Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsWe evaluated the predictive value of viral RNA loads and courses in the blood compared with the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by reverse transcription quantitative polymerase chain reaction were performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire intensive care unit (ICU) stay (4145 samples analyzed). Patients were grouped according to their 90-day outcome as survivors (n=100) or nonsurvivors (n=70).ResultsIn nonsurvivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (P=.0009). Failure of blood RNA clearance was observed in 33/50 (66%) of the nonsurvivors compared with 12/64 (19%) survivors (P<.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (odds ratio [OR; log10], 0.23; 95% CI, 0.12-0.42; P<.0001), with a significantly higher effect for survival compared with respiratory tract SARS-CoV-2 RNA loads (OR [log10], 0.75; 95% CI, 0.66-0.85; P<.0001). Blood RNA loads exceeding 2.51×103 SARS-CoV-2 RNA copies/mL were found to indicate a 50% probability of death. Consistently, 29/33 (88%) nonsurvivors with failure of virus clearance exceeded this cutoff value constantly.ConclusionsBlood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.
Project description:The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3-8] vs. 3 [2-4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.
Project description:PurposeDuodenal involvement in COVID-19 is poorly studied. Aim was to describe clinical and histopathological characteristics of critically ill COVID-19 patients suffering from severe duodenitis that causes a significant bleeding and/or gastrointestinal dysmotility.MethodsIn 51 critically ill patients suffering from SARS-CoV-2 pneumonia, severe upper intestinal bleeding and/or gastric feeding intolerance were indications for upper gastrointestinal endoscopy. Duodenitis was diagnosed according to macroscopic signs and mucosal biopsies. Immunohistochemistry was performed to detect viral specific protein and ACE2. In situ hybridization was applied to confirm viral replication.ResultsNine of 51 critically ill patients (18%) suffering from SARS-CoV-2 pneumonia had developed upper GI bleeding complications and/or high gastric reflux. Five of them presented with minor and four (44%) with severe duodenitis. In two patients, erosions had caused severe gastrointestinal bleeding requiring PRBC transfusions. Immunohistochemical staining for SARS-CoV-2 spike protein was positive inside duodenal enterocytes in three of four patients suffering from severe duodenitis. Viral replication could be confirmed by in situ hybridization.ConclusionOur data suggest that about 8% of critically ill COVID-19 patients may develop a severe duodenitis presumably associated with a direct infection of the duodenal enterocytes by SARS-CoV-2. Clinical consequences from severe bleeding and/or upper gastrointestinal dysmotility seem to be underestimated.
Project description:Patients with severe cases of COVID-19 are at high nutritional risk during their ICU stay. Prolonged immobilization associated with an exacerbated systemic inflammatory response is a major provider of ICU-acquired muscle weakness. Early enteral nutrition is recommended to gradually reach the energy target of 25 kcal/kg/day and protein target of 1.3 g/kg/day around D4. The occurrence of a Refeeding syndrome should be closely monitored. In case of feeding intolerance refractory to a prokinetic treatment, complementary or total parenteral nutrition is advised, favouring new generation mixed lipid emulsions (containing fish oil) and regular monitoring of triglyceridemia. Nutrition care of critically ill patients should be carried out with limited procedures that may pose a risk of contamination for the healthcare staff.
Project description:BackgroundThe current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear.MethodsIn total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38+HLA-DR+ and CD38+PD-1+ CD8+ T cells, IFN?+CD4+ and IFN?+CD8+ T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored.FindingsCD4+ T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38+HLA-DR+ and CD38+PD-1+ on CD8+ T cells, low expression of SARS-CoV-2-specific IFN?+CD4+ and IFN?+CD8+ T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFN?+CD8+and IFN?+CD4+ T cells, IgG, IgM, and IgA.InterpretationT lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8+ T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.
Project description:AimSome patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rapidly develop to critical condition. Here, we investigated the clinical features of critically ill SARS-CoV-2 patients with and without diabetes and identified risk factors for death of these patients.MethodsThe medical records including epidemiological, demographic, clinical, and laboratory data from 49 critically ill SARS-CoV-2 patients were collected and analyzed in Huanggang City and Xiaogan City, Hubei Province, outside Wuhan.ResultsSixty-seven percent (33) of patients survived and 33% (16) of patients died in 49 critically ill patients (32 men, 17 women), with a median age of 63 years (IQR 53-73). Univariate analyses indicated that the deceased patients were more often associated with two or more comorbidities, one or more gastrointestinal symptoms, high neutrophil percentage, low lymphocytes and lymphocyte percentage, high C-reactive protein, high procalcitonin, high fasting blood glucose (FBG), and high lactate dehydrogenase (LDH) compared with the survivors; moreover, the patients with T2DM had the higher neutrophil percentage, the lower lymphocyte percentage, and the higher levels of FBG and LDH compared with the patients without T2DM. Multivariable logistic regression analyses indicated that gastrointestinal symptoms (≥ 1 symptoms), decreased lymphocytes (< 1.1 × 109/L), and increased FBG (≥ 7.0 mmol/L) were the independent risk factors for death of critically ill patients.ConclusionsCritically ill COVID patients with T2DM had more severe damages of the lymphocytes, islet cells, and heart function, and gastrointestinal symptoms, lymphopenia, and increased FBG may be early predictors for poor prognosis.Supplementary informationThe online version contains supplementary material available at 10.1007/s13410-020-00888-3.
Project description:ObjectivesThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has heavily impacted Italy. The government's restriction measures have attenuated the burden on hospitals. The association of high viral replication with disease severity suggests the potential for lower viral load in milder clinical presentations.MethodsThe reverse-transcription-polymerase-chain-reaction (RT-PCR) profile of 944 consecutive, non-replicate, positive retropharyngeal swabs was collected from 3 March to 8 June 2020 to investigate the temporal profile of SARS-CoV-2 viral load in the region of Capitanata, Apulia. Cycle threshold (Ct) values of 3 targets (N [nucleocapsid protein], E [envelope protein] and RdRP [RNA-dependent RNA-polymerase]) were analysed.ResultsThe median Ct values of the 3 targets increased considerably over the study period, showing a progressive and constant weekly change. The negative detection rate of E and RdRP increased over time. These data suggest that SARS-CoV-2 viral load progressively decreased along the outbreak course. During the first epidemic peak (March and April) the viral load among patients >80-years was significantly higher than for younger subjects. However, in May this age-dependent difference disappeared, underlying viral load reduction in the elderly.ConclusionsAn attenuation of viral transmission or pathogenicity during the epidemic course is suggested, likely due to restriction measures, although viral factors might also be considered.
Project description:There remains an urgent need to delinate immune cell states that contribute to mortality in critially ill COVID-19 patients. To better understand determinants of mortality, we performed high dimensional profiling of blood and respiratory samples from critially ill COVID-19 patients. Single-cell RNAseq based characterization of peripheral immune states reveal distinct expression profiles that were predictive of COVID-19 mortality. Temporal analysis revealed a that persistently elevated levels of inflammatory monocyte signatures and persistent interferon signaling preceeded concerted upregulation of inflammatory cytokines. Interrogation of lower respiratory tract saples revelaed that infected myeliod cells upregulated CXCL10, and elevated levels of CXCL10 in plasma were associated with a high risk of death. Overall, our data suggest a pivotal role for myeloid cell states in severe COVID-19 and may faciliate discovery of new diagnostics and therapeutics.