key: cord-0888466-kp8re2cn authors: Oshiro, Telma Miyuki; da Silva, Lais Teodoro; Ortega, Marina Mazzilli; Perazzio, Sandro Felix; Duarte, Alberto Jose da Silva; Carneiro-Sampaio, Magda title: Patient with agammaglobulinemia produces anti-SARS-CoV-2 reactive T-cells after CoronaVac vaccine date: 2022-02-02 journal: Clinics (Sao Paulo) DOI: 10.1016/j.clinsp.2022.100007 sha: c98803eda56863536df2f7ed1dbb0560722c5aeb doc_id: 888466 cord_uid: kp8re2cn nan low mature B lymphocytes in blood and tissues. [3] XLA is caused by BTK gene mutations, which code the Bruton or B-cell Tyrosine Kinase (BTK) protein, and plays a pivotal role in pro-and pre-B cell maturation. BTK loss-of-function mutation interferes with B cell development resulting in very low (or absent) levels of serum and mucosal immunoglobulins and high susceptibility to extracellular bacterial, entero-, and respiratory viruses' infections. [4] On the other hand, T-cells are normal in number and functions, with no change in their proliferative responses to antigens. [5] Previous reports have demonstrated that XLA patients are at risk of severe disease with SARS-CoV-2 infection. Authors related clinical symptoms with important inflammatory marker increase, associated with long viral persistence, suggesting a role for antibodies in reduction of viral load. [6, 7] Ponsford et al. (2021) observed that XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant risk of novel variant evolution. [6, 7] Vaccination is a safe and effective tool to induce a protective immune response in immunocompetent individuals. Immunocompromised patients, in turn, have an increased susceptibility to vaccine-preventable infections, [8, 9] As expected, no detectable levels of serological antibodies were observed. On the other hand, IFN-γ production by T-lymphocytes was comparable to samples from 36 vaccinated age-matched health controls, who also received 2 CoronaVac doses, presenting the same median value of healthy individuals (Fig. 1) . Vaccine-induced immunity depends on a complex and multifaceted mechanism involving many immune components. However, single components, such as antibody responses, are often accepted as an immune correlate of protection, mainly because serologies are accessible and practical tests. [11] In fact, as most vaccines under current use, the immunizing agent's effectiveness has been commonly related to its ability to induce specific antibody production. Specific T-cell mediated immunity has been rarely assessed due to technical complexity and high costs A recent publication has shown evidence for neutralizing SARS-CoV-2 antibodies as protective correlates for COVID-19 vaccines. [12] On the other hand, serological tests for antibodies are not a precise indicator of the complexity and durability of immune memory to SARS-CoV-2 (ref). In fact, sustained T-cell immunity, despite a decline in antibody response, was observed months after infection, [13, 14] suggesting that other immune components can contribute to protective immunity. Moreover, a robust T-cell response was observed in IEI patients after infection with SARS-CoV-2, [15] showing the contribution of other immune compartments in the protective response. Together, these emphasize the need for cellular response assessment in individuals with antibody deficiency for a better understanding of the anti-SARS-CoV-2 viral or vaccine-induced immune response. Some studies have shown that mRNA-based vaccines are able to stimulate a cellular response in IEI patients, although therapies being used and gene defects may affect vaccine immunogenicity. [16] Interestingly, particularly for XLA patients, immunization with the mRNA-based vaccine BNT162b2 (Pfizer Biontech) resulted in a robust T-cell response comparable to healthy donors. [17, 18] This case report highlights the relevance of immunizing patients with antibody production disorders. To our knowledge, this is the first description of cellular response in an XLA patient immunized with CoronaVac. The authors declare no conflicts of interest. New primary immunodeficiencies 2021 context and future Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene X-linked agammaglobulinemia COVID-19 and X-linked agammaglobulinemia (XLA) -insights from a monogenic antibody deficiency Increased Respiratory Viral Detection and Symptom Burden Among Patients with Primary Antibody Deficiency: Results from the BIPAD Study Vaccination in Primary Immunodeficiency Disorders ESID positions on SARS-CoV-2 infections in Inborn errors of immunity A correlate of protection for SARS-CoV-2 vaccines is urgently needed Evidence for antibody as a protective correlate for COVID-19 vaccines Decline in neutralising antibody responses, but sustained T-cell immunity, in COVID-19 patients at 7 months postinfection Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery Robust Antibody and T Cell Responses to SARS-CoV-2 in Patients with Antibody Deficiency Antibody responses to the SARS-CoV-2 vaccine in individuals with various inborn errors of immunity SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity PBMCs from CoronaVac vaccinated healthy donors (gray triangles) (n=36) and the XLA patient (black triangle) were incubated for 18h with a mixture of grouped SARS-CoV-2 peptide pools (membrane, nucleocapsid and spike) at a final concentration of 1 μg/mL Scatterplots show lines at the median with interquartile ranges. IFN-γ production was analyzed by intracellular flow cytometry