Reply to: Epidemiological evidence for an association between higher influenza vaccine uptake in the elderly and lower COVID-19 deaths in Italy.

PEER REVIEW TRANSPARENT

The peer review history for this article is available at https://publons.com/publon/10.1002/jmv.26841

DATA AVAILABILITY STATEMENT

Our data are available for external review if requested.

To the Editor,

We read with great interest the paper by Marín‐Hernández and colleagues on the potential interplay between seasonal influenza vaccination and COVID‐19 outcome in Italy. The authors, using data on vaccination in adults older than 65 years published in 1999, found a moderate/strong negative correlation between vaccination and COVID‐19‐related deaths: they calculate that each unit of percentage individuals vaccinated against influenza would result in a 0.3450 decrease in mortality.

ASST Grande Ospedale Metropolitano Niguarda is one of the largest hospitals in the Lombardy Region, the area mainly involved in the first COVID‐19 outbreak in Europe, with in‐hospital mortality above 10% and with an excess of deaths higher than 20% compared with the previous 5 years. We cross‐sectionally evaluated 893 patients admitted to our hospital between February and May 2020 with a diagnosis of COVID‐19. Follow‐up ended in September 2020. Demographic and clinical information was obtained from the hospital's electronic patient records. Data about flu immunizations were retrieved from the Agency of Health Protection which manages public vaccinations in Lombardy.

The study population had a median age of 64 years (interquartile range [IQR], 52–77; 49.8% was older than 65), males were 553 (61.9%) and 385 individuals (43.1%) had a severe or critical disease as defined according to the Chinese guidelines. Charlson Comorbidity Index (CCI) was ≥5 in 232 subjects (26.0%). Two hundred thirteen individuals (23.9%) received flu vaccination between October and December 2019. The in‐hospital mortality was 21.2%.

Vaccine status had only a limited impact on disease severity (41.5% of unvaccinated and 48.4% of vaccinated individuals had severe or critical disease, p = .076). In the Cox univariate analysis, flu vaccination was significantly associated with death (hazard ratio [HR], 1.934; 95% confidence interval, 1.108–2.062; p = .009), but, after adjusting for age, sex, and CCI, such an association went lost in the Cox multivariable regression (HR, 0.948; 95% confidence interval, 0.689–1.304; p = .742).

Some studies suggested potential benefits from influenza vaccination, but they have been performed in other geographical areas where the case fatality rate was not comparable with what registered in Northern Italy. , Several mathematical models were developed to predict a beneficial effect but clinical validation is still missing. , Amato and colleagues reported a relationship between the flu vaccine and a reduced spread and disease severity in Italy. In this paper, data about vaccination were not related to the 2019/2020 season and the analyses were adjusted for epidemiological and economic factors but not for clinical issues.

Other risk factors—especially age—seem to play a major role rather than flu vaccination. Published literature generally provides analyses in populations older than 65 years, but the elderly could not be all grouped together as clinical evolution might be diverse in different age classes. Additionally, the high mortality rate observed in the Lombardy Region might be distinctive of this first outbreak and could not be compared with studies performed elsewhere.

Although influenza vaccination is strongly recommended for clinical, epidemiological, and management issues, our data do not support its beneficial effect in terms of COVID‐19‐related disease severity and mortality in Italy.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.