key: cord-0860009-fnssoa6u
authors: Pozzi, Maria Rosa; Baronio, Manuela; Janetti, Maria Bianchi; Gazzurelli, Luisa; Moratto, Daniele; Chiarini, Marco; Plebani, Alessandro; Lougaris, Vassilios
title: Fatal SARS-CoV-2 infection in a male patient with Good's syndrome
date: 2020-12-08
journal: Clin Immunol
DOI: 10.1016/j.clim.2020.108644
sha: 998d30bd6ed8a0a08f662cad45ae2d93a50e3b6e
doc_id: 860009
cord_uid: fnssoa6u

• This study describes for the first time the clinical course of SARS-CoV-2 infection in a male patient affected with Good's syndrome.

The authors declare no conflict of interest.

Good's syndrome (GS) is a rare disorder that typically affects both sexes after the 5 th decade of life.

GS is characterized by the presence of thymoma associated with hypogammaglobulinemia and low to absent peripheral B cells in most cases [1, 2] . In addition, altered T cell function in the presence of normal or elevated T cell counts has been reported [1, 2] . Opportunistic and viral infections may complicate the clinical course of affected patients and frequently lead to exitus [1, 2] . Recently, a novel virus, namely SARS-CoV-2, has been identified as responsible for a pandemic causing millions of affected patients and more than 1 million of deaths worldwide [3] . To date, no cases of patients with GS and COVID-19 have been reported. We report on the first GS patient that was infected with SARS-CoV-2 and albeit appropriate treatment was initiated, he succumbed to the infection.

The index patient was a 51 years old male Italian with a positive maternal family history for thymoma and myasthenia gravis. At the age of 48, he was diagnosed with thymoma and underwent surgical excision and left pneumonectomy. Upon dismissal, he presented recurrent respiratory and gastrointestinal infections. The first immunological evaluation showed a reduction of the gammaglobulin peak in serum electrophoresis with reduced immunoglobulin serum levels: IgG= 351 mg/dl, IgA <8 mg/dl, IgM= 6 mg/dl. He came to our attention at the age of 49. His immunological work-up is summarized in Figure 1A . Briefly, while his differential white blood cell count was normal, evaluation of peripheral lymphocyte subsets showed inversion of the CD4/CD8 ratio with complete lack of peripheral B cells. Proliferative responses to mitogens were normal.

Immunoglobulin serum levels were extremely low for all classes ( Figure 1A ). The patient was diagnosed with Good's syndrome (GS) and was put on facilitated subcutaneous immunoglobulin replacement treatment, with good control of the respiratory infections.

The patient encountered SARS-CoV-2 during the second wave in Italy in November 2020. His initial symptoms were low grade fever, myalgias and asthenia. Nasopharyngeal swab resulted UI/daily was maintained, while azythromycin 500 mg/daily was stopped after six days. According to local COVID-19 treatment guidelines, Remdesivir was not administered due to the interval from symptoms' onset.

The patient responded positively for the following four days, remained afebrile, with normalization of CRP (<3 mg/dl). Ferritin was 659 ng/ml, while IgG were 1022 mg/dl. Oxygen saturation was 96%. Nonetheless, control chest x-ray at day 4 showed some scattered pulmonary opacities on the right lung ( Figure 1C ). Starting on day 6 after admission, the index patient presented breathing difficulty, with an increase of respiratory rate (32/min) that required high flow O 2 administration (fiO 2 50 to 90%). CRP rapidly increased to 19 mg/dl, together with D-Dimer (779 ng/ml) and LDH (554 U/L). Lymphocytes showed transient and mild decrease. Procalcitonin was negative and so were NtproBNP and t-troponin. Blood cultures, Legionella/Pneumococcus urinary antigens and blood galactomann antigen were negative. IgG plasma levels decreased to 790 mg/dl. Broadspectrum antibiotic therapy with Piperacillin-Tazobactam, Linezolid and Levofloxacin was initiated empirically, and intravenous immunoglobulins (30 gr) were administered.

Invasive ventilation with helmet CPAP was started due to severe hypoxemia in O 2 reservoir bag 15 l/min (PaO2 64 mmHg P/F 71) but was not tolerated well from the patient. Pronation protocol was also attempted, even though not well tolerated by the patient. Oro-tracheal intubation was excluded by ICU specialist because of underlying oncological disease and anatomical condition. Subsequent chest X-ray showed progressive extension and consolidation of lung opacities, leading to a "white lung" (Figure 1D ). Palliative therapy to relieve severe respiratory distress was started 24 hours before the death that occurred at day 13.

Recent evidence from patients affected with primary immunodeficiencies that developed COVID-19 suggests that the lack of B cells, as observed in agammaglobulinemic patients (X-linked agammaglobulinemia, XLA; autosomal recessive agammaglobulinemia, ARA), may play a protective role on the evolution of the SARS-CoV-2 infection [4, 5] . Nonetheless, this was not the case for the index patient that completely lacked peripheral B cells but presented a severe clinical course. Considering the diversity of these conditions, GS vs XLA/ARA, this different clinical outcome may be due to T cell, NK cell or other immune cell dysfunction in the setting of GS but may also be related to anatomical alterations due to thymoma and/or lung surgery.

In conclusion, we report on the first patient with GS that developed COVID-19 and despite medical treatment, the viral infection resulted fatal. This should underline the fact that the immunological findings so far reported in COVID-19 patients may not be applicable in all conditions and therefore cautiousness should always be used when SARS-CoV-2 infection affects patients with rare diseases such as GS.

J o u r n a l P r e -p r o o f Journal Pre-proof

Good's syndrome remains a mystery after 55 years: A systematic review of the scientific evidence

Good syndrome: an adult-onset immunodeficiency remarkable for its high incidence of invasive infections and autoimmune complications

COVID-19 pathophysiology: A review

A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia