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1.
Cell Reports Medicine ; : 100640, 2022.
Article in English | ScienceDirect | ID: covidwho-1819630

ABSTRACT

Summary SARS-CoV-2-specific CD4+ T cells are likely important in immunity against COVID-19, but our understanding of CD4+ longitudinal dynamics following infection, and specific features that correlate with the maintenance of neutralizing antibodies, remains limited. Here, we characterize SARS-CoV-2-specific CD4+ T cells in a longitudinal cohort of 109 COVID-19 outpatients enrolled during acute infection. The quality of the SARS-CoV-2-specific CD4+ response shifts from cells producing IFNγ to TNFα from five days to four months post-enrollment, with IFNγ-IL21-TNFα+ CD4+ T cells the predominant population detected at later timepoints. Greater percentages of IFNγ-IL21-TNFα+ CD4+ T cells on day 28 correlate with SARS-CoV-2 neutralizing antibodies measured seven months post-infection (⍴=0.4, P=0.01). mRNA vaccination following SARS-CoV-2 infection boosts both IFNγ and TNFα producing, spike protein-specific CD4+ T cells. These data suggest that SARS-CoV-2-specific, TNFα-producing CD4+ T cells may play an important role in antibody maintenance following COVID-19.

2.
Viruses ; 14(3)2022 03 07.
Article in English | MEDLINE | ID: covidwho-1732249

ABSTRACT

Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glycoisoform distributions of 597 abundant serum glycopeptides and nonglycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure. We found statistically significant differences, at FDR < 0.05, for normalized abundances of 374 of the 597 peptides and glycopeptides interrogated between symptomatic and asymptomatic COVID-19 patients. Similar statistically significant differences were seen when comparing symptomatic COVID-19 patients to healthy controls (350 differentially abundant peptides and glycopeptides) and common cold coronavirus seropositive subjects (353 differentially abundant peptides and glycopeptides). Among healthy controls and sepsis patients, 326 peptides and glycopeptides were found to be differentially abundant, of which 277 overlapped with biomarkers that showed differential expression between symptomatic COVID-19 cases and healthy controls. Among symptomatic COVID-19 cases and sepsis patients, 101 glycopeptide and peptide biomarkers were found to be statistically significantly abundant. Using both supervised and unsupervised machine learning techniques, we found specific glycoprotein profiles to be strongly predictive of symptomatic COVID-19 infection. LASSO-regularized multivariable logistic regression and K-means clustering yielded accuracies of 100% in an independent test set and of 96% overall, respectively. Our findings are consistent with the interpretation that a majority of glycoprotein modifications observed which are shared among symptomatic COVID-19 and sepsis patients likely represent a generic consequence of a severe systemic immune and inflammatory state. However, there are glycoisoform changes that are specific and particular to severe COVID-19 infection. These may be representative of either COVID-19-specific consequences or susceptibility to or predisposition for a severe course of the disease. Our findings support the potential value of glycoproteomic biomarkers in the biomedical understanding and, potentially, the clinical management of serious acute infectious conditions.


Subject(s)
COVID-19 , Artificial Intelligence , COVID-19/diagnosis , Chromatography, Liquid/methods , Glycopeptides/analysis , Glycopeptides/chemistry , Glycopeptides/metabolism , Glycoproteins , Humans
3.
Sci Transl Med ; 14(634): eabn7842, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1723505

ABSTRACT

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , /immunology
4.
Nat Rev Cardiol ; 2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1632773

ABSTRACT

Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and D-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research.

5.
Sci Transl Med ; 14(635): eabm7853, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1630954

ABSTRACT

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , COVID-19 Vaccines , Humans , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
6.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750507

ABSTRACT

During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.

7.
Nat Commun ; 12(1): 5417, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1410404

ABSTRACT

COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Aged , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoantibodies/blood , Autoantigens/immunology , Connective Tissue Diseases/immunology , Cytokines/immunology , Female , Hospitalization , Humans , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2/pathogenicity , Viral Proteins/immunology
8.
Immunity ; 54(9): 1912-1914, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1370547

ABSTRACT

Monoclonal antibodies show efficacy in treating COVID-19, but the functional requirements for protection are unclear. In this issue of Immunity, Ullah et al. (2021) develop a stable SARS-CoV-2 reporter virus and use bioluminescence imaging to longitudinally monitor infection and assess neutralizing monoclonal antibody interventions in mice. They find that antibody-mediated protection depends on the Fc domain and Fc-gamma receptor-expressing immune cells.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Animals , Antibodies, Viral , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
9.
Cell Host Microbe ; 29(7): 1043-1047, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1309197

ABSTRACT

Severe COVID-19 arises from the convergence of inadequate pre-existing immunity and a host response that damages, rather than repairs, tissues. We outline clinical presentations of COVID-19 that are likely driven by dysregulated host immunity, discuss potential mechanisms underlying pathological responses, and highlight important areas for basic research on this topic.


Subject(s)
COVID-19/immunology , Host Microbial Interactions/immunology , Inflammation/immunology , COVID-19/pathology , Humans , Immunity , Immunocompromised Host , SARS-CoV-2/immunology
10.
Nat Immunol ; 22(5): 539-540, 2021 05.
Article in English | MEDLINE | ID: covidwho-1193592
11.
Nat Biotechnol ; 39(8): 928-935, 2021 08.
Article in English | MEDLINE | ID: covidwho-1152862

ABSTRACT

Current serology tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies mainly take the form of enzyme-linked immunosorbent assays, chemiluminescent microparticle immunoassays or lateral flow assays, which are either laborious, expensive or lacking sufficient sensitivity and scalability. Here we present the development and validation of a rapid, low-cost, solution-based assay to detect antibodies in serum, plasma, whole blood and to a lesser extent saliva, using rationally designed split luciferase antibody biosensors. This new assay, which generates quantitative results in 30 min, substantially reduces the complexity and improves the scalability of coronavirus disease 2019 (COVID-19) antibody tests. This assay is well-suited for point-of-care, broad population testing, and applications in low-resource settings, for monitoring host humoral responses to vaccination or viral infection.


Subject(s)
Antibodies, Viral/blood , Biosensing Techniques/methods , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Point-of-Care Systems , SARS-CoV-2/immunology , COVID-19/virology , Humans , Luminescence
12.
Nat Immunol ; 22(1): 67-73, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065904

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Immunoglobulin G/immunology , Receptors, IgG/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , COVID-19/metabolism , COVID-19/virology , Child , Cytokines/metabolism , Female , Glycosylation , Humans , Immunoglobulin G/metabolism , Interleukin-6 , Male , Middle Aged , Receptors, IgG/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Severity of Illness Index , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism
13.
Adv Drug Deliv Rev ; 172: 314-338, 2021 05.
Article in English | MEDLINE | ID: covidwho-1039241

ABSTRACT

The ongoing SARS-CoV-2 pandemic has led to the focused application of resources and scientific expertise toward the goal of developing investigational vaccines to prevent COVID-19. The highly collaborative global efforts by private industry, governments and non-governmental organizations have resulted in a number of SARS-CoV-2 vaccine candidates moving to Phase III trials in a period of only months since the start of the pandemic. In this review, we provide an overview of the preclinical and clinical data on SARS-CoV-2 vaccines that are currently in Phase III clinical trials and in few cases authorized for emergency use. We further discuss relevant vaccine platforms and provide a discussion of SARS-CoV-2 antigens that may be targeted to increase the breadth and durability of vaccine responses.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Clinical Trials, Phase III as Topic/methods , SARS-CoV-2/drug effects , Animals , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Drug Evaluation, Preclinical/methods , Drug Evaluation, Preclinical/trends , Humans , Protein Structure, Secondary , Protein Structure, Tertiary , SARS-CoV-2/chemistry , SARS-CoV-2/immunology
14.
Sci Immunol ; 5(54)2020 12 07.
Article in English | MEDLINE | ID: covidwho-963892

ABSTRACT

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients and 175 SARS-CoV-2-infected outpatients and asymptomatic individuals. Within this cohort, 25 patients died of their illness. Higher ratios of IgG antibodies targeting S1 or RBD domains of spike compared to nucleocapsid antigen were seen in outpatients who had mild illness versus severely ill patients. Plasma antibody increases correlated with decreases in viral RNAemia, but antibody responses in acute illness were insufficient to predict inpatient outcomes. Pseudovirus neutralization assays and a scalable ELISA measuring antibodies blocking RBD-ACE2 interaction were well correlated with patient IgG titers to RBD. Outpatient and asymptomatic individuals' SARS-CoV-2 antibodies, including IgG, progressively decreased during observation up to five months post-infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/blood , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/blood , COVID-19/genetics , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
15.
Res Sq ; 2020 May 06.
Article in English | MEDLINE | ID: covidwho-829290

ABSTRACT

During virus infection B cells are critical for the production of antibodies and protective immunity. Establishment of a diverse antibody repertoire occurs by rearrangement of germline DNA at the immunoglobulin heavy and light chain loci to encode the membrane-bound form of antibodies, the B cell antigen receptor. Little is known about the B cells and antigen receptors stimulated by the novel human coronavirus SARS-CoV-2. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of V genes, and extensive activation of IgG and IgA subclasses without significant somatic mutation. We detect expansion of B cell clones as well as convergent antibodies with highly similar sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. A shared convergent B cell clonotype in SARS-CoV-2 infected patients was previously seen in patients with SARS. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.

16.
mSphere ; 5(5)2020 09 16.
Article in English | MEDLINE | ID: covidwho-772263

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Here, we present an efficient, competitive serological assay that can simultaneously determine an individual's seroreactivity against the SARS-CoV-2 Spike protein and determine the proportion of anti-Spike antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. In this approach based on the use of enzyme-linked immunosorbent assays (ELISA), we present natively folded viral Spike protein receptor-binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then competed with soluble ACE2-Fc, or with a higher-affinity variant thereof, to determine the proportion of ACE2 blocking anti-RBD antibodies. Assessment of sera from 144 SARS-CoV-2 patients ultimately revealed that a remarkably consistent and high proportion of antibodies in the anti-RBD pool targeted the epitope responsible for ACE2 engagement (83% ± 11%; 50% to 107% signal inhibition in our largest cohort), further underscoring the importance of tailoring vaccines to promote the development of such antibodies.IMPORTANCE With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Peptidyl-Dipeptidase A/immunology , Serologic Tests/methods , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2 , Antigens, Viral/immunology , Binding Sites/immunology , COVID-19 , Coronavirus Infections/prevention & control , High-Throughput Screening Assays/methods , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Protein Binding , Protein Domains/immunology , SARS-CoV-2
17.
Cell Host Microbe ; 28(4): 516-525.e5, 2020 10 07.
Article in English | MEDLINE | ID: covidwho-743914

ABSTRACT

B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibody Formation , Betacoronavirus/genetics , COVID-19 , Female , HEK293 Cells , Humans , Immunogenetics , Immunoglobulin A/genetics , Immunoglobulin A/immunology , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Male , Middle Aged , Pandemics , SARS-CoV-2 , Sequence Analysis , Spike Glycoprotein, Coronavirus/immunology
18.
Cell ; 181(5): 1036-1045.e9, 2020 05 28.
Article in English | MEDLINE | ID: covidwho-72372

ABSTRACT

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , RNA Viruses/immunology , Animals , COVID-19 , Cells, Cultured , Chemokines/genetics , Chemokines/immunology , Coronavirus Infections/genetics , Disease Models, Animal , Host-Pathogen Interactions , Humans , Immunity, Innate , Inflammation/virology , Interferons/genetics , Interferons/immunology , Pandemics , Pneumonia, Viral/genetics , RNA Viruses/classification , SARS-CoV-2 , Transcription, Genetic
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