Potential of in vitro nuclear magnetic resonance of biofluids and tissues in clinical research.

Body fluids, cells, and tissues contain a wide variety of metabolites that consist of a mixture of various low-molecular-weight compounds, including amino acids, peptides, lipids, nucleic acids, and organic acids, which makes comprehensive analysis more difficult. Quantitative nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical technique for analyzing the metabolic profiles of body fluids, cells, and tissues. It enables fast and comprehensive detection, characterization, a high level of experimental reproducibility, minimal sample preparation, and quantification of various endogenous metabolites. In recent times, NMR-based metabolomics has been appreciably utilized in diverse branches of medicine, including microbiology, toxicology, pathophysiology, pharmacology, nutritional intervention, and disease diagnosis/prognosis. In this review, the utility of NMR-based metabolomics in clinical studies is discussed. The significance of in vitro NMR-based metabolomics as an effective tool for detecting metabolites and their variations in different diseases are discussed, together with the possibility of identifying specific biomarkers that can contribute to early detection and diagnosis of disease.

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

A pandemic of acute respiratory distress syndrome-role of lung transplant in coronavirus disease-2019-associated respiratory failure.

Lung transplantation may be appropriate, and may offer benefit only to a carefully selected subset of morbidly ill patients afflicted by coronavirus disease-2019. Identifying the appropriate recipient for the allocation of scarce resources, by safely navigating through the challenges that are unique to lung transplantation for coronavirus disease-2019-associated acute respiratory distress syndrome, demands a conscientious and meticulous approach. Categorizing the respiratory failure in coronavirus disease-2019 may facilitate the process of evaluation for the purpose of transplant. The progress in rescue transplants over the past two decades has greatly improved our ability to successfully perform high-risk lung transplantation.

Sequential battery of COVID-19 testing to maximize negative predictive value before surgeries

ABSTRACT SARS-CoV-2 is a novel virus which has proven to be highly contagious. Specific viral dynamics and immune response to the virus are yet to be fully defined and determining the sensitivity and specificity of the available testing methods is still a work in progress. This study examines the published information on the testing methods, and finds that yield of COVID-19 tests changes with specimen types and with time through course of illness. We propose a sequential battery of testing consisting of an epidemiologic survey, RT-PCR tests, serologic tests and chest CT on surgical candidates which may increase the negative predictive value, and facilitate surgical procedures. RESUMO O SARS-CoV-2 é um novo vírus que provou ser altamente contagioso. A dinâmica viral específica e a resposta imunológica ao vírus ainda não foram totalmente definidas e a determinação da sensibilidade e especificidade dos métodos de teste disponíveis ainda está em andamento. Este estudo examina as informações publicadas sobre os métodos de testagem e conclui que o rendimento dos testes COVID-19 muda de acordo com o tipo de amostra e com o tempo de progressão da doença. Propomos uma bateria sequencial de testes, que consiste em um levantamento epidemiológico, testes de RT-PCR, testes sorológicos e tomografia computadorizada de tórax em candidatos a cirurgia, que podem aumentar o valor preditivo negativo e facilitar procedimentos cirúrgicos.

Hydroxychloroquine and COVID-19.

Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.

Sequential battery of COVID-19 testing to maximize negative predictive value before surgeries.

SARS-CoV-2 is a novel virus which has proven to be highly contagious. Specific viral dynamics and immune response to the virus are yet to be fully defined and determining the sensitivity and specificity of the available testing methods is still a work in progress. This study examines the published information on the testing methods, and finds that yield of COVID-19 tests changes with specimen types and with time through course of illness. We propose a sequential battery of testing consisting of an epidemiologic survey, RT-PCR tests, serologic tests and chest CT on surgical candidates which may increase the negative predictive value, and facilitate surgical procedures.