Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Objective: To evaluate whether the current case-by-case practice leads to sufficient reporting of immunogenicity-related information in the Summary of Product Characteristics (SmPCs) of biological products approved in the European market.Methods: Immunogenicity-related information was identified and extracted from a group of 73 biological drugs that complied with drug-selection criteria. Afterwards, thirteen dichotomous questions were proposed to evaluate whether any issues are being commonly neglected.Results: Most SmPCs (92%) do not have any recommendations on how to report immunogenicity-related adverse drug reactions by patients or healthcare professionals. Furthermore, 80% of SmPCs do not identify the assay used to assess the reported immunogenicity rates, while 81% do not address the possible impact of immunogenicity on their drug's pharmacokinetics. It was also identified that a group factor (i.e. older drugs' SmPCs) could be influencing how/which issues were being addressed by newerdrugs SmPCs. To transform SmPCs into useful tools when an immunogenic response occurs, a proposal on how to report immunogenicity-related information in the SmPCs of biological products is advanced. This tool can be used by patients, healthcare professionals, regulators and businesses to evaluate the information of SmPCs. Conclusions:Based on these results, a case-by-case strategy does not yield enough reporting across products and thus immunogenicity-related information should be reported in a systematic way. Further guidance about reporting immunogenicity-related information is required, else SmPCs will not be the basis of information for healthcare professionals on how to use a biological product safely and effectively.

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Running Heading: Biosimilars as an opportunity to update the Product Information of biological drugs One of the greatest theoretical clinical concerns regarding the development of biosimilars has been that post-translational protein modifications, even while antigen binding remains essentially unaltered, might result in detrimental immunogenicity. We recently demonstrated [1] that the Summary of Product Characteristics (SmPCs) of biological drugs, approved by the European Medicines Agency (EMA), are very heterogeneous regarding the issues related to immunogenicity that are addressed within these documents.A complementary analysis, using the methodology advanced in [1], to the EMA's documents "Procedural steps taken and scientific information after the authorisation" shows that 57% (30/69) of the biological drugs that have been authorized prior to 2012 did not update their SmPC at least once when it comes to information related to unwanted immunogenicity. These are surprising results given the advancements that have been seen in the field of immunogenicity assessment [2], namely in the development of more