Multi-omics of NET formation and correlations with CNDP1, PSPB, and L-cystine levels in severe and mild COVID-19 infections.

The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.

Occurrence of influenza and bacterial infections in cancer patients receiving radiotherapy in Ghana.

BACKGROUND: Influenza co-infection with bacteria is a leading cause of influenza-related deaths and severe respiratory infections, especially among high-risk groups like cancer patients undergoing treatment. However, acute respiratory infection (ARI)-like symptoms developed by upper-torso cancer (UTC) patients receiving radiotherapy are considered as side-effects of the radiation. Hence influenza and bacterial pathogens implicated in ARI are not investigated. METHODS: This prospective cohort study examined 85 in-patients with upper-torso cancers undergoing radiotherapy at the National Radiotherapy, Oncology and Nuclear Medicine Centre (NRONMC) of Korle-Bu Teaching Hospital (KBTH) in Accra, Ghana. Eligible patients who consented were recruited into the study from September 2018 to April 2019. Influenza viruses A and B in addition to the following bacteria species Streptococcus pneumonia, Haemophilus influenzae, Neisseria meningitidis and Staphylococcus aureus were detected from oropharyngeal and nasopharyngeal swab specimens collected at three different time points. Presence of respiratory pathogens were investigated by influenza virus isolation in cell culture, bacterial culture, polymerase chain reaction (PCR) and next generation sequencing (NGS) assays. RESULTS: Of the 85 eligible participants enrolled into the study, 87% were females. Participants were 17 to 77 years old, with a median age of 49 years. Most of the participants (88%) enrolled had at least one pathogen present. The most prevalent pathogen was N. meningitidis (63.4%), followed by H. influenzae (48.8%), Influenza viruses A and B (32.9%), S. pneumoniae (32.9%) and S. aureus (12.2%). Approximately, 65% of these participants developed ARI-like symptoms. Participants with previous episodes of ARI, did not live alone, HNC and total radiation less than 50 Gy were significantly associated with ARI. All treatment forms were also significantly associated with ARI. CONCLUSION: Data generated from the study suggests that ARI-like symptoms observed among UTC patients receiving radiotherapy in Ghana, could be due to influenza and bacterial single and co-infections in addition to risk factors and not solely the side-effects of radiation as perceived. These findings will be prime importance for diagnosis, prevention, treatment and control for cancer patients who present with such episodes during treatment.

Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers.

BACKGROUND: mRNA COVID-19 vaccines are playing a key role in controlling the COVID-19 pandemic. The relationship between post-vaccination symptoms and strength of antibody responses is unclear. OBJECTIVE: To determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. DESIGN: Single center, prospective, observational cohort study. SETTING: Participants worked at Walter Reed National Military Medical Center and were seen monthly at the Naval Medical Research Center Clinical Trials Center. PARTICIPANTS: Generally healthy adults that were not severely immunocompromised, had no history of COVID-19, and were seronegative for SARS-CoV-2 spike protein prior to vaccination. MEASURES: Severity of vaccine-associated symptoms was obtained through participant completed questionnaires. Testing for IgG antibodies against SARS-CoV-2 spike protein and receptor binding domain was conducted using microsphere-based multiplex immunoassays. RESULTS: 206 participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers one month after vaccination. We also observed that 1) post-vaccination symptoms were inversely correlated with age and weight and more common in women, 2) systemic symptoms were more frequent after the second vaccination, 3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and 4) older age was associated with lower titers. LIMITATIONS: Study only observes antibody responses and consists of healthy participants. CONCLUSIONS: Lack of post-vaccination symptoms following receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies one month after vaccination. This study also suggests that it may be possible to design future mRNA vaccines that confer robust antibody responses with lower frequencies of vaccine-associated symptoms. FUNDING: This study was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded by the Defense Health Program, U.S. DoD, under award HU00012120067. Project funding for JHP was in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The funding bodies have had no role in the study design or the decision to submit the manuscript for publication.

Biomarkers of Inflammation Correlate With Clinical Scoring Indices in Human Immunodeficiency Virus-Infected Kenyans.

Background: In high-income countries, inflammation has been associated with increased morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals despite treatment with antiretroviral therapy (ART). However, these findings may not be generalizable to low-income settings. Methods: In this cross-sectional study, multivariable linear regression was used to compare 28 inflammatory biomarker levels in HIV-infected and -uninfected participants. Correlations between biomarkers and Veterans Aging Cohort Study (VACS) index, Fibrosis-4 (FIB-4) score, and Framingham risk score were assessed. Results: Plasma samples from 304 Kenyans were analyzed. Compared to HIV-uninfected controls, virologically suppressed HIV-infected participants had higher levels of CCL5, CXCL10, fatty acid binding protein (FABP) 2, fas ligand (FASLG), matrix metalloproteinase (MMP) 1, MMP7, soluble CD14 (sCD14), and soluble CD163 (sCD163) and lower MMP9 (P < .01). CD4+/HLA-DR+CD38+ (ρ = 0.32; P < .001), sCD14 (ρ = 0.25; P = .004), and sCD163 (ρ = 0.24; P = .006) were correlated with the VACS index. FABP2 was positively correlated (ρ = 0.29; P = .002), whereas MMP1 (ρ = -.32; P < .001) and MMP2 (ρ = -0.28; P = .002) were inversely correlated with the FIB-4 score. Conclusions: Differences in biomarker levels exist between well-controlled HIV-infected participants on ART and uninfected controls. Some biomarkers are correlated to scoring indices predictive of morbidity and mortality. These biomarkers could serve as prognostic indicators and inform therapeutic development.

Recommendations for Counseling and Education of Service Members on Endemic African Cutaneous Kaposi Sarcoma: A Case Study.

We report a case of Endemic African Cutaneous Kaposi Sarcoma (EACKS) on the lower extremity of an immunocompetent 31-yr-old male service member from Cameroon. Diagnosis was made using clinical and histologic findings. The service member was treated with local radiation therapy with resolution of his tumor.The goal of this article is to educate practitioners to counsel susceptible service members and leadership on the risk of developing EACKS when traveling to Sub-Saharan Africa, monitor for disease development, and guide in the diagnosis and treatment of patients with this rare disease.

Multimodality imaging of multivalvular endocarditis after transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgery for severe aortic stenosis in non-operable and high surgical risk patients. While endocarditis following TAVR is rare, the significant co-morbidities commonly found in this patient population can complicate evaluation and management. A case of TAVR endocarditis initially diagnosed by cardiac computed tomography angiography and confirmed with transesophageal echocardiogram is presented. In addition to demonstrating the appearance of vegetations and perivalvular involvement in endocarditis complicating TAVR, this case illustrates the utility of cardiac CT techniques in imaging suspected TAVR endocarditis.