Immunosuppressant and SARS-CoV-2 Vaccine Antibody Response After Lung Transplantation.

BACKGROUND: There are insufficient reports on the immunogenicity and safety of the COVID-19 vaccination after lung transplantation in Korea. METHODS: Between April and September 2021, lung transplant recipients (n = 52) and healthy controls (n = 22) underwent vaccination. The levels of antibodies were assessed prospectively at 4 weeks after priming and second dose. RESULTS: Of a total of 52 lung transplant recipients, there were 84.6% nonresponders, 15.4% second-dose responders, and 0% primary dose responders. Among healthy controls, 63.6% were priming responders, and 18.2% were second-dose responders, and 18.2% were nonresponders. Compared with the control group, lung recipients were less likely to develop antibodies (P < .001). Antibody formation tended to be higher in recipients more than 1 year after transplantation (0 vs 20.5%, P = .076). No major safety events were reported, and the adverse symptoms were mild and consistent with those of the general population. In a multivariate regression analysis, mycophenolic acid levels (µg/mL) (odds ratio 0.25, P = .005) and tacrolimus level (ng/mL) (odds ratio 0.65, P = .035) were significantly associated with antibody formation. CONCLUSIONS: The immunogenicity of the second dose of COVID-19 vaccination with various combinations was substantially low in lung transplants. A booster of the COVID-19 vaccine is warranted in lung transplants, especially a year later.

Impact of nutrition and physical activity on outcomes of hospital-acquired pneumonia.

Frailty is an important risk factor for adverse health-related outcomes. It is classified into several phenotypes according to nutritional state and physical activity. In this context, we investigated whether frailty phenotypes were related to clinical outcome of hospital-acquired pneumonia (HAP). During the study period, a total of 526 patients were screened for HAP and 480 of whom were analyzed. The patients were divided into four groups according to physical inactivity and malnutrition: nutritional frailty (Geriatric Nutritional Risk Index [GNRI] < 82 and Clinical Frailty Scale [CFS] ≥ 4), malnutrition (GNRI < 82 and CFS < 4), physical frailty (GNRI ≥ 82 and CFS ≥ 4), and normal (GNRI ≥ 82 and CFS < 4). Among the phenotypes, physical frailty without malnutrition was the most common (39.4%), followed by nutritional frailty (30.2%), normal (20.6%), and malnutrition (9.8%). There was a significant difference in hospital survival and home discharge among the four phenotypes (p = 0.009), and the nutritional frailty group had the poorest in-hospital survival and home discharge (64.8% and 34.6%, respectively). In conclusion, there were differences in clinical outcomes according to the four phenotypes of HAP. Assessment of frailty phenotypes during hospitalization may improve outcomes through adequate nutrition and rehabilitation treatment of patients with HAP.

Lung Transplantation for Patients with COVID-19 Acute Respiratory Distress Syndrome.

Patients with severe coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) may exhibit pulmonary fibrosis after the viral illness resolves. Some of these patients may experience severe functional lung impairment, and thus require transplants to prevent death or maintain a tolerable quality of life. Considering the reversibility of COVID-19 ARDS, lung transplant candidates are observed for 1-2 months and must be selected very carefully before transplantation. As the short-term outcomes of such patients are comparable to those of patients with other indications for transplantation, lung transplantation should be actively considered.

Successful Lung Transplantation From a Donor Who Had Recovered From Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

During the present coronavirus disease 2019 (COVID-19) pandemic, transplantation of donor lungs using patients with a history of COVID-19 infection is a critical issue. Donor-derived virus infection and graft dysfunction are possible after transplantation. However use of such lungs could save the lives of patients requiring emergency transplantation. We successfully transplanted lungs from a brain-dead donor who had recovered from severe acute respiratory syndrome coronavirus 2 into a severe respiratory failure patient supported with extracorporeal membrane oxygenation who needed an emergency transplant. At the 3-month follow-up our patient showed no evidence of COVID-19 transmission or graft dysfunction.

SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accompanied by chronic neurological sequelae such as cognitive decline and mood disorder, but the underlying mechanisms have not yet been elucidated. We explored the possibility that the brain-infiltrating SARS-CoV-2 spike protein contributes to the development of neurological symptoms observed in COVID-19 patients in this study. Our behavioral study showed that administration of SARS-CoV-2 spike protein S1 subunit (S1 protein) to mouse hippocampus induced cognitive deficit and anxiety-like behavior in vivo. These neurological symptoms were accompanied by neuronal cell death in the dorsal and ventral hippocampus as well as glial cell activation. Interestingly, the S1 protein did not directly induce hippocampal cell death in vitro. Rather, it exerted neurotoxicity via glial cell activation, partially through interleukin-1ß induction. In conclusion, our data suggest a novel pathogenic mechanism for the COVID-19-associated neurological symptoms that involves glia activation and non-cell autonomous hippocampal neuronal death by the brain-infiltrating S1 protein.

Possible Benefit of Angiotensin II Receptor Blockers in COVID-19 Patients: A Case Series.

INTRODUCTION: Dysfunction in the renin-angiotensin-aldosterone system (RAAS) has been observed in patients with coronavirus disease 2019 (COVID-19). It is presumed that the effect of reducing interleukin-6 (IL-6) levels by angiotensin II receptor blockers (ARBs) by RAAS modulation. We investigated changes in angiotensin II and IL-6 levels in four COVID-19 patients treated with ARBs. Case Presentation. Cases 1 and 2 were who had not received ARBs before and were newly administered ARBs. Case 3 restarted ARBs after discontinuation for 7 days, and case 4 received an increased dose of ARBs. The mean in angiotensin II levels (607.5 pg/mL, range: 488-850 pg/mL, reference range < 100 pg/mL), C-reactive protein (CRP) (10.58 mg/dL, range 4.45-18.05 mg/dL), and IL-6 (55.78 pg/mL, range: 12.86-144.82 pg/mL, reference range < 7 pg/mL) was observed at the admission in all patients. Upon clinical improvement, the mean decrease in CRP (1.02 mg/dL, range 0.06-3.78 mg/dL) and IL-6 (5.63 pg/mL, range 0.17-20.87 pg/mL) was observed in all patients. Conversely, angiotensin II levels gradually increased. CONCLUSION: This report supports the potential benefit of ARBs to improve the clinical outcomes of COVID-19 patients by controlling RAAS dysfunction.

Effectiveness of Steroid Treatment for SARS-CoV-2 Pneumonia With Cryptogenic Organizing Pneumonia-Like Reaction: A Case Report.

Several studies on the treatment of coronavirus disease 2019 (COVID-19) are being conducted, and various drugs are being tried; however, the results have not been uniform. Steroids have been widely used in the treatment of COVID-19, but their effects are controversial. As immunosuppressive and anti-inflammatory agents, steroids are considered to reduce lung damage by regulating various inflammatory responses. We report a case of severe acute respiratory syndrome coronavirus-2 pneumonia manifesting as a cryptogenic organizing pneumonia-like reaction and discuss its treatment, clinical course, and favorable outcomes after steroid administration.