Institut Pasteur, Université Paris Cité, Epidemiology and Modelling of Antibiotic Evasion (EMAE) unit, Paris, France; Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, Inserm U1018, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France
David RM Smith
Institut Pasteur, Université Paris Cité, Epidemiology and Modelling of Antibiotic Evasion (EMAE) unit, Paris, France; Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, Inserm U1018, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France; Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire national des arts et métiers, Paris, France; Health Economics Research Centre, Nuffield Department of Health, University of Oxford, Oxford, United Kingdom
Institut Pasteur, Université Paris Cité, Epidemiology and Modelling of Antibiotic Evasion (EMAE) unit, Paris, France; Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, Inserm U1018, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France
Sophie Novelli
Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, Inserm U1018, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France
Paul Henriot
Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire national des arts et métiers, Paris, France; PACRI unit, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France
Emmanuelle Varon
Centre National de Référence des Pneumocoques, Centre Hospitalier Intercommunal de Créteil, Créteil, France
Robert Cohen
Institut Mondor de Recherche Biomédicale-Groupe de Recherche Clinique Groupe d’Etude des Maladies Infectieuses Néonatales et Infantiles (IMRB-GRC GEMINI), Université Paris Est, 94000, Créteil, France; Groupe de Pathologie Infectieuse Pédiatrique (GPIP), 06200, Nice, France; Unité Court Séjour, Petits Nourrissons, Service de Néonatologie, Centre Hospitalier, Intercommunal de Créteil, Créteil, France; Association Clinique et Thérapeutique Infantile du Val-de-Marne (ACTIV), 94000, Créteil, France; Association Française de Pédiatrie Ambulatoire (AFPA), 45000, Orléans, France
Corinne Levy
Institut Mondor de Recherche Biomédicale-Groupe de Recherche Clinique Groupe d’Etude des Maladies Infectieuses Néonatales et Infantiles (IMRB-GRC GEMINI), Université Paris Est, 94000, Créteil, France; Groupe de Pathologie Infectieuse Pédiatrique (GPIP), 06200, Nice, France; Association Clinique et Thérapeutique Infantile du Val-de-Marne (ACTIV), 94000, Créteil, France; Association Française de Pédiatrie Ambulatoire (AFPA), 45000, Orléans, France
Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire national des arts et métiers, Paris, France; PACRI unit, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France
Lulla Opatowski
Institut Pasteur, Université Paris Cité, Epidemiology and Modelling of Antibiotic Evasion (EMAE) unit, Paris, France; Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines, Inserm U1018, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
