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As a reference laboratory for measles and rubella surveillance in Lombardy, we evaluated the association between SARS-CoV-2 infection and measles-like syndromes, providing preliminary evidence for undetected early circulation of SARS-CoV-2. Overall, 435 samples from 156 cases were investigated. RNA from oropharyngeal swabs (N = 148) and urine (N = 141) was screened with four hemi-nested PCRs and molecular evidence for SARS-CoV-2 infection was found in 13 subjects. Two of the positive patients were from the pandemic period (2/12, 16.7%, March 2020-March 2021) and 11 were from the pre-pandemic period (11/44, 25%, August 2019-February 2020). Sera (N = 146) were tested for anti-SARS-CoV-2 IgG, IgM, and IgA antibodies. Five of the RNA-positive individuals also had detectable anti-SARS-CoV-2 antibodies. No strong evidence of infection was found in samples collected between August 2018 and July 2019 from 100 patients. The earliest sample with evidence of SARS-CoV-2 RNA was from September 12, 2019, and the positive patient was also positive for anti-SARS-CoV-2 antibodies (IgG and IgM). Mutations typical of B.1 strains previously reported to have emerged in January 2020 (C3037T, C14408T, and A23403G), were identified in samples collected as early as October 2019 in Lombardy. One of these mutations (C14408T) was also identified among sequences downloaded from public databases that were obtained by others from samples collected in Brazil in November 2019. We conclude that a SARS-CoV-2 progenitor capable of producing a measles-like syndrome may have emerged in late June-late July 2019 and that viruses with mutations characterizing B.1 strain may have been spreading globally before the first Wuhan outbreak. Our findings should be complemented by high-throughput sequencing to obtain additional sequence information. We highlight the importance of retrospective surveillance studies in understanding the early dynamics of COVID-19 spread and we encourage other groups to perform retrospective investigations to seek confirmatory proofs of early SARS-CoV-2 circulation.

Objective and designRisk factors for severe measles are poorly investigated in high-income countries. The Italian Society for Paediatric Infectious Diseases conducted a retrospective study in children hospitalised for measles from January 2016 to August 2017 to investigate the risk factors for severe outcome defined by the presence of long-lasting sequelae, need of intensive care or death.ResultsNineteen hospitals enrolled 249 children (median age 14.5 months): 207 (83%) children developed a complication and 3 (1%) died. Neutropaenia was more commonly reported in children with B3-genotype compared with other genotypes (29.5% vs 7.7%, p=0.01). Pancreatitis (adjusted OR [aOR] 9.19, p=0.01) and encephalitis (aOR 7.02, p=0.04) were related to severe outcome in multivariable analysis, as well as C reactive protein (CRP) (aOR 1.1, p=0.028), the increase of which predicted severe outcome (area under the receiver operating characteristic curve 0.67, 95% CI 0.52 to 0.82). CRP values >2 mg/dL were related to higher risk of complications (OR 2.0, 95% CI 1.15 to 3.7, p=0.01) or severe outcome (OR 4.13, 95% CI 1.43 to 11.8, pConclusionThe risk of severe outcome in measles is independent of age and underlying conditions, but is related to the development of organ complications and may be predicted by CRP value.

In 2017, Italy experienced one of the largest outbreaks of measles in recent years, with 5404 notified cases and 4347 confirmed cases. A further 2029 cases were notified during the first 6 months of 2018, and 1516 of them were laboratory-confirmed. The B3 and D8 genotypes were identified as those responsible for the outbreak. Possible transmission routes can be established by monitoring the circulating measles virus strains in support of the national health authorities to warn people and travellers. Keywords: Outbreak, Measles, Genotype identification, Surveillance

In accordance with the goal of the World Health Organization Regional Office for Europe, the Italian National Measles and Rubella Elimination Plan aimed to interrupt indigenous measles transmission in Italy by the end of 2015. However, from 2013 to 2015, Italy experienced high measles burden with 4902 measles cases (49.3% laboratory-confirmed) reported to the enhanced measles surveillance system (cumulative incidence in the triennium reference period: 2.4/100,000 population). The measles elimination goal was not reached. Laboratory surveillance of measles circulating genotypes is performed by the Measles and Rubella National Reference Laboratory (NRL) at the Italian National Institute of Health (Istituto Superiore di Sanità - ISS), in Rome. Samples received from 1 January 2013-31 December 2015 were analysed. Those positive for measles genome by molecular tests were sequenced and phylogenetically analysed. Phylogenetic analysis performed by NRL identified that genotypes D4 and D8 were endemic and co-circulated in 2011-2013: study results show that genotype D4 disappeared during 2013. Sporadic cases were associated to genotype B3 during 2011-2013, which became endemic in Italy during 2014 and co-circulated with D8 until 2015. Sporadic cases were found belonging to genotypes D9 and H1 all over the period in exam. Similar trend has been observed in European WHO Region.

In 2013, the majority of the WHO/EUR countries reported an annual incidence of >1 case per one million population indicating that the elimination target is far from being met. Thus, there is the urgent need to uncover and analyze chains of measles virus (MV) transmission with the objective to identify vulnerable groups and avoid possible routes of introduction of MV variants in the European population. The analysis of molecular epidemiology of MV B3 strains identified in 2014 has shown that four different variants co-circulated in Italy, including the strain that caused a cruise-line ship outbreak at the beginning of the year