The recent SARS‐CoV‐2 pandemic, which has recently affected Italy since February 21, constitutes a threat to normal subjects, as the coronavirus disease‐19 (COVID‐19) can manifest with a broad spectrum of clinical phenotypes ranging from asymptomatic cases to pneumonia or even death. There is evidence that older age and several comorbidities can affect the risk to develop severe pneumonia and possibly the need of mechanic ventilation in subjects infected with SARS‐CoV‐2. Therefore, we evaluated the outcome of SARS‐CoV‐2 infection in patients with inborn errors of immunity (IEI) such as X‐linked agammaglobulinemia (XLA).

When the SARS‐CoV‐2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS‐CoV‐2 search by nasopharyngeal swab in patients presenting with symptoms that could be a manifestation of COVID‐19, such as fever, cough, diarrhea, or vomiting.

We describe two patients with X‐linked agammaglobulinemia (XLA) aged 34 and 26 years with complete absence of B cells from peripheral blood who developed COVID‐19, as diagnosed by SARS‐CoV‐2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough, and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care.

Our report suggests that XLA patients might present with high risk to develop pneumonia after SARS‐CoV‐2 infection, but can recover from infection, suggesting that B‐cell response might be important, but is not strictly required to overcome the disease. However, there is a need for larger observational studies to extend these conclusions to other patients with similar genetic immune defects.