Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations

Ohrui, Takashi; Nakayama, Katsutoshi; Fukushima, Toshiro; Chiba, Hiroshi; Sasaki, Hidetada

doi:10.3143/geriatrics.42.34

Cited by 69 publications

(65 citation statements)

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“…Encouraging data also emerged from a recent double-blind, randomized clinical trial, showing that patients ≥ 65 years vaccinated with BCG had a reduced incidence of infections, in particular respiratory tract infections 9 . This study is in line with other previous reports showing a reduction in respiratory tract infections in the BCG vaccinated cohort 10 , 11 .…”

Section: Introductionsupporting

confidence: 94%

Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses

Hensel

McAndrews

McGrail

et al. 2020

Sci Rep

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The Bacillus Calmette–Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is thought to provide protection against non-TB infectious diseases. BCG vaccination has recently been proposed as a strategy to prevent infection with SARS-CoV-2 (CoV-2) to combat the COVID-19 outbreak, supported by its potential to boost innate immunity and initial epidemiological analyses which observed reduced severity of COVID-19 in countries with universal BCG vaccination policies. Seventeen clinical trials are currently registered to inform on the benefits of BCG vaccinations upon exposure to CoV-2. Numerous epidemiological analyses showed a correlation between incidence of COVID-19 and BCG vaccination policies. These studies were not systematically corrected for confounding variables. We observed that after correction for confounding variables, most notably testing rates, there was no association between BCG vaccination policy and COVD-19 spread rate or percent mortality. Moreover, we found variables describing co-morbidities, including cardiovascular death rate and smoking prevalence, were significantly associated COVID-19 spread rate and percent mortality, respectively. While reporting biases may confound our observations, our epidemiological findings do not provide evidence to correlate overall BCG vaccination policy with the spread of CoV-2 and its associated mortality.

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Section: Introductionsupporting

confidence: 94%

Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses

Hensel

McAndrews

McGrail

et al. 2020

Sci Rep

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show abstract

“…A small study in Indonesia in the elderly reported that multiple doses of BCG vaccination resulted in a significant reduction in the number of respiratory tract infections compared with a placebo (Wardhana et al, 2011). A clinical trial in Japan found a reduced risk of pneumonia upon BCG vaccination in previously tuberculin-negative elderly people (Ohrui et al, 2005).…”

Section: Reprogramming Innate Immune Responses: Trained Immunity and mentioning

confidence: 99%

Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection

Netea

Giamarellos‐Bourboulis

Domínguez‐Andrés

et al. 2020

Cell

401

432

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SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed ''trained immunity,'' by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2. ll

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“…Importantly for the at-risk populations for severe COVID-19, it was shown that BCG had a similar protective effect on respiratory tract infections in older individuals in Indonesia (172). In addition, a clinical trial performed in older individuals in Japan established protection against pneumonia after pneumococcal, influenza and BCG vaccinations (173). Further confirmation of this effect has been demonstrated in a randomized controlled trial in which BCG vaccination protected against experimental infection of a yellow fever virus (174).…”

Section: Trained Immunity Utility For Vaccinesmentioning

confidence: 90%

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends”

et al. 2020

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The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."

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Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations

Cited by 69 publications

References 0 publications

Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses

Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses

Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection

Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends”

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