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Hypogammaglobulinemia Complicating Post-Acute Sequelae of COVID-19 (PASC).
Hypogammaglobulinemia (HGG) is a known complication in some patients on B cell depleting (BCD) therapies, but its impact on the development of post-acute sequelae of COVID (PASC) has not been previously examined. The recent identification that decreased levels of IgM and IgG3 are signature markers for development of PASC prompted examination of occurrence of PASC in this population of patients known to be prone to develop HGG.
Objectives:
To examine the impact of long COVID on immunoglobulin (Ig) levels in patients on BCD therapies and highlight the importance of early identification of HGG and initiation of appropriate replacement therapy for sustained recovery in these patients.
Methods:
We monitored serum Ig levels in patients on BCD therapies who developed COVID-19 and PASC. Three such patients are reported.
Results:
Each patient displayed low to lower limit of normal baseline for IgG and IgM prior to infection. Persistent decline in IgG levels from pre-COVID baseline was appreciated immediately following COVID-19 infection in every patient, each dropping below 400 mg/dL. There was also a decline in IgM titers from pre-COVID level in each patient. Following discontinuation of BCD therapy, return of B-cells to normal levels was observed in one patient who remained HGG but a good IgG response to SARS-CoV-2 spike protein following vaccination was documented despite the persisting HGG. The second patient was unable to respond to vaccination and the third patient declined vaccination. The third patient received passive immunization with monoclonal antibody.
Conclusions:
HGG seen with BCD therapy can be exacerbated by COVID-19 infection, and prompt recognition and treatment can be lifesaving especially with secondary bacterial pneumonias. These three patients illustrate that low levels of IgG and IgM may be markers for the development of long-COVID. Subsequently, patients who are on BCD with HGG are at high-risk to develop PASC and secondary infections. Further, the presence of HGG should not be a deterrent to vaccination since some patients on BCD therapy may mount a good humoral response to vaccination. It is important to monitor the response to vaccination since supplemental monoclonal antiviral antibodies can provide immune protection in individuals who do not respond adequately to vaccination, or who decline vaccination altogether.