Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.

Outcome and characteristics of invasive fungal infections in critically ill burn patients: A multicenter retrospective study.

BACKGROUND: Characteristics and outcome of invasive fungal infection (IFI) in critically ill burn patients have been poorly explored. OBJECTIVES: We report the factors associated with 90-day mortality in a multicentre retrospective European study. PATIENTS/METHODS: All burn patients with confirmed IFI admitted between 1 January 2010 to 31 December 2015 in 10 centres in France and Belgium were included. RESULTS: Ninety-four patients were enrolled with 110 cases of IFIs: 79 (71.8%) were yeasts IFI and 31 (28.2%) filamentous IFI. Incidence was 1% among admitted patients. The 90-day mortality was 37.2% for all IFIs combined, 52% for filamentous infection and 31.9% for yeast infection. Patients with more than one IFI had a higher 90-day mortality than patients with only one episode (61.5% vs 33.5% (P = .006)). In multivariate analysis, higher Simplified Acute Physiology Score II (OR = 1.05 (95% CI: 1.02-1.09) P = .003), bacterial co-infection (OR = 3.85 (95% CI: 1.23-12.01), P = .014) and use of skin allografts at the time of IFI diagnosis (OR = 3.87 (95% CI: 1.31-11.42), P = .021) were associated with 90-day mortality. CONCLUSIONS: Although rare, invasive fungal infections remain associated with poor outcome in burn patients. Bacterial co-infection and presence of allograft were potentially modifiable factors independently associated with outcome.

The SARS-CoV-2 spike residues 616/644 and 1138/1169 delineate two antibody epitopes in COVID-19 mRNA COMINARTY vaccine (Pfizer/BioNTech).

The newly identified coronavirus SARS-CoV-2 is responsible for the worldwide pandemic COVID-19. Considerable efforts have been devoted for the development of effective vaccine strategies against COVID-19. The SARS-CoV-2 spike protein has been identified as the major antigen candidate for the development of COVID-19 vaccines. The Pfizer-BioNTech COVID-19 vaccine COMIRNATY is a lipid nanoparticle-encapsulated mRNA encoding a full-length and prefusion-stabilized SARS-CoV-2 spike protein. In the present study, synthetic peptide-based ELISA assays were performed to identify linear B-cell epitopes into the spike protein that contribute to elicitation of antibody response in COMIRNATY-vaccinated individuals. The synthetic S2P6 peptide containing the spike residues 1138/1169 and to a lesser extent, the synthetic S1P4 peptide containing the spike residues 616/644 were recognized by the immune sera from COMIRNATY vaccine recipients but not COVID-19 recovered patients. We assume that the synthetic S2P6 peptide and to a lesser extent the synthetic S1P4 peptide, could be of interest to measure the dynamic of antibody response to COVID-19 mRNA vaccines. The S2P6 peptide has been identified as immunogenic in adult BALB/c mice that received protein-peptide conjugates in a prime-boost schedule. This raises the question on the role of the B-cell epitope peptide containing the SARS-CoV-2 spike residues 1138/1169 in protective efficacy of the Pfizer-BioNTech COVID-19 vaccine COMIRNATY.

Altered high-density lipoprotein composition and functions during severe COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Co-infection in patients with hypoxemic pneumonia due to COVID-19 in Reunion Island.

ABSTRACT: This study aimed to evaluate the incidence of co-infection with different types of pathogens in patients with hypoxemic pneumonia due to coronavirus disease 2019 (COVID-19) in Reunion Island.This observational study using a prospectively collected database of hypoxemic pneumonia due to COVID-19 cases was conducted at Félix Guyon University Hospital in Reunion Island, France.Between 18 March 2020 and 15 April 2020, 156 patients were admitted to our hospital for COVID-19. A total of 36 patients had hypoxemic pneumonia (23.1%) due to COVID-19. Thirty of these cases (83.3%) were imported by travelers returning mainly from metropolitan France and Spain. Patients were screened for co-infection with other pathogens at admission: 31 (86.1%) by multiplex polymerase chain reaction (PCR) and 16 (44.4%) by cytobacteriological examination of sputum culture. Five patients (13.9%) were found to have co-infection: 1 with influenza virus A H1N1 (pdm09) associated with Branhamella catarrhalis, 1 with Streptococcus pneumoniae associated with Haemophilus influenzae, 1 with Human Coronavirus 229E, 1 with Rhinovirus, and 1 with methicillin-susceptible Staphylococcus aureus. Patients with co-infection had higher D-dimer levels than those without co-infection (1.36 [1.34-2.36] µg/mL vs 0.63 [0.51-1.12] µg/mL, P = .05).The incidence of co-infection in our cohort was higher than expected (13.9%). Three co-infections (with influenza virus A(H1N1) pdm09, Streptococcus pneumoniae, and Staphylococcus aureus) required specific treatment. Patients with hypoxemic pneumonia due to COVID-19 should be screened for co-infection using respiratory cultures or multiplex PCR. Whilst our study has a number of limitations, the results from our study suggest that in the absence of screening, patients should be commenced on treatment for co-infection in the presence of an elevated D-dimer.

Detection of Pulmonary Embolism in Returning Travelers with Hypoxemic Pneumonia due to COVID-19 in Reunion Island.

The aim of this study was to evaluate the occurrence of pulmonary embolism in returning travelers with hypoxemic pneumonia due to COVID-19. All returning travelers to Reunion Island with hypoxemic pneumonia due to COVID-19 underwent computed tomography pulmonary angiography (CTPA) and were included in the cohort. Thirty-five patients were returning travelers with hypoxemic pneumonia due to COVID-19 and had recently returned from one of the countries most affected by the COVID-19 outbreak (mainly from France and Comoros archipelago). Five patients (14.3%) were found to have pulmonary embolism and two (5.9%) were incidentally found to have deep vein thrombosis on CTPA. Patients with pulmonary embolism or deep vein thrombosis had higher D-dimer levels than those without pulmonary embolism or deep vein thrombosis (P = 0.04). Returning travelers with hypoxemic pneumonia due to COVID-19 should be systematically screened for pulmonary embolism.

Hepatitis C (HCV) therapy for HCV mono-infected and HIV-HCV co-infected individuals living in Nepal.

BACKGROUND: Despite direct-acting antivirals (DAA), aims to "eradicate" viral hepatitis by 2030 remain unlikely. In Nepal, an expert consortium was established to treat HCV through Nepal earthquakes aftermath offering a model for HCV treatment expansion in a resource-poor setting. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, we established a network of hepatologists, laboratory experts, and community-based leaders at 6 Opioid Substitution Treatment (OST) sites from 4 cities in Nepal screening 838 patients for a treatment cohort of 600 individuals with HCV infection and past or current drug use. During phase 1, patients were treated with interferon-based regimens (n = 46). During phase 2, 135 patients with optimal predictors (HIV controlled, without cirrhosis, low baseline HCV viral load) were treated with DAA-based regimens. During phase 3, IFN-free DAA treatment was expanded, regardless of HCV disease severity, HIV viremia or drug use. Sustained virologic response (SVR) was assessed at 12 weeks. Median age was 37 years and 95.5% were males. HCV genotype was 3 (53.2%) or 1a (40.7%) and 32% had cirrhosis; 42.5% were HIV-HCV coinfected. The intention-to-treat (ITT) SVR rates in phase 2 and 3 were 97% and 81%, respectively. The overall per-protocol and ITT SVR rates were 97% and 85%, respectively. By multivariable analysis, treatment at the Kathmandu site was protective and substance use, treatment during phase 3 were associated with failure to achieve SVR. CONCLUSIONS/SIGNIFICANCE: Very high SVR rates may be achieved in a difficult-to-treat, low-income population whatever the patient's profile and disease severity. The excellent treatment outcomes observed in this real-life community study should prompt further HCV treatment initiatives in Nepal.

A comprehensive strategy for the early treatment of COVID-19 with azithromycin/hydroxychloroquine and/or corticosteroids: Results of a retrospective observational study in the French overseas department of Réunion Island.

BACKGROUND: This study aimed to evaluate the prognosis of COVID-19 patients in Reunion Island, with a particular focus on the management of patients with hypoxemic pneumonia. METHODS: This retrospective observational study was conducted from 11 March to 17 April 2020 at the only hospital authorized to manage patients with COVID-19 in Reunion Island. RESULTS: Over the study period, 164 out of 398 patients (41.2%) infected with COVID-19 were admitted to Félix Guyon University Hospital. Of these, 36 (22%) developed hypoxemic pneumonia. Patients with hypoxemic pneumonia were aged 66 [56-77] years, 69% were male and 33% had hypertension. Ten patients (27.8%) were hospitalized in intensive care unit (ICU). Hydroxychloroquine/azithromycin treatment was associated with a lower ICU admission rate (P=0.008). None of the 6 patients treated with corticosteroids were hospitalized in ICU (P=0.16). There were no deaths at follow up (minimum 80 days). CONCLUSIONS: Despite the risk profile of COVID-19 patients with severe hypoxemic pneumonia, the mortality rate of the disease in Reunion Island was 0%. This may be due to the care bundle used in our hospital (early hospitalisation, treatment with hydroxychloroquine/azithromycin and/or corticosteroids, non-invasive respiratory support, etc).

Failure of atovaquone/proguanil to prevent Plasmodium ovale malaria in traveler returning from Cameroon.

We report a case of a patient returning from Cameroon who developed Plasmodium ovale malaria, despite atovaquone/proguanil (AP, Malarone) prophylaxis, which is widely used for the prevention of chloroquine-resistant malaria. AP is indeed active only on schizont blood forms of P. ovale but not against liver-stage hypnozoites and does not realize effective prophylaxis against delayed onset of P. ovale malaria. Hence, this case illustrates the risk of failure with Malarone for the prophylaxis of P. ovale infection for travelers in endemic regions. Travelers returned from risk areas with symptoms suggestive of malaria, should not have the diagnosis of P. ovale (or P. vivax) infection discounted, despite a history of compliance with a standard chemoprophylactic regimen.

High leptospiremia is associated with low gamma-delta T cell counts.

The role of innate immune cells either to mount appropriate defense mechanisms or to drive uncontrolled tissue injuries during acute leptospirosis is poorly understood. This study aimed at characterizing the selective mobilization of innate immune cells and the level of target organ injuries in response to leptospiremia. We focused on gamma-delta (γ-δ) T cells. Patients were prospectively assessed for cell count by cytometry, for bacterial load by PCR in plasma samples and for levels of soluble acute phase tissue enzymes. We found that the level of γ-δ T cells was low and inversely correlated to liver injuries and leptospiremia.

Treatment of parasitic diarrhea in HIV-infected patients.

Parasitic infections responsible for diarrhea have a worldwide distribution, overlapping with AIDS in most countries. Indeed, highly active antiretroviral therapy has markedly reduced the incidence of most parasitic opportunistic infections, but parasite-related diarrhea remains frequent and probably underestimated in developing countries. In this review, we focus on the advances in molecular epidemiology, diagnosis and current treatment of the most prevalent parasitic infections in HIV-infected patients. Most of these parasites are protozoa, whose diagnosis at the laboratory requires some adapted technique and expertise. We highlight the importance of diagnosis and the skill of the laboratory of parasitology, since most parasitic infections responsible for diarrhea in AIDS patients can be treated.

Severe Actinobacillus ureae meningitis in an immunocompromised patient: report of one case and review of the literature.

27 cases of Actinobacillus ureae infections including 14 cases of meningitis have been reported. We describe 1 case of Actinobacillus ureae meningitis in a 75-y-old patient. Risk factors, clinical outcome and treatment of Actinobacillus ureae infections are discussed. Actinobacillus ureae may behave as an opportunistic pathogen causing severe infections in immunocompromised patients.