Risk for Subsequent SARS-CoV-2 Infection and Severe COVID-19 Among Community-Dwellers With Pre-Existing Cervicocephalic Atherosclerosis: A Population-Based Study.

BACKGROUND: COVID-19 patients may develop atherosclerosis-related complications. Whether a proportion of these patients already had asymptomatic cervicocephalic atherosclerosis before SARS-CoV-2 infection is not known. This study assessed whether pre-existing cervicocephalic atherosclerosis increased the susceptibility to SARS-CoV-2 infection or resulted in more severe or fatal COVID-19. METHODS: Individuals enrolled in the Atahualpa Project cohort who received head CT (for assessing carotid siphon calcifications) and B-mode ultrasounds (for measurement of the carotid intima-media thickness) prior to the pandemic were eligible for this study. Among this cohort, those who also received serological tests for detection of SARS-CoV-2 antibodies and clinical evaluations for assessment of COVID-19 severity were enrolled. Multivariate logistic regression and exposure-effect models were fitted to assess the association between pre-existing atherosclerosis biomarkers, and SARS-CoV-2 seropositivity and COVID-19 severity. RESULTS: Overall, 154 of 519 study participants (30%) had evidence of cervicocephalic atherosclerosis. A total of 325 (63%) individuals became SARS-CoV-2 positive, and 65 (23.5%) of seropositive individuals had severe or fatal COVID-19. The risk of SARS-CoV-2 seropositive status did not differ across individuals with and without atherosclerosis biomarkers (P = .360). Likewise, seropositive individuals with pre-existing atherosclerosis were not more prone to develop severe or fatal COVID-19 than those without evidence of atherosclerosis (P = .274). Average estimated exposure effects of pre-existing cervicocephalic atherosclerosis versus no atherosclerosis over SARS-CoV-2 seropositivity and COVID-19 severity were not significant. CONCLUSIONS: Pre-existing cervicocephalic atherosclerosis does not increase the risk of acquiring SARS-CoV-2 infection nor the severity of COVID-19 among seropositive individuals.

Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: A longitudinal prospective study nested to a population cohort.

BACKGROUND AND PURPOSE: Neurological complications of SARS-CoV-2 infection are noticed among critically ill patients soon after disease onset. Information on delayed neurological sequelae of SARS-CoV-2 infection is nil. Following a longitudinal study design, the occurrence of cognitive decline among individuals with a history of mild symptomatic SARS-CoV-2 infection was assessed. METHODS: Stroke- and seizure-free Atahualpa residents aged ≥40 years, who had pre-pandemic cognitive assessments as well as normal brain magnetic resonance imaging and electroencephalogram recordings, underwent repeated evaluations 6 months after a SARS-CoV-2 outbreak infection in Atahualpa. Patients requiring oxygen therapy, hospitalization, and those who had initial neurological manifestations were excluded. Cognitive decline was defined as a reduction in the Montreal Cognitive Assessment (MoCA) score between the post-pandemic and pre-pandemic assessments that was ≥4 points greater than the reduction observed between two pre-pandemic MoCAs. The relationship between SARS-CoV-2 infection and cognitive decline was assessed by fitting logistic mixed models for longitudinal data as well as exposure-effect models. RESULTS: Of 93 included individuals (mean age 62.6 ± 11 years), 52 (56%) had a history of mild symptomatic SARS-CoV-2 infection. Post-pandemic MoCA decay was worse in seropositive individuals. Cognitive decline was recognized in 11/52 (21%) seropositive and 1/41 (2%) seronegative individuals. In multivariate analyses, the odds for developing cognitive decline were 18.1 times higher among SARS-CoV-2 seropositive individuals (95% confidence interval 1.75-188; p = 0.015). Exposure-effect models confirmed this association (ß = 0.24; 95% confidence interval 0.07-0.41; p = 0.006). CONCLUSIONS: This study provides evidence of cognitive decline among individuals with mild symptomatic SARS-CoV-2 infection. The pathogenesis of this complication remains unknown.

Cognitive sequelae of long COVID may not be permanent: A prospective study.

BACKGROUND AND PURPOSE: Cognitive decline is a recognized manifestation of long COVID, even among patients who experience mild disease. However, there is no evidence regarding the length of cognitive decline in these patients. This study aimed to assess whether COVID-19-related cognitive decline is a permanent deficit or if it improves over time. METHODS: Cognitive performance was evaluated by means of the Montreal Cognitive Assessment (MoCA) in COVID-19 survivors and noninfected individuals. All study participants had four cognitive evaluations, two of them before the pandemic and the other two, 6 and 18 months after the initial SARS-CoV-2 outbreak infection in the village. Linear mixed effects models for longitudinal data were fitted to assess differences in cognitive performance across COVID-19 survivors and noninfected individuals. RESULTS: The study included 78 participants, 50 with history of mild COVID-19 and 28 without. There was a significant-likely age-related-decline in MoCA scores between the two prepandemic tests (ß = -1.53, 95% confidence interval [CI] = -2.14 to -0.92, p < 0.001), which did not differ across individuals who later developed COVID-19 when compared to noninfected individuals. Six months after infection, only COVID-19 survivors had a significant decline in MoCA scores (ß = -1.37, 95% CI = -2.14 to -0.61, p < 0.001), which reversed after 1 additional year of follow-up (ß = 0.66, 95% CI = -0.11 to 1.42, p = 0.092). No differences were noticed among noninfected individuals when both postpandemic MoCA scores were compared. CONCLUSIONS: Study results suggest that long COVID-related cognitive decline may spontaneously improve over time.

Factors Associated With a Persistent Seronegative Status 1 Year After a SARS-CoV-2 Massive Infection Outbreak in Community Dwellers Living in Rural Ecuador: A Prospective Population-based Study.

BACKGROUND: The SARS-CoV-2 pandemic is affecting millions of people living in rural areas of Low- and Middle-Income Countries and is causing an already anticipated devastating effect on the health and economics of these populations. More information is needed to modify behaviors that may counterbalance the consequences of mass spread of the virus in these underserved communities. This study aimed to identify factors associated with a persistent SARS-CoV-2 seronegative status 1 year after a massive infection outbreak in middle-aged and older adults living in rural Ecuador. METHODS: Individuals enrolled in the Atahualpa Project Cohort as of March 2020 received 5 rounds of tests for determination of SARS-CoV-2 antibodies in blood. Individuals who remained seronegative up to April 2021 were considered "persistently seronegative." An adjusted Poisson regression model was fitted to estimate the incidence risk ratio of factors directly or inversely associated with a persistent seronegative status. RESULTS: A total of 673 individuals received baseline tests. Thirty-one declined consent or died and 429 seroconverted, leaving 213 seronegative subjects. Average SARS-CoV-2 incidence rate was 9.87 events (95% C.I.: 8.91-10.83) per 100 person-months of observation. The use of flushing toilet systems (instead of open latrines) increased 1.5 times the possibility of remaining seronegative. Likewise, every additional bedroom in the house increased by 15% the possibility of remaining seronegative. In contrast, every additional person in the house and having high cholesterol levels significantly reduced the possibility of remaining seronegative. CONCLUSIONS: The use of flushing toilet systems and the number of bedrooms in the house directly influenced the possibility of remaining seronegative among individuals living in this rural setting. Study results also demonstrated a sustained transmission of the virus even after a significant proportion of the population has been infected. Our findings reinforce the mass spread of SARS-CoV-2 in rural communities.

Body Composition in Community-Dwelling Older Adults Before and After SARS-CoV-2 Infection: A Longitudinal Prospective Study in a Rural Village Struck by the Pandemic.

BACKGROUND: Information on the body composition of inhabitants of remote communities during the SARS-CoV-2 pandemic is limited. Using a longitudinal population-based study design, we assessed the association between SARS-CoV-2 infection and changes in body composition. METHODS: Community-dwelling older adults living in a rural Ecuadorian village received body composition determinations before and 1 year after the pandemic as well as serological tests for detection of SARS-CoV-2 antibodies. The independent association between SARS-CoV-2 infection and abnormalities in body composition at follow-up was assessed by fitting linear mixed models for longitudinal data. RESULTS: Of 327 enrolled individuals, 277 (85%) received baseline and follow-up body composition determinations, and 175 (63%) of them became SARS-CoV-2 seropositive. Overall, diet and physical activity deteriorated during the follow-up. Multivariate random-effects generalized least squares regression models that included the impact of time and seropositivity on follow-up body composition, showed that neither variable contributed to a worsening in body composition. Multivariate logistic regression models disclosed that the serological status at follow-up cannot be predicted by differences in body composition and other baseline covariates. CONCLUSIONS: Study results suggest no increased susceptibility to SARS-CoV-2 infection among older adults with abnormal body composition and no significant changes as a result of worse physical activity and dietary habits or seropositivity during the length of the study. Together with a previous study in the same population that showed decrease in hand-grip strength after SARS-CoV-2, results confirm that dynapenia (and not sarcopenia) is associated with SARS-CoV-2 infection in older adults.

SARS-CoV-2 RNA in Swabbed Samples from Latrines and Flushing Toilets: A Case-Control Study in a Rural Latin American Setting.

Information about factors potentially favoring the spread of SARS-CoV-2 in rural settings is limited. Following a case-control study design in a rural Ecuadorian village that was severely struck by the pandemic, SARS-CoV-2 RNA were detected by real-time PCR in swabs obtained from inner and upper walls in 24/48 randomly selected latrines from case-houses and in 12/48 flushing toilets from paired control-houses (P = 0.014; McNemar's test). This association persisted in a conditional logistic regression model adjusted for relevant covariates (OR: 4.82; 95% CI: 1.38-16.8; P = 0.014). In addition, SARS-CoV-2-seropositive subjects were more often identified among those living in houses with a latrine (P = 0.002). Latrines have almost five times the odds of containing SARS-CoV-2 RNA than their paired flushing toilets. Latrines are reservoirs of SARS-CoV-2 RNA, and it cannot be ruled out that latrines could contribute to viral transmission in rural settings. Frequent disinfection of latrines should be recommended to reduce the likelihood of fecal contamination.

Sleep quality deterioration in middle-aged and older adults living in a rural Ecuadorian village severely struck by the SARS-CoV-2 pandemic. A population-based longitudinal prospective study.

STUDY OBJECTIVES: This study assessed changes in sleep quality before and after the peak of the SARS-CoV-2 pandemic in community dwellers enrolled in the Atahualpa Project. METHODS: Atahualpa residents aged ≥40 years were eligible if they had a Pittsburgh Sleep Quality Index (PSQI) 9 months before the pandemic and a lateral flow-based test for identification of SARS-CoV-2 antibodies during the peak of the pandemic. Six months later, individuals completed a follow-up PSQI. The independent relationship between SARS-CoV-2 infection and deterioration in sleep quality was assessed by fitting logistic mixed models for longitudinal data. RESULTS: Of 639 participants (mean age at baseline: 59 ± 12.8 years), 325 (51%) had SARS-CoV-2 antibodies. A total of 185 (29%) individuals at baseline and 311 (49%) at follow-up were poor sleepers (p < 0.001). Mixed logistic regression models demonstrated a significant increase in poor sleepers at follow-up (odds ratio [OR]: 2.85; 95% CI: 2.16 to 3.75), which was more marked among SARS-CoV-2 seropositive subjects (OR: 3.8; 95% CI: 2.48 to 5.81). The adjusted proportion of poor sleepers increased from 29% to 56.2% (95% CI: 50.9% to 61.6%) among SARS-CoV-2 seropositive individuals, but only to 40.7% (95% CI: 35.3% to 46.1%) in their seronegative counterparts (p < 0.001). Likewise, progression from a good to a poor sleeper status was higher among seropositive individuals than in their seronegative counterparts (38.1% vs 22.3%; p < 0.001), after adjusting for relevant covariates. CONCLUSIONS: This study shows a deleterious effect of SARS-CoV-2 in sleep quality. An effect of SARS-CoV-2 in disrupting sleep-related pathways cannot be ruled out. TRIAL REGISTRATION: The Atahualpa Project has been registered at ClinicalTrials.gov; the identifier number is NCT01627600, and the date was: 10/02/2012 (https://clinicaltrials.gov/ct2/show/NCT01627600?cond=Atahualpa&draw=2&rank=1). The Sleep Disorders substudy has been registered at ClinicalTrials.gov; the identifier number is NCT01877616, and the date was: 06/13/2013 (https://clinicaltrials.gov/ct2/show/NCT01877616?cond=Atahualpa&draw=2&rank=4).

Hand grip strength before and after SARS-CoV-2 infection in community-dwelling older adults.

OBJECTIVE: To assess the association between SARS-CoV-2 infection and decreased hand grip strength (HGS). DESIGN: Longitudinal population-based study. SETTING: Community-dwelling older adults (aged ≥60 years) living in a rural Ecuadorian village struck by the SARS-CoV-2 pandemic. PARTICIPANTS: Of 282 enrolled individuals, 254 (90%) finished the study. MEASUREMENTS: HGS was measured 3 months before (January 2020) and 9 months after the introduction of the virus into the population (January 2021). SARS-CoV-2 antibody testing was performed in two rounds: in May-June (early) and September-November (late), 2020. An independent association between SARS-CoV-2 infection and HGS decline was assessed by fitting linear mixed models for longitudinal data. Changes in HGS scores in SARS-CoV-2 seropositive subjects, according to the time elapsed since seroconversion, were compared with those who remained seronegative. RESULTS: Overall, 149 (59%) individuals became seropositive for SARS-CoV-2. The mean HGS (in kg) was 25.3 ± 8.3 at baseline and 23.7 ± 8.1 at follow-up (p = 0.028), with 140 individuals having >5% HGS decline between both measurements. The follow-up HGS measurement decreased by 1.72 kg in seropositive individuals, and by 0.57 kg in their seronegative counterparts (p < 0.001). SARS-CoV-2 seropositive individuals were 2.27 times more likely (95% CI: 1.33-3.87) to have a lower HGS measurement at the time of follow-up than those who remained seronegative. When compared with seronegative subjects, seropositive patients with early seroconversion were 3.41 times (95% CI: 1.73-6.74) more likely to have >5% HGS decline at the time of the follow-up than those with later, i.e., more recent, infections. CONCLUSIONS: This study shows an independent deleterious impact of SARS-CoV-2 on HGS that is more marked among individuals with infections that occurred more than 8 months before follow-up HGS. Results suggest the possibility of chronic damage to skeletal muscles by SARS-CoV-2.

Previously diagnosed obstructive sleep apnea is not associated with increased risk of SARS-CoV-2 infection in community-dwelling older adults living in a highly endemic setting.

OBJECTIVE: In view of the high prevalence of obstructive sleep apnea (OSA) and the increasing global pandemic of SARS-CoV-2 infection, it is likely that many patients with OSA get exposed to this virus. Besides theoretical assumptions, there is no evidence that OSA may favor SARS-CoV-2 acquisition or may lead to a more severe disease. Taking the opportunity of the Atahualpa Project cohort, we aimed to assess the relationship between previously diagnosed OSA and SARS-CoV-2 infection in older adults living in rural Ecuador. PATIENTS AND METHODS: SARS-CoV-2 antibodies were determined in 180 individuals aged > 60 years that underwent polysomnography previously to this novel pandemic. Those with OSA remained untreated due to income limitations. Exposure-effect models were fitted with OSA as the exposure, SARS-CoV-2 seropositivity and symptomatology as the outcomes, and confounders - age, gender, obesity, arterial hypertension, diabetes mellitus, hypercholesterolemia, individuals per house, home confinement - as independent variables. RESULTS: A total of 87 (48%) individuals were seropositive to SARS-CoV-2, 77% of whom were symptomatic. The mean apnea/hypopnea index was 11.1 ± 11.7 episodes per hour, with 83 (46%) individuals having mild, and 38 (21%) moderate-to-severe OSA. Exposure-effect models demonstrated lack of relationship between OSA and SARS-CoV-2 seropositivity and symptomatology. CONCLUSIONS: This study shows no relationship between history of OSA and SARS-CoV-2 seropositivity or symptomatology, opposing previous suggestions that persons with OSA are more prone to acquire the infection and have a more severe disease.

Late incidence of SARS-CoV-2 infection in a highly-endemic remote rural village. A prospective population-based cohort study.

Data on SARS-CoV-2 transmission in rural communities is scarce or non-existent. A previous cross-sectional study in middle-aged and older adults enrolled in the Atahualpa Project Cohort demonstrated that 45% of participants had SARS-CoV-2 antibodies, 77% of whom were symptomatic. Here, we assessed the incidence of SARS-CoV-2 infection in the above-mentioned rural population. One month after baseline testing, 362 of 370 initially seronegative individuals were re-tested to assess incidence of seroconversion and associated risk factors. Twenty-eight of them (7.7%) became seropositive. The overall incidence rate ratio was 7.4 per 100 person months of potential virus exposure (95% C.I.: 4.7-10.2). Six seroconverted individuals (21.4%) developed SARS-CoV-2-related symptomatology. The only covariate significantly associated with seroconversion was the use of an open latrine. Predictive margins showed that these individuals were 2.5 times more likely to be infected (95% C.I.: 1.03-6.1) than those using a flushing toilet. Therefore, along one month, approximately 8% of seronegative individuals became infected, even after almost half of the population was already seropositive. Nevertheless, a smaller proportion of incident cases were symptomatic (21% versus 77% of the earlier cases), and no deaths were recorded. Whether this decreased clinical expression resulted from a lower viral load in new infections cannot be determined. Increased seroconversion in individuals using latrines is consistent with a contributory role of fecal-oral transmission, although we cannot rule out the possibility that latrines are acting as a proxy for poverty or other unknown interacting variables.

Household Clustering of SARS-CoV-2 in Community Settings: A Study from Rural Ecuador.

The SARS-CoV-2 pandemic is now expanding into the developing world with devastating consequences. Departing from a population-based study in rural Ecuador where all adult individuals (aged 40 years or older) were tested for SARS-CoV-2 IgG and IgM antibodies, we expanded it to include a house-based case-control component assessing in-house clustering and other variables potentially associated with infection. We selected houses where exactly two study participants lived and were both seropositive (case-houses), and matched 1:1 to control-houses where both were seronegative. Younger household members had an antibody test performed. Infected household members were found in 33 (92%) case-houses and in only six (17%) control-houses. In 28/29 discordant house pairs, the case-house had seropositive household members and the control-house did not (odds ratio: 28; 95% CI: 4.6-1,144). Our data demonstrate strong in-house clustering of infection in community settings, stressing the importance of early case ascertainment and isolation for SARS-CoV-2 control.

SARS-CoV-2-related mortality in a rural Latin American population.

A sudden increase in adult mortality associated with respiratory diseases was noticed in Atahualpa (a rural Ecuadorian village), coinciding with the introduction of SARS-CoV-2 in the region. From a total of 1,852 individuals aged ≥18 years, 40 deaths occurred between January and June, 2020. In addition, a seroprevalence survey showed that 45% of the adult population have SARS-CoV-2 antibodies. Verbal autopsies revealed SARS-CoV-2 as the most likely cause of death in 29 cases. The mean age of suspected or confirmed SARS-CoV-2 cases was 76.9±12.1 years, while that of those dying from unrelated causes was 60.3±20.4 years (p=0.003). The overall mortality rate was 21.6 per 1,000 population (95% C.I.: 15.9 - 29.2), almost three-quarters of it due to SARS-CoV-2 (15.7 per 1,000; 95% C.I.: 11 - 22.4). This configures a 266% of excess mortality when compared to 5.9 per 1,000 (95% C.I.: 3.3 - 10.6) deaths from other causes. When SARS-CoV-2 mortality rate was calculated in individuals aged ≥60 years, it raised up to 68.9 per 1,000 (95% C.I.: 47.8 - 98.4). After peaking in April and May, mortality significantly decreased. It is possible that the high proportion of infected individuals and the resulting herd immunity contributed to the observed reduction in mortality.

SARS-CoV-2 in Rural Latin America. A Population-based Study in Coastal Ecuador.

Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were detected in 303/673 rural Ecuadorian adults (45%), 77% of whom had compatible clinical manifestations. Seropositivity was associated with the use of open latrines. Our findings support the fears of mass spread of SARS-CoV-2 in rural Latin America and cannot exclude a contributing role for fecal-oral transmission.

Social Determinants of Health and Risk of SARS-CoV-2 Infection in Community-Dwelling Older Adults Living in a Rural Latin American Setting.

High social risk, as measured by the social determinants of health (SDH), may increase the risk of SARS-CoV-2 infection. However, this association has not been studied in rural communities. Using the Atahualpa Project cohort, we aimed to assess the association between SDH and SARS-CoV-2 seropositivity in community-dwelling older adults living in rural Ecuador. SARS-CoV-2 antibodies were determined in 319 individuals aged ≥ 60 years that completed a validated field instrument to assess their social risk before the introduction of this novel pandemic. Multivariate models were fitted to assess the independent association between SDH-and each of their components-and SARS-CoV-2 seropositivity, after adjusting for relevant covariates. According to the Gijon scale, 102 (32%) individuals had a high social risk (≥ 10 points). A total of 141 (44%) individuals were seropositive to SARS-CoV-2. A fully-adjusted logistic regression model showed an independent) association between social risk and SARS-CoV-2 positivity (OR 1.15; 95% CI 1.04-1.27; p = 0.008). For every unit of the total SDH score, the odds of SARS-CoV-2 seropositivity increased 15% (95% CI 3.7-27%). In addition, multivariate models showed that the individual component of SDH more strongly associated with SARS-CoV-2 seropositivity was housing, which suggested that lack of basic home facilities may increase the risk of SARS-CoV-2 infection. Knowledge on the association between high social risk and SARS-CoV-2 infection is indispensable for the development of cost-effective preventive strategies for controlling modifiable factors that are in the path of SARS-CoV-2 infection among older adults living in underserved communities.