Serological investigation of SARS-CoV-2 infection in patients with suspect measles, 2017-2022

Background: Several studies suggested that SARS-CoV-2 was already spreading worldwide during the last months of 2019 before the first outbreak was detected in Wuhan, China. Lombardy (Northern Italy) was the first European region with sustained SARS-CoV-2 transmission and recent investigations detected SARS-CoV-2-RNA-positive patients in Lombardy since late 2019. Methods: We tested for anti-SARS-CoV-2 IgG all serum samples available in our laboratory (N = 235, collected between March 2017 and March 2022) that we received within the framework of measles/rubella surveillance from measles and rubella virus-negative patients. Results: Thirteen of 235 samples (5.5%) were IgG-positive. The positivity rate increased starting in 2019 and was significantly different from the expected false positive rate from 2019 onwards. Additionally, in 2019 the percentage of IgG-positive patients was significantly lower among SARS-CoV-2 RNA-negative patients (3/92) compared to SARS-CoV-2 RNA-positive patients (2/7, p = 0.04). The highest percentage of IgG positivity in the pre-pandemic period was recorded during the second half of 2019. This coincided with an increase in negativity for measles and a widening of the peak of the number of measles discarded cases per 100,000 inhabitants, indicating a higher-than-normal number of measles-negative patients experiencing fever and rash. This also coincided with the first patient positive for SARS-CoV-2 RNA (September 12th, 2019); this patient was also positive for anti-SARS-CoV-2 IgG and IgM. Conclusions: Although the number of samples was low and one cannot conclusively establish that the virus started circulating in Lombardy around September 2019, our findings should stimulate similar research investigating the possibility of undetected SARS-CoV-2 pre-pandemic circulation.