Severe Influenza Is Characterized by Prolonged Immune Activation: Results From the SHIVERS Cohort Study.

Background: The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of nonhospitalized individuals with influenza-like illness (ILI). Methods: Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay. Results: During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus-specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus-specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor ß) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI. Conclusions: Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation, compared with mild influenza cases.

A multi-country study of intussusception in children under 2 years of age in Latin America: analysis of prospective surveillance data.

BACKGROUND: Intussusception (IS) is a form of acute intestinal obstruction that occurs mainly in infants and is usually of unknown cause. An association between IS and the first licensed rotavirus vaccine, a reassortant-tetravalent, rhesus-based rotavirus vaccine (RRV-TV), led to the withdrawal of the vaccine. New rotavirus vaccines have now been developed and extensively studied for their potential association with IS. This study aimed to describe the epidemiology and to estimate the incidence of IS in Latin American infants prior to new vaccine introduction. METHODS: Children under 2 years of age representing potential IS cases were enrolled in 16 centers in 11 Latin American countries from January 2003 to May 2005. IS cases were classified as definite, probable, possible or suspected as stated on the Brighton Collaboration Working Group guidelines. RESULTS: From 517 potential cases identified, 476 (92%) cases were classified as definite, 21 probable, 10 possible and 10 suspected for intussusception. Among the 476 definite IS cases, the median age at presentation was 6.4 months with 89% of cases aged <1 year. The male to female ratio was 1.5:1. The incidence of definite IS per 100,000 subject-years ranged from 1.9 in Brazil to 62.4 in Argentina for children <2 years of age, and from 3.8 in Brazil to 105.3 in Argentina for children aged <1 year. Median hospital stay was 4 days with a high prevalence of surgery as the primary treatment (65%). Most cases (88%) made a complete recovery, but 13 (3%) died. No clear seasonal pattern of IS cases emerged. CONCLUSIONS: This study describes the epidemiology and estimates the incidence of IS in Latin American infants prior to the introduction of new rotavirus vaccines. The incidence of IS was found to vary between different countries, as observed in previous studies. TRIAL REGISTRATION: Clinical study identifier 999910/204 (SERO-EPI-IS-204).

Transmission of varicella zoster virus from individuals with herpes zoster or varicella in school and day care settings.

BACKGROUND: Because the varicella incidence has declined following varicella vaccine licensure, herpes zoster (HZ) cases may play a larger role in varicella zoster virus (VZV) transmission. We investigated how HZ and varicella cases contribute to the varicella incidence in schools and day care centers. METHODS: Surveillance data collected in Philadelphia during September 2003-June 2010 were analyzed. A varicella case was considered to be sporadic if it was reported from a school or day care facility >6 weeks after or ≥10 days before other reports of VZV transmission. A varicella case was considered to be secondary if it occurred 10-21 days after report of a case of HZ or sporadic varicella. Analysis compared VZV transmission from individuals with HZ or sporadic varicella, stratified by varicella vaccination status and disease severity. RESULTS: Of 290 HZ cases reported, 27 (9%) resulted in 84 secondary varicella cases. Of 1358 sporadic varicella cases reported, 205 (15%) resulted in 564 secondary varicella cases. Approximately half of the HZ and sporadic varicella cases resulted in single secondary cases. The proportion of individuals who had secondary cases with mild disease was similar for those exposed to HZ and those exposed to varicella (70% and 72%, respectively). VZV transmission was highest from unvaccinated individuals with sporadic varicella (P < .01). CONCLUSIONS: VZV transmission from individuals with HZ contributes to varicella morbidity. More research is needed to understand risk factors and guide recommendations for preventing VZV transmission from individuals with HZ.

SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed three-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of 1.25-3.18). This study thus provides a detailed picture of viral evolution in the Delaware Valley and a geographically matched analysis of vaccine breakthroughs; it also introduces a rigorous statistical approach to interrogating enrichment of viral variants.

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

Risk of Fall-Related Injury due to Adverse Weather Events, Philadelphia, Pennsylvania, 2006-2011.

OBJECTIVES: Following a surge in fall-related visits to local hospital emergency departments (EDs) after a severe ice storm, the Philadelphia Department of Public Health examined the association between inclement winter weather events and fall-related ED visits during a 5-year period. METHODS: Using a standardized set of keywords, we identified fall-related injuries in ED chief complaint logs submitted as part of Philadelphia Department of Public Health's syndromic surveillance from December 2006 through March 2011. We compared days when falls exceeded the winter fall threshold (ie, "high-fall days") with control days within the same winter season. We then conducted matched case-control analysis to identify weather and patient characteristics related to increased fall-related ED visits. RESULTS: Fifteen high-fall days occurred during winter months in the 5-year period. In multivariable analysis, 18- to 64-year-olds were twice as likely to receive ED care for fall-related injuries on high-fall days than on control days. The crude odds of ED visits occurring from 7:00 am to 10:59 am were 70% higher on high-fall days vs control days. Snow was a predictor of a high-fall day: the adjusted odds of snow before a high-fall day as compared with snow before a control day was 13.4. CONCLUSIONS: The association between the number of fall-related ED visits and weather-related fall injuries, age, and timing suggests that many events occurred en route to work in the morning. Promoting work closures or delaying openings after severe winter weather would allow time for better snow or ice removal, and including "fall risk" in winter weather advisories might effectively warn morning commuters. Both strategies could help reduce the number of weather-related fall injuries.

It's not the heat, it's the humidity: wet weather increases legionellosis risk in the greater Philadelphia metropolitan area.

BACKGROUND: Legionella species are abundant in the environment and are increasingly recognized as a cause of severe pneumonia. Increases in cases of community-acquired legionellosis in the greater Philadelphia metropolitan area (GPMA) led to concern that changing environmental factors could influence occurrence of disease. METHODS: We evaluated the association between weather patterns and occurrence of legionellosis in the GPMA, using both traditional Poisson regression analysis and a case-crossover study approach. The latter approach controls for seasonal factors that could confound the relationship between weather and occurrence of disease and permits the identification of acute weather patterns associated with disease. RESULTS: A total of 240 cases of legionellosis were reported between 1995 and 2003. Cases occurred with striking summertime seasonality. Occurrence of cases was associated with monthly average temperature (incidence rate ratio [IRR] per degree Celsius, 1.07 [95% confidence interval [CI], 1.05-1.09]) and relative humidity (IRR per 1% increase in relative humidity, 1.09 [95% CI, 1.06-1.12]) by Poisson regression analysis. However, case-crossover analysis identified an acute association with precipitation (odds ratio [OR], 2.48 [95% CI, 1.30-3.12]) and increased humidity (OR per 1% increase in relative humidity, 1.08 [95% CI, 1.05-1.11]) 6-10 days before occurrence of cases. A significant dose-response relationship for occurrence of cases was seen with both precipitation and increased humidity. CONCLUSIONS: Although, in the GPMA, legionellosis occurred predominantly during summertime, the acute occurrence of disease is best predicted by wet, humid weather. This finding is consistent with the current understanding of the ecological profile of this pathogen and supports the contention that sporadic legionellosis occurs through contamination of water sources.

Lack of SARS transmission among healthcare workers, United States.

Healthcare workers accounted for a large proportion of persons with severe acute respiratory syndrome (SARS) during the worldwide epidemic of early 2003. We conducted an investigation of healthcare workers exposed to laboratory-confirmed SARS patients in the United States to evaluate infection-control practices and possible SARS-associated coronavirus (SARS-CoV) transmission. We identified 110 healthcare workers with exposure within droplet range (i.e., 3 feet) to six SARS-CoV-positive patients. Forty-five healthcare workers had exposure without any mask use, 72 had exposure without eye protection, and 40 reported direct skin-to-skin contact. Potential droplet- and aerosol-generating procedures were infrequent: 5% of healthcare workers manipulated a patient's airway, and 4% administered aerosolized medication. Despite numerous unprotected exposures, there was no serologic evidence of healthcare-related SARS-CoV transmission. Lack of transmission in the United States may be related to the relative absence of high-risk procedures or patients, factors that may place healthcare workers at higher risk for infection.