non-specific effects of flu-mmr vaccines in adults

Conditions: COVID-19

Summary: various observational studies have reported an association between influenza vaccination and lower rates of infection with sars-cov-2 and less covid-19 disease severity have been reported in large epidemiological studies in us, brazil and italy. observational studies from the netherlands showed also strongly reduced covid-19 infection rates among influenza-vaccinated healthcare workers, with ors of 0.61 and 0.49 for the first and second wave of covid-19, respectively. in addition, in-vitro immunological analyses showed that the quadrivalent inactivated influenza vaccine can induce a trained immunity program against sars-cov-2 (2). in-vivo vaccination against influenza was also shown to induce improved interferon responses against sars-cov-2, with modulation of hyperinflammatory responses. trained immunity could be the underlying mechanism for the potential protective effect of influenza vaccine, a mechanism that has also been proven for bcg vaccination, and epidemiological evidence suggests similar non-specific effects of mmr and opv vaccination. currently, various clinical trials are being conducted to study the impact of bcg, mmr and opv vaccination on covid-19, but prospective clinical data on influenza vaccination are lacking. although specific covid-19 vaccines have been developed and are proven effective, there are important reasons for assessing in a controlled randomized trial the effect of influenza and mmr vaccine on covid19: * specific covid-19 vaccines are still not yet available for all segments of the population, and especially not for the majority of the population in developing countries. * the emergence of new sars-cov-2 variants, especially the p1 variant from brazil, may very well be associated with reduced response to vaccines. an immunomodulatory protective vaccine that protects in an antigen-independent manner would be of great importance. * it would also be conceptually important to know whether influenza and the mmr vaccine can induce heterologous protection against another viral infection, in the context of future pandemics.


Eligibility criteria:
inclusion criteria: to be eligible to participate in this study, the participant must meet the following criteria: • be older than 18 years old. observation: the elderly is at risk for severe forms of covid-19, therefore, the evidence in this age group is very relevant. however, they can also be a first priority population to receive a specific vaccine, limiting the time to follow-up on the study. in addition, influenza and mmr vaccines can lead to a lower immune system in the elderly than in young people. therefore, it is likely that a more rational choice will be to carry out the study in a young population. exclusion criteria: participants will not be included in the study if they present (reported by the research participants): * known allergy to components of influenza and mmr vaccines or serious adverse events to previous administration. * fever (\> 38 degrees celsius) in the last 24 hours. * pregnancy. note: pregnancy should be avoided for one month after vaccination. * symptoms of active viral or bacterial infection. * documented diagnosis of covid-19. * vaccination in the last 4 weeks against sars-cov-2. * immunocompromised participants. this exclusion category includes: a) infection with the human immunodeficiency virus (hiv-1); b) neutropenic participant with less than 500 neutrophils/mm3; c) participant with organ transplantation; d) participants with bone marrow transplantation; e) participants in chemotherapy treatment; f) participants with primary immunodeficiency; g) participants with severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine medication; i) treatment with oral or intravenous steroids, for example, daily doses of prednisone or equivalent for more than 3 months, or probable use of oral or intravenous steroids within next four weeks. * some type of lymphoma or malignancy in the previous two years. * direct involvement in the design or execution of the study. * absence from work for more than 4 weeks within the next 12 weeks after study admission (vacation, maternity leave, retirement, planned surgery, etc.)

Keywords: sars-cov-2 heterologous effects of vaccines other viral infections