Impaired humoral immunity is associated with prolonged COVID-19 despite robust CD8 T cell responses

Coronavirus Disease-2019 in the Immunocompromised Host

“…In addition to impaired cellular immunity, immunocompromised hosts may have diminished humoral immunity, defined by an impaired ability to produce pathogen-specific antibodies against COVID-19 and other pathogens. For example, a study of 103 cancer patients showed that delayed viral clearance was associated with loss of antibody production, despite adequate T cell response to infection 17 . Prolonged viremia was driven by B-cell depletion, potentially indicating that resolution of infection depends upon adequate humoral immunity.…”

Re: ‘the unique COVID-19 presentation of patients with B cell depletion’ by Belkin et al.

“…It has been described that CD8+ T-cell response is responsible for the course of acute infection, while humoral B-lymphocyte response together with a robust CD4+ T-cell response are necessary to achieve long-lasting viral clearance. Therefore, patients with B cell depletion are associated with prolonged viral replication ( 5 ). The prolonged presence of the virus in respiratory cells and its sustained replication may cause a local and systemic inflammatory response, which results in recurrent and relapsing symptoms in these patients, which can sometimes progress to more severe forms of COVID-19 due to exaggerated release of cytokines, as occurs in the general population or other immunocompromised patients.…”

“…We believe that the mainstay of treatment for this entity should target viral replication, and therefore should focus on antiviral drugs. In our experience, when these patients are treated with immunomodulatory drugs, they initially improve, but frequently present later with a new relapse ( 4 ) We also believe that the combination of antiviral drugs with effective monoclonal antibodies or hyperimmune plasma is important, therapies that compensate the impair of these patients to mount an adequate humoral response, so necessary to achieve viral clearance ( 5 ).…”

CD8+ T cells: An ineffective armor against prolonged COVID-19 in cancer patients

“…

In a diverse cohort of cancer patients, Lyudovyk et al 1 show that persistent COVID-19 infection is associated with weaker humoral responses and increased CD8 + T cell responses that are ineffective in clearing virus, particularly in patients receiving B cell-depleting therapies.

…”

“…To characterize the factors impacting immune recovery from COVID-19, Lyudovyk et al performed a multimodal analysis on blood samples collected longitudinally in a mixed cohort of more than 100 solidtumor and heme-malignancy patients who developed COVID-19 and recovered clinically. 1 Prolonged SARS-CoV-2 posi-tivity (i.e., a positive SARS-CoV-2 PCR test R30 days after the initial positive test) was observed in 22% of patients overall but was significantly more common in the patients with hematologic malignancies. The clinical relevance of persistent PCR positivity is highlighted by the fact that 18% of patients who initially were considered convalescent subsequently required re-hospitalization, and that 8% of patients ultimately died of COVID-19.…”