Vaccination with >2 Doses of Mrna Vaccines is Needed to Reduce Mortality Among Lung Transplant Recipients with Covid-19

Vaccination reduces COVID-19-related morbidity and mortality in the general population, however, the response to vaccination is attenuated among immunosuppressed lung transplant recipients (LTR). Boyarski et al noted that 61% of LTR had no serologic response to the first or second dose of mRNA vaccines, with an additional 31% only responding to the second dose. We sought to compare the impact of vaccination status on COVID-19-related morbidity and mortality in LTR. We conducted a retrospective chart review of LTR with COVID-19 that did not receive Tixagevimab-Cilgavimab (Tix-Cil) prophylaxis. We compared outcomes based on vaccination status using chi-square and binomial exact tests. Between March 2020 and August 2022, 195 LTR developed COVID-19, 24 received Tix-Cil and were excluded from the analysis. The median age was 66.6 (58.8-71.9), 100 (58.5%) were male, 166 (97.1%) had a bilateral lung transplant, 91 (53.2%) had diabetes, 55 (32.2%) were obese, and 126 (73.7%) had chronic kidney disease with an eGFR <60. The most common immunosuppressive regimen included mycophenolate mofetil, tacrolimus, and prednisone (124 (72.5%)). The median percent predicted FEV1 was 78% (IQR 62, 94) and the median time from LT to COVID-19 diagnosis was 38.3 months (IQR 20.3, 66.9). LTR with COVID-19 that received at least 2 doses of the mRNA vaccines were less likely to be hospitalized compared to their unvaccinated counterparts. However, 2 vaccine doses alone did not reduce ICU admission, intubation, or mortality. LTR with COVID-19 that received >2 vaccines were less likely to be hospitalized, admitted to the ICU, or intubated, and had a lower mortality. Two doses of mRNA vaccines reduced COVID-19-related hospitalization among LTR with COVID-19;additional vaccine doses were needed to reduce risk of ICU admission, intubation, and death. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Covid-19 is Less Severe with the Omicron Variant Compared to Prior Variants and the Original Sars-Cov-2 Strain in Lung Transplant Recipients

Multiple variants of SARS-CoV-2 have been documented throughout the COVID-19 pandemic. Mutations that lead to these variants can affect viral spread, disease severity, and the efficacy of vaccines and therapeutics. Lung transplant (LT) recipients (LTRs) are at high risk of COVID-19-related morbidity and mortality;however, disease severity may differ between SARS-CoV-2 variants. We sought to describe the clinical outcomes of LTRs with COVID-19 at different stages of the pandemic. We performed a retrospective chart review of LTRs with COVID-19 and categorized them into 4 groups according to the prevalent variant on the date of the positive test. Chi-square and non-parametric binomial exact tests were used for comparative analyses. Since March 2020, 195 LTRs at our institute developed COVID-19;the median age was 66.6 years (58.7-72);114 (58.5%) were male;190 (97.4%) had received a bilateral LT;106 (54.4%) had diabetes;63 (32.3%) were obese;and 145 (74.4%) had chronic kidney disease with an eGFR <60. The most common immunosuppressive regimen included mycophenolate mofetil, tacrolimus, and prednisone (n=142;72.8%). The median percent predicted FEV1 was 81% (IQR 63-96) and the median time from LT to COVID-19 diagnosis was 37.3 months (IQR 18.5-66.7). Rates of hospitalization, ICU admission, need for mechanical ventilation, and death were significantly lower for the Omicron variant than the original strain, the Alpha variant, and the Delta variant. However, there was no difference in length of hospital stay, development of extrapulmonary end-organ dysfunction, or persistent drop in spirometric flows (Table 1). Lastly, the utilization of vaccination and monoclonal antibodies grew over time and likely contributed to reduced COVID-19 severity in the latter part of the pandemic. COVID-19 continues to drive morbidity and mortality among LTRs;however, the severity of disease is lower with the omicron variant. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In it for the long run! Long-Term ECMO as a Bridge to Recovery in Severe COVID-19 ARDS

Introduction: During the pandemic, various guidelines were developed for the utilization of extracorporeal membrane oxygenation (ECMO) for COVID-19 ARDS. However, once patients were cannulated for ECMO, the timeframe for lung recovery and referral for lung transplantation was less clear. To date, there are few reported cases of successful long-term (>28 days) ECMO as a bridge to lung recovery. Method(s): We present three patients who were referred for lung transplantation for severe COVID-19 associated respiratory failure and ultimately achieved successful lung recovery following long-term venovenous ECMO support. Patients presented at different stages of the pandemic, were of different ethnicities, aged 35-54 years old, average BMI of 27.6 and two were male. Prior to cannulation, all patients failed mechanical ventilation, prone positioning, neuromuscular blockade and pulmonary vasodilators. Patients were cannulated within 7 days of intubation, underwent early tracheostomy and participated in ambulatory physical therapy. Complications during ECMO included acute renal failure requiring renal replacement therapy, pneumothorax, right ventricular dysfunction and concomitant bacterial pneumonia with bacteremia. The median duration of ECMO was 104 days (range 84-142 days). Radiographic imaging reported end stage restrictive changes in all patients. Survival to hospital discharge was 100%. All patients had complete renal recovery, resolution of RV dysfunction and functional independence without oxygen. Radiographic changes and pulmonary function continued to improve after decannulation. Conclusion(s): Long-term ECMO is an effective strategy for lung recovery in severe COVID-19 ARDS. Duration of ECMO support and radiographic findings should not be used alone to determine recoverability or need for lung transplantation.

Methylene blue and hydroxocobalamin in a severely vasoplegic lung transplant recipient

INTRODUCTION: Vasoplegia is defined as a refractory shock state with profound hypotension in the setting of reduced systemic vascular resistance and high cardiac output. Lung transplantation is an arduous surgery often requiring cardiopulmonary bypass, which ultimately predisposes to vasoplegia. We detail the treatment of a patient with end-stage lung disease secondary to COVID-19 pneumonia undergoing lung transplant who developed vasoplegia. DESCRIPTION: The patient is a 36-year-old female who was admitted with profound hypoxemic respiratory failure secondary to COVID-19 pneumonia. Despite initial therapy, she remained ventilator-dependent with need for extracorporeal membrane oxygenation (ECMO) support. Given her single organ failure status - lungs being solely affected - she was promptly considered for lung transplant evaluation upon resolution of her active SARS-CoV-2 infection. She was ultimately deemed appropriate for listing and underwent subsequent transplant. The surgery required the use of cardiopulmonary bypass, given the extensive adhesions of the native COVID-19-infected lungs. The lungs were, unfortunately, quite necrotic, with multiple purulent pockets. She was profoundly hypotensive throughout the surgery and required massive fluid resuscitation, as well as multiple vasopressors. In the setting of this vasoplegia, she received multiple doses of methylene blue at 2 mg/kg, with only marginal improvement in blood pressure. Decision was made to add high-dose (5 g) hydroxocobalamin in an attempt to synergistically stabilize blood pressure. Intraoperatively, her blood pressure stabilized within hours;she remained on ECMO support and was transferred to the ICU postoperatively. Eventually, she was slowly weaned from her vasopressors, with stable blood pressure. DISCUSSION: Methylene blue mechanistically inhibits inducible nitric oxide synthase and guanylyl cyclase, while hydroxycobalamin acts as a nitric oxide scavenger. Both agents have been used independently to treat vasoplegia during cardiopulmonary bypass. Together, they may be used as a salvage therapy to improve blood pressure in refractory cases of shock seemingly exacerbated by the cytokine milieu promoted by recent SARS-CoV-2 infection.