Distinct Early Serological Signatures Track with SARS-CoV-2 Survival.

As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. Although no differences in SARS-CoV-2-specific IgG levels were observed, spike-specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant spike-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.

Fecal calprotectin level is nonlinearly associated with GI pathogen detection in patients with and without inflammatory bowel disease.

Fecal calprotectin (FCP) is used to monitor inflammatory bowel disease (IBD) activity and can also be elevated in gastrointestinal infections. Our study's objective was to quantify the relationship between FCP levels and lab-confirmed infections in people with and without IBD. We performed a cross-sectional study at a tertiary-care center of all encounters during which FCP and gastrointestinal pathogen polymerase-chain reaction (GI PCR) panel testings were conducted. Using non-parametric tests and quantile regression, we compared the FCP levels by IBD status and pathogen detection. There were 3,347 encounters with FCP and GI PCR testings from 2,780 unique individuals between 1 August 2016 and 17 February 2022. Overall, 54.4% had IBD (n = 1,819). Pathogens were detected in 744 encounters (22.2%), and the detection rate did not differ by IBD status. Median FCP without IBD was significantly elevated when a pathogen was detected (64 vs 41 mg/kg, P = 0.0003, normal ≤50.0 mg/kg), but FCP with IBD was not significantly elevated when a pathogen was detected (299 vs 255 mg/kg, P = 0.207). In quantile regression adjusted for age and IBD, pathogen detection was only significantly associated with higher FCP in the lower two quartiles, though IBD remained significantly associated with higher FCP at all levels (P > 0.001). Pathogen detection by GI PCR is associated with elevated FCP, though this relationship is nonlinear and varies by IBD status. Our findings indicate that FCP may be an adjunct to, but not a substitute for, stool pathogen testing.

Nausea, Vomiting, and Diarrhea Are Common in Community-Acquired Acute Viral Respiratory Illness.

BACKGROUND: Gastrointestinal (GI) symptoms are recognized sequelae of acute respiratory illness (ARI), but their prevalence is not well documented. Our study aim was to assess the incidence of GI symptoms in community ARI cases for persons of all ages and their association with clinical outcomes. METHODS: We collected mid-nasal swabs, clinical, and symptom data from Seattle-area individuals during the 2018-2019 winter season as part of a large-scale prospective community surveillance study. Swabs were tested by polymerase chain reaction (PCR) for 26 respiratory pathogens. Likelihood of GI symptoms given demographic, clinical, and microbiological covariates were analyzed with Fisher's exact, Wilcoxon-rank-sum, and t-tests and multivariable logistic regression. RESULTS: In 3183 ARI episodes, 29.4% had GI symptoms (n = 937). GI symptoms were significantly associated with pathogen detection, illness interfering with daily life, seeking care for the illness, and greater symptom burden (all p < 0.05). Controlling for age, > 3 symptoms, and month, influenza (p < 0.001), human metapneumovirus (p = 0.004), and enterovirus D68 (p = 0.05) were significantly more likely to be associated with GI symptoms than episodes with no pathogen detected. Seasonal coronaviruses (p = 0.005) and rhinovirus (p = 0.04) were significantly less likely to be associated with GI symptoms. CONCLUSION: In this community-surveillance study of ARI, GI symptoms were common and associated with illness severity and respiratory pathogen detection. GI symptoms did not track with known GI tropism, suggesting GI symptoms may be nonspecific rather than pathogen-mediated. Patients presenting with GI and respiratory symptoms should have respiratory virus testing, even if the respiratory symptom is not the primary concern.

Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study.

BACKGROUND: Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities. OBJECTIVE: To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area. DESIGN: Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917). SETTING: 14 homeless shelters in King County, Washington. PARTICIPANTS: A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms. INTERVENTION: 2 strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing ("surge testing") events. MEASUREMENTS: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity. RESULTS: Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most (n = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most (n = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room. LIMITATION: Selection bias due to voluntary participation and a relatively small case count. CONCLUSION: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations. PRIMARY FUNDING SOURCE: Gates Ventures.

Remote Household Observation for Noninfluenza Respiratory Viral Illness.

BACKGROUND: Noninfluenza respiratory viruses are responsible for a substantial burden of disease in the United States. Household transmission is thought to contribute significantly to subsequent transmission through the broader community. In the context of the coronavirus disease 2019 (COVID-19) pandemic, contactless surveillance methods are of particular importance. METHODS: From November 2019 to April 2020, 303 households in the Seattle area were remotely monitored in a prospective longitudinal study for symptoms of respiratory viral illness. Enrolled participants reported weekly symptoms and submitted respiratory samples by mail in the event of an acute respiratory illness (ARI). Specimens were tested for 14 viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using reverse-transcription polymerase chain reaction. Participants completed all study procedures at home without physical contact with research staff. RESULTS: In total, 1171 unique participants in 303 households were monitored for ARI. Of participating households, 128 (42%) included a child aged <5 years and 202 (67%) included a child aged 5-12 years. Of the 678 swabs collected during the surveillance period, 237 (35%) tested positive for 1 or more noninfluenza respiratory viruses. Rhinovirus, common human coronaviruses, and respiratory syncytial virus were the most common. Four cases of SARS-CoV-2 were detected in 3 households. CONCLUSIONS: This study highlights the circulation of respiratory viruses within households during the winter months during the emergence of the SARS-CoV-2 pandemic. Contactless methods of recruitment, enrollment, and sample collection were utilized throughout this study and demonstrate the feasibility of home-based, remote monitoring for respiratory infections.

Incidence and Risk Factors of Postoperative Mortality and Morbidity After Elective Versus Emergent Abdominal Surgery in a National Sample of 8193 Patients With Cirrhosis.

OBJECTIVE: To describe the incidence and risk factors for mortality and morbidity in patients with cirrhosis undergoing elective or emergent abdominal surgeries. BACKGROUND: Postoperative morbidity and mortality are higher in patients with cirrhosis; variation by surgical procedure type and cirrhosis severity remain unclear. METHODS: We analyzed prospectively-collected data from the Veterans Affairs (VA) Surgical Quality Improvement Program for 8193 patients with cirrhosis, 864 noncirrhotic controls with chronic hepatitis B infection, and 5468 noncirrhotic controls without chronic liver disease, who underwent abdominal surgery from 2001 to 2017. Data were analyzed using random-effects models controlling for potential confounders. RESULTS: Patients with cirrhosis had significantly higher 30-day mortality than noncirrhotic patients with chronic hepatitis B [4.4% vs 1.3%, adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.57-4.98] or with no chronic liver disease (0.8%, aOR 4.68, 95% CI 3.27-6.69); mortality difference was highest in patients with Model for End-stage Liver Disease (MELD) score ≥10. Among patients with cirrhosis, postoperative mortality was almost 6 times higher after emergent rather than elective surgery (17.2% vs. 2.1%, aOR 5.82, 95% CI 4.66-7.27). For elective surgeries, 30-day mortality was highest after colorectal resection (7.0%) and lowest after inguinal hernia repair (0.6%). Predictors of postoperative mortality included cirrhosis-related characteristics (high MELD score, low serum albumin, ascites, encephalopathy), surgery-related characteristics (emergent vs elective, type of surgery, intraoperative blood transfusion), comorbidities (chronic obstructive pulmonary disease, cancer, sepsis, ventilator dependence, functional status), and age. CONCLUSIONS: Accurate preoperative risk assessments in patients with cirrhosis should account for cirrhosis severity, comorbidities, type of procedure, and whether the procedure is emergent versus elective.

Gastroenteritis in Men Who Have Sex With Men in Seattle, Washington, 2017-2018.

BACKGROUND: Men who have sex with men (MSM) are at risk for sexual transmission of enteric pathogens. The microbiology of gastroenteritis in MSM has not been examined since the advent of antiretroviral therapy and molecular diagnostics. Our objective was to assess the causes of gastroenteritis among MSM living with and without human immunodeficiency virus (HIV) coinfection in Seattle, Washington. METHODS: We conducted a retrospective cohort study of 235 MSM who underwent multiplex stool polymerase chain reaction (PCR) testing between 1 January 2017 and 1 June 2018. We abstracted clinical and laboratory data from electronic medical records. Parallel or reflexive culture and susceptibility testing were performed when PCR detected cultivable pathogens. RESULTS: Among 235 MSM tested (268 episodes), 131 had 151 episodes with positive test results. 148 (63.0%) individuals were living with HIV. Among positive tests, 88.7% detected a bacterial pathogen, 26% a virus, and 40% a parasite. Diarrheagenic Escherichia coli (enteroaggretative, enteropathogenic), Shigella, and Campylobacter were the most commonly detected bacteria (33.1%, 30.5%, and 17.2% of positive samples, respectively). Forty-three percent of positive specimens had ≥2 pathogens. Etiologies and clinical presentations were similar between men living with and without HIV. Cultured Shigella and Campylobacter isolates were frequently resistant to multiple antibiotics. CONCLUSIONS: MSM present with gastroenteritis from varied pathogens, including some not detected by conventional stool culture. High levels of antibiotic resistance are consistent with frequent antibiotic exposure in this population and the transmission of multiresistant strains. New approaches are needed to detect, treat, and prevent enteric infections in MSM.

Perioperative Evaluation and Management of Patients With Cirrhosis: Risk Assessment, Surgical Outcomes, and Future Directions.

BACKGROUND AND AIMS: Patients with cirrhosis are at increased risk of perioperative morbidity and mortality. We provide a narrative review of the available data regarding perioperative morbidity and mortality, risk assessment, and management of patients with cirrhosis undergoing non-hepatic surgical procedures. METHODS: We conducted a comprehensive review of the literature from 1998-2018 and identified 87 studies reporting perioperative outcomes in patients with cirrhosis. We extracted elements of study design and perioperative mortality by surgical procedure, Child-Turcotte-Pugh (CTP) class and Model for End-stage Liver Disease (MELD) score reported in these 87 studies to support our narrative review. RESULTS: Overall, perioperative mortality is 2-10 times higher in patients with cirrhosis compared to patients without cirrhosis, depending on the severity of liver dysfunction. For elective procedures, patients with compensated cirrhosis (CTP class A, or MELD <10) have minimal increase in operative mortality. CTP class C patients (or MELD >15) are at high risk for mortality; liver transplantation or alternatives to surgery should be considered. Very little data exist to guide perioperative management of patients with cirrhosis, so most recommendations are based on case series and expert opinion. Existing risk calculators are inadequate. CONCLUSIONS: Severity of liver dysfunction, medical comorbidities and the type and complexity of surgery, including whether it is elective versus emergent, are all determinants of perioperative mortality and morbidity in patients with cirrhosis. There are major limitations to the existing clinical research on risk assessment and perioperative management that warrant further investigation.

Cross-Sectional Prevalence of SARS-CoV-2 Among Skilled Nursing Facility Employees and Residents Across Facilities in Seattle.

BACKGROUND: Skilled nursing facilities (SNFs) are high-risk settings for SARS-CoV-2 transmission. Infection rates among employees are infrequently described. OBJECTIVE: To describe SARS-CoV-2 rates among SNF employees and residents during a non-outbreak time period, we measured cross-sectional SARS-CoV-2 prevalence across multiple sites in the Seattle area. DESIGN: SARS-CoV-2 testing was performed for SNF employees and residents using quantitative real-time reverse transcription polymerase chain reaction. A subset of employees completed a sociodemographic and symptom questionnaire. PARTICIPANTS: Between March 29 and May 13, 2020, we tested 1583 employees and 1208 residents at 16 SNFs for SARS-CoV-2. MAIN MEASURE: SARS-CoV-2 testing results and symptom report among employees and residents. KEY RESULTS: Eleven of the 16 SNFs had one or more resident or employee test positive. Overall, 46 (2.9%) employees had positive or inconclusive testing for SARS-CoV-2, and among those who completed surveys, most were asymptomatic and involved in direct patient care. The majority of employees tested were female (934, 73%), and most employees were Asian (392, 30%), Black (360, 28%), or white (360, 28%). Among the 1208 residents tested, 110 (9.1%) had positive or inconclusive results. There was no association between the presence of positive residents and positive employees within a SNF (p = 0.62, McNemar's test). CONCLUSIONS: In the largest study of SNFs to date, SARS-CoV-2 infections were detected among both employees and residents. Employees testing positive were often asymptomatic and involved in direct patient care. Surveillance testing is needed for SNF employees and residents during the pandemic response.

Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal.

PROBLEM: Rhinoviruses (RVs), the most common causes of acute respiratory infections in young children and infants, are highly diverse genetically. OBJECTIVE: To characterize the RV types detected with respiratory illness episodes in infants in Nepal. STUDY METHODS: Infants born to women enrolled in a randomized trial of maternal influenza immunization in rural, southern Nepal were followed with household-based weekly surveillance until 180 days of age. Infants with respiratory symptoms had nasal swabs tested for twelve respiratory viruses. A subset with RV alone was selected for sequencing of the VP4/2 gene to identify RV types. RESULTS: Among 547 RV-only positive illnesses detected from December 2012 to April 2014, 285 samples (52%) were sequenced. RV-A, B, and C species were detected in 193 (68%), 18 (6%), and 74 (26%) specimens, respectively. A total of 94 unique types were identified from the sequenced samples, including 52 RV-A, 11 RV-B, and 31 RV-C. Multiple species and types circulated simultaneously throughout the study period. No seasonality was observed. The median ages at illness onset were 88, 104, and 88 days for RV-A, B, and C, respectively. The median polymerase chain reaction cycle threshold values did not differ between RV species. No differences between RV species were observed for reported respiratory symptoms, including pneumonia, or for medical care-seeking. CONCLUSIONS: Among very young, symptomatic infants in rural Nepal, all three species and many types of RV were identified; RV-A was detected most frequently. There was no association between RV species and disease severity.

Contamination of Fresh Produce by Microbial Indicators on Farms and in Packing Facilities: Elucidation of Environmental Routes.

To improve food safety on farms, it is critical to quantify the impact of environmental microbial contamination sources on fresh produce. However, studies are hampered by difficulties achieving study designs with powered sample sizes to elucidate relationships between environmental and produce contamination. Our goal was to quantify, in the agricultural production environment, the relationship between microbial contamination on hands, soil, and water and contamination on fresh produce. In 11 farms and packing facilities in northern Mexico, we applied a matched study design: composite samples (n = 636, equivalent to 11,046 units) of produce rinses were matched to water, soil, and worker hand rinses during two growing seasons. Microbial indicators (coliforms, Escherichia coli, Enterococcus spp., and somatic coliphage) were quantified from composite samples. Statistical measures of association and correlations were calculated through Spearman's correlation, linear regression, and logistic regression models. The concentrations of all microbial indicators were positively correlated between produce and hands (ρ range, 0.41 to 0.75; P < 0.01). When E. coli was present on hands, the handled produce was nine times more likely to contain E. coli (P < 0.05). Similarly, when coliphage was present on hands, the handled produce was eight times more likely to contain coliphage (P < 0.05). There were relatively low concentrations of indicators in soil and water samples, and a few sporadic significant associations were observed between contamination of soil and water and contamination of produce. This methodology provides a foundation for future field studies, and results highlight the need for interventions surrounding farmworker hygiene and sanitation to reduce microbial contamination of farmworkers' hands.IMPORTANCE This study of the relationships between microbes on produce and in the farm environment can be used to support the design of targeted interventions to prevent or reduce microbial contamination of fresh produce with associated reductions in foodborne illness.