Prevention Of Respiratory Tract Infection And Covid-19 Through BCG Vaccination In Vulnerable Older Adults

Publication date: Sep 03, 2020

On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. In the Netherlands, although the incidence is currently low due to social distancing measures, recurrence of infections is expected once measures are going to be lifted. Although individuals of any age can acquire SARS-CoV-2, adults of middle and older age are at highest risk for developing severe COVID-19 disease. Moreover, recent reports demonstrate that mortality rates rise significantly among patients 60 years and older. Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences in vulnerable populations are urgently needed. Bacille Calmette-Gu’erin (BCG) vaccine not only protects against tuberculosis, but also induces protection against various respiratory infections, including those with a viral etiology. We hypothesize that BCG vaccination reduces clinically relevant respiratory tract infections requiring medical intervention, including COVID-19, in vulnerable elderly. The objective of this trial is to determine the impact of BCG vaccination on the incidence of clinically relevant respiratory infections or COVID-19 in vulnerable elderly. The trial is designed as an adaptive multi-center double-blind randomized placebo-controlled trial. The attempt is to include 5,200 to 7,000 vulnerable elderly, defined as ?60 years of age being discharged from hospital in the last 6 weeks, or visiting a medical outpatient clinic, thrombosis care services, or chronic renal replacement departments. Patients with contraindications to BCG vaccination as stipulated in the Summary of Product Characteristics (SPC) and patients with a history of COVID-19 will be excluded. Participants will be randomized between intracutaneous administration of BCG vaccine (Danish strain 1331) or placebo (0.1ml 0.9% NaCl) in a 1:1 ratio.The trial has an adaptive primary endpoint. Based on accrual of the two endpoints, the primary endpoint will be either (a) COVID-19 or (b) clinically relevant respiratory tract infection requiring medical intervention, potentially including COVID-19 episodes. The other will be declared secondary endpoint. Other secondary endpoints include: all SARS-CoV-2 infections (including asymptomatic infections), influenza infection, acute respiratory infection (ARI; all infections regardless of medical intervention), ARI-related hospital admission, COVID-19 related hospital admission, pneumonia, mental, physical and social functioning, serious adverse events and adverse events, and death.

Concepts Keywords
Acute Respiratory Infection Outpatient clinic thrombosis
Antibiotic Hematological malignancy
Asymptomatic Protection respiratory infections
Attending Physician SARS
Bacterial Infection Tuberculosis
BCG Chemo
BCG Vaccine Vaccination
Bone Marrow Transplantation Immunotherapy
Cardiology Major surgery
Coronavirus Health
Corticosteroids Medicine
Cytokine Medical specialties
Danish Zoonoses
Double Blind Sarbecovirus
Etiology BCG vaccine
Hematological Malignancy RTT
HIV Coronavirus disease
Hospital Transplantation
Immunocompromised
Immunodeficiency
Immunosuppressant
Immunotherapy
Incidence
Infection
Influenza
Informed Consent
Internal Medicine
Intravenous
Lymphocytes
Lymphopenia
Malignancy
Morbidity
NaCl
Netherlands
Neurology
Neutropenic
Neutrophils
Organ
Pandemic
Placebo
Pneumonia
Prednisone
Primary Endpoint
Pulmonology
Renal
Respiratory Tract
Respiratory Tract Infection
SARS
Steroids
Suspicion
Thrombosis
Tuberculosis
Utrecht
Vaccination
Vaccine
Viral
Virus
WHO

Semantics

Type Source Name
drug DRUGBANK BCG vaccine
disease MESH Respiratory Tract Infection
disease MESH recurrence
disease MESH infections
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease MESH thrombosis
disease MESH renal
disease MESH contraindications
disease MESH asymptomatic infections
pathway REACTOME Influenza Infection
disease MESH pneumonia
disease MESH death
disease MESH chronic disease
disease MESH bacterial infection
disease MESH hematological malignancy
disease MESH malignancy
pathway KEGG Primary immunodeficiency
disease MESH lymphopenia
drug DRUGBANK Prednisone
disease MESH diagnosis

Original Article

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