Rotavirus A during the COVID-19 Pandemic in Brazil, 2020–2022: Emergence of G6P[8] Genotype

Rotavirus A (RVA) remains a leading cause of acute gastroenteritis (AGE) hospitalizations in children worldwide. During the COVID-19 pandemic, a reduction in vaccination coverage in Brazil and elsewhere was observed, and some reports have demonstrated a reduction in AGE notifications during the pandemic. This study aims to investigate the diversity and prevalence of RVA genotypes in children and adults presenting with AGE symptoms in Brazil during the COVID-19 pandemic between 2020 and 2022. RVA was screened using RT-qPCR; then, G and P genotypes were characterized using one-step multiplex RT-PCR. A total of 2173 samples were investigated over the three-year period, and we detected RVA in 7.7% of samples (n = 167), being 15.5% in 2020, 0.5% in 2021, and 13.8% in 2022. Higher RVA prevalence was observed in the Northeastern region (19.3%) compared to the Southeastern (6.1%) and Southern regions (5.5%). The most affected age group was children aged between 0 and 6 months old; however, this was not statistically significant. Genotyping and phylogenetic analysis identified the emergence of G6P[8] during the period; moreover, it was detected in 10.6% of samples in 2020 and in 83.5% in 2022. In contrast, the prevalence of G3P[8], the previous dominant genotype, decreased from 72.3% in 2020 to 11.3% in 2022. We also identified unusual strains, such as G3P[9] and G9P[4], being sporadically detected during the period. This is the first report on the molecular epidemiology and surveillance of RVA during the COVID-19 pandemic period in Brazil. Our study provides evidence for the importance of maintaining high and sustainable levels of vaccine coverage to protect against RVA disease. Furthermore, it highlights the need to maintain nationwide surveillance in order to monitor future trends and changes in the epidemiology of RVA in Brazil.

[1]  H. Ushijima,et al.  Predominance of DS‐1‐like G8P[8] rotavirus reassortant strains in children hospitalized with acute gastroenteritis in Thailand, 2018–2020 , 2023, Journal of medical virology.

[2]  J. Tate,et al.  Predicting norovirus and rotavirus resurgence in the United States following the COVID-19 pandemic: a mathematical modelling study , 2023, BMC Infectious Diseases.

[3]  F. Bert,et al.  Risk perception, knowledge about SARS-CoV-2, and perception towards preventive measures in Italy: a nationwide cross-sectional study , 2023, Journal of preventive medicine and hygiene.

[4]  C. D. F. de Souza,et al.  Change in Rotavirus Vaccine Coverage in Brazil from before (2015–2019) through the COVID-19 Pandemic Period (2020–2021) , 2023, Viruses.

[5]  G. Barnes,et al.  Australian Rotavirus Surveillance Program annual report, 2012. , 2022, Communicable diseases intelligence quarterly report.

[6]  P. Brasil,et al.  Circulation of Vaccine-derived Rotavirus G1P[8] in a Vulnerable Child Cohort in Rio de Janeiro , 2022, The Pediatric infectious disease journal.

[7]  F. Martinón-Torres,et al.  The Value of Rotavirus Vaccination in Europe: A Call for Action , 2022, Infectious Diseases and Therapy.

[8]  T. Fumian,et al.  Full genotype constellations analysis of unusual DS-1-like G12P[6] and G6P[8] rotavirus strains detected in Brazil, 2019. , 2022, Virology.

[9]  M. Renko,et al.  Noro‐ and rotavirus detections in children during COVID‐19 pandemic—A nationwide register study in Finland , 2022, Acta paediatrica.

[10]  A. Thongprachum,et al.  Changing distribution of rotavirus A genotypes circulating in Japanese children with acute gastroenteritis in outpatient clinic, 2014-2020. , 2022, Journal of infection and public health.

[11]  Guilherme Silveira Procianoy,et al.  Impact of the COVID-19 pandemic on the vaccination of children 12 months of age and under: an ecological study. , 2022, Ciencia & saude coletiva.

[12]  E. Burnett,et al.  Trends in Rotavirus Laboratory Detections and Internet Search Volume Before and After Rotavirus Vaccine Introduction and in the Context of the Coronavirus Disease 2019 Pandemic—United States, 2000–2021 , 2022, The Journal of infectious diseases.

[13]  J. Sabatier,et al.  Impact of COVID‐19 pandemic on routine vaccination coverage of children and adolescents: A systematic review , 2022, Health science reports.

[14]  U. Parashar,et al.  The efficacy and safety of rotavirus vaccines in countries in Africa and Asia with high child mortality , 2022, Vaccine.

[15]  M. Chan Return of Norovirus and Rotavirus Activity in Winter 2020‒21 in City with Strict COVID-19 Control Strategy, China , 2022, Emerging infectious diseases.

[16]  S. M. Driedger,et al.  COVID-19 pandemic impact on childhood vaccination coverage in Quebec, Canada , 2021, Human vaccines & immunotherapeutics.

[17]  S. Dudman,et al.  The incidence of infectious diseases and viruses other than SARS-CoV-2 amongst hospitalised children in Oslo, Norway during the Covid-19 pandemic 2020–2021 , 2021, Journal of Clinical Virology Plus.

[18]  M. Miagostovich,et al.  Nosocomial acute gastroenteritis outbreak caused by an equine-like G3P[8] DS-1-like rotavirus and GII.4 Sydney[P16] norovirus at a pediatric hospital in Rio de Janeiro, Brazil, 2019 , 2021, Human vaccines & immunotherapeutics.

[19]  P. Buchy,et al.  Rotavirus vaccines performance: dynamic interdependence of host, pathogen and environment , 2021, Expert review of vaccines.

[20]  J. Degiuseppe,et al.  Emergence of unusual rotavirus G9P[4] and G8P[8] strains during post vaccination surveillance in Argentina, 2017-2018. , 2021, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[21]  Sudhir Kumar,et al.  MEGA11: Molecular Evolutionary Genetics Analysis Version 11 , 2021, Molecular biology and evolution.

[22]  Sebastian B. Mohr,et al.  Relaxing restrictions at the pace of vaccination increases freedom and guards against further COVID-19 waves , 2021, PLoS Comput. Biol..

[23]  Jianhua Mao,et al.  Rotavirus and adenovirus infections in children during COVID-19 outbreak in Hangzhou, China , 2021, Translational pediatrics.

[24]  Angela K. Shen,et al.  Decline in child vaccination coverage during the COVID-19 pandemic — Michigan Care Improvement Registry, May 2016-May 2020 , 2020, American Journal of Transplantation.

[25]  J. Leite,et al.  Rotavirus A in Brazil: Molecular Epidemiology and Surveillance during 2018–2019 , 2020, Pathogens.

[26]  H. Bedford,et al.  Routine vaccination during covid-19 pandemic response , 2020, BMJ.

[27]  L. Cuevas,et al.  Impact of a twelve-year rotavirus vaccine program on acute diarrhea mortality and hospitalization in Brazil: 2006-2018 , 2020, Expert review of vaccines.

[28]  G. Dbaibo,et al.  Full genome characterization of human G3P[6] and G3P[9] rotavirus strains in Lebanon. , 2019, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[29]  J. Tate,et al.  Current and new rotavirus vaccines , 2019, Current opinion in infectious diseases.

[30]  N. Betrapally,et al.  Whole-gene analysis of inter-genogroup reassortant rotaviruses from the Dominican Republic: Emergence of equine-like G3 strains and evidence of their reassortment with locally-circulating strains. , 2019, Virology.

[31]  Kwe Claude Yinda,et al.  Molecular characterization of human group A rotavirus genotypes circulating in Rawalpindi, Islamabad, Pakistan during 2015-2016 , 2019, PloS one.

[32]  Rodrigo C. Barros,et al.  Rotavirus antigenemia as a common event among children hospitalised for severe, acute gastroenteritis in Belém, northern Brazil , 2019, BMC Pediatrics.

[33]  G. Ianiro,et al.  First detection of a reassortant G3P[8] rotavirus A strain in Italy: a case report in an 8-year-old child , 2019, Virology Journal.

[34]  J. Leite,et al.  The evolving epidemiology of rotavirus A infection in Brazil a decade after the introduction of universal vaccination with Rotarix® , 2019, BMC Pediatrics.

[35]  M. D'Errico,et al.  Uncommon G9P[4] group A rotavirus strains causing dehydrating diarrhea in young children in Italy. , 2018, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[36]  U. Liebert,et al.  Evidence for presumable feline origin of sporadic G6P[9] rotaviruses in humans. , 2018, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[37]  Sumit Sharma,et al.  Rotavirus and norovirus in children with severe diarrhea in Burkina Faso before rotavirus vaccine introduction , 2018, Journal of medical virology.

[38]  C. Murray,et al.  Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years , 2018, JAMA pediatrics.

[39]  S. Komoto,et al.  Characterization of unusual DS‐1‐like G3P[8] rotavirus strains in children with diarrhea in Japan , 2018, Journal of medical virology.

[40]  G. Kang,et al.  Estimating global, regional and national rotavirus deaths in children aged <5 years: Current approaches, new analyses and proposed improvements , 2017, PloS one.

[41]  A. Linhares,et al.  Analysis of a genotype G3P[9] rotavirus a strain that shows evidence of multiple reassortment events between animal and human rotaviruses , 2017, Journal of medical virology.

[42]  Mika Shigematsu,et al.  Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015 , 2017, The Lancet. Infectious diseases.

[43]  J. Matthijnssens,et al.  Human P[6] Rotaviruses From Sub-Saharan Africa and Southeast Asia Are Closely Related to Those of Human P[4] and P[8] Rotaviruses Circulating Worldwide. , 2016, The Journal of infectious diseases.

[44]  M. Iturriza-Gómara,et al.  Emergence and spread of G3P[8] rotaviruses possessing an equine-like VP7 and a DS-1-like genetic backbone in the Basque Country (North of Spain), 2015. , 2016, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[45]  K. Bányai,et al.  Equine-like G3 rotavirus in Hungary, 2015 - Is it a novel intergenogroup reassortant pandemic strain? , 2016, Acta microbiologica et immunologica Hungarica.

[46]  Wonyong Kim,et al.  Evidence of multiple reassortment events of feline-to-human rotaviruses based on a rare human G3P[9] rotavirus isolated from a patient with acute gastroenteritis. , 2016, Comparative immunology, microbiology and infectious diseases.

[47]  C. Donato,et al.  Emergence of a novel equine-like G3P[8] inter-genogroup reassortant rotavirus strain associated with gastroenteritis in Australian children. , 2016, The Journal of general virology.

[48]  H. Kubo,et al.  Detection and characterization of a human G9P[4] rotavirus strain in Japan , 2015, Journal of medical virology.

[49]  M. C. Timenetsky,et al.  ROTAVIRUS GENOTYPES CIRCULATING IN BRAZIL, 2007-2012: IMPLICATIONS FOR THE VACCINE PROGRAM , 2015, Revista do Instituto de Medicina Tropical de Sao Paulo.

[50]  U. Parashar,et al.  Review of global rotavirus strain prevalence data from six years post vaccine licensure surveillance: is there evidence of strain selection from vaccine pressure? , 2014, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[51]  L. Cuevas,et al.  Incidence of Rotavirus and Circulating Genotypes in Northeast Brazil during 7 Years of National Rotavirus Vaccination , 2014, PloS one.

[52]  A. Linhares,et al.  Diversity of rotavirus strains circulating in Northern Brazil after introduction of a rotavirus vaccine: High prevalence of G3P[6] genotype , 2014, Journal of medical virology.

[53]  J. Matthijnssens,et al.  Genetic characterization of a rare bovine-like human VP4 mono-reassortant G6P[8] rotavirus strain detected from an infant in Bangladesh. , 2013, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[54]  R. Scheuermann,et al.  Virus Pathogen Database and Analysis Resource (ViPR): A Comprehensive Bioinformatics Database and Analysis Resource for the Coronavirus Research Community , 2012, Viruses.

[55]  J. Tate,et al.  Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: a case series. , 2012, The Journal of infectious diseases.

[56]  R. Glass,et al.  Rotavirus , 2011, Clinical Veterinary Advisor.

[57]  Jelle Matthijnssens,et al.  Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG) , 2011, Archives of Virology.

[58]  T. Dallman,et al.  Rotavirus genotypes co-circulating in Europe between 2006 and 2009 as determined by EuroRotaNet, a pan-European collaborative strain surveillance network , 2010, Epidemiology and Infection.

[59]  M. Estes,et al.  Rotaviruses: from pathogenesis to vaccination. , 2009, Gastroenterology.

[60]  A. Linhares,et al.  Group A rotavirus genotypes and the ongoing Brazilian experience: a review. , 2008, Memorias do Instituto Oswaldo Cruz.

[61]  T. Vesikari,et al.  One-step quantitative RT-PCR for the detection of rotavirus in acute gastroenteritis. , 2008, Journal of virological methods.

[62]  J. Matthijnssens,et al.  Two out of the 11 genes of an unusual human G6P[6] rotavirus isolate are of bovine origin. , 2008, The Journal of general virology.

[63]  Jelle Matthijnssens,et al.  Full Genome-Based Classification of Rotaviruses Reveals a Common Origin between Human Wa-Like and Porcine Rotavirus Strains and Human DS-1-Like and Bovine Rotavirus Strains , 2008, Journal of Virology.

[64]  Roger I Glass,et al.  Serotype diversity and reassortment between human and animal rotavirus strains: implications for rotavirus vaccine programs. , 2005, The Journal of infectious diseases.

[65]  G. Kang,et al.  Rotavirus genotyping: keeping up with an evolving population of human rotaviruses. , 2004, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[66]  R. Glass,et al.  Genetic variability among serotype G6 human rotaviruses: Identification of a novel lineage isolated in Hungary , 2003, Journal of medical virology.

[67]  R. Glass,et al.  Characterization of nontypeable rotavirus strains from the United States: identification of a new rotavirus reassortant (P2A[6],G12) and rare P3[9] strains related to bovine rotaviruses. , 2002, Virology.

[68]  M. Iturriza-Gómara,et al.  Reassortment In Vivo: Driving Force for Diversity of Human Rotavirus Strains Isolated in the United Kingdom between 1995 and 1999 , 2001, Journal of Virology.

[69]  E. Palombo,et al.  Genetic and antigenic characterization of a serotype G6 human rotavirus isolated in melbourne, Australia , 1995, Journal of medical virology.

[70]  R. Glass,et al.  Identification of group A rotavirus gene 4 types by polymerase chain reaction , 1992, Journal of clinical microbiology.

[71]  G. Gerna,et al.  Isolation and characterization of two distinct human rotavirus strains with G6 specificity , 1992, Journal of clinical microbiology.

[72]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[73]  R. Glass,et al.  Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens , 1990, Journal of clinical microbiology.

[74]  E. Sabino,et al.  Spread of the emerging equine-like G3P[8] DS-1-like genetic backbone rotavirus strain in Brazil and identification of potential genetic variants. , 2019, The Journal of general virology.

[75]  J. Bines,et al.  Australian Rotavirus Surveillance Program: Annual Report, 2017 , 2019, Communicable diseases intelligence.

[76]  U. Liebert,et al.  Molecular characterization of different equine-like G3 rotavirus strains from Germany. , 2018, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[77]  M. Iturriza-Gómara,et al.  Increased detection of G3P[9] and G6P[9] rotavirus strains in hospitalized children with acute diarrhea in Bulgaria. , 2015, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[78]  J. Mossong,et al.  Validation of neonatal tetanus elimination in Zambia by lot quality-assurance cluster sampling. , 2008, Releve epidemiologique hebdomadaire.