Positive outcome in a patient with coronavirus disease 2019 and common variable immunodeficiency after intravenous immunoglobulin

We present a case of a patient with immunodeficiency who has recovered from coronavirus disease 2019 (COVID-19). The patient is a 53-year-old woman who received a diagnosis of common variable immunodeficiency in 1996 and has been on regular intravenous immunoglobulin (IVIG) replacement therapy with Gamunex-C 40 g (520 mg/kg/dose) every 2 weeks. The last immunoglobulin G trough level was 1478 mg/dL on November 12, 2019, and a high-dose influenza vaccine was administered in September 2019. The patient also has hypothyroidism, bronchiectasis, and Sjogren's syndrome treated with hydroxychloroquine 400 mg daily. Her last chest computed tomography (CT) scan in March 2018 revealed mild central bronchiectasis. On March 13, 2020, the patient received her routine scheduled IVIG infusion, and on March 16, 2020, the patient reported that her spouse was in contact with a patient with COVID-19 and that he was feeling ill.

The patient presented to the emergency department on March 17, 2020, with complaints of fever, chills, productive cough, shortness of breath, nausea, vomiting, and diarrhea. She appeared well on admission without evidence of respiratory distress. Her chest CT scan revealed multifocal, bilateral, patchy, and confluent ground-glass opacities with interlobular septal thickening and microvascular dilatation sign—all characteristic of the COVID-19 pulmonary infection.

Initial laboratory results revealed leukopenia (lymphopenia), normal coagulation profile, electrolytes, and liver function. Influenza/respiratory syncytial virus panels were negative. The patient was admitted to a regular nursing floor and started receiving ceftriaxone and doxycycline. At this time, we decided to administer another 40-g dose of IVIG.

On day 2 of hospitalization, she required 2 L/min oxygen by nasal cannula. On day 5, the patient had an increased oxygen requirement and was transferred to the intensive care unit. Her respiratory status worsened and needed escalation of support to noninvasive positive pressure ventilation/continuous positive airway pressure, and ultimately, intubation and mechanical ventilation on hospital day 7. Her medical treatment included ceftriaxone and doxycycline for the duration of hospitalization and hydroxychloroquine, which was increased from her home regimen to 600 mg/d. She was successfully weaned and extubated on hospital day 13. On day 14, the second dose of 40-g IVIG was administered, after which, the patient was discharged home to self-quarantine owing to a positive repeat COVID-19 testing. The patient never received any convalescent COVID-19 plasma.

The underlying pathophysiology of COVID-19 is under investigation in animal models. It seems that the virus induces an inflammatory response involving macrophage hyperactivation, leading to a cytokine storm responsible for severe lung and systemic complications, making IVIG's anti-inflammatory effect potentially useful in treating COVID-19,^{1 , 2} especially in cases of severe COVID-19 associated with lymphopenia and increased cytokine levels.³

We present a case of COVID-19 at a very high risk for morbidity and mortality secondary to underlying immunodeficiency and bronchiectasis. Despite presenting with classical pneumonia requiring intubation and mechanical ventilation, the patient recovered completely and had a relatively short hospital course. Patients who have had similar courses had a reported mortality rate of 49% to 97%.^{4 , 5} It is hard to ascertain if this was a result of the hydroxychloroquine, high-dose IVIG, or a combination of both. In addition, IVIG has been shown to have an immunomodulatory, anti-inflammatory effect especially if given in higher doses. The exact mechanism is still unknown, but it has been suggested that it occurs through an Fc-mediated mechanism or Fab-mediated mechanisms.⁶ Azithromycin was not included in the patient's therapy owing to a history of allergic reaction to the antibiotic. Hydroxychloroquine has been found to be associated with viral load reduction/disappearance and its effects reinforced by azithromycin in a small group of patients⁷ However, its efficacy in improving clinical course is yet to be determined.

Our findings suggest that the early administration of IVIG may be beneficial in improving the outcome of this illness, especially in patients with an immunodeficiency disorder. A similar report of 3 patients from the People's Republic of China noted that high-dose IVIG had a significant impact on improving symptoms, fever curve, and lymphopenia,⁸ although the selected patients in that report were not immunodeficient. We speculate that IVIG, in addition to its immunomodulatory effect, may contain antibodies to other coronaviruses that are cross-reactive with COVID-19. This might lead to modulation of the severity of the illness similar to what is observed in the pediatric population who, in general, present with a milder form of this disease that is speculated to be secondary to previous exposure to other coronavirus infection.