As the cases of severe COVID-19 decline, long COVID is emerging as the major complication of SARS CoV2 infection. We have reasoned that the dysregulated immune response characterising acute COVID-19 is unlikely to resolve in an orderly fashion and that persistence of some features may be present in patients with long COVID. We have extended our landmark acute COVID-19 studies [1, 2], following up 53 patients one year into convalescence. This unique cohort includes 30 people who are fully recovered and 23 with long COVID. All have been evaluated by multi-parameter flow cytometry and a subset have had B cell receptor repertoire sequencing. The main perturbations of B/T cell phenotypes in acute COVID-19 resolve, however, there was an unexpected peak in the complementarity determining region of the B cell receptor repertoire in long COVID patients. Interestingly, the consensus sequence is an 82% match to spike protein monoclonal antibody sequences (Figure 1) and only present in IgM and IgD receptors. This implies that patients with long COVID have a different humoral response to those with a full recovery from acute COVID-19.

References:
[1] Mann ER, Menon M, Knight SB, et al. Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19. Sci Immunol. 2020;5(51).
[2] Shuwa HA, Shaw TN, Knight SB, et al. Alterations in T and B cell function persist in convalescent COVID-19 patients. Med (N Y). 2021;2(6):720-35 e4.