G6PD deficiency and severity of COVID19 pneumonia and acute respiratory distress syndrome: tip of the iceberg?

The severe pneumonia caused by the human coronavirus (hCoV)-SARS-CoV-2 has inflicted heavy casualties, especially among the elderly and those with co-morbid illnesses irrespective of their age. The high mortality in African-Americans and males, in general, raises the concern for a possible X-linked mediated process that could affect the viral pathogenesis and the immune system. We hypothesized that G6PD, the most common X-linked enzyme deficiency, associated with redox status, may have a role in severity of pneumonia. Retrospective chart review was performed in hospitalized patients with COVID19 pneumonia needing supplemental oxygen. A total of 17 patients were evaluated: six with G6PD deficiency (G6PDd) and 11 with normal levels. The two groups (normal and G6PDd) were comparable in terms of age, sex, co-morbidities, and laboratory parameters-LDH, IL-6, CRP, and ferritin, respectively. Thirteen patients needed ventilatory support ; 8 in the normal group and 5 in the G6PDd group (72% vs.83%). The main differences indicating increasing severity in normal vs. G6PDd groups included G6PD levels (12.2 vs. 5.6, P = 0.0002), PaO2/FiO2 ratio (159 vs. 108, P = 0.05), days on mechanical ventilation (10.25 vs. 21 days P = 0.04), hemoglobin level (10 vs. 8.1 P = 0.03), and hematocrit (32 vs. 26 P = 0.015). Only one patient with G6PDd died; 16 were discharged home. Our clinical series ascribes a possible biological role for G6PDd in SARS-CoV2 viral proliferation. It is imperative that further studies are performed to understand the interplay between the viral and host factors in G6PDd that may lead to disparity in outcomes. KEY POINTS: • COVID19 studies show higher mortality in men, due to severe pneumonia and ARDS, indicating possible X-linked mediated differences • G6PD, the most common X-linked enzymopathy, highly prevalent in African Americans and Italians, maintains redox homeostasis. • Preclinical studies using G6PD deficient (G6PDd) cells infected with human coronavirus (hCoV), show impaired cellular responses, viral proliferation and worsening oxidative damage. • Retrospective chart review in hospitalized patients with COVID19 pneumonia needing supplemental oxygen shows differences between the two groups (Normal and G6PDd) in hematological indices; the G6PDdgroup demonstrated prolonged PaO2/FiO2 ratio, and longer days on mechanical ventilation indicating the severity of the pneumonia.

Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide.

BACKGROUND: Aviptadil, a synthetic form of human vasoactive intestinal peptide, has entered clinical trials to treat critical coronavirus disease 2019 pneumonia with respiratory failure. Vasoactive intestinal peptide protects the lung against a broad array of injuries by binding to the vasoactive intestinal peptide receptor 1 receptor of alveolar type II cells, the cells that severe acute respiratory syndrome coronavirus 2 binds to. As the role of Aviptadil in treating pregnant patients with critical coronavirus disease 2019 pneumonia is unknown, the authors report successful treatment in such a patient who is ineligible for phase 3 trials of Aviptadil. CASE SUMMARY: Under an open-label Food and Drug Administration-approved Expanded Access Protocol NCT04453839, a 32-year-old female patient Gravida 6 Para 4 at 27-week gestation, body mass index 42.5 kg/m2, admitted to the ICU of a quaternary care hospital with critical coronavirus disease 2019 was treated in January 2021 and followed for 4 months post-ICU admission. Standard of care included remdesivir, methylprednisolone, enoxaparin, and inhaled epoprostenol. In addition, the patient received three successive 12-hour IV infusions of Aviptadil at 50/100/150 pmol/kg/hr escalating doses, per randomized clinical trial NCT04311697. Human subjects' protection was overseen by the Institutional Review Board of the Houston Methodist Hospital. The patient was enrolled in the treatment and was given informed consent approved by the Food and Drug Administration and the Institutional Review Board. Data on the patient was incorporated based on her consent for de-identified data to be used in research given at the time of hospital admission in a manner approved by the Institutional Review Board (PRO00025607). Baseline inflammatory markers, arterial blood gases, radiologic imaging, oxygen requirements, Pao2/Fio2, continuous fetal monitoring at baseline, throughout the patient's treatment with the investigational drug, and throughout the patient's hospital course. CONCLUSION: The rapid clinical improvement seen in this patient treated with IV vasoactive intestinal peptide is consistent with the theory that vasoactive intestinal peptide protects the alveolar type II cell, ameliorates cytokine storm, and improves oxygenation in acute lung injury. This specific role of vasoactive intestinal peptide in the lung may be vital to combating the lethal effects of severe acute respiratory syndrome coronavirus 2 infection. In addition, the role of vasoactive intestinal peptide in the human maternal-fetal interface suggests that vasoactive intestinal peptide is a safe treatment of severe coronavirus disease 2019 respiratory failure during pregnancy.