LitCovid-sentences  

PMC:7402624 / 4746-11994 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T34 0-99 Sentence denotes Acute SARS-CoV2 infection in humans results in broad changes in circulating immune cell populations
T35 100-321 Sentence denotes We conducted an observational study of hospitalized patients with COVID-19 at the University of Pennsylvania (UPenn IRB 808542) that included 149 hospitalized adults with confirmed SARS-CoV2 infection (COVID-19 patients).
T36 322-406 Sentence denotes Blood was collected at enrollment (typically ~24-72 hours after admission; Fig. 1A).
T37 407-489 Sentence denotes Additional samples were obtained from patients who remained hospitalized on day 7.
T38 490-706 Sentence denotes Blood was also collected from non-hospitalized patients who had recovered from documented SARS-CoV2 infection (Recovered Donors (RD); n = 46), as well as from healthy donors (HD; n = 70) (UPenn IRB 834263) (Fig. 1A).
T39 707-804 Sentence denotes Clinical metadata are available from the COVID-19 patients over the course of disease (table S1).
T40 805-1008 Sentence denotes Of the total patients and donors, flow cytometry data from PBMCs was collected from COVID-19 patients (n = 125), RDs (n = 36), and HDs (n = 60) along with clinical metadata (Fig. 1A and tables S2 to S4).
T41 1009-1128 Sentence denotes Fig. 1 Clinical characterization of patient cohorts, inflammatory markers, and quantification of major immune subsets.
T42 1129-1315 Sentence denotes (A) Overview of patient cohorts in study, including healthy donors (HD), recovered donors (RD), and COVID-19 patients. (B) Quantification of key clinical parameters in COVID-19 patients.
T43 1316-1685 Sentence denotes Each dot is a COVID-19 patient; Healthy donor range indicated in green. (C) Spearman correlation and hierarchical clustering of indicated features for COVID-19 patients. (D) Representative flow cytometry plots and (E) frequencies of major immune subsets. (F) Ratio of CD4:CD8 T cells. (G) Spearman correlation of CD4:CD8 ratio and clinical lymphocyte count per patient.
T44 1686-1802 Sentence denotes Dark and light gray shaded regions represent clinical normal range and normal range based on study HD, respectively.
T45 1803-2053 Sentence denotes Vertical dashed line indicates clinical threshold for lymphopenia. (H) Spearman correlations of indicated subsets with various clinical features. (E and F) Each dot represents an individual healthy donor (green), RD (blue), or COVID-19 patient (red).
T46 2054-2180 Sentence denotes Significance determined by unpaired Wilcoxon test with BH correction: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.
T47 2181-2391 Sentence denotes COVID-19 patients had a median age of 60 and were significantly older than HD and RD (median age of 41 and 29 respectively), though the age distributions for all three cohorts overlapped (Fig. 1A and fig. S1A).
T48 2392-2489 Sentence denotes For COVID-19 patients, median BMI was 29 (range 16-78), and 68% were African American (table S2).
T49 2490-2591 Sentence denotes Comorbidities in COVID-19 patients were dominated by cardiovascular risk factors (83% of the cohort).
T50 2592-2696 Sentence denotes Nearly 20% of subjects suffered from chronic kidney disease and 18% had a previous thromboembolic event.
T51 2697-2866 Sentence denotes A subset of patients (18%) were immunosuppressed, and 7% and 6% of patients were known to have a diagnosis of cancer or a pre-existing pulmonary condition, respectively.
T52 2867-2974 Sentence denotes 45% of the patients were treated with hydroxychloroquine (HCQ), 31% with steroids, and 29% with remdesivir.
T53 2975-3046 Sentence denotes Eighteen individuals died in the hospital or within a 30 day follow-up.
T54 3047-3161 Sentence denotes The majority of the patients were symptomatic at diagnosis and were enrolled ~9 days after initiation of symptoms.
T55 3162-3314 Sentence denotes Approximately 30% of patients required mechanical ventilation at presentation, with additional extracorporeal membrane oxygenation (ECMO) in four cases.
T56 3315-3439 Sentence denotes As has been reported for other COVID-19 patients (31), this COVID-19 cohort presented with a clinical inflammatory syndrome.
T57 3440-3645 Sentence denotes C reactive protein (CRP) was elevated in over 90% of subjects and LDH and D-dimer were increased in the vast majority, whereas ferritin was above normal in ~75% of COVID-19 patients (Fig. 1B and fig. S1B).
T58 3646-3723 Sentence denotes Similarly, troponin and NT-proBNP were increased in some patients (fig. S1B).
T59 3724-3908 Sentence denotes In a subset of patients where it was measured, IL-6 levels were normal in 5 patients, moderately elevated in 5 patients (6-20 pg/ml), and high in 31 patients (21-738 pg/ml) (fig. S1B).
T60 3909-4045 Sentence denotes Although white blood cell counts (WBC) were mostly normal, individual leukocyte populations were altered in COVID-19 patients (Fig. 1B).
T61 4046-4160 Sentence denotes A subset of patients had high PMN counts (fig. S1B) as described previously (8, 32) and in a companion study (33).
T62 4161-4271 Sentence denotes Furthermore, approximately half of the COVID-19 patients were clinically lymphopenic (ALC <1 THO/ul, Fig. 1B).
T63 4272-4369 Sentence denotes In contrast, monocyte, eosinophil, and basophil counts were mostly normal (Fig. 1B and fig. S1B).
T64 4370-4494 Sentence denotes To examine potential associations between these clinical features, we performed correlation analysis (Fig. 1C and fig. S1C).
T65 4495-4728 Sentence denotes This analysis revealed correlations between different COVID-19 disease severity metrics, as well as clinical features or interventions associated with more severe disease (e.g., D-dimer, vasoactive medication) (Fig. 1C and fig. S1C).
T66 4729-4861 Sentence denotes WBC and PMN also correlated with metrics of disease severity (e.g., APACHE III), as well as with IL-6 levels (Fig. 1C and fig. S1C).
T67 4862-5104 Sentence denotes Other relationships were also apparent, including correlations between age or mortality and metrics of disease severity and many other correlations between clinical measures of disease, inflammation, and co-morbidities (Fig. 1C and fig. S1C).
T68 5105-5291 Sentence denotes Thus, COVID-19 patients presented with varied pre-existing comorbidities, complex clinical phenotypes, evidence of inflammation in many patients, and clinically altered leukocyte counts.
T69 5292-5497 Sentence denotes To begin to interrogate immune responses to acute SARS-CoV2 infection, we compared peripheral blood mononuclear cells (PBMC) of COVID-19 patients, RD, and HD subjects using high dimensional flow cytometry.
T70 5498-5551 Sentence denotes We first focused on the major lymphocyte populations.
T71 5552-5790 Sentence denotes B cell and CD3+ T cell frequencies were decreased in COVID-19 patients compared to HD or RD subjects, reflecting clinical lymphopenia, whereas the relative frequency of non-B and non-T cells was correspondingly elevated (Fig. 1, D and E).
T72 5791-5958 Sentence denotes Although a numerical expansion of a non-B, non-T cell type is possible, loss of lymphocytes likely results in an increase in the relative frequency of this population.
T73 5959-6052 Sentence denotes This non-B, non-T cell population is also interrogated in more detail in the companion study.
T74 6053-6509 Sentence denotes Examining only CD3 T cells revealed preferential loss of CD8 T cells compared to CD4 T cells (Fig. 1, F and G, and fig. S1D); this pattern was reflected in absolute numbers estimated from the clinical data, where both CD4 and CD8 T cell counts in COVID-19 patients were lower than the clinical reference range, though the effect was more prominent for CD8 T cells (49/61 subjects below normal) than for CD4 T cells (38/61 subjects below normal) (fig. S1E).
T75 6510-6660 Sentence denotes These findings are consistent with previous reports of lymphopenia during COVID-19 disease (17–20) but highlight a preferential impact on CD8 T cells.
T76 6661-6765 Sentence denotes We next asked if the changes in these lymphocyte populations were related to clinical metrics (Fig. 1H).
T77 6766-6918 Sentence denotes Lower WBC counts were associated preferentially with lower frequencies of CD4 and CD8 T cells and increased non-T non-B, but not with B cells (Fig. 1H).
T78 6919-7093 Sentence denotes These lower T cell counts were associated with clinical markers of inflammation including ferritin, D-dimer, and hsCRP (Fig. 1H), whereas altered B cell frequencies were not.
T79 7094-7248 Sentence denotes Thus, hospitalized COVID-19 patients present with a complex constellation of clinical features that may be associated with altered lymphocyte populations.