LitCovid-sentences  

PMC:7402624 / 34703-41269 JSONTXT 10 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T200 0-73 Sentence denotes Temporal changes in immune cell populations occur during COVID-19 disease
T201 74-165 Sentence denotes A key question for hospitalized COVID-19 patients is how immune responses change over time.
T202 166-377 Sentence denotes Thus, we used the global tSNE projections of overall CD8 T cell, CD4 T cell, and B cell differentiation states to interrogate temporal changes in these populations between D0 and D7 of hospitalization (Fig. 5A).
T203 378-594 Sentence denotes Combining data for all patients revealed considerable stability of the tSNE distributions between D0 and D7 in CD8 T cell, CD4 T cell, and B cell populations, particularly for key regions of interest discussed above.
T204 595-793 Sentence denotes For example, for CD8 T cells, the region of the tSNE map containing KI67+ and CD38+HLA-DR+ CD8 T cell populations that was enriched in COVID-19 patients at D0 (Fig. 2) was preserved at D7 (Fig. 5A).
T205 794-887 Sentence denotes A similar temporal stability of CD4 T cell and B cell activation was also observed (Fig. 5A).
T206 888-970 Sentence denotes Fig. 5 Temporal relationships between immune responses and disease manifestation.
T207 971-1158 Sentence denotes (A) Global viSNE projection of non-naïve CD8 T cells, non-naïve CD4 T cells, and B cells for all subjects pooled, with cells from COVID-19 patients at D0 and D7 concatenated and overlaid.
T208 1159-1430 Sentence denotes Frequencies of (B) KI67+ and HLA-DR+CD38+ CD4 T cells, (C) KI67+ and HLA-DR+CD38+ CD8 T cells, or (D) PBs as indicated for healthy donor (HD; green), recovered donor (RD; blue), or COVID-19 patients (red) with paired samples at D0 and D7 indicated by the connecting line.
T209 1431-1536 Sentence denotes Significance determined by paired Wilcoxon test: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.
T210 1537-1799 Sentence denotes Longitudinal patterns (see Methods) of (E) HLA-DR+CD38+ CD4 T cells or (F) PBs in COVID-19 patients shown as frequency and representative flow cytometry plots. (G) Spearman correlations of clinical parameters with longitudinal fold changes in immune populations.
T211 1800-1928 Sentence denotes Given this apparent stability between D0 and D7, we next investigated temporal changes in lymphocyte subpopulations of interest.
T212 1929-2239 Sentence denotes Although there were no obvious temporal changes in major phenotypically defined CD4 and CD8 T cell or B cell subsets, including plasmablasts (Fig. 5D), the frequencies of HLA-DR+CD38+ and KI67+ non-naïve CD4 (Fig. 5B) and KI67+ non-naïve CD8 T cells were statistically increased at D7 compared to D0 (Fig. 5C).
T213 2240-2419 Sentence denotes However, in all cases, these temporal patterns were complex, with frequencies of subpopulations in individual patients appearing to increase, decrease, or stay the same over time.
T214 2420-2590 Sentence denotes To quantify these inter-patient changes, we used a previously described data set (46) to define the stability of populations of interest in healthy individuals over time.
T215 2591-2770 Sentence denotes We then used the range of this variation over time to identify COVID-19 patients with changes in immune cell subpopulations beyond that expected in healthy subjects (see methods).
T216 2771-2966 Sentence denotes Using this approach, ~50% of patients had an increase in HLA-DR+CD38+ non-naïve CD4 T cells over time, whereas in ~30% of patients, these cells were stable and, in ~20%, they decreased (Fig. 5E).
T217 2967-3057 Sentence denotes For KI67+ non-naïve CD8 T cells, there were no individuals in whom the response decreased.
T218 3058-3157 Sentence denotes Instead, this proliferative CD8 T cell response stayed stable (~70%) or increased (~30%; fig. S6A).
T219 3158-3338 Sentence denotes Notably, for patients in the stable category, the median frequency of KI67+ non-naïve CD8 T cells was ~10%, almost 5-fold higher than the ~1% detected for HD and RD subjects (Figs.
T220 3339-3421 Sentence denotes 5C and 2E), suggesting a sustained CD8 T cell proliferative response to infection.
T221 3422-3613 Sentence denotes A similar pattern was observed for HLA-DR+CD38+ non-naïve CD8 (fig. S6B), where only ~10% of patients had a decrease in this population, whereas ~65% were stable and ~25% increased over time.
T222 3614-4014 Sentence denotes The high and even increasing activated or proliferating CD8 and CD4 T cell responses over ~1 week during acute viral infection contrasted with the sharp peak of KI67 in CD8 and CD4 T cells during acute viral infections, including smallpox vaccination with live vaccinia virus (47), live attenuated yellow fever vaccine YFV-17D (48), acute influenza virus infection (49), and acute HIV infection (35).
T223 4015-4130 Sentence denotes Approximately 42% of patients had sustained PB responses, at high levels (>10% of B cells) in many cases (Fig. 5F).
T224 4131-4292 Sentence denotes Thus, some patients displayed dynamic changes in T cell or B cell activation over 1 week in the hospital, but there were also other patients who remained stable.
T225 4293-4484 Sentence denotes In the latter case, some patients remained stable without clear activation of key immune populations whereas others had stable T and or B cell activation or numerical perturbation (fig. S6C).
T226 4485-4677 Sentence denotes We next asked whether these T and B cell dynamics related to clinical measures of COVID-19 disease, by correlating changes in immune features from D0 to D7 with clinical information (Fig. 5G).
T227 4678-4724 Sentence denotes These analyses revealed distinct correlations.
T228 4725-4967 Sentence denotes Decreases in all populations of responding CD4 and CD8 T cells (HLA-DR+CD38+, KI67+, or activated cTfh) between D0 and D7 were positively correlated with PMN and WBC counts, suggesting a relationship between T cell activation and lymphopenia.
T229 4968-5071 Sentence denotes Furthermore, decreases in CD4 and CD8 HLA-DR+CD38+ T cells positively correlated with APACHE III score.
T230 5072-5177 Sentence denotes However, stable HLA-DR+CD38+ CD4 T cell responses correlated with coagulation complications and ferritin.
T231 5178-5292 Sentence denotes Whereas decreasing activated cTfh over time was related to co-infection, the opposite pattern was observed for PB.
T232 5293-5574 Sentence denotes Increases in proliferating KI67+ CD4 and CD8 T cells over time were positively correlated to increasing anti-SARS-CoV2 antibody from day 0 to day 7, suggesting that some individuals might have been hospitalized during the expansion phase of the antiviral immune response (Fig. 5G).
T233 5575-5678 Sentence denotes Finally, neither Remdesivir nor HCQ treatment correlated with any of these immune features in Fig. 5G).
T234 5679-5894 Sentence denotes Examining categorical rather than continuous clinical data, 80% of patients with decreasing PB over time had hyperlipidemia, whereas only 20% of patients with increasing PB over time had this comorbidity (fig. S6D).
T235 5895-6159 Sentence denotes All patients who had decreasing CD38+HLA-DR+ CD8 T cells from day 0 to day 7 were treated with early vasoactive medication or inhaled nitric oxide whereas these treatments were less common for patients with stable or increasing CD38+HLA-DR+ CD8 T cells (fig. S6E).
T236 6160-6322 Sentence denotes In contrast, vasoactive medication, inhaled nitric oxide, and early steroid treatment were equally common in patients with increasing or decreasing PB (fig. S6D).
T237 6323-6430 Sentence denotes Similar patterns were apparent for other T cell populations and these categorical clinical data (fig. S6F).
T238 6431-6566 Sentence denotes Thus, the trajectory of change in the T and B cell response in COVID-19 patients was strongly connected to clinical metrics of disease.