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PMC:7736111 / 78325-88681 JSONTXT

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LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T19 240-255 Phenotype denotes lymphocytopenia http://purl.obolibrary.org/obo/HP_0001888

LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
1948 51-59 Disease denotes COVID-19 MESH:C000657245
1949 60-69 Disease denotes Infection MESH:D007239
1955 337-345 Species denotes patients Tax:9606
1956 240-255 Disease denotes lymphocytopenia MESH:D008231
1957 328-336 Disease denotes COVID-19 MESH:C000657245
1958 584-592 Disease denotes COVID-19 MESH:C000657245
1959 791-801 Disease denotes infections MESH:D007239
1970 891-894 Gene denotes CD4 Gene:920
1971 900-903 Gene denotes CD8 Gene:925
1972 1317-1320 Gene denotes CD4 Gene:920
1973 1326-1329 Gene denotes CD8 Gene:925
1974 1507-1510 Gene denotes CD8 Gene:925
1975 1553-1563 Gene denotes granzyme B Gene:3002
1976 838-845 Species denotes patient Tax:9606
1977 1030-1037 Species denotes patient Tax:9606
1978 1145-1153 Species denotes patients Tax:9606
1979 1136-1144 Disease denotes COVID-19 MESH:C000657245
1982 1632-1635 Gene denotes CD4 Gene:920
1983 1641-1644 Gene denotes CD8 Gene:925
2001 2338-2341 Gene denotes CD4 Gene:920
2002 2349-2352 Gene denotes CD8 Gene:925
2003 2401-2406 Gene denotes IFN-γ Gene:3458
2004 2408-2413 Gene denotes TNF-α Gene:7124
2005 2415-2420 Gene denotes IL-17 Gene:3605
2006 2426-2430 Gene denotes IL-2 Gene:3558
2007 2704-2707 Gene denotes CD8 Gene:925
2008 2719-2722 Gene denotes CD4 Gene:920
2009 2803-2806 Gene denotes CD8 Gene:925
2010 2945-2948 Gene denotes CD8 Gene:925
2011 3012-3022 Gene denotes granzyme B Gene:3002
2012 2248-2251 Gene denotes CD8 Gene:925
2013 2239-2242 Gene denotes CD4 Gene:920
2014 2184-2192 Species denotes patients Tax:9606
2015 2596-2604 Species denotes patients Tax:9606
2016 2769-2777 Species denotes patients Tax:9606
2017 2175-2183 Disease denotes COVID-19 MESH:C000657245
2021 3419-3422 Gene denotes CD4 Gene:920
2022 3428-3431 Gene denotes CD8 Gene:925
2023 3363-3371 Species denotes patients Tax:9606
2034 3972-3975 Gene denotes CD8 Gene:925
2035 4031-4036 Gene denotes NKG2A Gene:3821
2036 4071-4076 Gene denotes IFN-γ Gene:3458
2037 4078-4082 Gene denotes IL-2 Gene:3558
2038 4088-4098 Gene denotes granzyme B Gene:3002
2039 4468-4471 Gene denotes CD8 Gene:925
2040 4494-4497 Gene denotes CD4 Gene:404704
2041 3944-3952 Species denotes patients Tax:9606
2042 4645-4653 Species denotes patients Tax:9606
2043 3935-3943 Disease denotes COVID-19 MESH:C000657245
2062 4888-4891 Gene denotes CD4 Gene:920
2063 4981-4986 Gene denotes IFN-γ Gene:3458
2064 4991-4995 Gene denotes IL-2 Gene:3558
2065 5007-5010 Gene denotes CD4 Gene:920
2066 5027-5031 Gene denotes IL-2 Gene:3558
2067 5043-5046 Gene denotes CD4 Gene:920
2068 5130-5133 Gene denotes CD8 Gene:925
2069 5194-5200 Gene denotes CTLA-4 Gene:1493
2070 5328-5331 Gene denotes CD4 Gene:920
2071 5337-5340 Gene denotes CD8 Gene:925
2072 5476-5481 Gene denotes Tim-3 Gene:84868
2073 5523-5526 Gene denotes CD8 Gene:925
2074 5533-5536 Gene denotes CD4 Gene:920
2075 5371-5379 Species denotes patients Tax:9606
2076 5880-5888 Species denotes patients Tax:9606
2077 5645-5648 Gene denotes CD4 Gene:920
2078 5654-5657 Gene denotes CD8 Gene:925
2079 5231-5235 Disease denotes TGIT
2095 6207-6210 Gene denotes CD4 Gene:920
2096 6216-6219 Gene denotes CD8 Gene:925
2097 6442-6445 Gene denotes CD8 Gene:925
2098 6531-6534 Gene denotes CD8 Gene:925
2099 6681-6684 Gene denotes CD4 Gene:920
2100 6690-6693 Gene denotes CD8 Gene:925
2101 6785-6788 Gene denotes CD8 Gene:925
2102 6818-6822 Gene denotes GZMA Gene:3001
2103 6827-6831 Gene denotes GZMK Gene:3003
2104 6030-6038 Species denotes patients Tax:9606
2105 6648-6656 Species denotes patients Tax:9606
2106 6021-6029 Disease denotes COVID-19 MESH:C000657245
2107 6098-6107 Disease denotes infection MESH:D007239
2108 6639-6647 Disease denotes COVID-19 MESH:C000657245
2109 7022-7031 Disease denotes infection MESH:D007239
2130 7149-7152 Gene denotes CD4 Gene:920
2131 7158-7161 Gene denotes CD8 Gene:925
2132 7367-7370 Gene denotes CD4 Gene:920
2133 7425-7430 Gene denotes IFN-γ Gene:3458
2134 7432-7436 Gene denotes IL-2 Gene:3558
2135 7445-7449 Gene denotes IL-6 Gene:3569
2136 7455-7461 Gene denotes GM-CSF Gene:1437
2137 7481-7484 Gene denotes CD8 Gene:925
2138 7564-7569 Gene denotes IFN-γ Gene:3458
2139 7657-7677 Gene denotes granzyme A, B, and K Gene:3001
2140 7686-7691 Gene denotes GZM-A Gene:3001
2141 7883-7887 Gene denotes Tim3 Gene:84868
2142 7893-7898 Gene denotes NKG2A Gene:3821
2143 8411-8415 Gene denotes IL4R Gene:3566
2144 8417-8425 Gene denotes TNFSF13B Gene:10673
2145 8431-8435 Gene denotes XBP1 Gene:7494
2146 7610-7613 Gene denotes CD8 Gene:925
2147 7098-7118 Disease denotes SARS-CoV-2 infection MESH:C000657245
2148 7277-7286 Disease denotes infection MESH:D007239
2149 7578-7598 Disease denotes SARS-CoV-2 infection MESH:C000657245
2163 8651-8654 Gene denotes CD4 Gene:920
2164 8690-8693 Gene denotes CD8 Gene:925
2165 8840-8843 Gene denotes CD8 Gene:925
2166 9093-9096 Gene denotes CD8 Gene:925
2167 9495-9498 Gene denotes CD4 Gene:920
2168 9675-9678 Gene denotes CD8 Gene:925
2169 9183-9186 Gene denotes CD8 Gene:925
2170 8876-8884 Species denotes patients Tax:9606
2171 9073-9083 Species denotes SARS-CoV-2 Tax:2697049
2172 9245-9253 Species denotes patients Tax:9606
2173 9052-9061 Species denotes Influenza Tax:11320
2174 9236-9244 Disease denotes COVID-19 MESH:C000657245
2175 9711-9720 Disease denotes infection MESH:D007239
2184 9834-9837 Gene denotes CD4 Gene:920
2185 9843-9846 Gene denotes CD8 Gene:925
2186 9931-9934 Gene denotes CD4 Gene:920
2187 9971-9974 Gene denotes CD4 Gene:920
2188 9982-9987 Gene denotes CD127 Gene:3575
2189 10067-10070 Gene denotes CD8 Gene:925
2190 10098-10101 Gene denotes CD8 Gene:925
2191 10347-10355 Species denotes patients Tax:9606

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T458 0-69 Sentence denotes Activation and Exhaustion Status of T Cells During COVID-19 Infection
T459 70-205 Sentence denotes The activation, exhaustion, and proliferation response of T and B cells are considered an integral determinant of the disease severity.
T460 206-477 Sentence denotes Unequivocally, studies have shown lymphocytopenia as a predictive marker which may also determine the disease severity in COVID-19 patients (Liu J. et al., 2020; Tan L. et al., 2020b; Wang et al., 2020b; Yang A.P. et al., 2020; Yang X. et al., 2020; Zhang et al., 2020a).
T461 478-593 Sentence denotes However, contradictory reports exist regarding the functional and exhaustion status of these cells during COVID-19.
T462 594-802 Sentence denotes Further, understanding these changes throughout the disease has remained a challenge, considering the complexity in the underlying immune response, comorbid condition, and previous exposure to the infections.
T463 803-962 Sentence denotes Peripheral blood study of a single patient (50-year male) revealed robust activation of CD4+ and CD8+ T cells marked by HLA-DR expression (Xu Z. et al., 2020).
T464 963-1050 Sentence denotes However, the major limitation of this study was that only a single patient was studied.
T465 1051-1189 Sentence denotes Using multiparameter flow cytometry approach Kuri-Cervantes et al. (2020) studied 35 COVID-19 patients (n = 7 moderate and n = 28 severe).
T466 1190-1369 Sentence denotes The study revealed that a subset of severe cases displayed T cell activation as revealed by CD38 and HLA-DR expression in both CD4+ and CD8+ T cells (Kuri-Cervantes et al., 2020).
T467 1370-1564 Sentence denotes By analyzing, PBMCs derived from healthy (n = 5) and severe cases (n = 16), the authors found an increase in the percentage of cytotoxic CD8+ memory cells as revealed by perforin and granzyme B.
T468 1565-1680 Sentence denotes Similarly, a subset of severe cases had increased Ki-67 expressing CD4+ and CD8+ T cells, displaying proliferation.
T469 1681-1873 Sentence denotes At the same time, these findings revealed heterogeneous T cell response but overall suggested a skew towards the activation and proliferation status of these cells in a subset of severe cases.
T470 1874-2043 Sentence denotes The limitation of this finding is again the small sample size which may be the reason for the inconclusive findings of the T cell status concerning the disease severity.
T471 2044-2202 Sentence denotes Similar multiparameter flow cytometry approach was used by De Biasi et al. (2020) to study T cell response in healthy (n = 12) and COVID-19 patients (n = 21).
T472 2203-2313 Sentence denotes The study found activated status of CD4+ and CD8+ T cells as revealed by an increase in CD38+HLA-D population.
T473 2314-2456 Sentence denotes Activated status of the CD4+ T and CD8+ T cells was further confirmed by production of IFN-γ, TNF-α, IL-17, and IL-2 when stimulated in vitro.
T474 2457-2635 Sentence denotes The major limitation of this study was that the sample size was small, which restricted the comparison between the T cell responses across patients with various disease severity.
T475 2636-2778 Sentence denotes In another study, Song et al. (2020) showed the activated status of CD8+ T but not CD4+ T cells in severe (n = 9) than mild (n = 20) patients.
T476 2779-2935 Sentence denotes The activated status of CD8+ T cells reflected by the increased population of CD38+HLA-DR+, HLA-DR+, and CD38+HLA-DR+ marker expression (Song et al., 2020).
T477 2936-3101 Sentence denotes Further, CD8+ T cells were associated with increased cytolytic markers like granzyme B, perforin, and granulysin with more pronounced activation in severe than mild.
T478 3102-3229 Sentence denotes While across studies, it has become apparent that T cells show robust activation status in severe cases than mild and moderate.
T479 3230-3333 Sentence denotes These cells also exhibit exhaustion status, which may occur concomitantly with their activation status.
T480 3334-3557 Sentence denotes Deep immune profiling of 125 patients by Mathew et al. (2020) demonstrated that both CD4+ and CD8+ T cells exhibit activation status as revealed by coexpression of CD38 and HLA-DR which corresponded to the disease severity.
T481 3558-3683 Sentence denotes Further, these cells were also associated with concomitant expression of proliferation (Ki-67) and exhaustion (PD-1) markers.
T482 3684-3882 Sentence denotes This study thus suggests that hyperactivated status of T cells may eventually lead to their exhaustion, and thus these functional and exhaustion features of T cells may reflect the disease severity.
T483 3883-4037 Sentence denotes A study by Zheng M. et al. (2020) in a cohort of 68 COVID-19 patients revealed extensive CD8+ T cell exhaustion as shown by increased expression of NKG2A.
T484 4038-4265 Sentence denotes Intracellular cytokine staining (IFN-γ, IL-2, and granzyme B) further confirmed a decrease in the activation profile of these cells, which was more pronounced in severe (n = 55) than mild (n = 13) cases (Zheng M. et al., 2020).
T485 4266-4505 Sentence denotes As mentioned earlier in the study by Song et al. (2020) and De Biasi et al. (2020) T cells showed activation status that was also concomitantly seen with express of exhaustion markers PD-1 and TIM-3 on CD8+ T cells and TIM-3 on CD4+ cells.
T486 4506-4584 Sentence denotes The exhaustion was more pronounced in severe cases (n = 9) than mild (n = 20).
T487 4585-4690 Sentence denotes However, both these studies did not consider the age of the patients when comparing the disease severity.
T488 4691-4808 Sentence denotes Further, the study did not consider the temporal dynamics of these cells while measuring their functional properties.
T489 4809-5020 Sentence denotes In agreement, Zheng H.Y. et al. (2020) showed reduced functional activation of CD4+ T cells in severe (n = 6) than mild (n = 10) group as revealed by a lower proportion of IFN-γ and IL-2 expressing CD4+ T cells.
T490 5021-5120 Sentence denotes While IL-2 expressing CD4+ T cell population was also significantly lower in healthy vs mild group.
T491 5121-5301 Sentence denotes Further, CD8+ T cells displayed exhaustion as revealed by an increase in CTLA-4 in severe cases than mild and TGIT in severe than healthy, while PD-1 was more in mild than healthy.
T492 5302-5414 Sentence denotes Exhaustive states of both CD4+ and CD8+ T cells were also present in patients requiring ICU (Diao et al., 2020).
T493 5415-5546 Sentence denotes The exhaustive state was apparent by an increase in PD-1 and Tim-3 expression, which was more pronounced in CD8+ than CD4+ T cells.
T494 5547-5889 Sentence denotes These studies along with others thus suggest that robust activation followed by the exhaustion of CD4+ and CD8+ T cells may be responsible for the disease progression, while therapies like checkpoint inhibitors (anti-PD-1 antibody; NCT04268537) which may prevent T cell exhaustion and restore their functional state may benefit some patients.
T495 5890-5988 Sentence denotes More studies are necessary before using such an approach can be used for therapeutic intervention.
T496 5989-6108 Sentence denotes A post-mortem study of deceased COVID-19 patients conducted to find the status of these cells at the site of infection.
T497 6109-6278 Sentence denotes T cell profiling and their activation status in the lungs revealed an increase in the presence of CD4+ and CD8+ T cells exhibiting activation status (Song et al., 2020).
T498 6279-6392 Sentence denotes This increase in infiltration of these cells was concomitantly associated with their decline in peripheral blood.
T499 6393-6506 Sentence denotes Others presented a similar activation profile of CD8+ T cells (Kuri-Cervantes et al., 2020; Mathew et al., 2020).
T500 6507-6852 Sentence denotes This activated state of CD8+ T cells was consistently present across studies, with reports of immune profiling in BALF samples from COVID-19 patients, which showed increased CD4+ and CD8+ T cells in the lungs in both mild and severe cases along with the increased expression of CD8+ T cell cytolytic genes like GZMA and GZMK (Liao et al., 2020).
T501 6853-7051 Sentence denotes Thus, these studies point towards heterogeneous activation and exhaustion status of T cells in peripheral blood, while a more consistent activated status at the site of infection (lungs) (Figure 4).
T502 7052-7214 Sentence denotes FIGURE 4 T and B cell immune response during SARS-CoV-2 infection. (A) The activation status of CD4+ and CD8+ T in the circulation is indicated by CD38+ HLA-DR+.
T503 7215-7352 Sentence denotes These activated T cells are further recruited at the sites of infection (initially lungs) in the presence of their respective chemokines.
T504 7353-7570 Sentence denotes The activated CD4+ T cells are marked by the presence of cytokines like IFN-γ, IL-2, IL-12, IL-6, and GM-CSF, whereas activated CD8+T (cytotoxic T cells) are marked by the secretion of granzymes, perforins, and IFN-γ.
T505 7571-7899 Sentence denotes During SARS-CoV-2 infection, activated CD8+T cells exhibiting increased expression of granzyme A, B, and K (GZM-B, GZM-A, and GZM-K) were found in the lungs (Liao et al., 2020; Song et al., 2020; Zheng M. et al., 2020). (B) T cells were also found to exhibit exhausted state as marked by the expression of PD-1, Tim3, and NKG2A.
T506 7900-8166 Sentence denotes However, most studies showing exhausted T cells were confined to the peripheral blood, while lungs were mostly shown to have activated T cells but with concomitant expression of some exhaustive markers, suggesting that the activation state is followed by exhaustion.
T507 8167-8539 Sentence denotes The exhaustive T cells are marked by the reduced expression of respective chemokines and cytolytic granules. (C) Similarly, antibody-producing B cells (plasmablasts; PB) were shown to exhibit activation status as reflected by the expression of IL4R, TNFSF13B, and XBP1, while at the same time, the exhausted status of these cells was also reported in the peripheral blood.
T508 8540-8618 Sentence denotes Exhaustive state of B cells is reflected by a decrease in antibody production.
T509 8619-8808 Sentence denotes Further, it appears that unlike CD4+ T cells, the activation status of CD8+ T cells is more pronounced, which may account for their relatively faster exhaustion state (Wherry et al., 2007).
T510 8809-9017 Sentence denotes Interestingly, by studying the CD8+T cell response in convalescent patients, Habel et al. (2020) found that these cells skewed toward naïve, stem cell and central memory phenotypes, with low effector T cells.
T511 9018-9134 Sentence denotes While comparing the response with Influenza A viruses, SARS-CoV-2 directed CD8+ T exhibit relatively lower response.
T512 9135-9477 Sentence denotes Others have also shown a significant decline in CD8+ T cell subsets (naïve, effector, and memory) in COVID-19 patients, with a more pronounced decline in critical (n = 3) than severe (n = 5), and mild (n = 4), suggesting their robust activation during early disease followed by exhaustion during the critical condition (Wang W. et al., 2020).
T513 9478-9598 Sentence denotes On the contrary, CD4+ T cells were higher in the mild and critical cases than severe cases and healthy control (n = 12).
T514 9599-9828 Sentence denotes These results imply that the overall T cell response is heterogenous, while CD8+ response, though robust during infection and correlates with the disease severity; but the response may not be long-lasting, at least in some cases.
T515 9829-9910 Sentence denotes Both CD4+ and CD8+ T cells also exhibit dysregulated response (Qin et al., 2020).
T516 9911-10029 Sentence denotes Decreased levels of CD4+ regulatory cells as marked by CD3+ CD4+ CD25+ CD127low+ population was found in severe cases.
T517 10030-10127 Sentence denotes Similarly, the study found decreased CD8+ suppressor T cells (CD3+, CD8+, CD28+) in severe cases.
T518 10128-10356 Sentence denotes Overall, more comprehensive studies are warranted with larger cohort size, to profile local vs systemic T cell response and persistence simultaneously, and correlate these responses with disease severity in age-matched patients.