Immunological Responses In Patients Research Articles

Impact of personalized peptide neoantigen vaccines on immunologic responses in patients with pancreatic cancer.

e16351 Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer that often resists conventional therapies. One of the most promising alternative treatments is personalized neoantigen vaccines that target specific mutations in each patient’s tumor. These vaccines aim to activate the immune system to fight cancer cells. However, how this type of vaccine affects immune cells across different vaccination phases is poorly understood. Methods: Here we report the safety and dynamic immunological responses of peptide-based vaccines after chemotherapy in patients with resected PDAC in a single-center open-label phase 1b trial (registered at ClinicalTrials.gov [NCT03558945]). The primary endpoint was safety, assessed by the incidence of adverse events in all vaccinated patients. The key secondary endpoints included prognosis assessed by recurrence-free survival and overall survival rate. Results: We observed only 3 grade ≥3 adverse events in 2 patients (12.5%) and no grade ≥4 events. Vaccinated patients achieved favorable survival outcomes, with a 3-year recurrence-free survival rate of 56% and a 3-year overall survival rate of 74%. Using single-cell sequencing, we revealed the dynamics of vaccine-induced immune responses, with CD8+ cytotoxic T cells expanding at the priming phase and CD4+ T cells at the boosting phase. The CD8+ cytotoxic T cells had a higher proportion (average, 38.4%) of persistent expansion than the CD4+ T cells (average, 3.7%), with a range of 2.8~21.8 months duration. We also discovered a helper B-cell subtype that interacted with T cells and was associated with prognosis, suggesting a role for B-cell epitopes in vaccine effectiveness. Conclusions: These results provide valuable insights for optimizing peptide-based neoantigen vaccine design, regimen, and evaluation strategies. Clinical trial information: NCT03558945 .

Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study

BackgroundTo compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy.MethodsThirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1β, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes.ResultsClinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 and p = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 and p = 0.008, respectively).ConclusionUpregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.

Comparison of Viral Load, CD4 and Hematological Parameters Amongst HIV, Patients on Tenofovir and Zidovudine-Based ARV Therapy in Nasarawa State, Nigeria

HIV is a global public health concern and people diagnosed with HIV are treated with Antiretroviral therapy. Until 2017, Tenofovir and Zidovudine-based ART were the two major first line drugs for PLHIVs in Nasarawa Nigeria. This study aims to compare the HIV viral load suppression amongst patients on these two ART combinations in Nasarawa State, Nigeria. The study was conducted in three (3) secondary health facilities in Nasarawa State using one hundred subjects selected randomly from the three facilities comprising 50 HIV Sero-positive individuals on Tenofovir-based ART and 50 HIV sero-positive individuals on Zidovudine-based ART. Ethylene diamine Tetra Acetic (EDTA) blood specimen was obtained from each study participant for Full blood count (FBC) using haematology auto-analyser (Sysmex K21N), CD4 count using Partec Cyflow Counter II and HIV viral load analysis using real-time polymerase chain reaction. The demographic data of study participants shows that more females (72) were involved in the study making up 64% of the subjects on Tenofovir and 80% of those on Zidovuine and most of the subjects were within the ages of 26-35years. There was no significant difference (p=0.666) in the viral load of the subjects on any of the regimen. The red blood cells count (RBC) and platelet counts were significantly different (p&amp;lt;0.0001) amongst the subjects on the two ART regimen whereas CD4 count, white blood cells count, lymphocytes count, granulocytes count and Packed cell volume (PCV) were not significantly different within the two groups. Age affected some of the haematological parameters (granulocytes, PCV, RBCs and platelets) within the two groups at different ages. Sex only affected the PCV and granulocytes of subjects within the two different groups (p=0.0069), occupation, knowledge about HIV/AIDS disease and care, duration of ART treatment and year of initial diagnosis of HIV did not affect the haematological and immunological parameters of subjects on the two ART regimen. Conclusively, there is no significant difference in the virologic and immunological response of patients on the two ART therapy but some haematological parameters of subjects on Zidovudine were statistically different from those on Tenofovir.

Abstract A083: Personalized targeted circulating tumor DNA (ctDNA) and T-cell responses after combined neoantigen vaccine and immune checkpoint blockade in ovarian cancer

Abstract A083: Personalized targeted circulating tumor DNA (ctDNA) and T-cell responses after combined neoantigen vaccine and immune checkpoint blockade in ovarian cancer

Immunological Responses Associated With Neoadjuvant Therapy in the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma.

Development of multidisciplinary therapies including immune checkpoint inhibitors for esophageal squamous cell carcinoma (ESCC) requires a clear understanding of immunological responses induced by chemotherapy with/without radiotherapy in the tumor microenvironment. This is a retrospective analysis of paired pretreatment biopsy samples and surgically resected tumor samples of 49 patients who underwent radical surgery for ESCC with/without neoadjuvant therapy at Fukushima Medical University Hospital. The cohort included 30 patients treated with neoadjuvant chemotherapy (NAC), 11 treated with neoadjuvant chemoradiotherapy (NACRT), and eight who underwent surgery alone and did not receive neoadjuvant antitumor therapy. Chemotherapy included fluoropyrimidine- and platinum-based agents in all treated patients, and radiotherapy included 40 or 42 Gy administered in 20 or 21 fractions. Expression of CD8, human leukocyte antigen (HLA) class I-ABC, PD-L1, PD-L2, CEACAM-1, LSECtin, and p-STAT1, were determined using immunohistochemistry. The frequency of tumor-infiltrating CD8+ T cells was significantly increased by NAC (p<0.05), and the expression of HLA class I-ABC on tumor cells was significantly increased by NAC and NACRT (p<0.05). Furthermore, the ESCC cells expressed PD-L1, PD-L2, and CEACAM-1, whereas the expression of PD-L1 on ESCC cells was significantly correlated with the expression of p-STAT1 in ESCC cells (p<0.05). NAC and NACRT induced both positive and negative immunological responses in patients with ESCC. These results may be a part of basis for multidisciplinary therapy including immune checkpoint inhibitors for patients with advanced ESCC.

Therapy with direct antiviral drugs in patients with HCVassociated cryoglobulinemic vasculitis – is it always possible to achieve complete clinical and immunological responses after the virus eradication?

Background. The use of direct acting antiviral drugs (DAАs) leads to the achievement of a stable virological response (SVR) in 95–100 % of patients with HCV-associated cryoglobulinemic vasculitis (HCV-CV). However, in some patients, despite the eradication of the virus, clinical and immunological markers of vasculitis still remain.The aim: to evaluate clinical and immunological responses in patients with HCV-CV in comparison with patients with "asymptomatic" HCV- associated cryoglobulinemia (HCV- СG) after achieving SVR with the help of DAАs with long-term dynamic observation (12 months).Patients and Methods: The study included 45 patients: 23 with HCV-CV and 22 with "asymptomatic" HCV-CG, who underwent antiviral therapy with DAAs. Clinical-immunological, virological data were evaluated: before treatment, 12 weeks (3 months) and 48 weeks (12 months) after the end of treatment.Results: After a course of DAAs, SVR was diagnosed in all 45 (100 % of patients). In patients with HCV-CV, an immunological response (complete and partial) was observed by week 12 (SVR12) – in 56.5 % and by week 48 (SVR48) – in 73.9 % patients. In 6 patients (26.1 %), the immunological response was not achieved by SVR48. The rate of complete and partial clinical response 12 weeks after the end of treatment at the SVR12 period in patients with HCV-CV was 65.2 %, to the time of SVR48 amounted to 78.3 % patients. In 5 (21.7 %) individual manifestations of CV persisted and/or relapsed. In patients with HCV-CG, the frequency of complete and partial immunological responses after DAAs therapy was 77.3 % – by SVR12 and 86.3 % – by SVR48, respectively. No response was observed in 3 patients and it was characterized by trace-level of cryoglobulinemia.Conclusion: In most patients with HCV-CV eradication of HCV with help of DAAs leads to the achievement of clinical and immunological remission of the disease. However, in 20 % of patients manifestations of HCV-CV persist / recur immediately after the end of treatment or later relapses are observed. Based on these observations, patients with HCV-CV, especially those with severe underlying skin and kidney disease, are required long-term monitoring after SVR is achieved.

Impact of CytoSorb® on interleukin-6 in cardiac surgery.

Cardiac surgery is known to activate a cascade of inflammatory mediators leading to a systemic inflammatory response. Hemadsorption (HA) devices such as CytoSorb® have been postulated to mitigate an overshooting immune response, which is associated with increased morbidity and mortality, and thus improve outcome. We aimed to investigate the effect of CytoSorb® on interleukin (IL)-6 levels in patients undergoing complex cardiac surgery in comparison to a control group. A total of 56 patients (28 CytoSorb®, 28 control) undergoing acute and elective cardiac surgery between January 2020 and February 2021 at the Department of Cardiac and Vascular Surgery, Clinic Floridsdorf, Vienna, were retrospectively analyzed. The primary endpoint was the difference in IL-6 levels between the CytoSorb® and control group. Secondary endpoint was periprocedural mortality. CytoSorb®, installed in the bypass circuit, had no significant effect on IL-6 levels. IL-6 peaked on the first postoperative day (HA: 775.3 ± 838.4 vs. control: 855.5 ± 1,052.9 pg/ml, p = 0.856). In total, three patients died in the HA group, none in the control (logistic regression model, p = 0.996). Patients with an increased Euroscore II of 7 or more showed a reduced IL-6 response compared to patients with an Euroscore II below 7 (178.3 ± 63.1 pg/ml vs. 908.6 ± 972.6 pg/ml, p-value = 0.00306). No significant reduction of IL-6 levels or periprocedural mortality through intraoperative HA with CytoSorb® in patients undergoing cardiac surgery was observed. However, this study was able to show a reduced immunologic response in patients with a high Euroscore II. The routine application of CytoSorb® in cardiac surgery to reduce inflammatory mediators has to be scrutinized in future prospective randomized studies.

Humoral and Cellular Immunological Response in Patients with Kidney Transplantation After messenger-RNA-COVID-19 Vaccination: A Systematic Review and Meta-Analysis

A comprehensive search was carried out in mainstream bibliographic databases or Medical Subject Headings, including ScienDirect, PubMed, Scopus, and ISI Web of Science, following the PRISMA 2020 Guideline. The search was applied to the articles that were published between 2021 and mid-2023. With strict literature search and screening processes, it yielded 7 articles from 349 articles of initial literature database. A number of previous studies demonstrated that KTRs or non-KTRs with renal failure markedly reduced vaccine response, whereas adaptive protocols of mRNA COVID-19 vaccination or alternative adjuvant vaccines is now not known yet. A recent study revealed that acute kidney injury and mortality could be caused by SARS-CoV-2 (COVID-19) around 50 % and 23 % of the infected KTRs. In conclusion, among the immunocompromised population, including KTRs, DPs, PDs, at least three doses of mRNA-COVID-19 vaccination was recommended to be the preparation of choice. Withdrawal of the immunosuppressants in KTRs and immunocompromised individual’s prior COVID-19 vaccination and at least third dose of mRNA-COVID-19 vaccination should be performed.

Celiac Disease and the Potential of Stems Cells as Treatment

Celiac disease is characterized by having a broad spectrum of clinical presentations ranging from asymptomatic cases to classical gastrointestinal manifestations of disease and cases of severe progression in refractory celiac disease and the development of certain types of cancers. The age of onset of disease also varies greatly, with genetics, environmental and immunological factors. While this autoimmune disease currently affects 1% of Western populations, cases have been increasing globally due to presence of gluten in westernized diets and improved diagnostic testing and awareness. The only current treatment for celiac disease is a strict lifelong adherence to a gluten free diet; however, patient reports suggest they are not satisfied with quality of life and clinical improvement involving only dietary treatment and future routes of treatment should be explored. The overall lack of understanding of a complex model of this disease has led to notable obstacles when conducting clinical trials investigating future treatments. Stem cells play a crucial role in the human body as they could help regulate inflammation that is often associated with autoimmune disorders by regenerating and differentiating into several different cell types. Mesenchymal stem cells and hematopoietic stem cells are highly proliferating, while mesenchymal stem cells can cross the HLAQ barrier and prevent an adverse immunological response in patients. For this reason, stem cells, especially mesenchymal stem cells, are prime candidates for investigation of future treatments designed with a goal of restoring the epithelial barrier and preventing villous atrophy while reducing inflammation.

Correlations between antimicrobial peptides and spectrophotometric skin color parameters in patients with basal cell carcinoma

BackgroundAntimicrobial peptides (AMPs) are active molecules in the human innate immune system, that participate in host defense and regulate the inflammation process. Previous reports have confirmed that antimicrobial peptides play a critical role in carcinogenesis.ObjectiveThe present study aimed to evaluate the correlations between plasma concentrations of AMPs and spectrophotometric parameters of skin color in patients with basal cell carcinoma and compare the results with those of healthy controls.MethodsThe plasma concentrations of cathelicidin and beta-defensin-2 in 100 patients (50 with skin cancer and 50 healthy control subjects) were measured, and skin color parameters were tested using a DermaSpectrophotometer.ResultsIn patients with basal cell carcinoma, the concentrations of cathelicidin and beta-defensin-2 were significantly higher than those in healthy controls. In healthy control patients, when erythema increases, the levels of cathelicidin and beta-defensin-2 also increase. The direction of the relationship is opposite in people with basal cell carcinoma—the concentration of antimicrobial peptides decreases and the level of erythema increases.ConclusionA significantly higher level of plasma concentrations of cathelicidin and HBD-2 are correspondent to the presence of basal cell carcinoma. Skin cancer modifies the relationship between intensity of skin erythema and the levels of cathelicidin and HBD-2. This can be related to inadequate immunological response in patients with skin cancers. New direction of research may be pioneered in searching for cytokine or mast cells disorders.

Single-cell RNA sequencing reveals rebalancing of immunological response in patients with periodontitis after non-surgical periodontal therapy

BackgroundPeriodontitis is a major inflammatory disease of the oral mucosa that is not limited to the oral cavity but also has systemic consequences. Although the importance of chronic periodontitis has been emphasized, the systemic immune response induced by periodontitis and its therapeutic effects remain elusive. Here, we report the transcriptomes of peripheral blood mononuclear cells (PBMCs) from patients with periodontitis.MethodsUsing single-cell RNA sequencing, we profiled PBMCs from healthy controls and paired pre- and post-treatment patients with periodontitis. We extracted differentially expressed genes and biological pathways for each cell type and calculated activity scores reflecting cellular characteristics. Intercellular crosstalk was classified into therapy-responsive and -nonresponsive pathways.ResultsWe analyzed pan-cellular differentially expressed genes caused by periodontitis and found that most cell types showed a significant increase in CRIP1, which was further supported by the increased levels of plasma CRIP1 observed in patients with periodontitis. In addition, activated cell type-specific ligand-receptor interactions, including the BTLA, IFN-γ, and RESISTIN pathways, were prominent in patients with periodontitis. Both the BTLA and IFN-γ pathways returned to similar levels in healthy controls after periodontal therapy, whereas the RESISTIN pathway was still activated even after therapy.ConclusionThese data collectively provide insights into the transcriptome changes and molecular interactions that are responsive to periodontal treatment. We identified periodontitis-specific systemic inflammatory indicators and suggest unresolved signals of non-surgical therapy as future therapeutic targets.

Immunologic response in patients with polytrauma.

PurposeIt is now known that traumatic injury initiates a complex and dynamic immune response on the first day. It is believed that in patients with polytrauma, these immune responses contribute to the development of infectious complications. Therefore, understanding the immune response to trauma is critical to improving patient outcomes through the development of new therapies and improved resuscitation strategies. The purpose of this study is to examine the parameters of immunity in patients with severe polytrauma at the stages of surgical treatment (the nearest post-traumatic period and long-term periods) in the absence and presence of purulent-inflammatory complications.MethodsWe retrospectively enrolled 188 patients after severely injured trauma and 210 control group at two Level-1 Trauma Centers. Peripheral blood was collected upon presentation to the hospital and at the following time points: 1, 3, 7, 14, 21, 30, 60 and 90 days, and daily during intensive care unit admission. T-lymphocytes analyses performed using a Beckman Coulter EPICS XL flow cytometer (USA) with monoclonal antibodies (Immunotech, France). Analyses of protein levels of cytokines/chemokines, immunoglobulins, and circulating immune complexes was using ELISA.ResultsUnder the influence of trauma, the content of T lymphocytes decreased due to the population of T-helpers. However, the number of B lymphocytes increased. The most pronounced activation of humoral immunity was observed by the 30th day of the post-traumatic period. Concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-a), interleukin-10 (IL-10) on day 1 after injury were the highest. Later, in the post-traumatic period, a gradual decrease in the initially elevated cytokines was noted.ConclusionsAs we continue to extrapolate new information on immune response factors associated with polytrauma, we will be better equipped to develop new therapeutic strategies to treat this serious clinical and social problem. In addition, individually adjusted immune control is an important interactive concept in polytrauma management.

1078P Correlation between T cell immunity and EGFR-TKI treatment in patients harboring EGFR driver mutation

Although osimertinib provides a longer survival time than first/second-generation EGFR tyrosine kinase inhibitor (TKI) for non-small cell lung cancer (NSCLC) harboring EGFR mutations, acquired resistance is inevitable. Since the time to acquire resistance to TKI is shorter for cancers with a higher mutational burden and mutations increase after TKI resistance is acquired, the acquired resistance mechanism depends primarily on acquired mutations. Although the cancer immunoediting theory indicates that the process of genetic mutation accumulation by cancer cells involves a conflict with T-cell immunity, which recognizes gene mutation products as neoantigens and destroys them, the relationship between TKI treatment effect and immunological response in patients with EGFR-bearing NSCLC is unknown.To identify the correlation between T-cell immunity and the duration of TKI response, we examined the peripheral blood mononuclear cells (PBMCs) of patients with lung cancer prior to osimertinib therapy.

CHARACTERISTICS OF IMMUNOREACTIVITY IN PATIENTS WITH VARIOUS FORMS OF DIABETIC FOOT ULCER

The article presents a comparative assessment of the levels of cytokines that regulate the differentiation of various macrophage phenotypes, as well as immunological responses in patients with diabetes. We examined and treated 245 patients who were allocated to two groups. The first group comprised neuropathic patients (comparison subgroup 1A without DFU, n=30 and subgroup 1B with DFU, n=80). The second group included patients with neuroischemic type 2 diabetes (comparison subgroup 2A without DFU, n=35 and subgroup 2B with DFU, n=100). As an indicator of hyperglycemia, the glycated hemoglobin level (HbA1c) was used, which was determined on the DCA 2000 device by the method of latex immunoagglutination inhibition using the “Hemoglobin A1c Reagent kit”. The concentration of cytokines TNF-α, IFN-γ, IL-6, and OPG in blood serum was determined on the first day of hospitalization before surgery using enzyme immunoassay test systems (OOO “Cytokine”, St. Petersburg) in accordance with the manufacturer's instructions. An imbalance of cytokines was revealed, indicating a shift in immunomodulatory responses, aggravation of metabolic and vascular disorders in tissues, accompanied by an inadequate course of the inflammatory and reparative process and the formation of a diabetic foot ulcer.

PARAMETERS OF ENDOTHELIAL DYSFUNCTION AND IMMUNE RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH AND WITHOUT ISCHEMIC HEART DISEASE.

The aim: To determine changes in endothelial dysfunction and immunological response in patients with rheumatoid arthritis with and without coronary heart disease. Materials and methods: The study involved 151 patients with RA and coronary heart disease. The ED was assessed by examining the NO system in RA for determination of the content in the blood of the product of NO synthase - the final metabolites of NO2- and NO3- and the level of VEGF and CD28 in the serum. Results: The results of the study of the levels of metabolites NO2- and NO3- in the first and second groups showed their increased content. Analysis of the content of VEGF in the blood for patients with different durations of the disease showed that the concentration of the studied protein grows larger with increasing duration of the disease. The maximum of sCD28 concentration was found in middle-aged patients, and the minimum (the difference was significant) - in the elderly. Conclusions: As the duration of the disease increases, the content of VEGF in the blood of patients increases, which, at the same time, did not show age dependence on RA and did not change further with concomitant coronary heart disease. Detected concentrations of sCD28 are higher in patients with less prolonged RA, and begin to decrease with increasing duration of the disease.

Therapeutic Approaches in Modulating the Inflammatory and Immunological Response in Patients With Sepsis, Acute Respiratory Distress Syndrome, and Pancreatitis: An Expert Opinion Review.

Immunomodulation has long been an adjunct approach in treating critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP). Hyperactive immune response with immunopathogenesis leads to organ dysfunction and alters the clinical outcomes in critically ill. Though the immune response in the critically ill might have been overlooked, it has gathered greater attention during this novel coronavirus disease 2019 (COVID-19) pandemic. Modulating hyperactive immune response, the cytokine storm, especially with steroids, has shown to improve the outcomes in COVID-19 patients. In this review, we find that immune response pathogenesis in critically ill patients with sepsis, ARDS, and AP is nearly similar. The use of immunomodulators such as steroids, broad-spectrum serine protease inhibitors such as ulinastatin, thymosin alpha, intravenous immunoglobulins, and therapies such as CytoSorb and therapeutic plasma exchange may help in improving the clinical outcomes in these conditions. As the experience of the majority of physicians in using such therapeutics may be limited, we provide our expert comments regarding immunomodulation to optimize outcomes in patients with sepsis/septic shock, ARDS, and AP.

Immunological Traits of Patients with Coexistent Inflammatory Bowel Disease and Periodontal Disease: A Systematic Review.

This systematic review assessed studies that evaluated the immunological traits of patients with both inflammatory bowel disease (IBD) and periodontal disease. An electronic search for literature was conducted on PubMed, Embase, Scopus, Cochrane and Web of Science. Studies that evaluated the immunological response in patients with IBD and periodontal disease were considered eligible for inclusion. A total of 6 cross-sectional studies of 275 patients were included. Immunological analyses were performed in gingival crevicular fluid, saliva, serum, intestinal and gingival biopsies. Four studies identified that the presence of IBD and periodontal disease was associated with higher levels of prostaglandin E2, aMMP8, IL-18 and S100A12, respectively, when compared to patients without the coexistence of both diseases. Furthermore, another study identified higher aMMP-8 levels with increasing severity of periodontitis in Crohn’s disease patients. The quality of overall evidence ranged from high to low due to the observational nature of contributing studies. The coexistence of IBD and periodontal disease seems to be associated with a more responsive inflammatory reaction compared with individuals having one or the other. More randomized controlled studies evaluating the coexistence of IBD and periodontitis are required to better explore the immunological interplay between them.

HPV-16 E6/E7 DNA tattoo vaccination using genetically optimized vaccines elicit clinical and immunological responses in patients with usual vulvar intraepithelial neoplasia (uVIN): a phase I/II clinical trial

BackgroundUsual vulvar intraepithelial neoplasia (uVIN) is a premalignancy caused by persistent infection with high-risk types of human papillomavirus (HPV), mainly type 16. Even though different treatment modalities are available (eg,...

The challenges and opportunities of traditional Chinese medicines against COVID-19: a way out from a network perspective.

The purpose of this perspective is to provide insights into the current challenges and opportunities of applying network pharmacology (NP) to illustrate the effectiveness of traditional Chinese medicines (TCMs) against the coronavirus disease 2019 (COVID-19). Emerging studies have indicated that the progression of COVID-19 is associated with hematologic and immunologic responses in patients, and TCMs may fight against COVID-19 regarding the two aspects. However, the underlying mechanisms remain largely unclear [1]. This perspective is intended as a brief report derived from our previous experience in investigating the efficacy of TCMs, via conventional reductionism-based research methods, holistic NP, systems biology, or “omics” research, and prevailing big data analysis.

Single-cell landscape of immunological responses in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.