key: cord-0768683-20zkkrys authors: Kow, Chia Siang; Ramachandram, Dinesh Sangarran; Hasan, Syed Shahzad title: Ingestion of beta‐glucans could stimulate longer‐lasting cellular immunity upon administration of COVID‐19 vaccines date: 2021-10-05 journal: J Food Biochem DOI: 10.1111/jfbc.13959 sha: 7056d5ead0d7a58aab213ee18086f177556ceeb1 doc_id: 768683 cord_uid: 20zkkrys nan We read with interest the article by Basak and Gokhale (2021) which reviewed the immunity boosting nutraceuticals and functional foods in the context of coronavirus disease 2019 , one of them being beta-glucans. The authors described several immunemodulating effects of beta-glucans, and went on to propose that beta-glucans can act as a nutraceutical-based intervention to boost the immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of COVID-19. Indeed, as previously reported, yeast (1,3)-(1,6)-beta-glucan supplements can decrease the incidence of symptomatic common cold infections and also the severity and/or duration of symptomatic upper respiratory tract infection in healthy cohorts (Shokri-Mashhadi et al., 2021) . Nevertheless, considering that the SARS-CoV-2 replicates predominantly in upper respiratory epithelia where angiotensin-converting enzyme 2 is expressed and thus facilitates its cellular entry, it might be too far-fetched to expect the immune-stimulatory activities of beta-glucans to augment adequate antiviral innate immunity to protect against the acquisition of COVID-19. We would like to complement the discussion of the authors (Basak & Gokhale, 2021) about the potential of beta-glucans to stimulate adaptive immunity to protect against the acquisition of COVID-19, which is more relevant in the current context where COVID-19 vaccines have been rolled out. The humoral immunity (mediated by B cells) and cellular immunity (mediated by T cells) are two types of adaptive immune response which are of utmost importance to eliminate SARS-CoV-2. Nevertheless, the relative contribution of B cells and T cells to the immunity to SARS-CoV-2 merits further discus- in patients with COVID-19 after clearance of SARS-CoV-2 infection (Sharma et al., 2020; Ward et al., 2021) . For instance, a community study in England of over 365,000 adults demonstrated that adjusted antibody prevalence declined from 6.0% to 4.4%, which represents a fall of 26.5% over 3 months of the study (Ward et al., 2021) . In a population-based seroepidemiological study in India of over 12,000 adults, it was reported that adjusted antibody prevalence declined from 28.4% to 24.7%, which represents a fall of 13.0% over 3 months of the study (Sharma et al., 2020) . Attention has thus been shifted toward cellular immunity, which has been previously reported to maintain for a longer period than the humoral immunity in patients infected with SARS-CoV-1 (Channappanavar et al., 2014) . Indeed, available studies to date T-cell responses over the same period (Bilich et al., 2021) . the key for COVID-19 vaccines to provide long-term protection. In fact, there is a recent study which investigated T cell immunity in patients with documented SARS-CoV-2 infection and individuals who had been fully vaccinated with BNT162b2 vaccine (1 month after the second vaccine dose) reported that induced T cell reactivity to Spike-specific peptides in vaccinated individuals was equivalent to that of infected patients after recovery (Jordan et al., 2021) . We are still learning how long can the available vaccines protect against COVID-19 in real-world conditions, especially on hospitalization and death from COVID-19. However, based on current observations, vaccine adjuvants that could specifically stimulate T-cell responses should be explored. In addition to its ability to promote trained immunity, beta-glucan could also augment cellular immunity, and has been previously touted to be promising as oral anti-infective vaccine adjuvants (Jin et al., 2018) . β-Glucans as vaccine adjuvants have been found to enhance the immunogenicity of hepatitis B vaccine and influenza vaccine in animal studies (Dong et al., 2007; Le et al., 2011) . Indeed, the potential of oral beta-glucans supplementation to stimulate cellular immunity upon administration of COVID-19 vaccines to provide long-term protection is suggested in an observational study of healthy adults aged 50 or older, whereby supplementation with active hexose correlated compound (mixture of alpha-and betaglucans; 3 g/day for 60 days) increased the frequency of peripheral CD4+ and CD8+ T cells producing interferon-gamma and/or tumor necrosis factor-alpha at 30 and 60 days compared to baseline and such findings were still observed at 30 days upon discontinuing the supplementation (Yin et al., 2010) . In the current context where herd immunity should be achieved as soon as possible due to the emergence of different variants of concern of SARS-CoV-2 which might one day completely escape neutralization by the available COVID-19 vaccines, attention should be focused on the armamentarium that we possess currently, where we can recommend oral beta-glucans supplementation among Immunity boosting nutraceuticals: Current trends and challenges T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection Specific immune response to HBsAg is enhanced by beta-glucan oligosaccharide containing an alpha-(1->3)-linked bond and biased towards M2/Th2 February). β-glucans: Wide-spectrum immunebalancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach to COVID-19 β-glucans as potential immunoadjuvants: A review on the adjuvanticity, structure-activity relationship and receptor recognition properties T cell immune responses to SARS-CoV-2 and variants of concern (Alpha and Delta) in infected and vaccinated individuals The adjuvant effect of Sophy β-glucan to the antibody response in poultry immunized by the avian influenza A H5N1 and H5N2 vaccines The seroprevalence and trends of SARS-CoV-2 in Delhi, India: A repeated population-based seroepidemiological study Effects of select dietary supplements on the prevention and treatment of viral respiratory tract infections: A systematic review of randomized controlled trials Prevalence of antibody positivity to SARS-CoV-2 following the first peak of infection in England: Serial cross-sectional studies of 365,000 adults. The Lancet Regional Health -Europe, 4, 100098 Effects of active hexose correlated compound on frequency of CD4+ and CD8+ T cells producing interferon-γ and/or tumor necrosis factor-α in healthy adults Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection