years (CI 29.1–37.6) and mortality was 55.1 per 1000 person-years. Advanced age, male sex, lower occupational status during productive years, dependency, frailty, dementia, depression, cerebrovascular disease and diabetes were all associated with higher risk of death. CONCLUSIONS Given the challenge for developing countries presented by demographic and epidemiologic transition; the high prevalence in older adults of frailty syndrome, dependency and chronic non-communicable diseases; and the association of all these with higher mortality, attention should be targeted to older adults as a risk group. This should include greater social protection, age-appropriate health services, and modification and control of cardiovascular risk factors.

KEYWORDS Frail elderly, frail older adults, aged, elderly, dependency, mortality, chronic disease, dementia, Alzheimer disease, risk factors, Cuba

The following error has been corrected in all online versions of this article.

Page 24, Introduction, first paragraph, line 2, “600,000 to 2 billion” should read “600 million to 2 billion.”

INTRODUCTION Acute myocardial infarction is one of the leading causes of death in the world. This is also true in Cuba, where no national-level epidemiologic studies of related mortality have been published in recent years.

OBJECTIVE Describe acute myocardial infarction mortality in Cuba from 1999 through 2008.

METHODS A descriptive study was conducted of persons aged ≥25 years with a diagnosis of acute myocardial infarction from 1999 through 2008. Data were obtained from the Ministry of Public Health’s National Statistics Division database for variables: age; sex; site (out of hospital, in hospital or in hospital emergency room) and location (jurisdiction) of death. Proportions, age- and sex-specific rates and age-standardized overall rates per 100,000 population were calculated and compared over time, using the two five-year time frames within the study period.

RESULTS A total of 145,808 persons who had suffered acute myocardial infarction were recorded, 75,512 of whom died, for a case-fatality rate of 51.8% (55.1% in 1999–2003 and 49.7% in 2004–2008). In the first five-year period, mortality was 98.9 per 100,000 population, falling to 81.8 per 100,000 in the second; most affected were people aged ≥75 years and men. Of Cuba’s 14 provinces and special municipality, Havana, Havana City and Camagüey provinces, and the Isle of Youth Special Municipality showed the highest mortality; Holguín, Ciego de Ávila and Granma provinces the lowest.
Out-of-hospital deaths accounted for the greatest proportion of deaths in both five-year periods (54.8% and 59.2% in 1999–2003 and 2004–2008, respectively).

CONCLUSIONS Although risk of death from acute myocardial infarction decreased through the study period, it remains a major health problem in Cuba. A national acute myocardial infarction case registry is needed. Also required is further research to help elucidate possible causes of Cuba’s high acute myocardial infarction mortality: cardiovascular risk studies, studies of out-of-hospital mortality and quality of care assessments for these patients.

KEYWORDS Acute myocardial infarction, ischemic heart disease, cardiovascular diseases, chronic disease, mortality, case-fatality, epidemiology, surveillance, registries, Cuba

INTRODUCTION Chronic non-communicable diseases are the leading cause of death worldwide, except in Sub-Saharan Africa. Nonetheless, one of these conditions, dementia, is the major contributor to disability-adjusted life years in people aged ≥60 years. Few epidemiological studies exist of the prevalence and impact of dementia and selected chronic diseases in older adults in Latin America.

OBJECTIVE Describe prevalence of dementia, other chronic vascular diseases and cardiovascular risk factors, as well as resulting disabilities and care needs generated in adults aged ≥65 years in Havana City and Matanzas provinces, Cuba.

METHODS The 10/66 study is a prospective longitudinal study involving a cohort of 3015 adults aged ≥65 years in municipalities of Havana City and Matanzas provinces, divided into two phases: a cross-sectional door-to-door study conducted in 2003–2006, and a follow-up and assessment phase in 2007–2010. This article reports findings from the first phase. Hypertension diagnosis was based on criteria from the International Society for Hypertension; diabetes mellitus on American Diabetes Association criteria; stroke according to WHO definitions; and dementia according to criteria of the American Psychiatric Society’s Diagnostic and Statistical Manual of Mental Disorders DSM-IV and the 10/66 International Dementia Research Group. Ischemic heart disease was defined by self-report of previous physician diagnosis. Study variables included age, sex, educational level, substance use (alcohol, tobacco) and dietary habits. A structured physical and neurological exam, including blood pressure measurement, was performed on all participants. Laboratory tests included complete blood count, fasting blood glucose, total cholesterol and lipoprotein fractions, triglycerides and apolipoprotein E genotype. Prevalence and standardized morbidity ratios (crude and adjusted) were calculated for chronic diseases studied with 95% confidence intervals, using a Poisson regression model and indirect standardization.

RESULTS The study assessed 2944 older adults (response rate 97.6%) and found high prevalence of vascular risk factors and of chronic non-communicable diseases: hypertension 73.0% (95% CI 71.4–74.7), diabetes mellitus 24.8% (95% CI 22.9–26.5), ischemic heart disease 14.1% (95% CI 12.9–15.4), dementia 10.8% (95% CI 9.7–12.0) and stroke 7.8% (95% CI 6.9–8.8). The majority of participants (85%) had more than one cardiovascular risk factor. The main cause of disability and dependency in the study population was dementia.

CONCLUSION The high prevalence of chronic diseases observed in the elderly—with the consequent morbidity, disability and dependency—highlights the need for prevention, early diagnosis and risk factor control, particularly given the demographic and epidemiologic transition faced by Cuba and other developing countries.

KEYWORDS Dementia, chronic disease, cardiovascular diseases, heart disease, stroke, diabetes mellitus, disability, hypertension, aging, prevalence, epidemiology, Cuba

INTRODUCTION Information on acute myocardial infarction incidence and mortality is essential for determining the efficacy of the health system’s cardiovascular disease prevention activities; however, in Cuba, sufficient data related to acute myocardial infarction are lacking, particularly at the local level.

OBJECTIVE Describe acute myocardial infarction incidence, mortality and case fatality rates from January 2007 through December 2008 in persons aged 45-74 in the municipality of Santa Clara, Villa Clara Province, Cuba.

METHODS A retrospective descriptive study was conducted. The World Health Organization MONItoring Trends and Determinants in CArdiovascular Disease Project (MONICA) methodology was used, but only in part, since out-of-hospital case fatalities were not investigated, resulting in insufficient data for such cases. Cases of acute myocardial infarction covered under MONICA definition 1 were included (non-fatal definite, fatal definite, fatal possible, and unclassifiable deaths). Hospitalized patients were followed for 28 days. Incidence, mortality and case fatality rates in the population were calculated by age group (45–54, 55–64 and 65–74 years) and sex. Age-standardized incidence and mortality rates were calculated using the direct method, with the world population as a reference.

RESULTS A total of 482 cases of acute myocardial infarction were registered. The percentage of cases of non-fatal definite, fatal definite, fatal possible and fatal with insufficient data were 32%, 18.3%, 26.3% and 13.9% respectively. The cumulative age-standardized incidence per 100,000 population was 433 (95% CI 365–501) in men and 195 (95% CI 152–237) in women, while mortality per 100,000 population was 242 (95% CI 192–292) in men and 120 (95% CI 87–153) in women. Case fatality was 56.4% in men and 62.6% in women. Most fatal cases (65.6%) occurred out of hospital, a trend that was more marked in men (73.9%) than in women (51%).

CONCLUSIONS Case fatality from acute myocardial infarction in Santa Clara residents was high, especially in women. Two thirds of fatalities occurred out of hospital, a higher proportion of these deaths in men. It is recommended that the AMI registry be completed by investigating out-of-hospital case fatalities with insufficient data; expanding it to include the 35-44 age group; and that the supply of cardiac marker enzyme immunoassay test kits in Santa Clara be stabilized.

KEYWORDS Myocardial infarction, heart disease, cardiovascular disease, chronic disease, epidemiology, mortality, incidence, surveillance, registries, Cuba

The benefits of an interconnected world for health care remain untapped. As a result of the politics of inequality between rich and poor countries, one or a few health systems are set up as models. Every country, irrespective of political or economic status, should be open to learning from others to build relevant and cost-effective systems. To combat the current global challenge of chronic non-communicable diseases, poor countries have the advantage of flexible health systems that are veritable laboratories of health systems research. Not only can research conducted in these health systems help harness the potential of mobile communication technologies and informal health providers, it can also help rich country health systems adapt to meet the chronic disease challenge.

KEYWORDS Health care delivery, health care systems, access to health care, telemedicine, health manpower, chronic disease, Nigeria

Introduction Prevalence of overweight and obesity is increasing worldwide in parallel with the growing burden of noncommunicable chronic diseases. According to the World Health Organization, in 2005 approximately 1.6 billion individuals aged ≥15 years were overweight and at least 400 million were obese; by 2015 these figures will almost double. Central distribution of adiposity has also been associated with higher rates of cardiovascular diseases and other conditions.

Objective Determine the prevalence of overweight, obesity and central adiposity, and their association with noncommunicable chronic diseases and related lifestyle risk factors in Cuban adults.

Methods The Second National Survey on Risk Factors and Chronic Diseases (ENFRENT II), conducted in 2000–2001, surveyed a representative sample of males and females aged ≥15 years using a stratified, multi-stage cluster sampling design. Data from a sub-sample of 19,519 individuals aged ≥20 years were analyzed and prevalence calculated for diabetes, hypertension, cardiovascular and cerebrovascular diseases, and for each of these variables in association with overweight, obesity and central distribution of adiposity, and with the presence of sedentary lifestyle, smoking, alcohol consumption, eating regular daily meals and daily breakfast.

Results Estimated prevalence of overweight and obesity in the adult population was 30.8% (CI: 30.1–31.5) and 11.8% (CI: 11.2–12.4), respectively. Obesity prevalence was twice as high in women (15.4%; CI: 14.5–16.3) as in men (7.9%; CI: 7.3–8.6). Obesity was significantly more frequent in diabetics, hypertensives and people with heart disease, while central adiposity was significantly associated with a higher prevalence of diabetes mellitus, cardiovascular and cerebrovascular diseases, hypertension, obesity and overweight. Smoking and alcohol consumption were low among overweight and obese subjects, who exhibited a higher prevalence of irregular and inadequate eating patterns.

Conclusions Prevalence of overweight, obesity and central adiposity, and comorbidity with diabetes mellitus, hypertension and heart disease, are growing public health problems in Cuba. A multi-sector strategy is needed to develop comprehensive food and nutrition policies and programs aimed at halting these trends, including interventions that encourage healthy eating patterns and regular physical activity in adults and children.

Keywords: Overweight, obesity, comorbidity, chronic disease, prevalence, nutrition disorders