ABSTRACT
Purpose: Lung transplant is the last resort for COVID-19 refractory ARDS. Dual organ transplant is seen as a relative contraindication at many institutions. We describe a case of simultaneous Lung-Kidney transplant (SLK) in a patient with COVID-19 ARDS. Method(s): A 24-year-old patient with no PMH presented to an outside hospital with a week of shortness of breath, cough, and fever. Despite treatment with Remdesivir and dexamethasone, the patient developed hypoxemic respiratory failure with acute renal injury requiring ICU care and intubation, V-V ECMO, and dialysis. Additionally, Intravenous and inhaled Aviptadil were given under emergency use authorization. While oxygenation improved, the patient could not be weaned off ECMO. With a LAS score of 90.29, the patient underwent an SLK transplant on HD 53, requiring standard induction and maintenance immunosuppression therapy. The patient was treated post-operatively for PGD as well as for subclinical AMR. After successful inpatient rehabilitation, the patient was discharged home after four months and had a one-month follow-up on room air and normal creatinine clearance. Result(s): Patients with pre-existing renal dysfunction who have undergone lung transplants have a significantly higher one- and three-year mortality than patients with normal GFR. The patient's survival after SLK was similar to isolated lung transplants at one and five years, according to an analysis of the UNOS/OPTN database. Still, dual organ transplant in the COVID-19 ARDS population is considered a contraindication at many centers, given these patients' critical illness and frailty. However, the frailty in this population is reversible due to the rapid onset of disease in an otherwise previously healthy younger population with minimal comorbidities. Thus, multiorgan transplantation should be considered in such a patient population. Our patient received Aviptadil as part of an EIND to stabilize patients and improve oxygenation while waiting on the transplant list. Conclusion(s): We propose that SLK transplantation should be considered for carefully selected patients with COVID-19 ARDS.
ABSTRACT
Background: COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus in alveolar type II cells, inhibits cytokine synthesis, prevents cytopathy, and up regulates surfactant production. Synthetic VIP-aviptadil is a novel strategy to treat patients with COVID-19 and respiratory failure. Methods: This was a prospective, multicenter, randomized, placebo-controlled trial with 196 patients, nasal swab PCR+ for COVID-19 receiving intensive care at 10 U.S. hospitals (6 tertiary care and 4 regional hospitals) to determine if intravenous aviptadil is superior to placebo in achieving recovery from respiratory failure and survival at 60 days post treatment. The analysis was by modified intent to treat (ITT) using a pre-specified logistic regression model. The primary pre-specified endpoint was being alive with no respiratory failure at day 60. Results: There were 213 subjects screened, with 203 eligible and 196 randomized and treated. Baseline characteristics were comparable except for worse NIAID severity for aviptadil (Table 1). All subjects were followed up to 60 days. A favorable trend (OR 1.63;P=.14) was seen for the primary endpoint at 60 days with significance achieved after adjusting for hospital setting. Overall, there was 2.0-fold increased odds of survival (95% CI 1.05-3.88;P<.035) for aviptadil at Day 60 controlling for baseline NIAID score. Odds of survival increased to over 4-fold after adjusting for site of care (Tertiary care vs regional hospital, OR 4.35 (95% CI 1.91, 9.90;P<.035). Logistic regression indicated aviptadil treated patients were also significantly more likely to be discharged earlier than placebo-treated patients (p=0.01). The most common adverse events noted were diarrhea (32.8% vs. 1.5%) and hypotension (26% vs.21.5%) for aviptadil vs. placebo. Additional adverse events occurring more frequently in aviptadil treated patients included acute kidney injury (23.7% vs 20%), hyperkalemia (12.2% vs 6.2%), and atrial fibrillation (11.5% vs 4.6%). Multiple organ dysfunction syndrome (6.9% vs 13.8%) and respiratory failure (12.2% vs 13.8%) occurred more commonly in placebo-treated patients. Conclusion: Treatment with aviptadil demonstrates efficacy in improving the likelihood of recovering from respiratory failure, surviving to 60 days, and reducing hospital stay in critically ill patients with respiratory failure caused by COVID-19.
ABSTRACT
Introduction RLF-100 (Aviptadil), a synthetic form of human Vasoactive Intestinal Peptide (VIP), is in clinical trials for treatment of critical COVID-19 pneumonia with respiratory failure. VIP was shown to protect the lung against a broad array of injuries by binding to the VPAC1 receptor of alveolar type II (ATII) cells, the cells that SARS-CoV-2 binds to. The role of RLF-100 in treating lung transplant patients with COVID-19 pneumonia is unknown. Case Report A 54 year old man with double lung transplant presented with headache, fever and productive cough. COVID-19 infection was confirmed by positive RT-PCR of nasopharyngeal swab. The patient required only supportive care for three days and was discharged home. Two weeks later he presented with worsening dyspnea, fever and severe hypoxemia requiring high flow O2 and ICU admission. Chest CT showed diffuse bilateral consolidations. He had markedly elevated inflammatory markers. He was treated with dexamethasone and tocilizumab without improvement. He was not a candidate for Remdesivir due to chronic kidney disease. Convalescent plasma was not available. Pro-BNP level was normal;echocardiogram showed preserved biventricular function. He received Aviptadil, a total of three doses, per an open label access under an emergency use approved by US FDA. Rapid improvement in oxygenation and radiologic findings were noticed. No adverse effects were recorded. The patient was transferred out of the ICU 24 hours following the third dose and discharged home on room air 15 days later. Summary We report a case of lung transplant recipient with critical COVID-19 pneumonia treated with RLF-100 chieving rapid clinical and radiologic improvement. This is consistent with that VIP protects ATII cells, ameliorating the inflammation and improving oxygenation in critical COVID-19 pneumonia. A randomized prospective trial is underway to evaluate the efficacy of RLF-100 in reducing mortality and improving oxygenation in patients with critical COVID-19 pneumonia.