PMC:7736111 / 118777-142839 JSONTXT 3 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T698 0-35 Sentence denotes Cytokine Storm in COVID-19 Patients
T699 36-242 Sentence denotes Severe and critically ill COVID-19 patients exhibit cytokine storm (CS) as a reflection of the hyperimmune activation mediated by lung resident and infiltrated inflammatory immune cells, as mentioned above.
T700 243-447 Sentence denotes CS is manifested by the release of potent inflammatory cytokines, chemokines, and in some instances, interferons (as a late response) into the circulation that serves as an indicator of early lung damage.
T701 448-604 Sentence denotes Though the term CS is generally used with cytokine release syndrome (CRS) during CAR-T cell immunotherapy, it can reflect different pathological conditions.
T702 605-739 Sentence denotes While IL-6, TNF-α, and IL1-β predominantly represent CRS, CS is a much more complex response mounted by a range of inflammatory cells.
T703 740-906 Sentence denotes Further, differences are also apparent in the kinetics, and the concentration of the cytokines released, as discussed in a recent review (Vardhana and Wolchok, 2020).
T704 907-1156 Sentence denotes Data from moderate, severe, critically ill, and recovered patients reveal a close correlation between the presence of proinflammatory cytokines with disease severity (Huang C. et al., 2020; Liao et al., 2020; Liu J. et al., 2020; Zhao et al., 2020).
T705 1157-1210 Sentence denotes Clinical evaluation of 41 COVID-19 patients (Non-ICU:
T706 1211-1222 Sentence denotes 28 and ICU:
T707 1223-1424 Sentence denotes 13) for over 26 chemokines and cytokines revealed increased levels of 16 of them such as IL-1β, IL-1RA, IL-17, IL-8, IL-9, IL-10, basic FGF, G-CSF, GM-CSF, IFN-γ, CXCL10, CCL2, CCL3, CCL4, PDGF, TNF-α.
T708 1425-1632 Sentence denotes In comparison to non-ICU cases, patients admitted to ICU exhibited increased levels of IL1-β, IFN-γ, and IL-6, suggesting TH1 immune cell response as reported previously for SARS-CoV (Huang C. et al., 2020).
T709 1633-1827 Sentence denotes Further, higher levels of G-CSF, CXCL10, CCL2, CCL3, and TNF-α indicated activation of monocytes and macrophages and damage to lung epithelial cells that were strongly correlated with ICU cases.
T710 1828-2009 Sentence denotes The strength of this study is that this is the first comprehensive cytokine profiling study of the COVID-19 patients, where disease severity was compared with the cytokine response.
T711 2010-2262 Sentence denotes The major limitation with this study is the small sample size for comparison between groups, and the use of lower respiratory specimen for testing rather nasopharyngeal swab sample – which is a sensitive specimen and commonly used for COVID-19 testing.
T712 2263-2432 Sentence denotes Working on relatively similar sample size (n = 40), Liu J. et al. (2020) found increased serum levels of IL-2, IL-6, IL-10 and IFN-γ corresponding with disease severity.
T713 2433-2542 Sentence denotes By performing longitudinal analysis, IL-6, IL-10 levels were consistently increased in severe cases (n = 13).
T714 2543-2811 Sentence denotes Besides small sample size, the major limitation with this study was that most of the patients had a comorbid condition like diabetes, hypertension, fungal infection and other chronic ailments, which may complicate the data interpretation and comparison between groups.
T715 2812-3050 Sentence denotes By working on a relatively larger cohort (n = 799), Chen T. et al. (2020) found that increased levels of IL-2R, IL-6, IL-8, IL-10, TNF-α in patients who had to succumb to the disease (n = 113) as compared to those who recovered (n = 161).
T716 3051-3092 Sentence denotes However, unlike the study by Huang et al.
T717 3093-3164 Sentence denotes IL-1β was not found to be significantly increased in deceased patients.
T718 3165-3347 Sentence denotes This discrepancy could be because the samples used by Huang C. et al. (2020) were from critically ill (5 deceased out of 13) patients, whereas Chen et al. analyzed deceased patients.
T719 3348-3465 Sentence denotes Thus, observed differences in levels of cytokines may reflect the disease severity and underlying comorbid condition.
T720 3466-3674 Sentence denotes In addition to the peripheral blood profiles, transcription profiling of BALF revealed higher expression of IL-10, CCL2, CXCL10, CCL3, and CCL4, a representation of lung immunopathology. (Xiong et al., 2020).
T721 3675-3992 Sentence denotes Similarly, in another study measurement of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-α, IFN-γ, and TNF-α were performed in the BALF, and the results revealed a significant increase in IL-1β, IL-6, and IL-8 levels in critically ill patients as compared to moderate condition (Liao et al., 2020).
T722 3993-4256 Sentence denotes BALF fluid analysis of 8 COVID-19 patients by Zhou Z. et al. (2020) also showed upregulation of key chemokine transcripts that are involved in the recruitment of inflammatory cells (IL1RN, IL1β, CXCL17, CXCL8, CXCL1, CXCL2, CCL2, and CCL7) (Zhou Z. et al., 2020).
T723 4257-4408 Sentence denotes ScRNA-seq analysis of BALF also revealed increased expression of CXCL9, CXCL10, CXCL11, and CXCL16 in all tested COVID-19 patients (Liao et al., 2020).
T724 4409-4550 Sentence denotes Lung macrophages displayed increased transcripts of IL-1β, IL-6, TNF-α along with chemokines like CCL2, CCL3, CCL4, and CCL7 in severe cases.
T725 4551-4774 Sentence denotes In terms of the contribution by the lung resident cells, tissue immunohistochemistry data revealed increased levels of IL-6, TNF-a and IL-10 in the AMs of biopsy samples obtained from deceased patients (Wang et al., 2020b).
T726 4775-4957 Sentence denotes Together, these studies unequivocally show heightened proinflammatory cytokine and chemokine response in circulation as well as at the site of infection in severe and critical cases.
T727 4958-5202 Sentence denotes Since these initial reports, all the subsequent studies revealed a consistent increase in IL-6, and to some extent TNF-α (Chen G. et al., 2020; Diao et al., 2020; Luo et al., 2020; Qin et al., 2020; Tan M. et al., 2020c; Zheng M. et al., 2020).
T728 5203-5463 Sentence denotes Based on the clinical cytokine profile across the studies in critical/deceased patients, serum IL-6 level is well established as a reliable predictive marker for COVID-19 severity and a potential marker of ARDS along with increased neutrophil/lymphocyte ratio.
T729 5464-5648 Sentence denotes Thus, considering a robust increase in IL-6 levels in the majority of the severe COVID-19 patients, currently, treatments are underway to lower the levels of this pleiotropic cytokine.
T730 5649-5816 Sentence denotes For example, antibodies directed against IL-6R (such as tocilizumab) have shown promising clinical outcomes (Capra et al., 2020; Luo et al., 2020; Xu X. et al., 2020).
T731 5817-5980 Sentence denotes Similarly, antibodies directed against GM-CSF (NCT04351243) and IL-β (NCT04348448) are also being explored for their efficacy to attenuate CS in COVID-19 patients.
T732 5981-6127 Sentence denotes A detailed list of the recent papers which reported clinical profiles of these inflammatory molecules in COVID-19 patients is provided in Table 1.
T733 6128-6268 Sentence denotes TABLE 1 List of some research articles from December 2019 to May 2020 establishing lymphocytopenia and cytokine storm in COVID-19 patients.
T734 6269-6271 Sentence denotes S.
T735 6272-6325 Sentence denotes No No. of patients Findings Sample References
T736 6326-6328 Sentence denotes 1.
T737 6330-6336 Sentence denotes Total:
T738 6337-6345 Sentence denotes 40 Mild:
T739 6346-6356 Sentence denotes 27 Severe:
T740 6357-6765 Sentence denotes 13 • Decrease in CD8+ and CD4+ T cell counts were observed suggesting lymphocytopenia• Increase in IL-2, IL-6, IL-10, and IFN-γ levels in severe cases• No significant changes were observed in IL-4 and TNF-α levels• The number of T cells increased in patients who recovered from the disease, along with a decrease in the cytokine levels comparable to mild cases Peripheral blood/Serum (Liu J. et al., 2020)
T741 6766-6768 Sentence denotes 2.
T742 6770-6776 Sentence denotes Total:
T743 6777-6797 Sentence denotes 147 Healthy control:
T744 6798-6815 Sentence denotes 45 Mild/moderate:
T745 6816-6826 Sentence denotes 42 Severe:
T746 6827-6839 Sentence denotes 43 Critical:
T747 6840-7179 Sentence denotes 17 • Increased levels of serum cytokines like TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10 were found in all COVID-19 patients• Similarly, CRP levels were increased in all COVID-19 patients, which showed positive correlation with IL-10• IL-6 and IL-10 levels were suggested as predictive disease severity biomarkers Serum (Han et al., 2020)
T748 7180-7182 Sentence denotes 3.
T749 7184-7202 Sentence denotes Total:138 Non-ICU:
T750 7203-7211 Sentence denotes 102 ICU:
T751 7212-7511 Sentence denotes 32 • Ninety-seven patients from both the groups showed lymphocytopenia.• Neutrophil count was significantly higher in ICU patients.• ICU patients showed significantly elevated levels of D-dimer, creatine kinase–MB, LD, ALT, AST, and procalcitonin suggesting multiple organ dysfunction in ICU cases.
T752 7513-7559 Sentence denotes Peripheral blood/Serum (Wang D. et al., 2020)
T753 7560-7562 Sentence denotes 4.
T754 7564-7584 Sentence denotes Total:191 Recovered:
T755 7585-7598 Sentence denotes 137 Deceased:
T756 7599-7673 Sentence denotes 58 • Deceased patients had lower levels of lymphocyte and platelet count.
T757 7674-7989 Sentence denotes Whereas higher levels of ALT, LDH, creatinine, creatinine kinase, troponin I, Serum ferritin, and D-dimer was observed in deceased patients’ samples• d-DIMER was suggested as a potential marker for COVID-19 severity• Higher IL-6 levels were found in deceased patients Peripheral blood/Serum (Zhou F. et al., 2020)
T758 7990-7992 Sentence denotes 5.
T759 7994-8011 Sentence denotes Total:41 Non-ICU:
T760 8012-8019 Sentence denotes 28 ICU:
T761 8020-8380 Sentence denotes 13 • Decrease in total lymphocyte count while increase in neutrophil count was observed in ICU patients.• Higher plasma levels of IL-2, IL-7, IL-10, GCSF, IP-10 (CXCL10), CCL2, CCL3, and TNF-α were observed in ICU patients as compared to non-ICU.• Increased levels of TH2 cytokine IL-4 was reported.• Increased levels of D-dimer, ALT, and AST in ICU patients.
T762 8382-8429 Sentence denotes Peripheral blood/Serum (Huang C. et al., 2020)
T763 8430-8432 Sentence denotes 6.
T764 8434-8454 Sentence denotes Total:150 Recovered:
T765 8455-8467 Sentence denotes 82 Deceased:
T766 8468-8694 Sentence denotes 68 • Increased levels of absolute lymphocyte count.• Significantly increased levels of IL-6, blood creatinine, myoglobin, cardiac troponin, CRP, total bilirubin, and blood urea nitrogen were observed in the deceased patients.
T767 8695-8784 Sentence denotes Further, higher levels of ALT, AST, LDH, creatinine, and creatinine kinase were observed.
T768 8786-8829 Sentence denotes Peripheral blood/Serum (Ruan et al., 2020)
T769 8830-8832 Sentence denotes 7.
T770 8834-8852 Sentence denotes Total:50 moderate:
T771 8853-8863 Sentence denotes 14 Severe:
T772 8864-8882 Sentence denotes 25 Critically ill:
T773 8883-9366 Sentence denotes 11 • Total percentage CD4+ T and CD8+ T cells was significantly lower in the severe cases along with increase in total neutrophil percentage, indicating overall dysfunctional immune response.• Increased levels of IFN-γ, IL-1ra, IL-2ra, IL-6, IL-10, IL-18, HGF, CCL7, MIG, M-CSF, G-CSF, MIG-1a, CTACK, and IP-10.• IP-10, CCL7, and IL-1RA were higher in severe cases compared to moderate.• Lymphocytopenia and increased neutrophil count was suggested to correlate with disease severe.
T774 9368-9414 Sentence denotes Peripheral blood/Serum (Yang Y. et al., 2020)
T775 9415-9417 Sentence denotes 8.
T776 9419-9437 Sentence denotes Total:21 moderate:
T777 9438-9833 Sentence denotes 10 Severe:11 • Absolute count of lymphocytes was decreased and specifically levels of CD4+ T and CD8+ T were lower in severe cases.• Higher levels of IL-2R, IL-6, IL-10, and TNF-α were observed in severe cases.• Higher levels of ALT, LDH, CRP, ferritin, and D-dimer was detected in severe cases.• Further, levels of IFN-γ levels specifically measured in CD4+ T cells were lower in severe cases.
T778 9835-9881 Sentence denotes Peripheral blood/Serum (Chen G. et al., 2020)
T779 9882-9884 Sentence denotes 9.
T780 9886-9985 Sentence denotes Total:1 deceased • CD4+ T and CD8+ T cells were reduced, however, they exhibited activated status.
T781 9986-10158 Sentence denotes Higher cytotoxic granules in CD8+ T cells indicated overactivation.• Increased levels of TH17 cells.• Inflammatory mononuclear infiltrates were observed in the lung tissue.
T782 10160-10204 Sentence denotes Peripheral blood/Serum (Xu Z. et al., 2020)
T783 10205-10208 Sentence denotes 10.
T784 10210-10216 Sentence denotes Total:
T785 10217-10232 Sentence denotes 452 Non-Severe:
T786 10233-10244 Sentence denotes 166 Severe:
T787 10245-10310 Sentence denotes 286 • The total number of T cells were decreased in severe case.
T788 10311-10487 Sentence denotes Further lower levels of CD4+ regulatory and CD8+ suppressor T cells was observed in severe cases.• Severe cases exhibited higher neutrophil counts and an increase in NLR ratio.
T789 10488-10701 Sentence denotes Whereas blood monocytes and eosinophil counts were lower.• Among the proinflammatory markers, increased levels of TNF-α, IL-2R, and IL-6, IL-8, IL-10 along with CRP, serum ferritin, and procalcitonin was observed.
T790 10702-10755 Sentence denotes Whereas no significant difference in IL-1β was found.
T791 10757-10799 Sentence denotes Peripheral blood/Serum (Qin et al., 2020)
T792 10800-10803 Sentence denotes 11.
T793 10805-10811 Sentence denotes Total:
T794 10812-10829 Sentence denotes 56 Mild/Moderate:
T795 10830-10839 Sentence denotes 31 Sever:
T796 10840-10929 Sentence denotes 25 • The levels of CD4+, CD8+ T cells, NK cells, and B cells were lower in severe cases.
T797 10930-11077 Sentence denotes Whereas, TREG cells were found to be moderately increased in mild cases.• Higher levels of IL-2, IL-6, IL-10, and TNF-α were found in severe cases.
T798 11078-11137 Sentence denotes Increase in IL-4 was observed in mild but not severe cases.
T799 11138-11302 Sentence denotes Further, IL-2 and IL-6 were suggested as reliable indicators for disease severity.• Serum leves were inconsistent with low levels or unchanged in COVID-19 patients.
T800 11304-11350 Sentence denotes Peripheral blood/Serum (Tan M. et al., 2020c)
T801 11351-11354 Sentence denotes 12.
T802 11356-11362 Sentence denotes Total:
T803 11363-11378 Sentence denotes 222 Non-severe:
T804 11379-11389 Sentence denotes 81 Severe:
T805 11390-11556 Sentence denotes 67 • Higher NLR with lower levels of CD4+, CD8+ T cells in severe cases.• Higher cytokine levels of IFN-γ, IL-2, IL-6, and IL-10 was found in patients with high NLR.
T806 11557-11745 Sentence denotes No significant difference in IL-4 levels were observed between severe and non-severe cases.• NLR was suggested as a predictive disease marker Peripheral blood/Serum (Zhang et al., 2020a)
T807 11746-11749 Sentence denotes 13.
T808 11751-11757 Sentence denotes Total:
T809 11758-11771 Sentence denotes 25 Recovered:
T810 11772-11789 Sentence denotes 14 Non-recovered:
T811 11790-11908 Sentence denotes 11 • Lower levels of CD3+ T cells, CD4+ T cells, CD8+ T, NK cells as well as B cells were found in COVID-19 patients.
T812 11909-12146 Sentence denotes Treated patients who exhibited clearance of virus showed restoration in levels of CD3+ T cells, CD4+ T cells, CD8+ T cells, whereas NK cell count was inconsistent.• Lymphocytopenia was considered as predicative biomarker for the disease.
T813 12148-12188 Sentence denotes Peripheral blood (Chen X. et al., 2020)
T814 12189-12192 Sentence denotes 14.
T815 12194-12200 Sentence denotes Total:
T816 12201-12212 Sentence denotes 22 Healthy:
T817 12213-12230 Sentence denotes 10 Mild/Moderate:
T818 12231-12241 Sentence denotes 10 Severe:
T819 12242-12399 Sentence denotes 6 • Marked reduction in functional CD4+ T cells was observed, as revealed by decrease in IFN-γ, and TNF-α produced by these cells in severe group than mild.
T820 12400-12758 Sentence denotes CD8+ T cells revealed activation profile as marked by increased levels of granzyme B and perforin in severe than mild cases.• CD8+ cells had increased expression of exhaustion marker CTLA-4 in severe than mild and increased PD-1 in mild than healthy group.• No significant differences in IL-6 and TNF-α was observed between severe, mild and healthy controls.
T821 12759-12801 Sentence denotes However, an increasing trend was observed.
T822 12803-12852 Sentence denotes Peripheral blood/Serum (Zheng H.Y. et al., 2020)
T823 12853-12856 Sentence denotes 15.
T824 12858-12864 Sentence denotes Total:
T825 12865-12882 Sentence denotes 68 Mild/Moderate:
T826 12883-12893 Sentence denotes 55 Severe:
T827 12894-13139 Sentence denotes 13 • Decreased number of CD8+ T and NK cells in patients showing severe symptoms.• Decrease in expression of IFN-γ, IL-2, granzyme-B by CD8+ T, and decrease in TNF-α expression by NK cells was observed, indicating CD8+ T and NK cell exhaustion.
T828 13141-13188 Sentence denotes Peripheral blood/Serum (Zheng M. et al., 2020)
T829 13189-13192 Sentence denotes 16.
T830 13194-13200 Sentence denotes Total:
T831 13201-13530 Sentence denotes 99 patients with mild to severe symptoms • Decrease in lymphocyte count and increase in neutrophils was observed when compared to the normal range.• Increased serum levels of IL-6, D-dimer, ALT, AST, LDH, Myoglobin, Procalcitonin, Serum ferritin, Erythrocyte sedimentation rate, and CRP was observed in all the studied patients.
T832 13531-13597 Sentence denotes Serum creatinine, and creatinine kinase showed inconsistent trend.
T833 13599-13645 Sentence denotes Peripheral blood/Serum (Chen N. et al., 2020)
T834 13646-13649 Sentence denotes 17.
T835 13651-13657 Sentence denotes Total:
T836 13658-13676 Sentence denotes 522 Mild/moderate:
T837 13677-13688 Sentence denotes 151 Severe:
T838 13689-14010 Sentence denotes 53 • Decreased number of total CD4+ and CD8+ T cells were observed in most of the patients with further decrease reported in patients who were admitted to ICU.• T cell exhaustion markers like PD1 and TIM3 were higher in severe disease patients.• Serum levels of TNF-α, IL-6 and IL-10 were higher in symptomatic patients.
T839 14011-14236 Sentence denotes However, no significant changes in the levels of IFN-γ, IL-2, and IL-4 were observed across groups.• T cell count restored and levels of IFN-γ, IL-10, IL-6, and TNF-α decreased as the disease resolved in a subset of patients.
T840 14238-14281 Sentence denotes Peripheral blood/Serum (Diao et al., 2020)
T841 14282-14285 Sentence denotes 18.
T842 14287-14293 Sentence denotes Total:
T843 14294-14307 Sentence denotes 710 Survivor:
T844 14308-14325 Sentence denotes 20 Non-survivors:
T845 14326-14438 Sentence denotes 32 • Blood analysis of non-survivors revealed decreased total lymphocyte count, and increase in platelet count.
T846 14439-14530 Sentence denotes Serum analysis revealed increase in total bilirubin, creatinine, and lactate concentration.
T847 14532-14578 Sentence denotes Peripheral blood/Serum (Yang X. et al., 2020)
T848 14579-14582 Sentence denotes 19.
T849 14584-14590 Sentence denotes Total:
T850 14591-14785 Sentence denotes 34 patients with varying disease severity • Presence of increased levels of inflammatory monocytes in the blood which were found to secrete proinflammatory cytokines like IL-10, IL6, and TNF-α.
T851 14787-14834 Sentence denotes Peripheral blood/Serum (Zhang D. et al., 2020)
T852 14835-14838 Sentence denotes 20.
T853 14840-14860 Sentence denotes Total:80 Non-severe:
T854 14861-14871 Sentence denotes 11 Severe:
T855 14872-15090 Sentence denotes 69 • The levels of CRP, ferritin, IL-6 and LDH were shown to be associated with longer treatment modality.• IL-6 levels were shown to positively correlate with disease severity and suggested as a predictive biomarker.
T856 15092-15120 Sentence denotes Serum (Liu T. et al., 2020)
T857 15121-15124 Sentence denotes 21.
T858 15126-15143 Sentence denotes Total:36 Healthy:
T859 15144-15155 Sentence denotes 10 Non-ICU:
T860 15156-15163 Sentence denotes 16 ICU:
T861 15164-15296 Sentence denotes 10 • Significant decrease in total lymphocytes including CD4+ and CD8+ T cells was observed in ICU patients as compared to non-ICU.
T862 15297-15354 Sentence denotes Both CD4+ and CD8+ T cells exhibited activated phenotype.
T863 15355-15566 Sentence denotes However, no changes were observed in B cells and NK cells between ICU and non-ICU patients.• Higher percentage of inflammatory monocytes were detected in COVID-19 patients, with further increase in ICU patients.
T864 15567-15638 Sentence denotes These monocytes were shown to secrete higher levels of GM-CSF and IL-6.
T865 15640-15678 Sentence denotes Peripheral blood (Zhou et al., 2020a)
T866 15679-15682 Sentence denotes 22.
T867 15684-15704 Sentence denotes Total:799 Recovered:
T868 15705-15718 Sentence denotes 161 Deceased:
T869 15719-15795 Sentence denotes 113 • Leukocytosis was observed in 56 patients who died due to the disease.
T870 15796-16153 Sentence denotes Deceased patients had robust decrease in lymphocytes and displayed lymphocytopenia.• Levels of IL-2, IL-6, IL-8, IL-10, and TNF-α were higher in deceased as compared to the recovered patients.• Serum levels of D-dimer, ferritin, ALT, AST, procalcitonin, creatinine creatine kinase, total bilirubin, ALP, and GGT were markedly increased in deceased patients.
T871 16155-16201 Sentence denotes Peripheral blood/Serum (Chen T. et al., 2020)
T872 16202-16205 Sentence denotes 23.
T873 16207-16213 Sentence denotes Total:
T874 16214-16233 Sentence denotes 70 Moderate- cured:
T875 16234-16250 Sentence denotes 40 Severe-cured:
T876 16251-16260 Sentence denotes 15 Death:
T877 16261-16356 Sentence denotes 15 • Robust decline in lymphocyte percentage in blood of patients who died due to the disease.
T878 16357-16561 Sentence denotes Whereas, substantial recovery of the blood lymphocyte percentage was seen in the patients who recovered from the disease.• The study suggests lymphocytopenia as a predictive prognosis marker for COVID-19.
T879 16563-16603 Sentence denotes Peripheral blood (Tan L. et al., 2020b)
T880 16604-16607 Sentence denotes 24.
T881 16609-16615 Sentence denotes Total:
T882 16616-16633 Sentence denotes 70 Mild/Moderate:
T883 16634-16645 Sentence denotes 8 Critical:
T884 16646-16657 Sentence denotes 10 Control:
T885 16658-16872 Sentence denotes 10 • Serum levels of CCL5 was highly increased in critically ill patients as compared to mild/moderate and healthy control.• Levels of IL-1β, IL-6, IL-8, and other chemokines CXCL8, CCL4, CCL3 were also increased.
T886 16874-16905 Sentence denotes Serum (Patterson et al., 2020)
T887 16906-16909 Sentence denotes 25.
T888 16911-16917 Sentence denotes Total:
T889 16918-16935 Sentence denotes 54 Mild/Moderate:
T890 16936-16946 Sentence denotes 26 Severe:
T891 16947-17205 Sentence denotes 28 • Macrophage activation syndrome along with hyperactivation of monocytes was found in severe cases.• Decrease in lymphocyte number (CD4+T and B cells) along with decline in NK cells was observed.• Blood IL-6 and CRP levels were increased in severe cases.
T892 17206-17294 Sentence denotes Further, increased levels of fibrinogen, D-dimers, creatinine was found in severe cases.
T893 17296-17357 Sentence denotes Peripheral blood/Serum (Giamarellos-Bourboulis et al., 2020)
T894 17358-17361 Sentence denotes 26.
T895 17363-17369 Sentence denotes Total:
T896 17370-17393 Sentence denotes 48 SARS-CoV-2 positive:
T897 17394-17417 Sentence denotes 24 SARS-CoV-2 negative:
T898 17418-17710 Sentence denotes 24 • Reduced IFN-I and IFN-III response was observed in patient samples as well as in in-vitro cell culture model of primary respiratory epithelial cells.• Increase in serum levels of IL-6, IL1RA, CCL2, CCL8 CXCL2, CXCL8, CXCL9, and CXCL16 were observed in Serum (Blanco-Melo et al., 2020)
T899 17711-17714 Sentence denotes 27.
T900 17716-17725 Sentence denotes COVID-19:
T901 17726-17739 Sentence denotes 1484 Healthy:
T902 17740-17749 Sentence denotes 9 Others:
T903 17750-18048 Sentence denotes 272 • Significantly higher levels of IL-6, IL-8, and TNF-α were observed in serum of COVID-19 patients as compared to the healthy control or patients with multiple myeloma.• IL-6, IL-8, and TNF-α were associated with worst disease outcome and suggested as the predictive indicators of the disease.
T904 18050-18081 Sentence denotes Serum (Del Valle et al., 2020)
T905 18082-18085 Sentence denotes 28.
T906 18087-18093 Sentence denotes Total:
T907 18094-18107 Sentence denotes 102 COVID-19:
T908 18108-18115 Sentence denotes 27 Flu:
T909 18116-18299 Sentence denotes 75 • COVID-19 patients showed increased levels of serum CRP, which was associated with disease progression.• CRP levels were suggested as a predictive marker in early stage COVID-19.
T910 18301-18329 Sentence denotes Serum (Tan C. et al., 2020)
T911 18330-18333 Sentence denotes 29.
T912 18335-18341 Sentence denotes Total:
T913 18342-18360 Sentence denotes 132 Mild/moderate:
T914 18361-18371 Sentence denotes 60 Severe:
T915 18372-18384 Sentence denotes 56 Critical:
T916 18385-18470 Sentence denotes 16 • Decreased lymphocyte number was observed in severe and critically ill patients.
T917 18471-18612 Sentence denotes Similarly, increased levels of serum CRP and SAA was observed.• SAA along with lymphocytopenia was suggested as a predicative disease marker.
T918 18614-18658 Sentence denotes Peripheral blood/Serum (Li H. et al., 2020)
T919 18659-18662 Sentence denotes 30.
T920 18664-18670 Sentence denotes Total:
T921 18671-18689 Sentence denotes 377 Mild/moderate:
T922 18690-18701 Sentence denotes 260 Severe:
T923 18702-18900 Sentence denotes 117 • Increased NLR, along with increased levels of serum CRP and D-dimer were observed in patients with severe disease symptoms.• NLT, CRP and d-DIMER were suggested as predictive disease markers.
T924 18902-18946 Sentence denotes Peripheral blood/Serum (Zhou et al., 2020b)
T925 18947-18950 Sentence denotes 31.
T926 18952-18958 Sentence denotes Total:
T927 18959-18977 Sentence denotes 377 Mild/moderate:
T928 18978-18988 Sentence denotes 69 Severe:
T929 18989-19087 Sentence denotes 24 • Significantly higher NLR, PLR, LMR, and total neutrophil count was observed in severe cases.
T930 19088-19235 Sentence denotes Whereas, the count of lymphocytes was decreased.• Serum CRP levels were higher in severe cases.• NLR was suggested as predictive disease biomarker.
T931 19237-19279 Sentence denotes Peripheral blood (Yang A.P. et al., 2020)
T932 19280-19283 Sentence denotes 32.
T933 19285-19291 Sentence denotes Total:
T934 19292-19302 Sentence denotes 18 Severe:
T935 19303-19315 Sentence denotes 16 Critical:
T936 19316-19676 Sentence denotes 2 • Increased activation profile of CD4+, CD8+ and plasmablasts was seen in COVID-19 patients.• Interestingly severe cases were associated with activated profile of CD4+ T cells, lower number of TFH cells and exhaustive CD8+ T cells.• Increased levels of serum AST, CRP, and creatinine kinase was observed.• CRP was suggested as the predictive disease marker.
T937 19678-19724 Sentence denotes Peripheral blood/Serum (Wang G. et al., 2020)
T938 19725-19728 Sentence denotes 33.
T939 19730-19736 Sentence denotes Total:
T940 19737-19748 Sentence denotes 221 Normal:
T941 19749-19762 Sentence denotes 36 Recovered:
T942 19763-19775 Sentence denotes 60 COVID-19:
T943 19776-20332 Sentence denotes 125 • CD4+ and CD8+ T cells were associated with the expression of activation markers (CD38 and HLA-DR), proliferation markers (Ki-67), and exhaustion markers (PD-1).• This elaborate study characterized 200 immune parameters and correlated with clinical features and disease severity.• Increase in chemokines like CXCL10, CXCL9, CCL2, and IL-1RA were observed in half of the COVID-19 patients.• Increased levels of ferritin, D-dimer, and CRP were observed in COVID-19 patients as compared to healthy controls or recovered patients. (Mathew et al., 2020)
T944 20333-20336 Sentence denotes 34.
T945 20338-20344 Sentence denotes Total:
T946 20345-20353 Sentence denotes 41 Mild:
T947 20354-20364 Sentence denotes 29 Severe:
T948 20365-20701 Sentence denotes 12 • Slight lymphocytopenia was observed in mild patients and significantly higher in severe COVID-19 patients as revealed by decrease in CD4+, CD8+ and NK cell number.• Peripheral blood showed increased activation status of CD8+ T with higher percentage of CD38+CD8+, CD38+HLA-DR, and CD38+HLA-DR+CD8+ cells in severe than mild cases.
T949 20702-21003 Sentence denotes While no significant changes were seen in CD4+• Increased expression of exhaustion markers PD-1 and TIM-3 was observed in CD8+, and PD-1 in CD4+ T cells in case of severe cases than mild.• Increased levels of IL-6, TNF-α, IL-17A, IFN-γ, MCP-1, IL-10, IL-4, and IL-5 were observed in COVID-19 patients.
T950 21005-21042 Sentence denotes Peripheral blood (Song et al., 2020)
T951 21043-21046 Sentence denotes 35.
T952 21048-21054 Sentence denotes Total:
T953 21055-21260 Sentence denotes 82 (deceased) • Lymphopenia, neutrophilia, and thrombocytopenia was observed.• Increased levels of CRP, LDH, ALT, and D-dimer were found.• Increased levels of IL-6 Peripheral blood (Zhang et al., 2020b)
T954 21261-21264 Sentence denotes 36.
T955 21266-21280 Sentence denotes Total:24 Mild:
T956 21281-21290 Sentence denotes 4 Severe:
T957 21291-21302 Sentence denotes 5 Critical:
T958 21303-21534 Sentence denotes 3 • Innate immune cells like monocytes, NK cells and myeloid-derived suppressor cells increased from mild to severe cases than declined in the critically ill patients.• CD8+ T cell subsets were decreased in all the disease groups.
T959 21535-21616 Sentence denotes However, CD4+ T, naïve CD4+ T, and TGF-β+CD28- naïve CD4+ T cells were increased.
T960 21617-21789 Sentence denotes On the contrary memory CD4+ T cells were decreased.• Levels of functional molecules such as CXCR3, CD28, and TGF-β were increased in patients as compared to health control.
T961 21791-21820 Sentence denotes PBMCs (Wang W. et al., 2020)
T962 21821-21824 Sentence denotes 37.
T963 21826-21832 Sentence denotes Total:
T964 21833-21845 Sentence denotes 53 Moderate:
T965 21846-21856 Sentence denotes 21 Severe:
T966 21857-21869 Sentence denotes 18 Critical:
T967 21870-21975 Sentence denotes 14 • CD11a expressing lymphocytes (CD4+ and CD8+) and B cells were decreased in critically ill patients.
T968 21976-22133 Sentence denotes Interestingly, it was suggested that T cell decline in circulation may be associated with increased infiltration of these cells toward the site of infection.
T969 22134-22201 Sentence denotes Whereas recovered patients showed reduced decline in CD11a T cells.
T970 22202-22372 Sentence denotes Thus, CD11a positive T cells were suggested as a possible prognostic marker of COVID-19.• Interestingly, eosinophil number was increased patients who were critically ill.
T971 22374-22400 Sentence denotes PBMCs (Anft et al., 2020)
T972 22401-22404 Sentence denotes 38.
T973 22406-22419 Sentence denotes BALF Healthy:
T974 22420-22431 Sentence denotes 3 Patients:
T975 22432-22448 Sentence denotes 2 PBMCs Healthy:
T976 22449-22460 Sentence denotes 3 Patients:
T977 22461-22692 Sentence denotes 3 • RNA-seq analysis was performed.• Increased transcript levels of IL-10, CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B in BALF.• Increased transcript levels of CXCL10, TNFSF10, TIMP1, C5, IL18, AREG, NRG1, IL10 in PBMCs.
T978 22694-22730 Sentence denotes PBMCs and BALF (Xiong et al., 2020)
T979 22731-22734 Sentence denotes 39.
T980 22736-22742 Sentence denotes Total:
T981 22743-22754 Sentence denotes 12 Healthy:
T982 22755-22766 Sentence denotes 3 Moderate:
T983 22767-22785 Sentence denotes 3 Severe/critical:
T984 22786-23510 Sentence denotes 6 • Single cell RNA-seq analysis was performed followed by cluster analysis to determine the immune cell type.• Proliferative and less expandable CD8+ T lymphocytes were present in severe/critically ill patient BALF samples, whereas moderate cases showed more expandable and less proliferative phenotype.• Increased macrophages and neutrophils were detected in the BALF of patients exhibiting severe/critical disease symptoms.• Higher levels of IL-1β, IL-6, and IL-8 were observed in all the patients.• Increased levels of CXCL9, CXCL10 and CXCL11 were consistently seen in all the patients.• Lung macrophages displayed higher transcripts of IL1B, IL6, TNFA, along with chemokines CCL2, CCL3, CCL4 and CCL7 in severe cases.
T985 23512-23537 Sentence denotes BALF (Liao et al., 2020)
T986 23538-23541 Sentence denotes 40.
T987 23543-23549 Sentence denotes Total:
T988 23550-23562 Sentence denotes 174 Healthy:
T989 23563-23575 Sentence denotes 20 COVID-19:
T990 23576-23585 Sentence denotes 8 Others:
T991 23586-23925 Sentence denotes 146 • Transcript levels of IL1RN, IL1B, CXCL17, CXCL8, CXCL1, CXCL2, and CCL2, CCL7 were increased in COVID-19 patients in comparison to healthy controls.• Upregulation of calgranulin genes S100A8, S100A9 and S100A12 were observed.• Interferon response was also observed as indicated by upregulation of about 83 ISGs in COVID-19 patients.
T992 23927-23955 Sentence denotes BALF (Zhou Z. et al., 2020)
T993 23956-24062 Sentence denotes The highlighted studies show the respective predictive biomarkers (in bold) which were found in the study.