Rational and irrational vaccine hesitancy.

In the paper published recently in this journal, Kumar et al. explained why the key to improved COVID-19 vaccine uptake is to understand societal reactions leading to vaccine hesitancy. They conclude that communications strategies should be tailored to the different phases of vaccine hesitancy. However, within the theoretical framework provided in their paper, vaccine hesitancy should be recognized as having both rational and irrational components. Rational vaccine hesitancy is a natural result of the inherent uncertainties in the potential impact of vaccines in controlling the pandemic. In general, irrational hesitancy is based on baseless information obtained from hearsay and deliberately false information. Risk communication should address both with transparent, evidence-based information. Rational concerns can be allayed by sharing the process in which dilemmas and uncertainties are dealt with by the health authorities. Messages on irrational concerns need to address head on the sources spreading unscientific and unsound information. In both cases, there is a need to develop risk communication that restores trust in the health authorities.

SARS-CoV-2 and seasonal influenza: similarities and disparities.

This report describes the differences in disease severity and clinical presentation between hospitalized patients with coronavirus disease 2019 (COVID-19) and others with seasonal influenza. A total of 136 influenza and 152 COVID-19 patients were included. Patients with influenza more frequently had dyspnea (p = 0.004), hypoxemia (p < 0.001), underlying diseases (p = 0.046), and elevated liver enzymes (p = 0.028). In contrast, patients with COVID-19 were overweight (p < 0.001), lymphopenic (p < 0.001), had elevated CRP (p = 0.011), and radiological abnormalities (p < 0.001). Patients with influenza were more severely ill on admission (NEWS > 5) (p < 0.001). However, length of hospital stay, ventilatory support, and 30-day-mortality were similar. Despite differences in clinical presentation and disease severity between influenza and COVID-19 patients, both groups had similar clinical outcomes.

Excess mortality in Israel associated with COVID-19 in 2020-2021 by age group and with estimates based on daily mortality patterns in 2000-2019.

BACKGROUND: We aimed to build a basic daily mortality curve in Israel based on 20-year data accounting for long-term and annual trends, influenza-like illness (ILI) and climate factors among others, and to use the basic curve to estimate excess mortality during 65 weeks of the COVID-19 pandemic in 2020-2021 stratified by age groups. METHODS: Using daily mortality counts for the period 1 January 2000 to 31 December 2019, weekly ILI counts, daily climate and yearly population sizes, we fitted a quasi-Poisson model that included other temporal covariates (a smooth yearly trend, season, day of week) to define a basic mortality curve. Excess mortality was calculated as the difference between the observed and expected deaths on a weekly and periodic level. Analyses were stratified by age group. RESULTS: Between 23 March 2020 and 28 March 2021, a total of 51 361 deaths were reported in Israel, which was 12% higher than the expected number for the same period (expected 45 756 deaths; 95% prediction interval, 45 325-46 188; excess deaths, 5605). In the same period, the number of COVID-19 deaths was 6135 (12% of all observed deaths), 9.5% larger than the estimated excess mortality. Stratification by age group yielded a heterogeneous age-dependent pattern. Whereas in ages 90+ years (11% excess), 100% of excess mortality was attributed to COVID-19, in ages 70-79 years there was a greater excess (21%) with only 82% attributed to COVID-19. In ages 60-69 and 20-59 years, excess mortality was 14% and 10%, respectively, and the number of COVID-19 deaths was higher than the excess mortality. In ages 0-19 years, we found 19% fewer deaths than expected. CONCLUSION: The findings of an age-dependent pattern of excess mortality may be related to indirect pathways in mortality risk, specifically in ages <80 years, and to the implementation of the lockdown policies, specifically in ages 0-19 years with lower deaths than expected.

Comparing Coronavirus Disease 2019 (COVID-19) Pandemic Waves in Hospitalized Patients: A Retrospective, Multicenter, Cohort Study.

BACKGROUND: Coronavirus disease 2019 was first diagnosed in Israel at the end of February 2020. By the end of June 2021, there were 842 536 confirmed cases and 6428 deaths. Our aim in this multicenter, retrospective, cohort study is to describe the demographic and clinical characteristics of hospitalized patients and compare the pandemic waves before immunization. METHODS: Of 22 302 patients hospitalized in general medical centers, we randomly selected 6329 for the study. Of these, 3582 and 1106 were eligible for the study in the first period (first and second waves) and in the second period (third wave), respectively. RESULTS: Thirty-day mortality was higher in the second period than in the first period, 25.20% vs 13.68% (P < .001). Invasive mechanical ventilation supported 9.19% and 14.21% of patients in the first period and second period, respectively. Extracorporeal membrane oxygenation (ECMO) was used more than twice as often in the second period. CONCLUSIONS: Invasive ventilation, use of ECMO, and mortality rate were 1.5 to 2 times higher in the second period than in the first period. In the second period, patients had a more severe presentation and higher mortality than those in the first period.

Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine.

Background: The adverse events reported from the COVID-19 mRNA vaccines have varied from very mild, such as pain near the vaccination site, to more severe, with occasional anaphylaxis. Details of age-specific gender differences for the adverse effects are not well documented. Methods: Age and gender disaggregated data on reports of adverse events following two or three doses of the Pfizer-BioNTech COVID-19 vaccine were obtained from four cross-sectional studies. The first was from reports submitted to the Israel Ministry of Health national adverse events database (for ages 16 and above). The second was from a national cross-sectional survey based on an internet panel (for ages 30 and above), and the third and fourth were from cross-sectional surveys among employees of a large company (for ages 20-65) using links to a self-completed questionnaire. Results: In all studies, the risks of adverse events were higher following the second dose and consistently higher in females at all ages. The increased risk among females at all ages included local events such as pain at the injection site, systemic events such as fever, and sensory events such as paresthesia in the hands and face. For the combined adverse reactions, for the panel survey the female-to-male risk ratios (RRs) were 1.89 for the first vaccine dose and 1.82 for the second dose. In the cross-sectional workplace studies, the female-to-male RRs for the first, second and third doses exceeded 3.0 for adverse events, such as shivering, muscle pain, fatigue and headaches. Conclusions: The consistent excess in adverse events among females for the mRNA COVID-19 vaccine indicates the need to assess and report vaccine adverse events by gender. Gender differences in adverse events should be taken into account when determining dosing schedules.

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

A nationwide analysis of population group differences in the COVID-19 epidemic in Israel, February 2020-February 2021.

BACKGROUND: Social inequalities affect the COVID-19 burden and vaccine uptake. The aim of this study was to explore inequalities in the incidence and mortality rate of SARS-CoV-2 infection and vaccine uptake in various sociodemographic and population group strata in Israel. METHODS: We analysed nationwide publicly available, aggregated data on PCR-confirmed SARS-CoV-2 infections and COVID-19 deaths between March 2020 and February 2021, as well as the first three months of COVID-19 immunisation according to sociodemographics, including population group and residential socioeconomic status (SES). We computed incidence and mortality rates of COVID-19. Comparisons between towns with predominantly Arab, ultra-Orthodox Jewish (the minorities), general Jewish populations, and according to SES, were conducted using generalised linear models with negative binomial distribution. FINDINGS: Overall, 774,030 individuals had SARS-CoV-2 infection (cumulative incidence 84•5 per 1,000 persons) and 5687 COVID-19 patients had died (mortality rate 62•8 per 100,000 persons). The highest mortality rate was found amongst the elderly. Most (>75%) individuals aged 60 years or above have been vaccinated with BNT162b2 vaccine. The risk of SARS-CoV-2 infection was higher in towns with predominantly Arab and ultra-Orthodox Jewish populations than in the general Jewish population, and in low SES communities. COVID-19 mortality rate was highest amongst Arabs. Conversely, vaccine uptake was lower amongst Arab and ultra-Orthodox Jewish populations and low SES communities. INTERPRETATION: Ethnic and religious minorities and low SES communities experience substantial COVID-19 burden, and have lower vaccine uptake, even in a society with universal accessibility to healthcare. Quantifying these inequalities is fundamental towards reducing these gaps, which imposes a designated apportion of resources to adequately control the pandemic. FUNDING: No external funding was available for this study.

Sex differences in the case-fatality rates for COVID-19-A comparison of the age-related differences and consistency over seven countries.

BACKGROUND: Early in the COVID-19 pandemic, it was noted that males seemed to have higher case-fatality rates than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in seven countries. METHODS: Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the national official agencies from Denmark, England, Israel, Italy, Spain, Canada and Mexico. Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the seven countries, for all age-groups. Meta-regression and sensitivity analysis were conducted to evaluate the age and country contribution to differences. RESULTS: The CFRs were consistently higher in males at all ages. The pooled M:F CFR ratios were 1.71, 1.88, 2.11, 2.11, 1.84, 1.78 and 1.49, for ages 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80+ respectively. In meta-regression, age group and country were associated with the heterogeneity in the CFR ratios. CONCLUSIONS: The sex differences in the age-specific CFRs are intriguing. Sex differences in the incidence and mortality have been found in many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the consistently greater case-fatality rates in males at all ages suggests that sex-related factors impact on the natural history of the disease. This could provide important clues as to the mechanisms underlying the severity of COVID-19 in some patients.

A study of ethnic, gender and educational differences in attitudes toward COVID-19 vaccines in Israel - implications for vaccination implementation policies.

BACKGROUND: Vaccines for COVID-19 are currently available for the public in Israel. The compliance with vaccination has differed between sectors in Israel and the uptake has been substantially lower in the Arab compared with the Jewish population. AIM: To assess ethnic and socio-demographic factors in Israel associated with attitudes towards COVID-19 vaccines prior to their introduction. METHODS: A national cross-sectional survey was carried out In Israel during October 2020 using an internet panel of around 100,000 people, supplemented by snowball sampling. A sample of 957 adults aged 30 and over were recruited of whom 606 were Jews (49% males) and 351 were Arabs (38% males). RESULTS: The sample of Arabs was younger than for the Jewish respondents. Among the men, 27.3% of the Jewish and 23.1% of the Arab respondents wanted to be vaccinated immediately, compared with only 13.6% of Jewish women and 12.0% of Arab women. An affirmative answer to the question as to whether they would refuse the vaccine at any stage was given by 7.7% of Jewish men and 29.9% of Arab men, and 17.2% of Jewish women and 41.0% of Arab women. Higher education was associated with less vaccine hesitancy. In multiple logistic regression analysis, the ethnic and gender differences persisted after controlling for age and education. Other factors associated with vaccine hesitancy were the belief that the government restrictions were too lenient and the frequency of socializing prior to the pandemic. CONCLUSIONS: The study revealed a relatively high percentage reported would be reluctant to get vaccinated, prior to the introduction of the vaccine. This was more marked so for Arabs then Jews, and more so for women within the ethnic groups. While this was not a true random sample, the findings are consistent with the large ethnic differences in compliance with the vaccine, currently encountered and reinforce the policy implications for developing effective communication to increase vaccine adherence. Government policies directed at controlling the pandemic should include sector-specific information campaigns, which are tailored to ensure community engagement, using targeted messages to the suspected vaccine hesitant groups. Government ministries, health service providers and local authorities should join hands with civil society organizations to promote vaccine promotion campaigns.

The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal-a comparison of age-specific and age-adjusted CFRs between seven countries.

BACKGROUND: Crude case-fatality rates (CFRs) for COVID-19 vary widely between countries. There are serious limitations in the CFRs when making comparisons. We examined how the age distribution of the cases is responsible for the COVID-19 CFR differences between countries. METHODS: COVID-19 cases and deaths, by ten-year age-groups, were available from the reports of seven countries. The overall and age-specific CFRs were computed for each country. The age-adjusted CFRs were computed by the direct method, using the combined number of cases in all seven countries in each age group as the standard population. A meta-analytic approach was used to obtain pooled age-specific CFRs. FINDINGS: The crude overall CFRs varied between 0.82% and 14.2% in the seven countries and the variation in the age-specific CFRs were much smaller. There was wide variation in the age distribution of the cases between countries. The ratio of the crude CFR for the country with the highest CFR to that with the lowest (6.28) was much lower for the age-adjusted CFRs rates (2.57). CONCLUSIONS: The age structure of the cases explains much of differences in the crude CFRs between countries and adjusting for age substantially reduces this variation. Other factors such as the definition of cases, coding of deaths and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. At the very least, age-specific and age-adjusted CFRs should be used for comparisons.