Infectious Complications of Lung Transplant for COVID-Associated Lung Injury (CALI): A Single Center Case-Control Cohort Study.

BACKGROUND: Lung transplantation is one of the only options for patients with severe COVID-19-associated lung injury (CALI). Studies on patients who received a lung transplant for CALI have, to date, not looked at the infectious outcomes. METHODS: After IRB approval, a retrospective case-control cohort study, matched 1:1, collected data on patients who underwent lung transplantation for CALI (case) and for non-COVID-19 end-stage lung disease (control) between June 1, 2020 and April 1, 2022 at a large academic hospital in Chicago. We assessed infectious complications and other key outcomes pre-transplant and for one-year post-transplant. RESULTS: Among 78 subjects (39 CALI and 39 matched control lung transplant patients), those in the CALI cohort were less likely to be vaccinated pre-transplant and were more likely to have diabetes, obesity, to not be ambulatory and to require pre-transplant ECMO and mechanical ventilation. Patients transplanted for CALI had higher rates of infection pre-transplant (66.7% vs 15.4% of patients in the control) and in the first 30 days post-transplant (43.6% vs. 20.5%). Numbers and types of infection were similar in both groups at other time points. One year mortality was similar (12.8% vs. 10.3%) for CALI and control populations, respectively. CONCLUSIONS: Patients who received a lung transplant for CALI are more deconditioned with prolonged hospital stays and experience more infectious complications immediately pre- and post-transplant. Infections due to MDROs are important contributors to morbidity and mortality in this population and antimicrobial stewardship is urgently needed.

Update on Covid-19: vaccines, timing of transplant after COVID-19 infection and use of positive donors.

PURPOSE OF REVIEW: SARS-CoV-2 resulted in a global pandemic that had a chilling effect on transplantation early in the pandemic and continues to result in significant morbidity and mortality of transplant recipients. Over the past 2.5 years, our understanding of the clinical utility of vaccination and mAbs to prevent COVID-19 in solid organ transplant (SOT) recipients has been studied. Likewise, approach to donors and candidates with SARS-CoV-2 has been better understood. This review will attempt to summarize our current understanding of these important COVID-19 topics. RECENT FINDINGS: Vaccination against SARS-CoV-2 is effective in reducing the risk of severe disease and death among transplant patients. Unfortunately, humoral and, to a lesser extent, cellular immune response to existing COVID-19 vaccines is reduced in SOT recipients compared with healthy controls. Additional doses of vaccine are required to optimize protection of this population and still may be insufficient in those who are highly immunosuppressed, those receiving belatacept, rituximab and other B-cell active mAbs. Until recently, mAbs were options for the prevention of SARS-CoV-2 but are markedly less effective with recent omicron variants. SARS-CoV-2-infected donors can generally be used for nonlung, nonsmall bowel transplants unless they have died of acute severe COVID-19 or COVID-19-associated clotting disorders. SUMMARY: Our transplant recipients require a three-dose mRNA or adenovirus-vector and one dose of mRNA vaccine to be optimally protected initially; they then need to receive a bivalent booster 2+ months after completing their initial series. Most nonlung, nonsmall bowel donors with SARS-CoV-2 can be utilized as organ donors.

Serum ß2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

ß2-microglobulin (ß2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed ß2-m is measurable in circulation, and various disorders are accompanied by increases in ß2-m levels, including several viral infections. Therefore, we explored whether ß2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum ß2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean ß2-m level was 3.25±1.68 mg/l (reference range 0.8-2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean ß2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean ß2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean ß2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression ß2-m levels were the only significant predictor of disease severity. Our findings suggest that higher ß2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of ß2-m measurements. The role of ß2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

Outcome of SARS-CoV-2 variant breakthrough infection in fully immunized solid organ transplant recipients.

SARS-CoV-2 vaccination in solid organ transplant recipients is associated with suboptimal immune response and risk for breakthrough infection. It is not known whether they are at risk of severe post-vaccine breakthrough infections in the presence of SARSCoV-2 variant of concern. We describe a case series of four fully vaccinated solid organ transplant recipients who developed SARS-CoV-2 variants of concern breakthrough infections. Three patients received BNT162b2 mRNA (Pfizer-BioNTech) and one patient received ChAdOx1 (AZD12220) COVID-19 vaccines. The patients were infected with SARS-CoV-2 variants circulating in Saudi Arabia. Two patients were infected with Alpha variant and had severe pneumonia requiring intensive care admission and ventilatory support and subsequently died. The other two patients recovered; one patient was infected with Beta variant required low supplemental oxygen via nasal flow and the other patient was infected with Delta variant and required high supplemental oxygen nasal flow. Younger patients had a better outcome than older patients. Future large studies are required to confirm our observations and to compare the different vaccine efficacy among solid organ transplants in the era of SARS-CoV-2 variants of concern.

Portable RT-PCR System: a Rapid and Scalable Diagnostic Tool for COVID-19 Testing.

Combating the ongoing coronavirus disease 2019 (COVID-19) pandemic demands accurate, rapid, and point-of-care testing with fast results to triage cases for isolation and treatment. The current testing relies on reverse transcriptase PCR (RT-PCR), which is routinely performed in well-equipped laboratories by trained professionals at specific locations. However, during busy periods, high numbers of samples queued for testing can delay the test results, impacting efforts to reduce the infection risk. Besides, the absence of well-established laboratories at remote sites and low-resourced environments can contribute to a silent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These reasons compel the need to accommodate point-of-care testing for COVID-19 that meets the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable). This study assessed the agreement and accuracy of the portable Biomeme SARS-CoV-2 system against the gold standard tests. Nasopharyngeal and nasal swabs were used. Of the 192 samples tested using the Biomeme SARS-CoV-2 system, the results from 189 samples (98.4%) were in agreement with the reference standard-of-care RT-PCR testing for SARS-CoV-2. The portable system generated simultaneous results for nine samples in 80 min with high positive and negative percent agreements of 99.0% and 97.8%, respectively. We performed separate testing in a sealed glove box, offering complete biosafety containment. Thus, the Biomeme SARS-CoV-2 system can help decentralize COVID-19 testing and offer rapid test results for patients in remote and low-resourced settings.