No evidence of MMR induced trained immunity to prevent SARS COV2: results from a multi-centre RCT

Sinead Delany-Moretlwe^1*Hakim-Moulay Dehbi²Izukanji Sikazwe³George Kyei^4,5Kwadwo Ansah Koram⁴Erik Dubberke⁵Noluthando Mwelase⁶Dominic Hague²Linda-Gail Bekker⁷Linda Yun⁵Annalene Nel⁸Leon du Toit⁵Bruce Biccard⁹Katherine Gill⁷Chikumbutso Chipeta³Kathryn Therese Mngadi¹⁰Limakatso Lebina¹¹Reshmi Dassaye¹²Villeshni Asari¹²Samantha Heather-lee Fry¹³Edwin Turton¹⁴Khatija Ahmed¹⁵Kwadwo Asamoah Kusi⁴Susan Adu-Amankwah⁴Roma Chilengi³Chilekwa Chinyama Joyce³Laurence Lovat¹⁶Dermot McGuckin¹⁶Emilia Caverly²Mary Politi⁵Ben Swan⁵Anne DeSchryver⁵Sherry McKinnon⁵Ananya Gupta⁵Gemma Jones²Nick Freemantle²Shabaana Khader²Helen Rees¹Mihai G Netea¹⁷Ramani Moonesinghe¹⁶Michael Simon Avidan⁵

• ¹University of the Witwatersrand, Johannesburg, South Africa
• ²Comprehensive Clinical Trials Unit - University College London, London, United Kingdom
• ³Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
• ⁴Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
• ⁵School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
• ⁶University of the Witwatersrand, Wits Clinical HIV Research Unit, Johannesburg, South Africa
• ⁷Desmond Tutu Health Foundation, Cape Town, South Africa
• ⁸Medinel, Western Cape, South Africa
• ⁹Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Western Cape, South Africa
• ¹⁰Aurum Institute, Johannesburg, South Africa
• ¹¹Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Soweto, South Africa
• ¹²HIV Prevention Unit - South African Medical Research Council, Durban, South Africa
• ¹³Family Centre for Research with Ubuntu (FAMCRU), Stellenbosch University, Cape Town, South Africa
• ¹⁴Department of Anesthesiology, University of the Free State, Free State, South Africa
• ¹⁵Setshaba Research Centre - Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa
• ¹⁶Department of Targeted Intervention, Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, England, United Kingdom
• ¹⁷Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Gelderland, Netherlands

ABSTRACT BACKGROUND Measles-containing vaccines (MCV), by training innate immune cells, are hypothesized to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). METHODS In this international, double-blind, placebo-controlled trial, we randomly assigned adults, 18 years and older, to receive MCV or saline. The primary outcome was polymerase chain reaction (PCR) confirmed symptomatic COVID-19, up to 60 days after intervention. Secondary outcomes were PCR-confirmed symptomatic COVID-19 and serologically confirmed SARS-CoV-2 infection, up to 150 days after intervention. RESULTS Of 3411 randomised participants, the modified intention-to-treat population included 1607 in the MCV and 1545 in the saline group. The estimated risk of symptomatic COVID-19 by 60 days was 1.5% in the MCV and 1.2% in the saline group (risk difference, 0.3 percentage points, 95% CI, -0.5 to 1.1; p=0.52). At 150 days, these percentages were 4.1% (65/1585) and 4.1% (64/1544) in the MCV and saline groups, respectively (risk difference, 0.04 percentage points, 95% CI, -1.4 to 1.3; p=0.95). Based on serology results available at 0 and 150 days, 10.6% (100/945) of participants in the MCV and 10.3% (98/951) in the saline group had infection with SARS-CoV-2 over the course of the trial (risk difference, 0.3 percentage points, 95% CI, -2.6 to 3.1; p=0.84). Three patients were hospitalised with COVID-19 disease in the MCV and one in the saline group.