The 'X' Factor: Exploring COVID-19 Viral Shedding in X-Linked Agammaglobulinemia. Can PCR Cell Cycle Threshold Play a Role?

Abstract

Coronavirus Disease 2019 (COVID-19) is known to have severe outcomes in patients with underlying comorbidities. Particularly, patients with compromised humoral immunity may face an increased risk for severe illness, as antibodies are essential for antiviral responses. Here, we present a COVID-19 patient with Bruton's X-linked agammaglobulinemia (XLA). A 46-year-old male with XLA receiving immunoglobulin replacement (IVIG) every three weeks, who contracted COVID-19 1-month ago, was admitted for 10-days of severe diarrhea and 3-days of exertional dyspnea. Repeat SARS-Co-V-2 PCR on admission was positive. Workup showed leukopenia and negative blood cultures. CT Chest Angiogram, performed for elevated D-dimer, revealed patchy bilateral ground-glass opacities, suggestive of viral/atypical pneumonia without pulmonary embolism. He received a 7-day course of Ceftriaxone and Azithromycin for community-acquired pneumonia and IVIG for low immunoglobulin levels. CT Abdomen and Pelvis, as well as a workup for infectious causes of diarrhea, were unremarkable. Colonoscopy ruled out microscopic and inflammatory colitis. Two stool SARS-Co-V-2 PCRs were negative. COVID IgG was negative, so he received COVID-19 Convalescent Plasma (CCP). Given his persistent fever spikes, bronchoscopy was performed, which was unremarkable;however, the bronchoalveolar lavage sample was positive for SARS-Co-V-2 PCR. The patient was hypoxemic and was started on Dexamethasone 6mg for 10-days. He was not a candidate for Remdesivir due to his delayed presentation. Tagged white blood cell (WBC) nuclear scan revealed mild pneumonia and mild sigmoid colonic WBC accumulation. The patient underwent prolonged hospitalization before improvement. As per the CDC's current recommendation to discontinue isolation 10-days from symptom onset, his isolation precautions were discontinued on the 16th day of hospitalization, 42 days after the first SARS-CoV-2 positive test. Given his underlying immunodeficiency, there was high suspicion that the patient was still infectious, putting frontline healthcare workers at risk. This was confirmed when an RT-PCR cell cycle threshold value (Ct) of 10.03 was obtained, which correlates to a highly culturable viral load and a highly infectious state. Isolation precautions were reinstated, and he was later discharged after another dose of CCP. Strict self-isolation for an additional ten days was advised. In summary, this patient with XLA had a lengthy hospital stay and prolonged viral shedding, likely due to an insufficient antibody response. In such patients, caution must be exercised when following the CDC recommendations for removing isolation precautions. RT-PCR Ct could be a valuable proxy in evaluating the state of infection and implementing appropriate infection control measures.