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3.
Aging Cell ; 21(4): e13582, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1788809

ABSTRACT

Older humans and animals often exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naive T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of West Nile virus (WNV) in both humans naturally exposed to, and mice experimentally infected with, WNV. To examine possible causality, we sought to increase the number of CD8 Tn cells by treating C57BL/6 mice with IL-7 complexes (IL-7C, anti-IL-7 mAb bound to IL-7), shown previously to efficiently increase peripheral T-cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL-7C administration to old mice increasing the number of total T cells (>fourfold) and NS4b:H-2Db -restricted antigen-specific CD8 T cells (twofold). This improved the numbers of NS4b-specific CD8 T cells detected at the peak of the response against WNV, but not survival of WNV challenge. IL-7C-treated old animals also showed no improvement in WNV-specific effector immunity (neutralizing antibody and in vivo T-cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag-specific precursors into old mice and showed that injection of 5400 (but not of 1800 or 600) adult naive WNV-specific CD8 T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms and are discussed in light of targets of immune reconstitution.


Subject(s)
West Nile Fever , West Nile virus , Animals , CD8-Positive T-Lymphocytes , Cell Count , Interleukin-7 , Mice , Mice, Inbred C57BL
4.
Pathol Res Pract ; 231: 153782, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1655042

ABSTRACT

The novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 outbreak, spread rapidly and infected more than 140 million people with more than three million victims worldwide. The SARS-CoV-2 causes destructive changes in the immunological and hematological system of the host. These alterations appear to play a critical role in disease pathology and the emerging of clinical manifestations. In this review, we aimed to discuss the effect of COVID-19 on the count, function and morphology of immune and blood cells and the role of these changes in the pathophysiology of the disease. Knowledge of these changes may help with better management and treatment of COVID-19 patients.


Subject(s)
Blood Platelets/virology , Erythrocytes/virology , Granulocytes/virology , Monocytes/virology , SARS-CoV-2 , COVID-19/blood , COVID-19/virology , Cell Count , Cell Shape , Humans
5.
Mult Scler Relat Disord ; 59: 103560, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1650508

ABSTRACT

BACKGROUND: Antibody responses to SARS-CoV-2 vaccination are impaired in people with multiple sclerosis (MS) under anti-CD20 therapies. It is however unclear, whether patients who received the basic immunization prior to anti-B cell medication start respond to the COVID-19 booster dose, once B cells are depleted. AIM: To investigate the humoral response to recall antigen by COVID-19 booster vaccines in people with MS (pwMS), who recently started an anti-CD20 therapy compared to people with long-term B cell depletion. METHODS: We enrolled 15 pwMS who had received booster vaccination on anti-CD20 therapy. Of these, 11 had established anti-CD20 medications and were therefore vaccinated during a continuous state of B cell depletion (CD20-vaccine cohort). Four pwMS had received the basic immunization prior to anti-CD20 therapy commencement and only the booster dose (vaccine-CD20-vaccine cohort) under conditions of B cell depletion. We assessed SARS-CoV-2 specific antibody responses after booster vaccination among both groups and evaluated accompanying B cell numbers and proportions from the peripheral circulation. RESULTS: The booster dose of SARS-CoV-2 vaccination elicited measurable antibody responses in 18% of individuals from the CD20-vaccine cohort compared to 100% from the vaccine-CD20-vaccine cohort. Antibody-levels were significantly higher among patients from the vaccine-CD20-vaccine cohort compared to the CD20-vaccine cohort (mean 951.25 ± 1137.96 BAU/ml, vs mean 12.36 ± 11.94 BAU/ml; mean difference 938 BAU/ml (95% CI: 249-1629 BAU/ml), p <0.0001). Among the vaccine-CD20-vaccine cohort, the booster immunization led to augmentation of spike antibody levels in 75% despite concomitant B cell depletion, and values increased by 3.8 - 9.4-fold compared to basic immunization. We observed no correlation of B cell kinetics and SARS-CoV-2 antibody levels. CONCLUSION: Our study suggests that antibody production to recall COVID-19 antigens is preserved in pwMS despite concomitant anti-CD20 therapy. If corroborated in bigger cohorts, this could have implications in the management of individuals about to start B cell medications.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19 Vaccines , Cell Count , Humans , Multiple Sclerosis/drug therapy , Pilot Projects , SARS-CoV-2
6.
Biometals ; 35(1): 125-145, 2022 02.
Article in English | MEDLINE | ID: covidwho-1611429

ABSTRACT

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.


Subject(s)
COVID-19/blood , Copper/blood , SARS-CoV-2/pathogenicity , Selenium/blood , Zinc/blood , Adolescent , Adult , Aged , Aged, 80 and over , Asymptomatic Diseases , C-Reactive Protein/metabolism , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Cell Count , Cholecalciferol/blood , Humans , Lymphocytes/immunology , Lymphocytes/virology , Middle Aged , Monocytes/immunology , Monocytes/virology , Neutrophils/immunology , Neutrophils/virology , Regression Analysis , SARS-CoV-2/growth & development , Severity of Illness Index , Superoxide Dismutase/blood , Vitamin A/blood , Vitamin E/blood
8.
Biotechnol Bioeng ; 118(10): 3811-3820, 2021 10.
Article in English | MEDLINE | ID: covidwho-1263060

ABSTRACT

The most effective way to prevent and control infectious disease outbreak is through vaccines. The increasing use of vaccines has elevated the need to establish new manufacturing strategies. One of the major approaches is cell-based production, which creates a need for high cell density to enable higher cell production levels. This has led to development of the technology of cell carriers, including micro and macro cell carriers. To follow the production process, quantifying the number of cells on these carriers is required, as well as the tracking of their viability and proliferation. However, owing to various carriers' unique structures, tracking the cell's is challenging using current traditional assays that were originally developed for monolayers of adherent cells. The current "gold standard" method is counting cell nuclei, separating cells from the carrier, staining with crystal violet, and visually counting under a microscope. This method is tedious and counts both live and dead cells. A few other techniques were developed but were specific to the carrier type and involved specialized equipment. In this study, we describe a broadly ranging method for counting cells on carriers that was developed and employed as part of the development of severe acute respiratory syndrome coronavirus 2 vaccine. The method is based on the Alamar blue dye, a well-known, common marker for cell activity, and was found to be successful in tracking cell adsorption, cell growth, and viability on carriers. No separation of the cells from the carriers is needed, nor is any specialized equipment; the method is simple and rapid and provides comprehensive details necessary for process control of viral vaccine production in cells. This method can be easily implemented in any of a number of cell-based processes and other unique platforms for measuring the growth of encapsulated cells.


Subject(s)
COVID-19 Vaccines , COVID-19/metabolism , SARS-CoV-2/metabolism , Animals , COVID-19/pathology , Cell Count , Chlorocebus aethiops , Humans , Vero Cells
9.
J Med Internet Res ; 23(5): e25988, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1259298

ABSTRACT

BACKGROUND: Early detection and intervention are the key factors for improving outcomes in patients with COVID-19. OBJECTIVE: The objective of this observational longitudinal study was to identify nonoverlapping severity subgroups (ie, clusters) among patients with COVID-19, based exclusively on clinical data and standard laboratory tests obtained during patient assessment in the emergency department. METHODS: We applied unsupervised machine learning to a data set of 853 patients with COVID-19 from the HM group of hospitals (HM Hospitales) in Madrid, Spain. Age and sex were not considered while building the clusters, as these variables could introduce biases in machine learning algorithms and raise ethical implications or enable discrimination in triage protocols. RESULTS: From 850 clinical and laboratory variables, four tests-the serum levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), and the number of neutrophils-were enough to segregate the entire patient pool into three separate clusters. Further, the percentage of monocytes and lymphocytes and the levels of alanine transaminase (ALT) distinguished cluster 3 patients from the other two clusters. The highest proportion of deceased patients; the highest levels of AST, ALT, LDH, and CRP; the highest number of neutrophils; and the lowest percentages of monocytes and lymphocytes characterized cluster 1. Cluster 2 included a lower proportion of deceased patients and intermediate levels of the previous laboratory tests. The lowest proportion of deceased patients; the lowest levels of AST, ALT, LDH, and CRP; the lowest number of neutrophils; and the highest percentages of monocytes and lymphocytes characterized cluster 3. CONCLUSIONS: A few standard laboratory tests, deemed available in all emergency departments, have shown good discriminative power for the characterization of severity subgroups among patients with COVID-19.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Unsupervised Machine Learning , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , C-Reactive Protein/analysis , COVID-19/mortality , Cell Count , Cluster Analysis , Datasets as Topic , Emergency Service, Hospital , Humans , L-Lactate Dehydrogenase/blood , Longitudinal Studies , Lymphocytes , Monocytes , Neutrophils , Prognosis , Spain/epidemiology , Triage
10.
Eye Contact Lens ; 47(4): 168-173, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1140027

ABSTRACT

PURPOSE: To assess the effect of severe acute respiratory syndrome coronavirus-2 infection on the conjunctiva and tear film. METHODS: Thirty-eight patients with confirmed COVID-19 and 31 healthy controls were included in this prospective and observational study. Individuals with COVID-19 formed the patient group, and healthy individuals formed the control group. Conjunctival impression cytology (CIC), TBUT, Schirmer II test, and ocular surface disease index were evaluated in all participants. RESULTS: No significant difference was observed regarding the mean age and gender between the groups (P=0.786 and P=0.122, respectively). The mean TBUT and Schirmer II test results did not differ between the two groups (P=0.496 and P=0.447, respectively). The CIC results revealed decreased density and cell size of goblet cells and moderate to high enlargement, squamous changes, and increased nucleocytoplasmic ratio in nongoblet epithelial cells in the COVID-19 group compared with the control group. Based on the Nelson classification in CIC samples, 60.6% of the COVID-19 group and 19.4% of the control group had changes consistent with grade 2 or above. The presence of neutrophils in CIC was significantly higher in the COVID-19 group (P<0.001), whereas the presence of lymphocyte was similar between the two groups (P=0.247). CONCLUSION: This study revealed the pathological conjunctival alterations in patients with COVID-19 and demonstrated that pathological ocular surface alterations may present even at the beginning of COVID-19 without clinically significant ocular manifestation.


Subject(s)
COVID-19/diagnosis , Conjunctiva/pathology , Conjunctivitis, Viral/diagnosis , Dry Eye Syndromes/diagnosis , Eye Infections, Viral/diagnosis , SARS-CoV-2/isolation & purification , Tears/virology , Adult , COVID-19 Nucleic Acid Testing , Cell Count , Cell Size , Conjunctivitis, Viral/virology , Cross-Sectional Studies , Cytological Techniques , Dry Eye Syndromes/virology , Eye Infections, Viral/virology , Female , Goblet Cells/pathology , Humans , Lymphocytes/pathology , Male , Middle Aged , Neutrophils/pathology , Prospective Studies , SARS-CoV-2/genetics , Young Adult
11.
Front Immunol ; 12: 603563, 2021.
Article in English | MEDLINE | ID: covidwho-1090415

ABSTRACT

The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, with decreased IFNγ expression in CD4+ T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Killer Cells, Natural/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Cell Count , Cells, Cultured , Disease Progression , Female , Humans , Immunity, Cellular , Interferon-gamma/metabolism , Male , Middle Aged
13.
Eur Urol Focus ; 6(5): 1124-1129, 2020 Sep 15.
Article in English | MEDLINE | ID: covidwho-437089

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), involves multiple organs. Testicular involvement is largely unknown. OBJECTIVE: To determine the pathological changes and whether SARS-CoV-2 can be detected in the testes of deceased COVID-19 patients. DESIGN, SETTING, AND PARTICIPANTS: Postmortem examination of the testes from 12 COVID-19 patients was performed using light and electron microscopy, and immunohistochemistry for lymphocytic and histiocytic markers. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the virus in testicular tissue. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Seminiferous tubular injury was assessed as none, mild, moderate, or severe according to the extent of tubular damage. Leydig cells in the interstitium were counted in ten 400× microscopy fields. RESULTS AND LIMITATIONS: Microscopically, Sertoli cells showed swelling, vacuolation and cytoplasmic rarefaction, detachment from tubular basement membranes, and loss and sloughing into lumens of the intratubular cell mass. Two, five, and four of 11 cases showed mild, moderate, and severe injury, respectively. The mean number of Leydig cells in COVID-19 testes was significantly lower than in the control group (2.2 vs 7.8, p < 0.001). In the interstitium there was edema and mild inflammatory infiltrates composed of T lymphocytes and histiocytes. Transmission EM did not identify viral particles in three cases. RT-PCR detected the virus in one of 12 cases. CONCLUSIONS: Testes from COVID-19 patients exhibited significant seminiferous tubular injury, reduced Leydig cells, and mild lymphocytic inflammation. We found no evidence of SARS-CoV-2 virus in the testes in the majority (90%) of the cases by RT-PCR, and in none by electron microscopy. These findings can provide evidence-based guidance for sperm donation and inform management strategies to mitigate the risk of testicular injury during the COVID-19 disease course. PATIENT SUMMARY: We examined the testes of deceased COVID-19 patients. We found significant damage to the testicular parenchyma. However, virus was not detected in testes in the majority of cases.


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Seminiferous Tubules/pathology , Testis/pathology , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Cell Count , Coronavirus Infections/metabolism , Coronavirus Infections/physiopathology , Humans , Inflammation , Leydig Cells/pathology , Leydig Cells/ultrastructure , Male , Microscopy, Electron , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/physiopathology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Seminiferous Tubules/ultrastructure , Sertoli Cells/pathology , Sertoli Cells/ultrastructure , Spermatogenesis/physiology , Testis/metabolism , Testis/ultrastructure , Testis/virology
14.
Clin Chim Acta ; 508: 122-129, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-260025

ABSTRACT

BACKGROUND: The underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. MATERIAL AND METHODS: This retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. RESULTS: Compared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR = 7.701, 95%CI:1.265-46.893, P = 0.027), eosinopenia (OR = 5.595, 95%CI:1.008-31.054, P = 0.049), and worse one-month outcome (OR = 8.984; 95%CI:1.021-79.061, P = 0.048). CONCLUSION: Lymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnosis , Eosinophils/pathology , Lymphocyte Subsets/pathology , Lymphopenia/diagnosis , Pneumonia, Viral/diagnosis , Aged , Biomarkers/blood , COVID-19 , Cell Count , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Disease Progression , Eosinophils/virology , Female , Humans , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Lymphocyte Subsets/virology , Lymphopenia/blood , Lymphopenia/physiopathology , Lymphopenia/virology , Male , Middle Aged , Monocytes/pathology , Monocytes/virology , Neutrophils/pathology , Neutrophils/virology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
15.
Clin Chim Acta ; 508: 98-102, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-245188

ABSTRACT

BACKGROUND: Novel coronavirus infectious disease (COVID-19) has been spreading worldwide, and tracking laboratory indexes during the diagnosis and treatment of patients with severe COVID-19 can provide a reference for patients in other countries and regions. METHODS: We closely tracked the epidemiological history, diagnosis and treatment process, as well as dynamic changes in routine blood indicators, of a severe COVID-19 patient who was hospitalized for 26 days. RESULTS: Our study found that the patient's condition worsened in the first week after admission, white blood cells (WBCs), neutrophils, lymphocytes, monocytes, eosinophils, red blood cells (RBCs), hemoglobin, neutrophil lymphocyte ratio (NLR), platelets (PLT) and platelet lymphocyte ratio (PLR) decreased. On the 7th day of admission, the levels of these cells decreased to their lowest values, though the red blood cell distribution width (RDW) and C-reactive protein (CRP) level remained at high values. From 8 to 14 days of admission, the patient's condition improved, hypoxemia was corrected, and mechanical ventilation was discontinued. The number of WBCs, neutrophils, monocytes, eosinophils and lymphocytes increased gradually, and the erythrocyte parameters stopped declining and stabilized in a certain range; CRP decreased rapidly. On the 20th day of admission, the nucleic acid test was negative, WBC, neutrophil, CRP, NLR and PLR decreased gradually, and monocyte, lymphocyte, and eosinophil counts increased. Although RBCs and hemoglobin (Hb) levels continued to decrease, RDW gradually increased, indicating the recovery of hematopoiesis. In addition, it should be noted that monocytes and eosinophils were at extremely low levels within 10 days after admission; the recovery time of eosinophils was approximately 12 days after admission, which was earlier than other parameters, which might be of great value in judging the progress of the disease. CONCLUSIONS: Dynamic changes in routine blood parameters might be helpful for the prognosis of COVID-19 patients and evaluation of the treatment effect.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Anti-Bacterial Agents/therapeutic use , Betacoronavirus/drug effects , Biomarkers/blood , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , C-Reactive Protein/metabolism , COVID-19 , Cell Count , Convalescence , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Erythrocytes/drug effects , Erythrocytes/pathology , Erythrocytes/virology , Female , Humans , Middle Aged , Monocytes/drug effects , Monocytes/pathology , Monocytes/virology , Neutrophils/drug effects , Neutrophils/pathology , Neutrophils/virology , Oseltamivir/therapeutic use , Pandemics , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Prognosis , Respiration, Artificial , SARS-CoV-2 , Severity of Illness Index
16.
J Clin Invest ; 130(5): 2620-2629, 2020 05 01.
Article in English | MEDLINE | ID: covidwho-98087

ABSTRACT

BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokines/blood , Cytokines/immunology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , T-Lymphocytes/immunology , Adult , Aged , COVID-19 , Cell Count , China , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Female , Gene Expression Profiling , Gene Expression Regulation/immunology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Retrospective Studies , Severity of Illness Index
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