Israel Medical Association Journal

Background: Prior to the coronavirus disease 2019 (COVID-19) pandemic, bronchiolitis caused by respiratory syncytial virus (RSV) was primarily observed during the winter months. Recently, however, an increase in incidence during the warmer months has been noted. This trend suggests an interaction between RSV and coronavirus, as well as the impact of public health measures, such as hand hygiene, mask-wearing, and social distancing.

Objectives: To characterize bronchiolitis cases in children under 2 years old caused by RSV during the COVID-19 pandemic in Israel from 2018 to 2022.

Methods: We conducted retrospective study by analyzing medical records of children hospitalized with bronchiolitis from January 2018 to December 2022. A comparison was made between cases before and after the first COVID-19 lockdown.

Results: A total of 922 children with bronchiolitis were studied: 276 cases occurred before the lockdown and 646 cases afterward. We found an increase in bronchiolitis frequency during the summer following the lockdown and a decrease during the winter (P < 0.0001). In addition, there was a shift in the pathogenic profile, with a notable rise in mixed infections after the lockdown (P < 0.0001). No significant differences in clinical presentation were observed between pre- and post-lockdown periods.

Conclusions: There was a change in bronchiolitis seasonality after the lockdown, with a significant increase in cases during the summer and a rise in mixed infections. Further studies are needed to assess whether this shift is a lasting consequence of the pandemic or a temporary change.

Background: Acute bronchiolitis, primarily caused by respiratory syncytial virus (RSV), is the leading cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity.

Objectives: To evaluate the association between C-reactive protein (CRP) serum levels on admission and disease severity in children hospitalized due to RSV bronchiolitis.

Methods: This retrospective cohort study included children (0–24 months old) who were hospitalized due to RSV bronchiolitis (2018–2022), CRP levels taken at admission.

Results: We included 1874 children (mean age of 6.7 months, 59% males); median CRP level 1.92 mg/dl. Children with elevated CRP (> 1.92 mg/dl) were significantly older (5.1 vs. 3.8 months, P < 0.001) and had higher rates of pneumonia (9.4% vs. 4.3%, P < 0.001), urinary tract infection (UTI), (2.2% vs. 0.2%, P < 0.001), acute otitis media (AOM) (1.7% vs. 0.2%, P < 0.001), admissions to the pediatric intensive care unit (PICU) (7.4% vs. 3.7%, P < 0.001), antibiotic treatment (49.8% vs. 37.2%, P < 0.001), and longer hospitalizations (3.83 vs. 3.31 days, P < 0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk 11.6, 2.25, 1.98, 1.44, respectively, P < 0.001). CRP thresholds of 3.51, 1.9, and 2.81 mg/dl for PICU admission, UTI, and pneumonia, were calculated using Youden's index with AUC 0.72, 0.62, and 0.61, respectively.

Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

Background: Up to half the patients diagnosed with acute coronavirus disease 2019 (COVID-19) presented with gastrointestinal symptoms. Gastric mucosal cells, enterocytes, and colonocytes express the viral entry receptor angiotensin-converting enzyme 2 (ACE2) and coreceptor transmembrane protease serine 2 (TMPRSS2) and are prone to infection. Direct infection of gastrointestinal epithelial cells has been demonstrated. COVID-19 disease was first diagnosed in Israel at the end of February 2020 with 842,536 confirmed cases and 6428 deaths by the end of June 2021. In our multicenter, retrospective cohort study, we looked for gastrointestinal signs and symptoms in two periods and correlated them with mortality. Period 1 included the first and second waves and the original virus. Period 2 represented the third wave and the alpha variant.

Objectives: To reveal gastrointestinal signs and symptoms in two periods and correlate them with mortality.

Methods: From 22,302 patients hospitalized in general medical centers, we randomly selected 3582 from Period 1 and 1106 from Period 2. The study was performed before vaccinations were available.

Results: Gastrointestinal signs and symptoms, diarrhea, vomiting, abdominal pain, and taste/smell loss were significantly more prevalent during Period 1. Thirty-day mortality and in-hospital mortality were significantly higher in Period 2 than in Period 1, 25.20% vs. 13.68%, and 21.17% vs. 12.87%, respectively (P < 0.001).

Conclusions: Thirty-day mortality and in-hospital mortality rates were 1.84 and 1.64 times higher from 6 November 2020 to 15 January 2021, the alpha variant, and in negative correlation with gastrointestinal symptoms.

Background: During coronavirus disease 2019 (COVID-19) pandemic, less isolation of common winter viruses was reported in the southern hemisphere.

Objectives: To evaluate annual trends in respiratory disease-related admissions in a large Israeli hospital during and before the pandemic.

Methods: A retrospective analysis of medical records from November 2020 to January 2021 (winter season) was conducted and compared to the same period in two previous years. Data included number of admissions, epidemiological and clinical presentation, and isolation of respiratory pathogens.

Results: There were 1488 respiratory hospitalizations (58% males): 632 in 2018–2019, 701 in 2019–2020, and 155 in 2020–2021. Daily admissions decreased significantly from a median value of 6 (interquartile range [IQR] 4–9) and 7 per day (IQR 6–10) for 2018–2019 and 2019–2020, respectively, to only 1 per day (IQR 1–3) in 2020–2021 (P-value < 0.001). The incidence of all respiratory viruses decreased significantly during the COVID-19 pandemic, with no hospitalizations due to influenza and only one with respiratory syncytial virus. There was also a significant decline in respiratory viral and bacterial co-infections during the pandemic (P-value < 0.001).

Conclusions: There was a significant decline in pediatric respiratory admission rates during the COVID-19 pandemic. Possible etiologies include epidemiological factors such as mask wearing and social distancing, in addition to biological factors such as viral interference. A herd protection effect of adults and older children wearing masks may also have had an impact.

Background: Hepatitis D virus may cause a disease at various severities in the presence of hepatitis B virus, using hepatitis B surface antigen (HBsAg) on the external envelope in its replication process. Thus, people identified with HBsAg in blood tests should also be tested for hepatitis D virus.

Objectives: To describe the situation of performance of blood tests for detection of hepatitis D virus in patients positive for hepatitis surface antigen during 9 years in a population with heterogeneous origins in the north region of Israel.

Methods: We conducted a retrospective study using the database of Clalit Health Services.

Results: We found 3367 people were positive for HBsAg during the study period; 613 (18%) were tested for hepatitis D. People who tested for hepatitis D were younger (47.3 ± 15 years vs. 50.5) and showed a higher rate of visiting the gastroenterology clinic (80.6% vs. 41%). The rate of positive blood tests for hepatitis D was too small for analysis, but it still demonstrated tendency for higher rates in the Ethiopian Jewish group.

Conclusion: The recommendation for performance of blood test for hepatitis D virus was followed to a small extent. Considering the ethnic diversity of the population in Israel, activities to raise rates of performance should be considered.

Background: Infections in neonates with herpes simplex virus 1 (HSV-1) following circumcision due to Metzitzah Be'Peh (MBP) performed by a Mohel occur each year in small numbers. One solution to this problem is the use of a mucus extractor device instead of MBP, which has been authorized by some rabbis. Yet, using a mucus extractor remains controversial among ultra-Orthodox Jews; thus, creating a need for additional solutions.

Objectives: To seek to reduce HSV-1 infection of neonates due to MBP.

Methods: We tested several oral rinse solutions for their ability to destroy virus infectivity following incubation for 30 seconds and using plaque reduction assays.

Results: Corsodyl, Decapinol, and Listerine® all destroyed plaques formation of spiked virus, while Gengigel and Tantum Verde were found to be less effective. We focused specifically on Listerine® due to its efficacy in eliminating contagious HSV-1 from saliva after a 30-second oral rinse. Five different products of Listerine® reduced the infectivity of a spiked virus by more than 4 orders of magnitude in 30 seconds. We also showed that Listerine (up to 7% v/v) can stay in the mouth but did not harm living cells and therefore will not cause any damage to the injured tissue.

Conclusions: Significant reduction in cases of infection with HSV-1 due to MBP can be achieved if Mohalim consistently adopt the practice of careful mouth washing with Listerine® just before performing MBP.

Background: New direct acting antiviral agent (DAA) therapies are associated with a high sustained virological response rate (SVR) in hepatitis C virus (HCV) patients. The understanding of the impact of SVR on fibrosis stage is limited.

Objectives: To determine the effect of treatment with the DAAs on long-term liver fibrosis stages, as determined by shear-wave elastography (SWE) or FibroTest©.

Methods: Fibrosis stage was determined at baseline and at 6-month intervals after end of treatment (EOT), using two‐dimensional SWE or FibroTest©; APRI and FIB-4 scores.

Results: The study comprised 133 SVR12 patients. After a median follow-up of 15 months (range 6–33), liver fibrosis stage decreased by at least 1 stage in 75/133 patients (56%). Cirrhosis reversal was observed in 24/82 (29%). Repeated median liver stiffness SWE values in cirrhotic patients were 15.1 kPa at baseline (range 10.5–100), 13.4 kPa (range 5.5–51) at 6 months, and 11.4 kPa (range 6.1–35.8) at 12 months after EOT, P = 0.01. During the second year after EOT, no statistically significant differences in liver fibrosis stage in 12, 18, and 24 months were found. Splenomegaly was the only significant negative predictor of liver fibrosis regression during all time points of repetitive noninvasive assessment.

Conclusions: Following successful DAA treatment, the majority of our HCV patients with advanced fibrosis demonstrated significant improvement, as assessed by non-invasive methods. Advanced fibrosis stage was a negative predictor of fibrosis regression. Longer follow-up periods are required to further establish the impact of DAAs treatment in HCV patients with advanced fibrosis

Background: Surgery for hip fractures within 48 hours of admission is considered standard. During the lockdown period due to the coronavirus disease-2019 (COVID-19) epidemic, our medical staff was reduced.

Objectives: To compare the demographics, treatment pathways, and outcomes of patients with hip fractures during the COVID-19 epidemic and lockdown with the standard at routine times.

Methods: A retrospective study was conducted of all patients who were treated surgically for hip fracture in a tertiary center during the COVID-19 lockdown period between 01 March and 01 June 2020 and the equivalent period in 2019. Demographic characteristics, time to surgery, surgery type, hospitalization time, discharge destination, postoperative complications, and 30- and 90-day mortality rates were collected for all patients.

Results: During the COVID-19 period, 105 patients were operated due to hip fractures compared to 136 in the equivalent period with no statistical difference in demographics. The rate of surgeries within 48 hours of admission was significantly higher in the COVID-19 period (92% vs. 76%, respectively; P = 0.0006). Mean hospitalization time was significantly shorter (10 vs. 12 days, P = 0.037) with diversion of patient discharge destinations from institutional to home rehabilitation (P < 0.001). There was a significant correlation between the COVID-19 period and lower 90-day mortality rates (P = 0.034). No statistically significant differences in postoperative complications or 30-day mortality rates were noted.

Conclusions: During the COVID-19 epidemic, despite the limited staff and the lack of therapeutic sequence, there was no impairment in the quality of treatment and a decrease in 90-day mortality was noted.

Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease that presents an urgent challenge to global health and economy.

Objectives: To assess the effects of population median age and mean ambient temperature on the COVID-19 global pandemic burden.

Methods: We used databases from open access public domains to record population median age, mean ambient temperature, and the numbers of COVID-19 cases and deaths on days 14 and 28 from the pandemic outbreak for each country in the world. We then calculated the correlation between these parameters.

Results: The analysis included 202 countries. A univariate analysis showed that population median age significantly correlated with the cumulative number of cases and deaths, while mean ambient temperature showed a significant inverse correlation with the cumulative number of deaths on days 14 and 28 from the epidemic outbreak. After a multivariate logistic regression analysis only population median age retained its statistically significant correlation.

Conclusions: Country population median age significantly correlated with COVID-19 pandemic burden while mean ambient temperature shows a significant inverse correlation only in univariate analysis. Countries with older populations encountered a heavier burden from the COVID-19 pandemic. This information may be valuable for health systems in planning strategies for combating this global health hazard.

This mini review includes two case descriptions. It introduces the use of chicken egg yolk antibody (IgY) solutions in the prevention and cure of viral and bacterial infections. Application for the protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rotavirus, and influenza viruses, as well as for the eradication of Pseudomonas aeruginosa, caries, various enteric bacteria and other pathogens, and toxins have been developed. This approach is a fast, reliable, safe, and tested method for producing molecular shield and protection against emerging pathogens and epidemics. In the current pandemic situation caused by coronavirus disease-2019 (COVID-19), this method of passive immunization could be applied for rapid protection against modifiable agents. The specific IgY antibodies start to accumulate into egg yolks about 3 weeks after the immunization of the chicken. The product can be collected safely, as the antigen is not found in the eggs. This method for microbial safety uses natural means and commonly used food substances, which have been tested and could be produced for both blocking epidemics and applying personalized medicine

Background: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Several viral and host factors related to viral response have been reported in the era of treatment with pegylated (PEG)-interferon and ribavirin.

Objectives: To quantify histological findings from patients with chronic HCV using computerized morphometry and to investigate whether the results can predict response to medical treatment with peg-interferon and ribavirin.

Methods: We followed 58 patients with chronic HCV infection with METAVIR score F1 and F2 in our liver unit who were grouped according to treatment response sustained viral response (SVR) and non-SVR. Liver needle biopsies from these patients were evaluated and histological variables, such as inflammatory cells, collagen fibers and liver architecture, were quantified using computerized morphometrics. The pathologist who performed the histomorphometric analysis was blinded to previous patient clinical and histological information.

Results: Histomorphometric variables including the density of collagen fibers were collected. The number of inflammatory cells in the portal space and textural variable were found to be statistically significant and could be used together in a formula to predict response to treatment, with a sensitivity of 93% and a 100% specificity.

Conclusions: Histomorphometry may help to predict a patient's response to treatment at an early stage.