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1.
Biomed Pharmacother ; 144: 112346, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1466071

ABSTRACT

The expansion of myeloid-derived suppressor cells (MDSCs), known as heterogeneous population of immature myeloid cells, is enhanced during several pathological conditions such as inflammatory or viral respiratory infections. It seems that the way MDSCs behave in infection depends on the type and the virulence mechanisms of the invader pathogen, the disease stage, and the infection-related pathology. Increasing evidence showing that in correlation with the severity of the disease, MDSCs are accumulated in COVID-19 patients, in particular in those at severe stages of the disease or ICU patients, contributing to pathogenesis of SARS-CoV2 infection. Based on the involved subsets, MDSCs delay the clearance of the virus through inhibiting T-cell proliferation and responses by employing various mechanisms such as inducing the secretion of anti-inflammatory cytokines, inducible nitric oxide synthase (iNOS)-mediated hampering of IFN-γ production, or forcing arginine shortage. While the immunosuppressive characteristic of MDSCs may help to preserve the tissue homeostasis and prevent hyperinflammation at early stages of the infection, hampering of efficient immune responses proved to exert significant pathogenic effects on severe forms of COVID-19, suggesting the targeting of MDSCs as a potential intervention to reactivate T-cell immunity and thereby prevent the infection from developing into severe stages of the disease. This review tried to compile evidence on the roles of different subsets of MDSCs during viral respiratory infections, which is far from being totally understood, and introduce the promising potential of MDSCs for developing novel diagnostic and therapeutic approaches, especially against COVID-19 disease.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 , Myeloid-Derived Suppressor Cells , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Drug Discovery , Humans , Immune Tolerance , Immunity, Innate , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/physiology , SARS-CoV-2
2.
Front Immunol ; 12: 753558, 2021.
Article in English | MEDLINE | ID: covidwho-1463476

ABSTRACT

To date there is limited data on the immune profile and outcomes of solid organ transplant recipients who encounter COVID-19 infection early post-transplant. Here we present a unique case where the kidney recipient's transplant surgery coincided with a positive SARS-CoV-2 test and the patient subsequently developed symptomatic COVID-19 perioperatively. We performed comprehensive immunological monitoring of cellular, proteomic, and serological changes during the first 4 critical months post-infection. We showed that continuation of basiliximab induction and maintenance of triple immunosuppression did not significantly impair the host's ability to mount a robust immune response against symptomatic COVID-19 infection diagnosed within the first week post-transplant.


Subject(s)
Basiliximab/therapeutic use , COVID-19/immunology , Glomerulonephritis, IGA/therapy , Graft Rejection/immunology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , SARS-CoV-2/physiology , Adult , Humans , Immune Tolerance , Immunity , Male , Perioperative Period , Transcriptome
3.
Front Immunol ; 12: 733418, 2021.
Article in English | MEDLINE | ID: covidwho-1450812

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Myasthenia Gravis/immunology , Myasthenia Gravis/pathology , SARS-CoV-2/immunology , Autoimmunity/immunology , Humans , Immune Tolerance/immunology , Influenza Vaccines/immunology , Risk , Vaccination/adverse effects
5.
Nature ; 592(7853): 277-282, 2021 04.
Article in English | MEDLINE | ID: covidwho-1387425

ABSTRACT

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.


Subject(s)
COVID-19/drug therapy , COVID-19/therapy , COVID-19/virology , Evolution, Molecular , Mutagenesis/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Aged , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Chronic Disease , Genome, Viral/drug effects , Genome, Viral/genetics , High-Throughput Nucleotide Sequencing , Humans , Immune Evasion/drug effects , Immune Evasion/genetics , Immune Evasion/immunology , Immune Tolerance/drug effects , Immune Tolerance/immunology , Immunization, Passive , Immunosuppression , Male , Mutant Proteins/chemistry , Mutant Proteins/genetics , Mutant Proteins/immunology , Mutation , Phylogeny , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Viral Load/drug effects , Virus Shedding
6.
J Immunol ; 207(7): 1848-1856, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1377034

ABSTRACT

Immune cell responses are strikingly altered in patients with severe coronavirus disease 2019 (COVID-19), but the immunoregulatory process in these individuals is not fully understood. In this study, 23 patients with mild and 22 patients with severe COVID-19 and 6 asymptomatic carriers of COVID-19 were enrolled, along with 44 healthy controls (HC). Peripheral immune cells in HC and patients with COVID-19 were comprehensively profiled using mass cytometry. We found that in patients with severe COVID-19, the number of HLA-DRlow/- monocytes was significantly increased, but that of mucosal-associated invariant T (MAIT) cells was greatly reduced. MAIT cells were highly activated but functionally impaired in response to Escherichia coli and IL-12/IL-18 stimulation in patients with severe COVID-19, especially those with microbial coinfection. Single-cell transcriptome analysis revealed that IFN-stimulated genes were significantly upregulated in peripheral MAIT cells and monocytes from patients with severe COVID-19. IFN-α pretreatment suppressed MAIT cells' response to E. coli by triggering high levels of IL-10 production by HLA-DRlow/--suppressive monocytes. Blocking IFN-α or IL-10 receptors rescued MAIT cell function in patients with severe COVID-19. Moreover, plasma from patients with severe COVID-19 inhibited HLA-DR expression by monocytes through IL-10. These data indicate a unique pattern of immune dysregulation in severe COVID-19, which is characterized by enrichment of suppressive HLA-DRlow/- monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.


Subject(s)
COVID-19/immunology , Escherichia coli Infections/immunology , Escherichia coli/physiology , Interleukin-10/metabolism , Monocytes/immunology , Mucosal-Associated Invariant T Cells/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Asymptomatic Diseases , Cells, Cultured , Child , Coinfection , Disease Progression , Female , Humans , Immune Tolerance , Lymphocyte Activation , Male , Middle Aged , Severity of Illness Index , Young Adult
7.
Cell Signal ; 87: 110121, 2021 11.
Article in English | MEDLINE | ID: covidwho-1370457

ABSTRACT

The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive treatment protocol has been developed. The pathogenesis of the disease has not been clearly elucidated yet. A clear understanding of its pathogenesis will help develop effective vaccines and drugs. The immunopathogenesis of COVID-19 is characteristic with acute respiratory distress syndrome and multiorgan involvement with impaired Type I interferon response and hyperinflammation. The destructive systemic effects of COVID-19 cannot be explained simply by the viral tropism through the ACE2 and TMPRSS2 receptors. In addition, the recently identified mutations cannot fully explain the defect in all cases of Type I interferon synthesis. We hypothesize that retinol depletion and resulting impaired retinoid signaling play a central role in the COVID-19 pathogenesis that is characteristic for dysregulated immune system, defect in Type I interferon synthesis, severe inflammatory process, and destructive systemic multiorgan involvement. Viral RNA recognition mechanism through RIG-I receptors can quickly consume a large amount of the body's retinoid reserve, which causes the retinol levels to fall below the normal serum levels. This causes retinoid insufficiency and impaired retinoid signaling, which leads to interruption in Type I interferon synthesis and an excessive inflammation. Therefore, reconstitution of the retinoid signaling may prove to be a valid strategy for management of COVID-19 as well for some other chronic, degenerative, inflammatory, and autoimmune diseases.


Subject(s)
COVID-19/pathology , Signal Transduction/physiology , Vitamin A/metabolism , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Central Nervous System/metabolism , DEAD Box Protein 58/metabolism , Humans , Immune Tolerance , Interferon Type I/metabolism , Receptors, Immunologic/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Viral Tropism/physiology , Vitamin A/blood
8.
Curr Opin Immunol ; 72: 286-297, 2021 10.
Article in English | MEDLINE | ID: covidwho-1363939

ABSTRACT

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the Autoimmune Regulator (AIRE) gene, which impair the thymic negative selection of self-reactive T-cells and underlie the development of autoimmunity that targets multiple endocrine and non-endocrine tissues. Beyond autoimmunity, APECED features heightened susceptibility to certain specific infections, which is mediated by anti-cytokine autoantibodies and/or T-cell driven autoimmune tissue injury. These include the 'signature' APECED infection chronic mucocutaneous candidiasis (CMC), but also life-threatening coronavirus disease 2019 (COVID-19) pneumonia, bronchiectasis-associated bacterial pneumonia, and sepsis by encapsulated bacteria. Here we discuss the expanding understanding of the immunological mechanisms that contribute to infection susceptibility in this prototypic syndrome of impaired central tolerance, which provide the foundation for devising improved diagnostic and therapeutic strategies for affected patients.


Subject(s)
COVID-19/immunology , Candidiasis, Cutaneous/immunology , Polyendocrinopathies, Autoimmune/immunology , T-Lymphocytes/immunology , Transcription Factors/genetics , Animals , Autoimmunity , Bronchiectasis , COVID-19/epidemiology , COVID-19/genetics , Candidiasis, Cutaneous/epidemiology , Candidiasis, Cutaneous/genetics , Clonal Selection, Antigen-Mediated/genetics , Disease Susceptibility , Humans , Immune Tolerance/genetics , Polyendocrinopathies, Autoimmune/epidemiology , Polyendocrinopathies, Autoimmune/genetics
9.
Cytokine ; 146: 155637, 2021 10.
Article in English | MEDLINE | ID: covidwho-1333350

ABSTRACT

Interferons have prominent roles in various pathophysiological conditions, mostly related to inflammation. Interferon-gamma (IFNγ) was, initially discovered as a potent antiviral agent, over 50 years ago, and has recently garnered renewed interest as a promising factor involved in both innate and adaptive immunity. When new disease epidemics appear such as SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus), IAV (Influenza A virus), and in particular the current SARS-CoV-2 pandemic, it is especially timely to review the complexity of immune system responses to viral infections. Here we consider the controversial roles of effectors like IFNγ, discussing its actions in immunomodulation and immunotolerance. We explore the possibility that modulation of IFNγ could be used to influence the course of such infections. Importantly, not only could endogenous expression of IFNγ influence the outcome, there are existing IFNγ therapeutics that can readily be applied in the clinic. However, our understanding of the molecular mechanisms controlled by IFNγ suggests that the exact timing for application of IFNγ-based therapeutics could be crucial: it should be earlier to significantly reduce the viral load and thus decrease the overall severity of the disease.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Immune Tolerance/immunology , Immunity, Innate/immunology , Interferon-gamma/immunology , Antiviral Agents/immunology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Humans , Interferon-gamma/therapeutic use , Receptors, Interferon/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Signal Transduction/immunology
10.
J Allergy Clin Immunol ; 148(3): 679-688, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322161

ABSTRACT

In addition to being a source of nutrients for the developing newborn, human milk contains thousands of bioactive compounds, which influence infant health in the short-term as exemplified by its major benefits on infectious disease prevention. Many of the human milk compounds also have the required characteristics to instruct immune development and guide long-term health. Prebiotics, probiotics, and varied antimicrobial molecules all have the potential to shape the composition and function of the establishing gut microbiota, which is known to be a major determinant of immune function. Another and less explored way human milk can instruct long-term immunity is through antigen shedding. Here, we will review the evidence that antigens from maternal environment and more specifically from allergen sources are found in human milk. We will discuss data from rodent models and birth cohorts showing that allergen shedding in breast milk may influence long-term allergy risk. We will uncover the variables that may underlie heterogeneity in oral tolerance induction and allergy prevention in children breast-fed by allergen-exposed mothers. We will focus on the parameters that control antigen transfer to breast milk, on the unique biological characteristics of allergens in breast milk, and on the milk bioactive compounds that were found to influence immune response in offspring. We propose this understanding is fundamental to guide maternal interventions leading to lifelong allergen tolerance.


Subject(s)
Allergens/immunology , Hypersensitivity/prevention & control , Milk, Human/immunology , Animals , Female , Humans , Hypersensitivity/epidemiology , Immune System , Immune Tolerance , Risk
11.
Virulence ; 12(1): 1771-1794, 2021 12.
Article in English | MEDLINE | ID: covidwho-1305404

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a highly infectious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory findings from a significant number of patients with COVID-19 indicate the occurrence of leukocytopenia, specifically lymphocytopenia. Moreover, infected patients can experience contrasting outcomes depending on lymphocytopenia status. Patients with resolved lymphocytopenia are more likely to recover, whereas critically ill patients with signs of unresolved lymphocytopenia develop severe complications, sometimes culminating in death. Why immunodepression manifests in patients with COVID-19 remains unclear. Therefore, the evaluation of clinical symptoms and laboratory findings from infected patients is critical for understanding the disease course and its consequences. In this review, we take a logical approach to unravel the reasons for immunodepression in patients with COVID-19. Following the footprints of the virus within host tissues, from entry to exit, we extrapolate the mechanisms underlying the phenomenon of immunodepression.


Subject(s)
COVID-19/immunology , Immune Tolerance , SARS-CoV-2/pathogenicity , COVID-19/pathology , Cell Death , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Cytokines/metabolism , Humans , Immunity , Lymphopenia/immunology , Lymphopenia/pathology , SARS-CoV-2/physiology , Virus Replication
12.
PLoS Pathog ; 17(7): e1009721, 2021 07.
Article in English | MEDLINE | ID: covidwho-1298084

ABSTRACT

Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.


Subject(s)
COVID-19/immunology , Granulocytes/classification , Acute Disease , Adult , Aged , COVID-19/blood , Case-Control Studies , Cohort Studies , Convalescence , Disease Progression , Female , Follow-Up Studies , Granulocytes/cytology , Humans , Immune Tolerance/immunology , Male , Middle Aged , Scavenger Receptors, Class E/analysis , Severity of Illness Index
13.
Front Immunol ; 12: 667862, 2021.
Article in English | MEDLINE | ID: covidwho-1285290

ABSTRACT

With the pandemic of COVID-19, maintenance of oral health has increasingly become the main challenge of global health. Various common oral diseases, such as periodontitis and oral cancer, are closely associated with immune disorders in the oral mucosa. Regulatory T cells (Treg) are essential for maintaining self-tolerance and immunosuppression. During the process of periodontitis and apical periodontitis, two typical chronic immune-inflammatory diseases, Treg contributes to maintain host immune homeostasis and minimize tissue damage. In contrast, in the development of oral precancerous lesions and oral cancer, Treg is expected to be depleted or down-regulated to enhance the anti-tumor immune response. Therefore, a deeper understanding of the distribution, function, and regulatory mechanisms of Treg cells may provide a prospect for the immunotherapy of oral diseases. In this review, we summarize the distribution and multiple roles of Treg in different oral diseases and discuss the possible mechanisms involved in Treg cell regulation, hope to provide a reference for future Treg-targeted immunotherapy in the treatment of oral diseases.


Subject(s)
COVID-19/immunology , Immunotherapy/methods , Mouth Neoplasms/immunology , Periodontitis/immunology , SARS-CoV-2/physiology , T-Lymphocytes, Regulatory/immunology , Animals , Humans , Immune Tolerance , Self Tolerance
14.
Cells ; 10(6)2021 05 23.
Article in English | MEDLINE | ID: covidwho-1243957

ABSTRACT

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/ß and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/ß and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.


Subject(s)
COVID-19/immunology , Immune Tolerance , Lymphocyte Subsets/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Adaptive Immunity , Aged , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Clinical Deterioration , Critical Illness , Female , Hospital Mortality , Hospitalization , Humans , Immunity, Innate , Leukocyte Count , Male , Middle Aged , Poland/epidemiology , Prospective Studies , Risk Assessment/methods
15.
Transfusion ; 61(8): 2503-2511, 2021 08.
Article in English | MEDLINE | ID: covidwho-1243670

ABSTRACT

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation.


Subject(s)
COVID-19/complications , COVID-19/therapy , Immune Tolerance , COVID-19/immunology , Hematologic Neoplasms/complications , Hematologic Neoplasms/immunology , Humans , Immunization, Passive/methods , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/immunology , Organ Transplantation/adverse effects , Treatment Outcome
16.
Nat Biotechnol ; 39(4): 419-421, 2021 04.
Article in English | MEDLINE | ID: covidwho-1241985
18.
Clin Imaging ; 79: 104-109, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1208937

ABSTRACT

PURPOSE: To radiologically examine how the spleen size, which has important functions in hematological and immunological balance, is affected in COVID-19. METHODS: Between July 1 and August 31, 2020, consecutive patients diagnosed with COVID-19 were analyzed. Among these patients, those who underwent chest computed tomography (CT) examination at the time of presentation, patients with follow-up CT due to clinical deterioration were included in the study. The CTs of the patients were evaluated in terms of spleen size and volume. RESULTS: A total of 160 patients (88 females, 55%) were included in the study. The mean time between the initial and follow-up CT was 7.2 ± 2.8 days. The splenic volume (244.3 ± 136.7 vs. 303.5 ± 156.3 cm3) and splenic index (421.2 ± 235.5 vs. 523.2 ± 269.4 cm3) values were significantly higher in the follow-up CT compared to the initial CT (p < 0.001). The increase in the splenic volume and splenic index values was 59.2 ± 52.4 cm3 and 101.9 ± 90.3 cm3 (p < 0.001), respectively. The COVID-19 severity score was significantly higher in the follow-up CT compared to the initial CT (3.7 ± 4.2 vs. 12.5 ± 5.7, respectively; p < 0.001). The spleen width measured separately on the initial and follow-up CTs showed a highest positive correlation (r = 0.982, p < 0.001). CONCLUSION: Our study indicates that spleen size increases slightly-moderately in the first stages of the infection, and this increase is correlated with the COVID-19 severity score calculated on the chest CT data, and in this respect, it is similar to infections presenting with cytokine storm.


Subject(s)
COVID-19 , Immune Tolerance , COVID-19/immunology , Female , Humans , Retrospective Studies , SARS-CoV-2 , Spleen/diagnostic imaging , Tomography, X-Ray Computed
19.
Neuroimmunomodulation ; 28(1): 1-21, 2021.
Article in English | MEDLINE | ID: covidwho-1206095

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has devastating effects on the population worldwide. Given this scenario, the extent of the impact of the disease on more vulnerable individuals, such as pregnant women, is of great concern. Although pregnancy may be a risk factor in respiratory virus infections, there are no considerable differences regarding COVID-19 severity observed between pregnant and nonpregnant women. In these circumstances, an emergent concern is the possibility of neurodevelopmental and neuropsychiatric harm for the offspring of infected mothers. Currently, there is no stronger evidence indicating vertical transmission of SARS-CoV-2; however, the exacerbated inflammatory response observed in the disease could lead to several impairments in the offspring's brain. Furthermore, in the face of historical knowledge on possible long-term consequences for the progeny's brain after infection by viruses, we must consider that this might be another deleterious facet of COVID-19. In light of neuroimmune interactions at the maternal-fetal interface, we review here the possible harmful outcomes to the offspring brains of mothers infected by SARS-CoV-2.


Subject(s)
COVID-19/immunology , Neurodevelopmental Disorders/physiopathology , Neuroimmunomodulation/immunology , Pregnancy Complications, Infectious/immunology , Prenatal Exposure Delayed Effects/physiopathology , COVID-19/metabolism , COVID-19/physiopathology , Cytokine Release Syndrome/immunology , Decidua/immunology , Female , Humans , Immune Tolerance/immunology , Infectious Disease Transmission, Vertical , Neuroimmunomodulation/physiology , Placenta/immunology , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/physiopathology , SARS-CoV-2 , Umbilical Cord/immunology
20.
Aging (Albany NY) ; 13(5): 6236-6246, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1154948

ABSTRACT

BACKGROUND: The immune responses, hyper-inflammation or immunosuppression, may be closely related to COVID-19 progression. We aimed to evaluate the changes of frequency of CD14+HLA-DRlo/neg MDSCs, a population of cells with potent immunosuppressive capacity, in COVID-19 patients. METHODS: The levels of CD14+HLA-DRlo/neg MDSCs were determined by flow cytometry in 27 COVID-19 patients, and their association with clinical characteristics and laboratory data were analyzed. RESULTS: The frequency of CD14+HLA-DRlo/neg MDSCs was elevated in COVID-19 patients, particularly severe patients. A follow-up comparison revealed a decline of CD14+HLA-DRlo/neg MDSCs percentages in most patients 1 day after testing negative for SARS-CoV-2 nucleic acid, but the levels of CD14+HLA-DRlo/neg MDSCs were still greater than 50.0% in 3 ICU patients 4-10 days after negative SARS-CoV-2 results. Elevated frequency of CD14+HLA-DRlo/neg MDSCs was positively correlated with oropharyngeal viral loads and length of hospital stay, while negatively correlated with lymphocyte counts and serum albumin. Moreover, strong correlations were observed between the frequency of CD14+HLA-DRlo/neg MDSCs and T cell subsets, NK cell counts, and B cell percentages. The frequency of CD14+HLA-DRlo/neg MDSCs could be used as a predictor of COVID-19 severity. CONCLUSIONS: A high frequency of CD14+HLA-DRlo/neg MDSCs, especially in severe patients, may indicate an immunoparalysis status and could be a predictor of disease severity and prognosis.


Subject(s)
COVID-19/immunology , HLA-DR Antigens/immunology , Lipopolysaccharide Receptors/immunology , Myeloid-Derived Suppressor Cells/pathology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/pathology , Female , HLA-DR Antigens/analysis , Humans , Immune Tolerance , Lipopolysaccharide Receptors/analysis , Male , Middle Aged , Myeloid-Derived Suppressor Cells/immunology , Prognosis , SARS-CoV-2/isolation & purification
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