Genome-wide analysis to assess if heavy alcohol consumption modifies the association between SNPs and pancreatic cancer risk.

BACKGROUND: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk. METHODS: We conducted a genome-wide interaction analysis of single nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than 3 drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies (GWAS). Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed effect meta-analyses were conducted. RESULTS: A potential novel region of association on 10p11.22, lead SNP rs7898449 (Pinteraction = 5.1 x 10-8 in the meta-analysis, Pinteraction = 2.1x10-9 in the case-control studies, Pinteraction = 0.91 cohort studies) was identified. A SNP correlated with this lead SNP is an eQTL for the NRP1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004). CONCLUSIONS: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an eQTL for the NRP1, a protein that plays an important role in the development and progression of pancreatic cancer Impact: This work can provide insight into the etiology of pancreatic cancer particularly in heavy drinkers.

Cohort profile: the Johns Hopkins COVID Long Study (JHCLS)-a US nationwide prospective cohort study.

PURPOSE: COVID-19 continues to affect millions of individuals worldwide, both in the short and long term. The post-acute complications of SARS-CoV-2 infection, referred to as long COVID, result in diverse symptoms affecting multiple organ systems. Little is known regarding how the symptoms associated with long COVID progress and resolve over time. The Johns Hopkins COVID Long Study aims to prospectively examine the short-term and long-term consequences of COVID-19 in individuals both with and without a history of SARS-CoV-2 infection using self-reported data collected in an online survey. PARTICIPANTS: 16 764 adults with a history of SARS-CoV-2 infection and 799 adults without a history of SARS-CoV-2 infection who completed an online baseline survey. FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the Johns Hopkins COVID Long Study. Among 16 764 participants with a history of SARS-CoV-2 infection and defined long COVID status, 75% reported a very good or excellent health status prior to infection, 99% reported experiencing at least one COVID-19 symptom during the acute phase of infection, 9.9% reported hospitalisation and 63% were defined as having long COVID using the WHO definition. FUTURE PLANS: Analysis of longitudinal data will be used to investigate the progression and resolution of long COVID symptoms over time.

Cohort profile: the Johns Hopkins COVID Long Study (JHCLS), a United States Nationwide Prospective Cohort Study.

Purpose: COVID-19 disease continues to affect millions of individuals worldwide, both in the short and long term. The post-acute complications of SARS-CoV-2 infection, referred to as long COVID, result in diverse symptoms affecting multiple organ systems. Little is known regarding how the symptoms associated with long COVID progress and resolve over time. The Johns Hopkins COVID Long Study aims to prospectively examine the short- and long-term consequences of COVID-19 disease in individuals both with and without a history of SARS-CoV-2 infection using self-reported data collected in an online survey. Participants: Sixteen thousand, seven hundred sixty-four adults with a history of SARS-CoV-2 infection and 799 adults without a history of SARS-CoV-2 infection who completed an online baseline survey. Findings to date: This cohort profile describes the baseline characteristics of the Johns Hopkins COVID Long Study. Among 16,764 participants with a history of SARS-CoV-2 infection and defined long COVID status, 75% reported a good or excellent health status prior to infection, 99% reported experiencing at least one COVID-19 symptom during the acute phase of infection, 9.9% reported a hospitalization, and 63% were defined as having long COVID using the WHO definition. Future plans: Analysis of longitudinal data will be used to investigate the progression and resolution of long COVID symptoms over time.

Physical Health and Mental Fatigue Disability Associated with Long COVID: Baseline Results from a US Nationwide Cohort.

BACKGROUND: Persistent symptoms after severe acute respiratory disease coronavirus 2 (SARS-COV-2; long COVID) occur in 10%-55% of individuals, but the impact on daily functioning and disability remains unquantified. METHODS: To characterize disability associated with long COVID, we analyzed baseline data from an online, US-based cohort study. Adult participants included those reporting a history of COVID-19 (n = 8874) or never having COVID-19 (n = 633) without prior disability. The main outcomes were self-reported physical mobility, instrumental activities of daily living (IADL), and mental fatigue disability, assessed by measuring 5 disability components: difficulty walking a quarter mile or climbing 10 stairs (mobility), difficulty doing light or heavy housework (IADL), and Wood Mental Fatigue Inventory score (mental fatigue). RESULTS: Of 7926 participants with long COVID, 65% were classified with at least one disability, as compared with 6% and 14% for resolved COVID and no COVID, respectively. Additionally, 22% were classified as disabled in all 3 categories. Age, prior comorbidity, increased body mass index, female sex, COVID-19 hospitalization, non-white/multi-race were associated with higher disability burden. Dizziness and heavy limbs at infection were associated with disability regardless of hospitalization. Dyspnea and tremors were associated with disability in non-hospitalized individuals. Vaccination was protective against disability. CONCLUSIONS: We observed a high burden of new disability associated with long COVID, which has serious implications for individual and societal health. Longitudinal evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.

Prospective Cohort Study of Cryptosporidium Infection and Shedding in Infants and Their Households.

BACKGROUND: Cryptosporidium spp. are responsible for significant diarrheal morbidity and mortality in under-5 children. There is no vaccine; thus, a focus on prevention is paramount. Prior studies suggest that person-to-person spread may be an important pathway for transmission to young children. Here we describe a longitudinal cohort study of 100 families with infants to determine rates of cryptosporidiosis within households during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Families living in Mirpur, Bangladesh, with 1 infant aged 6-8 months were enrolled and followed with weekly illness survey and stool testing for Cryptosporidium for 8 months. RESULTS: From December 2020 to August 2021, 100 families were enrolled. Forty-four percent of index children and 35% of siblings had at least 1 Cryptosporidium infection. Shedding of Cryptosporidium occurred for a mean (standard deviation) of 19 (8.3) days in index infants, 16.1 (11.6) days in children 1-5 years, and 16.2 (12.8) days in adults. A longer duration of Cryptosporidium shedding was associated with growth faltering in infants. There was a spike in Cryptosporidium cases in May 2021, which coincided with a spike in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases in the region. CONCLUSIONS: In this intensive, longitudinal study of Cryptosporidium infection in families we found high rates of cryptosporidiosis in infants and children, and prolonged parasite shedding, especially among malnourished children. These data support that transmission within the household is an important route of exposure for young infants and that treatment of nondiarrheal infection to interrupt person-to-person transmission within the home may be essential for preventing cryptosporidiosis in infants.

Physical and mental health disability associated with long-COVID: Baseline results from a US nationwide cohort.

Importance: Persistent symptoms after SARS-COV-2 infection, or long-COVID, may occur in anywhere from 10-55% of those who have had COVID-19, but the extent of impact on daily functioning and disability remains unquantified. Objective: To characterize physical and mental disability associated with long-COVID. Design: Cross-sectional analysis of baseline data from a cohort study. Setting: Online US nationwide survey. Participants: Adults 18 years of age and older who live in the US who either report a history of COVID-19 illness (n=8,874) or report never having had COVID-19 (n=633). Main Outcome and Measures: Self-reported mobility disability (difficulty walking a quarter of a mile and/or up 10 stairs, instrumental activities of daily living [IADL] disability (difficulty doing light or heavy housework), and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI). Results: Of 7,926 participants with long-COVID, the median age was 45 years, 84% were female, 89% self-reported white race, and 7.4% self-reported Hispanic/Latino ethnicity. Sixty-five percent of long-COVID participants were classified as having at least one disability, compared to 6% of those with resolved-COVID (n=948) and 14% of those with no-COVID (n=633). Of long-COVID participants, about 1% and 5% were classified as critically physically disabled or mentally fatigued, respectively. Age, prior comorbidity, increased BMI, female gender, hospitalization for COVID-19, non-white race, and multi-race were all associated with significantly higher disability burden. Dizziness at the time of infection (33% non-hospitalized, 39% hospitalized) was associated with all five disability components in both hospitalized and non-hospitalized groups. Heavy limbs, dyspnea, and tremors were associated with four of the five components of disability in the non-hospitalized group, and heavy limbs was associated with four of the five components in the hospitalized group. Vaccination was protective against development of disability. Conclusion and Relevance: We observed a high burden of physical and mental disability associated with long-COVID which has serious implications for individual and societal health that may be partially mitigated by vaccination. Longitudinal characterization and evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.

Prospective cohort study of Cryptosporidium infection and shedding in infants and their households.

Background: Cryptosporidium spp are responsible for significant diarrheal morbidity and mortality in under-five children. There is no vaccine, thus a focus on prevention is paramount. Prior studies suggest that person-to-person spread may be an important pathway for transmission to young children. Here we describe a longitudinal cohort study of 100 families with infants to determine rates of cryptosporidiosis within households during the COVID-19 pandemic. Methods: Families living in Mirpur, Bangladesh with one infant age 6-8 months were enrolled and followed with weekly illness survey and stool testing for Cryptosporidium for 8 months. Results: From December 2020 to August 2021, 100 families were enrolled. Forty-four percent of index children, and 35% of siblings had at least one Cryptosporidium infection. Shedding of Cryptosporidium occurred for a mean of 19 days (sd 8.3 days) in index infants, 16.1 days (sd 11.6) in children 1-5 years, and 16.2 days (sd 12.8) in adults. A longer duration of Cryptosporidium shedding was associated with growth faltering in infants. There was a spike in Cryptosporidium cases in May 2021, which coincided with a spike in SARS-CoV-2 cases in the region. Conclusion: In this intensive, longitudinal study of Cryptosporidium infection in families we found high rates of cryptosporidiosis in infants and children, and prolonged parasite shedding, especially among malnourished children. These data support that transmission within the household is an important route of exposure for young infants, and that treatment of non-diarrheal infection to interrupt person-to-person transmission within the home may be essential for preventing cryptosporidiosis in infants. summary: Cryptosporidiosis is a leading cause of morbidity and mortality among children. We followed 100 families with infants living in Bangladesh and studied the incidence of Cryptosporidium infection. We found prolonged Cryptosporidium shedding in stool was common among infants and adults.