Cocirculation of A(H3N2) and B/Victoria increased morbidity in hospitalized patients in the 2019-2020 A(H1N1)pdm09 predominant influenza season in Israel.

Community surveillance found the 2019-2020 A(H1N1)pdm09 predominant influenza season in Israel to be a high-intensity season with an early and steep morbidity peak. To further characterize disease severity in the 2019-2020 season, we analyzed a cohort of hospitalized patients with laboratory-confirmed influenza from this season (n = 636). Quantitative polymerase chain reaction was performed on clinical samples to detect the presence of influenza. Demographic, clinical, and laboratory data were retrieved via electronic health records and MDClone. Electronic health records were accessed to obtain data on intensive care unit patients, missing data and for data verification purposes. Univariate analysis was performed to compare demographic, comorbidity, and clinical characteristics across the three influenza strains. The A(H1N1)pdm09 predominant 2019-2020 influenza season in Israel was characterized by an early and steep morbidity peak, vaccine delays and shortages, and with the A(H3N2) and B/Victoria strains disproportionately targeting children and young adults, most probably due to reduced immunity to these strains. A greater proportion of children <5 years infected with A(H3N2) and B/Victoria developed severe influenza compared with those infected with A(H1N1)pdm09. Our study emphasizes the vulnerability of infants and young children in the face of rapidly evolving influenza strains and underscores the importance of influenza prevention measures in this population.

Return of pandemic H1N1 influenza virus.

BACKGROUND: Influenza pandemics are usually caused by the re-assortment of several influenza viruses, results in the emergence of new influenza virus strains that can infect the entire population. These pandemic strains, as well as seasonal influenza viruses, are subjected to extensive antigenic change that has, so far, prevented the generation of a universal vaccine. METHODS: Samples of patients hospitalized due to infection with the pandemic H1N1 influenza virus (A(H1N1)pdm09) from 2009, when the virus first appeared, until 2013 were analyzed. RESULTS: While many patients were hospitalized in 2009 due to infection with the pandemic H1N1 influenza virus, only small percentages of patients were hospitalized later in 2010-2012. Surprisingly, however in 2012-2013, we noticed that the percentages of patients hospitalized due to the pandemic H1N1 influenza infection increased significantly. Moreover, the ages of hospitalized patients differed throughout this entire period (2009-2013) and pregnant women were especially vulnerable to the infection. CONCLUSIONS: High percentages of patients (especially pregnant women) were hospitalized in 2013 due to the A(H1N1)pdm09 infection, which may have been enabled by an antigenic drift from those which circulated at the onset of the pandemic.

Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift.

BACKGROUND: Little is known about the development of cross-reactive antibodies following natural exposure to pathogens. Such knowledge is critical in the development of new universal influenza vaccines. METHODS: To study the possibility of the presence of cross-reactive antibodies to influenza viruses which underwent a major antigenic drift between the years 1999 and 2007 sera from samples of 80 children and 400 adults were selected at random from the Israeli national serum bank. The sera was obtained in 2002 and in 2007, two time points that followed a major drift in the infectious H3N2 influenza virus strain (A/Panama/2007/99 to A/Wisconsin/67/2005). RESULTS: In the summer of 2002, 13% of the children had Hemagglutination Inhibition (HI) antibody titers of at least 40 and these antibodies recognized both A/Panama/2007/99 and A/Wisconsin/67/2005, where the latter strain only began to circulate in Israel in 2006. In 2007, 29% of the children had HI antibody titers of at least 40 directed against both A/Wisconsin/67/2005 and A/Panama/2007/99, even though they had never been exposed to the latter virus. Anti-A/Panama/2007/99 antibodies were detected in 58% and 68% of the 2002 and 2007 adult samples, respectively, while 8% and 39% had antibodies against A/Wisconsin/67/2005, respectively. CONCLUSIONS: The presence of naturally occurring cross-reactive influenza virus antibodies in a significant percentage of children has important implications for the development of a universal influenza vaccine.

Outbreak of Influenza and Other Respiratory Viruses in Hospitalized Patients Alongside the SARS-CoV-2 Pandemic.

Influenza A and other respiratory viruses, circulate each winter and cause respiratory illness that can lead to severe complications in hospitalized patients. During the COVID-19 pandemic, only a few cases of respiratory viruses were detected in Israel. Our study applied RT-PCR to examine 13,674 samples collected from patients hospitalized with respiratory symptoms in 2019, 2020, and 2021 and the first half of the 2022 winter. A sharp increase in influenza A(H3N2) cases was observed in winter 2021-2022 as compared to 2020, followed by a sudden decrease in influenza cases after the detection of the SARS-CoV-2 omicron variant in Israel. Comparison of the area under the curve (AUC) of influenza infection rates during 7 consecutive winter seasons found that the minimal AUC between 2015 and 2020 was 281.1, while in 2021-2022, it was significantly lower (162.6 AUC; p = 0.0017), although the percentage of positive influenza cases was similar to those of previous years. The presented findings show how the dominance of influenza A(H3N2) abruptly ended upon circulation of the SARS-CoV-2 omicron variant. However, a post-COVID-19 influenza outbreak is possible, hence the planning of the next influenza vaccine is critical to ensure lower influenza-related hospitalization rates.

Viral co-pathogens in COVID-19 acute respiratory syndrome - what did we learn from the first year of pandemic?

OBJECTIVE: This study aimed to describe the distribution of respiratory pathogens and the occurrence of co-pathogens during the first year of the COVID-19 pandemic. METHODS: We used a multiplex polymerase chain reaction (PCR) panel targeting 23 microorganisms to analyze the oro-pharyngeal samples of patients admitted to our hospital with acute respiratory infection (ARI) between March 1, 2020, and February 28, 2021. We matched 40 to 50 patients who were SARS-CoV-2 positive and SARS-CoV-2 negative per month for age and sex. RESULTS: A total of 939 patients with multiplex PCR test results were included in the study. Respiratory pathogens where detected in only 8/476 (1.6%) patients with COVID-19 versus 87/463 (18.7%) patients with non-COVID-19 ARI patients. Diversity and rates of pathogens vastly differed from previous years but showed seasonal variance. CONCLUSION: Patients with SARS-CoV-2 infection presenting with ARI during the first year of the COVID-19 pandemic demonstrated paucity of respiratory co-pathogens.

Adenovirus load correlates with respiratory disease severity among hospitalized pediatric patients.

OBJECTIVES: Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal and other infections. We investigated the correlation between adenovirus viral load in clinical respiratory samples and the respiratory disease severity in pediatric patients. METHODS: Medical records of patients hospitalized in the Sheba Medical Center (SMC) with confirmed adenovirus infection were retrospectively analyzed. The possible correlation between disease severity score and Real time PCR 'cycle threshold' (Ct), a proxy of viral load, was assessed in patients aged 9 years and under. In addition, Ct values of hospitalized versus community-care patient samples, positive for various respiratory viruses including adenovirus, were compared. RESULTS: Adenovirus load in respiratory samples, as measured by Ct values, was found to be negatively correlated with respiratory disease severity in hospitalized pediatric patients aged under 9 years. Moreover, hospitalized patients presented with significantly higher Ct levels for various respiratory viruses as compared to community-care patients. CONCLUSION: In this study we found a correlation between Ct values obtained from adenovirus q-PCR analysis of respiratory clinical samples and disease severity in patients aged 9 years and under. Such finding may serve as a predictor of respiratory disease course in pediatric patients and will be beneficial for the differential diagnosis and treatment of pediatric patients.

Rhinovirus infections in infants suggest that early detection can prevent unnecessary treatment.

BACKGROUND: Human rhinoviruses (hRV) are small, RNA viruses of the Picornaviridae family, which are divided into three subtypes (A, B, C). hRVs are among the most common causes for acute respiratory illnesses (ARI) involving both the upper and lower respiratory tract. OBJECTIVES: This study aimed to assess the magnitude and characteristics of hRV infections in hospitalized children, aged less than 5 years, hospitalized in Israel during 2011-2012. STUDY DESIGN: The 2503 respiratory samples were subjected to real-time PCR, to detect hRV and other respiratory viruses. Rhinovirus-positive samples were further tested by sequencing to identify the infecting species. RESULTS: Of these 2503 respiratory samples, 422 tested positive for hRV, of them, 243 were from children under 5 years of age (58% of all rhinoviral-positive samples). We also found that among the ARI-associated hospital admissions, 16% were positive for rhinovirus. hRV type A was the most common species. Laboratory data showed monocytosis in 51%, hypercalcemia in 61% and lower respiratory tract involvement in 75% of patients. CONCLUSIONS: We thus recommend including rhinovirus testing as part of the routine testing performed in young children presenting with ARI.

Treatment of adenoviral keratoconjunctivitis with a combination of povidone-iodine 1.0% and dexamethasone 0.1% drops: a clinical prospective controlled randomized study.

PURPOSE: To determine the efficacy of combination povidone-iodine (PVP-I) 1.0% eyedrops and dexamethasone 0.1% eyedrops in the treatment of adenoviral keratoconjunctivitis. MATERIALS AND METHODS: In a prospective, randomized, controlled, double-blinded clinical trial patients with recent adenoviral keratoconjunctivitis (diagnosed clinically and confirmed by PCR), we randomly divided into three treatment groups: study group - received PVP-I 1.0% and dexamethasone 0.1%, control 1 group - received dexamethasone 0.1% and control 2 group - received lubricating eyedrops (hypromellose 0.3%). The treatment was administered four times a day in each group. All patients were examined and filled a questionnaire before treatment and on the 3rd, 5th and 7th days of treatment. RESULTS: We included in the study 78 eyes (26 in each group). Adenovirus type 8 was the most common pathogen (83% of cases). The fastest improvement in patients red eyes, discharge, superficial punctate keratitis and pseudomembranes was observed in the study group (p < 0.001). Those patients reached a near complete recovery in 5-7 days, which was also confirmed by reduction in Adenovirus titres by PCR. The slowest improvement was in the control 2 group. Subepithelial infiltrates (SEI) were observed in 44% of the control 1 group, 20% of the control 2 group and in 0% of the study group. The rate of reduction in Adenovirus titres was the slowest in the control 1 group. CONCLUSION: The combination of PVP-I 1.0% and dexamethasone 0.1% four times a day can reduce symptoms and expedite recovery in epidemic keratoconjunctivitis patients.

Outbreak of adenovirus type 55 infection in Israel.

BACKGROUND: Different types of adenoviruses are associated with diverse diseases and with varied disease severity. Adenovirus 55 could be associated with severe respiratory infections. OBJECTIVES: Here, we report on an adenovirus 55 outbreak in two psychiatric institutions in Israel. The objective of this study was to investigate the adenovirus 55 outbreak. STUDY DESIGN: We studied the clinical parameters of the patients and sequencing analysis of certain parts of the virus gene was performed. RESULTS: We identified the first patient who developed symptoms (the index case) and we showed that while both patients and staff members of the institutions were infected, the disease in the psychiatric patients was more severe. We attributed these differences to their mental and underlying health conditions. CONCLUSIONS: It is important to monitor for adenovirus infection in the community, especially in mental health institutions to allow appropriate medical care.

Ineffectiveness of the 2014-2015 H3N2 influenza vaccine.

The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with Influenza-like-illness (ILI) were collected from over 20 outpatient clinics located in different geographic parts of Israel and were tested for the presence of influenza viruses (influenza A and influenza B). Here we show, that in the 2014-2015 season, the vaccine that included the A/Texas/50/2012 H3N2 virus was ineffective. Significant numbers of individuals vaccinated with the 2014-2015 vaccine, of all ages, were infected with influenza A (H3N2), manifesting similar symptoms as the non-vaccinated group. We further demonstrate that the Israeli circulating influenza A(H3N2) virus was different than that included in the 2014-2015 northern hemisphere vaccine, and that antibodies elicited by this vaccine were significantly less efficient in neutralizing influenza A(H3N2) infection.

Back-to-school upper respiratory infection in preschool and primary school-age children in Israel.

BACKGROUND: Increased upper respiratory infection (URI) among children at the beginning of school year is well known to parents and pediatricians. However, this phenomenon is not well documented or characterized. METHODS: Computerized datasets from a large health maintenance organization in Israel were used to calculate the weekly rates of URI among children 3-14 years old for the years 2007-2012. In addition, nasopharyngeal swabs were collected in 2010-2012 from children with URI symptoms and controls during school opening time. Swabs were tested by real-time polymerase chain reaction for the presence of respiratory viruses. RESULTS: Time-series analysis demonstrated a peak of URI in September each year. The peaks reached their height 2 weeks after school opening and returned to baseline within 4-7 weeks. The main 3 viruses detected both in URI patients and in healthy controls during the first weeks of school opening were rhinovirus, adenovirus and enterovirus. The detection rate of any respiratory virus, and of rhinovirus in particular, was significantly higher among cases than among controls (54% vs. 16%, P < 0.001 for any virus, and 35% vs. 6.0%, P < 0.01 for rhinovirus). When adjusting for age and sex cases had 5.8 times more viral detection when compared with controls. Upper respiratory symptoms were significantly more prevalent among the virus-positive cases when compared with negative ones. CONCLUSIONS: Back-to-school illness consisting of URI has a distinct epidemiological pattern demonstrating a rapid rise peaking within 2 weeks of school opening and is associated predominantly with rhinovirus.

Epidemiological changes of respiratory syncytial virus (RSV) infections in Israel.

RSV is the leading cause of lower respiratory-tract infections in infants and therefore demands in-depth epidemiological characterization. We investigated here the distribution of RSV types in Israel between the years 2005-2012. Clinical samples were collected from 11,018 patients hospitalized due to respiratory illnesses and were evaluated for the presence of various respiratory viruses, including RSV A and RSV B. Until 2008, each year was characterized by the presence of one dominant type of RSV. However, from 2008, both RSV A and B types were detected at significant levels, particularly among infants aged 0-2 years. Furthermore, significant changes in the RSV A and RSV B subtypes circulating in Israel since 2008 were observed. Finally, we demonstrate that, irrespectively of the changes observed in RSV epidemiology, when the pandemic H1N1pdm09 influenza virus appeared in 2009, RSV infections were delayed and were detected when infection with H1N1pdm09 had declined.

Relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses.

BACKGROUND: A(H1N1)pdm09, a new influenza pandemic virus emerged in 2009. The A(H1N1)pdm09 infection had several unique characteristics which included rapid transmissibility and high morbidity in obese individuals, pregnant women and individuals suffering from chronic diseases. OBJECTIVES: To study the relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses such as respiratory syncytial virus (RSV), human metapneumo virus (hMPV), adenovirus and seasonal influenza. METHODS: Samples (nasopharyngeal swabs or aspirates) collected between 2007 until 2012 from patients of various ages that were hospitalized due to respiratory virus infections were analyzed for the presence of various respiratory viruses, using qRT-PCR. RESULTS: In 2009-2010, when the pandemic influenza A(H1N1)pdm09 first appeared, two major infection peaks were noted and individuals of various ages were infected. Following the decline of the A(H1N1)pdm09 virus infection, the percentages of patients infected with adenovirus and hMPV increased, while infection frequency with RSV B and with seasonal influenza virus decreased. Furthermore, RSV infections were delayed and very few percentages of patients were co-infected with more than one virus. Interestingly, the A(H1N1)pdm09 virus lost its dominancy when it reappeared in the winter of 2010-2011, and at this time, only the incidence of RSV infections was affected by the A(H1N1)pdm09 virus. CONCLUSIONS: The A(H1N1)pdm09 virus had distinct effects on other respiratory viruses when it first appeared versus later, when it evolved from being a pandemic to a seasonal virus.