Immunopathology of galectin-3: an increasingly promising target in COVID-19.

The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the "Cytokine Storm Syndrome" (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages in vitro, and as such may hold promise in reducing the incidence of CSS. In addition, Gal-3 inhibition shows promise in reducing transforming growth factor ß (TGF-ß) mediated pulmonary fibrosis, likely to be a major consequence in survivors of severe COVID-19. Finally, a key domain in the spike protein of SARS-CoV2 has been shown to bind N-acetylneuraminic acid (Neu5Ac), a process that may be essential to cell entry by the virus. This Neu5Ac-binding domain shares striking morphological, sequence, and functional similarities with human Gal-3. Here we provide an updated review of the literature linking Gal-3 to COVID-19 pathogenesis. Dually targeting galectins and the Neu5Ac-binding domain of SARS-CoV2 shows tentative promise in several stages of the disease: preventing viral entry, modulating the host immune response, and reducing the post-infectious incidence of pulmonary fibrosis.

Is periodontal disease a risk factor for developing severe Covid-19 infection? The potential role of Galectin-3.

IMPACT STATEMENT: There could be a close relationship between periodontal diseases (PDs) severity and Covid-19 infections. This relationship could be caused by Galectin-3-mediated increased immune response and increased viral attachment. Keeping PDs under control and maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period is very important.Patients with older age and pre-existing conditions like cardiovascular disease, hypertension, diabetes, and obesity are in the higher risk group for developing severe Covid-19 infections. The inflammatory pathways that are involved in these conditions are the same pathways that we see in periodontal diseases (PDs). This raises a significant question: Is PD a pre-existing condition that can increase the risk of developing severe Covid-19 infection? Several studies have shown that Galectins play a key role in the homeostasis of immune cells, and recently, a relationship was found between Covid-19 and Galectin-3 (Gal-3).It has been determined that an important area in the spike protein of Coronavirus-19 is almost exactly the same as the morphology of Gal-3, and these spike proteins are critical for the entry of the virus into host cells. We suspect that there is enough evidence to support a close relationship between PDs severity and Covid-19 infections. There is accumulating evidence to suggest a relationship between the severity of PD and the risk of infection with Covid-19, which requires further investigation. This relationship could be caused by Gal-3-mediated increased immune response and increased viral attachment. In this context, we want to emphasize the importance of keeping PD under control by maintaining rigorous oral hygiene during this troubled Covid-19 pandemic period. We would also like to point out the possibility that having PD may be a pre-disposition toward developing a severe Covid-19 infection.