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COVID-19 is an infectious disease caused by a single-stranded RNA (ssRNA) virus, known as SARS-CoV-2. The disease, since its first outbreak in Wuhan, China, in December 2019, has led to a global pandemic. The pharmaceutical industry has developed several vaccines, of different vector technologies, against the virus. Of note, among these vaccines, seven have been fully approved by WHO. However, despite the benefits of COVID-19 vaccination, some rare adverse effects have been reported and have been associated with the use of the vaccines developed against SARS-CoV-2, especially those based on mRNA and non-replicating viral vector technology. Rare adverse events reported include allergic and anaphylactic reactions, thrombosis and thrombocytopenia, myocarditis, Bell’s palsy, transient myelitis, Guillen-Barre syndrome, recurrences of herpes-zoster, autoimmunity flares, epilepsy, and tachycardia. In this review, we discuss the potential molecular mechanisms leading to these rare adverse events of interest and we also attempt an association with the various vaccine components and platforms. A better understanding of the underlying mechanisms, according to which the vaccines cause side effects, in conjunction with the identification of the vaccine components and/or platforms that are responsible for these reactions, in terms of pharmacovigilance, could probably enable the improvement of future vaccines against COVID-19 and/or even other pathological conditions.

Protein replacement therapy is an umbrella term used for medical treatments that aim to substitute or replenish specific protein deficiencies that result either from the protein being absent or non-functional due to mutations in affected patients. Traditionally, such an approach requires a well characterized but arduous and expensive protein production procedure that employs in vitro expression and translation of the pharmaceutical protein in host cells, followed by extensive purification steps. In the wake of the SARS-CoV-2 pandemic, mRNA-based pharmaceuticals were recruited to achieve rapid in vivo production of antigens, proving that the in vivo translation of exogenously administered mRNA is nowadays a viable therapeutic option. In addition, the urgency of the situation and worldwide demand for mRNA-based medicine has led to an evolution in relevant technologies, such as in vitro transcription and nanolipid carriers. In this review, we present preclinical and clinical applications of mRNA as a tool for protein replacement therapy, alongside with information pertaining to the manufacture of modified mRNA through in vitro transcription, carriers employed for its intracellular delivery and critical quality attributes pertaining to the finished product.

Double Negative (DN) B cells constitute a B cell population that lacks expression of immunoglobulin D and CD27 memory marker. These cells expand in elderly healthy individuals, but also accumulate prematurely in autoimmune and infectious diseases. COVID-19 is a pandemic infectious disease caused by SARS-CoV-2, a coronavirus that was first observed in Wuhan, China in December 2019. In its more severe cases, COVID-19 causes severe pneumonia and acute respiratory syndrome with high morbidity and mortality. Recent studies have revealed that the extrafollicular DN2 B cell subset, previously described in lupus patients, does also expand in severe and/or critical groups of COVID-19 patients. These DN2 cells correlate with disease severity and laboratory parameters of inflammation. However, their exact role and function in COVID-19 require to be further investigated. In this review, we highlight the DN immune responses in both rheumatic diseases and COVID-19, and we point out the importance of clarifying DN’s role in the immunopathology of the aforementioned infection, as it could probably enable better management of rheumatic diseases during the pandemic. Of note, the symptomatology of COVID-19, as well as the potential outcome of death, have given rise to a worldwide concern and scare of exposition to SARS-CoV-2, especially among the rheumatological patients who believe to be at higher risk due to their immunological background and the immunosuppressive therapies. Nevertheless, there is no convincing evidence so far that these patients are truly at higher risk than others.