What is the impact of BCG compared to placebo vaccination on: 1) COVID-19 incidence, severity, and duration; 2) development and longevity of SARS-CoV-2-specific antibodies and on the immune system more generally; and 3) the upper respiratory tract microbiota.
We vaccinated health care workers in 9 Dutch hospitals at the start of the first epidemic wave, and follow-up sampling visits in three hospitals (UMCU, Radboud, and LUMC) at 12 and 24 weeks post-vaccination are planned. We request funding to enable laboratory-confirmed outcome assessments now that serology tests have become available. If required, data will be combined with data from a parallel trial in community-dwelling adults. If beneficial, BCG vaccination could be implemented rapidly to protect key populations until SARS-CoV-2-specific vaccines become available. Because its effects are nonspecific, BCG vaccination could also serve as a first response in future pandemics caused by novel pathogens.
Our primary hypothesis is that SARS-CoV-2 incidence will be similar in the two arms given the high infectiousness of the virus, but that disease severity and duration are reduced in the BCG arm.
PLAN VAN AANPAK
Vaccinations have been completed. Participants are reporting clinical data on an ongoing basis via a mobile phone app. SARS-CoV-2 RT-PCR testing was done at the time of symptom-reporting as part of routine hospital procedures; test results and stored nasopharyngeal swab rest materials will be retrieved. Serum and saliva specimens will be collected at the 12- and 24-week post-vaccination visits, and will be tested for IgG/IgA antibodies against SARS-CoV-2 and against all coronaviruses. The neutralising capacity of SARS-CoV-2 antibodies will be assessed in a subsample. Specimens from participants who were exposed to BCG and SARS-CoV-2, BCG only, SARS-CoV-2 only, or neither will be assessed for parameters of trained immunity and upper respiratory tract microbiota composition.