LitCovid-sentences  

PMC:7736111 / 62568-73958 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T365 0-70 Sentence denotes T and B Cell Response in Mild/Moderate and Recovered COVID-19 Patients
T366 71-216 Sentence denotes T cell response is an emerging critical determinant in keeping the SARS-CoV-2 infection under check (Huang C. et al., 2020; Liu J. et al., 2020).
T367 217-588 Sentence denotes Across studies, a decline in the number of these cells positively correlates with poor clinical outcome and immuno-pathogenesis, whereas adequate T cell number and proper effector function are prevalent in patients who develop mild disease symptoms or those who successfully recovered (Chen G. et al., 2020; Li H. et al., 2020; Sekine et al., 2020; Tan L. et al., 2020b).
T368 589-856 Sentence denotes Following a single patient (47-year-old woman) throughout the disease, Thevarajan et al. (2020) showed a concomitant increase in CD4+, CD8+, TFH cells, and antibody-secreting B cells from day seven after infection, which persisted for a week as the symptoms resolved.
T369 857-1062 Sentence denotes Other studies revealed a similar trend of revival in T cell response in patients who have successfully cleared the virus (Anft et al., 2020; Braun et al., 2020; Chen X. et al., 2020; Chen N. et al., 2020).
T370 1063-1192 Sentence denotes SARS-CoV-2 specific reactive CD4+ and CD8+ T cells were found in 100 and 80% patients who needed mechanical ventilation (n = 10).
T371 1193-1281 Sentence denotes PBMCs derived from these patients showed reactivity against the S protein of SARS-CoV-2.
T372 1282-1477 Sentence denotes Further, in vitro stimulation of CD4+ T cells led to their differentiation into TH1, TH2, and TH17 subsets, as revealed by the expression of their corresponding cytokines (Weiskopf et al., 2020).
T373 1478-1562 Sentence denotes Interestingly, 20% of non-infected healthy controls also displayed reactive T cells.
T374 1563-1714 Sentence denotes The main limitation with this study was that the T response was studied only in critically ill patients and the small sample size was small to provide.
T375 1715-1892 Sentence denotes By studying a cohort of 18 COVID-19 patients and 64 healthy donors, Braun et al. (2020) found reactive CD4+ (83%) cells in blood-derived from the convalescing COVID-19 patients.
T376 1893-1962 Sentence denotes These reactive T cells were found specifically against the S protein.
T377 1963-2156 Sentence denotes Interestingly about 35% of SARS-CoV-2 seronegative healthy donors also showed the presence of S protein reactive CD4+ T cells indicating previous exposure to the related coronavirus infections.
T378 2157-2311 Sentence denotes Simultaneously, another study has found SARS-CoV-2 specific CD4+ T (100%) and CD8+ T (70%) cells in convalescent patients (n = 20) (Grifoni et al., 2020).
T379 2312-2517 Sentence denotes In addition to being majorly reactive against S protein, the study found additional targets of these T cells in the form of M, N, and ORF8 proteins and other non-structural proteins like NSP3, NSP4, ORF3a.
T380 2518-2745 Sentence denotes Further, in line with the study by Braun et al. (2020), T cells were found reactive against 40–60% of the SARS-CoV-2 uninfected patients, suggesting the presence of these reactive cells in response to previous viral infections.
T381 2746-2922 Sentence denotes In a yet to be a peer-reviewed article, Schulien et al. (2020) has extensively studied the SARS-CoV-2 epitope-specific role of CD8+ T cells in COVID-19 (Schulien et al., 2020).
T382 2923-3106 Sentence denotes The study found the presence of newly generated and pre-existing SARS-CoV-2 specific cells with the positive response seen in 88.4% of patients who had mild disease symptoms (n = 26).
T383 3107-3175 Sentence denotes The most substantial response was found against N protein and ORF3a.
T384 3176-3276 Sentence denotes Further, CD8+ T cells response was shown persistent even in the individuals who became seronegative.
T385 3277-3384 Sentence denotes In a patient studied longitudinally (70 days), CD8+ T cell response prolonged but antibody did not persist.
T386 3385-3637 Sentence denotes All these three studies taken together point toward the presence of functional and long-lasting reactive T cells in convalescent individuals, while others also suggest the presence of reactive T cells in critically ill patients (Weiskopf et al., 2020).
T387 3638-3814 Sentence denotes Thus, based on these studies, it appears that COVID-19 patients who exhibit mild disease symptoms and successfully recover, display functional and long-lasting T cell response.
T388 3815-4005 Sentence denotes However, these findings may not be definitive to provide a coherent functional view of these cells during recovery, as none of these studies compared the T cell response to disease severity.
T389 4006-4093 Sentence denotes A further difference in the time of sample collection may also complicate the findings.
T390 4094-4284 Sentence denotes In the study by Grifoni et al. (2020) samples were collected throughout 20–35 days after symptom onset, whereas Weiskopf et al. (2020), used samples collected after 14 days of ICU admission.
T391 4285-4375 Sentence denotes Thus, more studies under controlled clinical settings and large cohort size are warranted.
T392 4376-4539 Sentence denotes While addressing some of these concerns, a recent study explored T cell response in convalescent COVID-19 patients concerning disease severity (Peng et al., 2020).
T393 4540-4722 Sentence denotes The study found robust CD4+ and CD8+ memory T cell response in severe cases (n = 14) than mild (n = 28), suggesting long-lasting memory of these cells to keep the infection in check.
T394 4723-4774 Sentence denotes The limitation again here is the small sample size.
T395 4775-4921 Sentence denotes Therefore, more such studies with large sample size are needed to fully understand the impact of T cell response and its long-term sustainability.
T396 4922-5080 Sentence denotes B cell response has a temporal dynamic to human infecting CoVs, with a median time of detection for SARS-CoV as 14 days, reviewed by Huang A.T. et al. (2020).
T397 5081-5338 Sentence denotes The peak antibody titer for IgG and IgM, and detection time of neutralizing antibody varied across studies with a lower time point of seroconversion for IgG, IgM, and IgA as 15 days (Hsueh et al., 2004; Mo et al., 2006; Cao et al., 2007; Yang et al., 2009).
T398 5339-5426 Sentence denotes A more dynamic range of seroconversion was observed in sera from the COVID-19 patients.
T399 5427-5608 Sentence denotes A study by Liu X. et al. (2020) on 32 patients with varying disease severity has shown detectable IgM antibodies from day four and peaked at day 20, since the onset of the symptoms.
T400 5609-5685 Sentence denotes At the same time, IgG antibodies appeared after day 7 with a peak on day 25.
T401 5686-5806 Sentence denotes When compared to the disease severity, mild cases had peak IgM response earlier than in severe cases (day 17 vs day 21).
T402 5807-5939 Sentence denotes Further, severe cases exhibited more robust IgG antibody response than mild cases, as will be discussed in the subsequent section C.
T403 5940-6217 Sentence denotes In terms of the antibody response seen after symptom onset, a similar trend was shown by Liu X. et al. (2020) who detected IgM antibodies in SARS-CoV-2 infected patients between 3 and 6 days and IgG antibodies after day 8 of symptom onset, irrespective of the disease severity.
T404 6218-6351 Sentence denotes A study by Zhou P. et al. (2020) also found mean times of IgM, IgG, and neutralizing antibodies at 12, 14, and 11 days, respectively.
T405 6352-6489 Sentence denotes These reports were consistent with the reports from Wu et al. (2020) in which neutralizing antibodies were detected starting from day 10.
T406 6490-6690 Sentence denotes An elaborate antibody profile of 285 COVID-19 patients revealed 100% IgG and 94.1% IgM antibody response with a peak around the 3rd and 4th week after symptom onset, respectively (Long et al., 2020a).
T407 6691-6975 Sentence denotes Thus, for a successful viral clearance, an adequate adaptive immune response is generated around 2nd week after symptom onset and peaks around the 3rd week for IgM and at the beginning of 4th week for IgG (Ni et al., 2020; Thevarajan et al., 2020; Wu et al., 2020; Zhao et al., 2020).
T408 6976-7280 Sentence denotes Based on these and several other studies, it is evident that the antibody response is very dynamic in COVID-19 which may be dependent on the age, sex, genetic factors, underlying disease condition and most importantly, the type of assay used for serological testing (Guan et al., 2020; Hou et al., 2020).
T409 7281-7536 Sentence denotes Overall, these initial reports unequivocally suggest an integral role of the regulated adaptive immune response in the early clearance of virus and thereby attenuation of the disease condition in almost 80% of the patients who show mild/moderate symptoms.
T410 7537-7723 Sentence denotes On the other hand, in the rest, 20% severe and critically ill patients, disease symptoms positively correlate with the degree of lymphocytopenia, as will be discussed later in section C.
T411 7724-7825 Sentence denotes A schematic representation of the functional immune response during COVID-19 is depicted in Figure 3.
T412 7826-7904 Sentence denotes FIGURE 3 Clearance of virus infected cells by engaging adaptive immune cells.
T413 7905-8015 Sentence denotes Virus infected ATII cells activate the neighboring lung resident AMs by minimizing the CD200-200L interaction.
T414 8016-8125 Sentence denotes Additional requisite activation signals are provided by DAMPs, viral derived PAMPs, and cytokines like IFN-γ.
T415 8126-8419 Sentence denotes Activated AMs along with infected ATII derived molecules activate and recruit other innate immune cells, like circulating monocytes, dendritic cells, NK cells, and neutrophils which act in a coordinated manner to eventually recruit the adaptive effector immune cells like CTLs and CD4+T cells.
T416 8420-8556 Sentence denotes These adaptive immune cells then specifically eliminate virus infected cells while minimizing the damage to the nearby uninfected cells.
T417 8557-8740 Sentence denotes Thus, a well-coordinated and regulated adaptive immune response with help from innate immune cells is critical for initial antiviral response to limit the further spread of the virus.
T418 8741-8935 Sentence denotes Green arrows indicate the cytokines released by the respective activated immune cells which activate other immune cells as well as mount an antiviral response by acting on lung epithelial cells.
T419 8936-9115 Sentence denotes An immunological enigma still eluding researchers worldwide is how the majority of COVID-19 patients remain asymptomatic, and even some with high viral load (Lee S. et al., 2020).
T420 9116-9240 Sentence denotes This dilemma can be partly explained based on the effective functional early immune response generated by the T and B cells.
T421 9241-9383 Sentence denotes Mathew et al. (2020) used a multidimensional immunoprobing study and functionally characterized clinical features with immunological features.
T422 9384-9468 Sentence denotes This study defined three immunotypes based on 50 clinical and 200 immune parameters.
T423 9469-9702 Sentence denotes The immunotype 1 was positively associated with disease severity and had hyperactivated CD4+ and CD8+ T cells, with concomitant expression of exhaustion markers, indicating robust activation followed by the exhaustion of these cells.
T424 9703-9968 Sentence denotes This immunotype may thus be vulnerable to cytokine storm, as discussed later in section “Cytokine Storm in COVID-19 Patients.” Immunotype 2 was associated with the presence of proliferating memory B cells with the optimal activation status of CD4+ and CD8+ T cells.
T425 9969-10025 Sentence denotes This immunotype did not associate with disease severity.
T426 10026-10162 Sentence denotes The immunotype 3 had no activation status of CD4+ and CD8+ T cells, and thus exhibited an inverse correlation with the disease severity.
T427 10163-10346 Sentence denotes Overall, this study addressed some of the above questions that suggested that the presence of a regulated and functional adaptive immune response is key to preventing immunopathology.
T428 10347-10485 Sentence denotes In a similar study, the activation status of T cells associated with disease severity (acute, moderate, and severe) (Sekine et al., 2020).
T429 10486-10610 Sentence denotes The activation status of these T cells correlated with the presence of SARS-CoV-2 specific IgG antibodies in these patients.
T430 10611-10899 Sentence denotes Interestingly, T cells derived from convalescent mild and asymptomatic patients exhibited functional status when stimulated in vitro with SARS-CoV-2 specific antigens, suggesting the presence of well-regulated and functional T cell response in mild and asymptomatic convalescent patients.
T431 10900-11102 Sentence denotes Thus, in patients with high viral load, an immunopathological state can be prevented if the adequate and regulated adaptive immune response is present in association with the proper interferon response.
T432 11103-11390 Sentence denotes While in patients with compromised immune response, like in comorbid conditions, even a low viral load is sufficient to induce immunopathological changes, due to either ineffective immune response or uncontrolled hyper-activated response, as will be discussed in the subsequent sections.