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1.
Sci Transl Med ; : eabm7853, 2022 Jan 18.
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 IgG antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by mRNA SARS-CoV-2 vaccines were instead highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. To study the biology 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 COVID-19 patients induced inflammatory cytokine production and robust infiltration of the lung by immune cells. By contrast, vaccine-elicited IgG did not promote an inflammatory lung response. Together, these results show that IgG-FcγR interactions are able to regulate inflammation in the lung and may define distinct lung activities associated with the IgG that are associated with severe COVID-19 and protection against infection with SARS-CoV-2.

2.
Nat Rev Immunol ; 21(5): 275, 2021 05.
Article in English | MEDLINE | ID: covidwho-1550310
4.
Non-conventional in English | [Unspecified Source], Grey literature | ID: grc-750490

ABSTRACT

Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

6.
Immunity ; 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1499987

ABSTRACT

The 2005 Immunity paper by Karikó et al. has been hailed as a cornerstone insight that directly led to the design and delivery of the mRNA vaccines against COVID-19. We asked experts in pathogen sensing, vaccine development, and public health to provide their perspective on the study and its implications.

7.
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
8.
Cell Host Microbe ; 29(7): 1040-1042, 2021 07 14.
Article in English | MEDLINE | ID: covidwho-1309194

ABSTRACT

A previously immune-naive world population is experiencing natural infection with SARS-CoV-2. Severe COVID-19 predominantly impacts adults, yet multisystem inflammatory disorder primarily impacts children. Herein, we discuss known clinical and biological features of SARS-CoV-2 in children and reflect on currently identified immune features and discuss what remains unknown.


Subject(s)
COVID-19/immunology , COVID-19/physiopathology , Child , Hospitalization , Humans , Immunity , SARS-CoV-2 , Vaccination
9.
Sci Rep ; 11(1): 13308, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281741

ABSTRACT

Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.


Subject(s)
COVID-19 , Feces , Gastrointestinal Microbiome , Nasopharynx/virology , RNA, Viral/isolation & purification , Aged , Biomarkers/metabolism , COVID-19/epidemiology , COVID-19/immunology , Cohort Studies , Cytokines/metabolism , Feces/virology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Male , Middle Aged , New York City/epidemiology , SARS-CoV-2/isolation & purification
10.
J Exp Med ; 218(5)2021 05 03.
Article in English | MEDLINE | ID: covidwho-1174833

ABSTRACT

COVID-19 has emerged as one of the worst pandemics in recent history and has exposed the weaknesses of healthcare systems worldwide. Here, we reflect on the lessons learned from a year in a pandemic. We discuss the extraordinary scientific advances made in our understanding of a new disease, the failed and successful attempts to halt its progression, and the impact of the pandemic on the scientific discourse within the global community.


Subject(s)
Biomedical Research , COVID-19/epidemiology , COVID-19/metabolism , Pandemics , SARS-CoV-2/metabolism , COVID-19/pathology , COVID-19/therapy , Humans
11.
Mod Pathol ; 34(8): 1456-1467, 2021 08.
Article in English | MEDLINE | ID: covidwho-1164812

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.


Subject(s)
COVID-19/physiopathology , Lung/physiopathology , Pulmonary Embolism/physiopathology , Adult , Aged , Aged, 80 and over , Autopsy , Blood Coagulation , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cause of Death , Cytokines/blood , Female , Host-Pathogen Interactions , Humans , Inflammation Mediators/blood , Lung/pathology , Lung/virology , Male , Middle Aged , New York City , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Pulmonary Embolism/virology , SARS-CoV-2/pathogenicity
12.
Gastroenterology ; 160(7): 2435-2450.e34, 2021 06.
Article in English | MEDLINE | ID: covidwho-1116737

ABSTRACT

BACKGROUND & AIMS: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance. METHODS: Human intestinal biopsy tissues were obtained from patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions. RESULTS: COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms. CONCLUSIONS: These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2-associated inflammation needs to be further examined.


Subject(s)
COVID-19/virology , Gastrointestinal Diseases/virology , Immunity, Mucosal , Intestinal Mucosa/virology , SARS-CoV-2/pathogenicity , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , Case-Control Studies , Cells, Cultured , Cytokines/blood , Female , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/immunology , Gastrointestinal Diseases/mortality , Host-Pathogen Interactions , Humans , Inflammation Mediators/blood , Intestinal Mucosa/immunology , Italy , Male , Middle Aged , New York City , Prognosis , Risk Assessment , Risk Factors , SARS-CoV-2/immunology , Viral Load
13.
Cytometry A ; 99(5): 446-461, 2021 05.
Article in English | MEDLINE | ID: covidwho-1047149

ABSTRACT

Mass cytometry (CyTOF) represents one of the most powerful tools in immune phenotyping, allowing high throughput quantification of over 40 parameters at single-cell resolution. However, wide deployment of CyTOF-based immune phenotyping studies are limited by complex experimental workflows and the need for specialized CyTOF equipment and technical expertise. Furthermore, differences in cell isolation and enrichment protocols, antibody reagent preparation, sample staining, and data acquisition protocols can all introduce technical variation that can confound integrative analyses of large data-sets of samples processed across multiple labs. Here, we present a streamlined whole blood CyTOF workflow which addresses many of these sources of experimental variation and facilitates wider adoption of CyTOF immune monitoring across sites with limited technical expertise or sample-processing resources or equipment. Our workflow utilizes commercially available reagents including the Fluidigm MaxPar Direct Immune Profiling Assay (MDIPA), a dry tube 30-marker immunophenotyping panel, and SmartTube Proteomic Stabilizer, which allows for simple and reliable fixation and cryopreservation of whole blood samples. We validate a workflow that allows for streamlined staining of whole blood samples with minimal processing requirements or expertise at the site of sample collection, followed by shipment to a central CyTOF core facility for batched downstream processing and data acquisition. We apply this workflow to characterize 184 whole blood samples collected longitudinally from a cohort of 72 hospitalized COVID-19 patients and healthy controls, highlighting dynamic disease-associated changes in circulating immune cell frequency and phenotype.


Subject(s)
COVID-19/diagnosis , Cell Separation , Flow Cytometry , Immunophenotyping , Leukocytes/immunology , SARS-CoV-2/immunology , Workflow , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Female , High-Throughput Screening Assays , Host-Pathogen Interactions , Humans , Leukocytes/metabolism , Leukocytes/virology , Male , Middle Aged , Predictive Value of Tests , SARS-CoV-2/pathogenicity , Severity of Illness Index , Young Adult
14.
Clin Infect Dis ; 71(11): 2933-2938, 2020 12 31.
Article in English | MEDLINE | ID: covidwho-1003539

ABSTRACT

BACKGROUND: There are limited data regarding the clinical impact of coronavirus disease 2019 (COVID-19) on people living with human immunodeficiency virus (PLWH). In this study, we compared outcomes for PLWH with COVID-19 to a matched comparison group. METHODS: We identified 88 PLWH hospitalized with laboratory-confirmed COVID-19 in our hospital system in New York City between 12 March and 23 April 2020. We collected data on baseline clinical characteristics, laboratory values, HIV status, treatment, and outcomes from this group and matched comparators (1 PLWH to up to 5 patients by age, sex, race/ethnicity, and calendar week of infection). We compared clinical characteristics and outcomes (death, mechanical ventilation, hospital discharge) for these groups, as well as cumulative incidence of death by HIV status. RESULTS: Patients did not differ significantly by HIV status by age, sex, or race/ethnicity due to the matching algorithm. PLWH hospitalized with COVID-19 had high proportions of HIV virologic control on antiretroviral therapy. PLWH had greater proportions of smoking (P < .001) and comorbid illness than uninfected comparators. There was no difference in COVID-19 severity on admission by HIV status (P = .15). Poor outcomes for hospitalized PLWH were frequent but similar to proportions in comparators; 18% required mechanical ventilation and 21% died during follow-up (compared with 23% and 20%, respectively). There was similar cumulative incidence of death over time by HIV status (P = .94). CONCLUSIONS: We found no differences in adverse outcomes associated with HIV infection for hospitalized COVID-19 patients compared with a demographically similar patient group.


Subject(s)
COVID-19 , Coronavirus , HIV Infections , COVID-19/mortality , COVID-19/therapy , HIV , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , New York City/epidemiology , Patient Discharge , Respiration, Artificial , SARS-CoV-2 , Treatment Outcome
15.
medRxiv ; 2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-955724

ABSTRACT

Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of coronavirus disease 2019 (COVID-19), we investigated intestinal infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its effect on disease pathogenesis. SARS-CoV-2 was detected in small intestinal enterocytes by immunofluorescence staining or electron microscopy, in 13 of 15 patients studied. High dimensional analyses of GI tissues revealed low levels of inflammation in general, including active downregulation of key inflammatory genes such as IFNG, CXCL8, CXCL2 and IL1B and reduced frequencies of proinflammatory dendritic cell subsets. To evaluate the clinical significance of these findings, examination of two large, independent cohorts of hospitalized patients in the United States and Europe revealed a significant reduction in disease severity and mortality that was independent of gender, age, and examined co-morbid illnesses. The observed mortality reduction in COVID-19 patients with GI symptoms was associated with reduced levels of key inflammatory proteins including IL-6, CXCL8, IL-17A and CCL28 in circulation but was not associated with significant differences in nasopharyngeal viral loads. These data draw attention to organ-level heterogeneity in disease pathogenesis and highlight the role of the GI tract in attenuating SARS-CoV-2-associated inflammation with related mortality benefit. One Sentence Summary: Intestinal infection with SARS-CoV-2 is associated with a mild inflammatory response and improved clinical outcomes.

16.
Immunity ; 53(3): 672-684.e11, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-797268

ABSTRACT

Autoinflammatory disease can result from monogenic errors of immunity. We describe a patient with early-onset multi-organ immune dysregulation resulting from a mosaic, gain-of-function mutation (S703I) in JAK1, encoding a kinase essential for signaling downstream of >25 cytokines. By custom single-cell RNA sequencing, we examine mosaicism with single-cell resolution. We find that JAK1 transcription was predominantly restricted to a single allele across different cells, introducing the concept of a mutational "transcriptotype" that differs from the genotype. Functionally, the mutation increases JAK1 activity and transactivates partnering JAKs, independent of its catalytic domain. S703I JAK1 is not only hypermorphic for cytokine signaling but also neomorphic, as it enables signaling cascades not canonically mediated by JAK1. Given these results, the patient was treated with tofacitinib, a JAK inhibitor, leading to the rapid resolution of clinical disease. These findings offer a platform for personalized medicine with the concurrent discovery of fundamental biological principles.


Subject(s)
Hereditary Autoinflammatory Diseases/genetics , Hereditary Autoinflammatory Diseases/pathology , Janus Kinase 1/genetics , Systemic Inflammatory Response Syndrome/genetics , Systemic Inflammatory Response Syndrome/pathology , Adolescent , COVID-19/mortality , Catalytic Domain/genetics , Cell Line , Cytokines/metabolism , Female , Gain of Function Mutation/genetics , Genotype , HEK293 Cells , Hereditary Autoinflammatory Diseases/drug therapy , Humans , Janus Kinase 1/antagonists & inhibitors , Mosaicism , Piperidines/therapeutic use , Precision Medicine/methods , Pyrimidines/therapeutic use , Signal Transduction/immunology , Systemic Inflammatory Response Syndrome/drug therapy
17.
Cell ; 183(4): 982-995.e14, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-756809

ABSTRACT

Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.


Subject(s)
Inflammation/pathology , Systemic Inflammatory Response Syndrome/pathology , Adolescent , Antibodies, Viral/blood , Autoantibodies/blood , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , Chemokine CCL3/metabolism , Child , Child, Preschool , Coronavirus Infections/complications , Coronavirus Infections/pathology , Coronavirus Infections/virology , Female , Humans , Immunity, Humoral , Infant , Infant, Newborn , Inflammation/metabolism , Interleukin-17/metabolism , Interleukin-18/metabolism , Killer Cells, Natural/cytology , Killer Cells, Natural/metabolism , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/metabolism , Young Adult
18.
Nat Med ; 26(10): 1636-1643, 2020 10.
Article in English | MEDLINE | ID: covidwho-728994

ABSTRACT

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1ß in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.


Subject(s)
Coronavirus Infections/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Interleukin-8/immunology , Pneumonia, Viral/immunology , Tumor Necrosis Factor-alpha/immunology , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Cytokines/immunology , Female , Hospitalization , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , SARS-CoV-2 , Severity of Illness Index , Survival Rate
19.
medRxiv ; 2020 Jul 06.
Article in English | MEDLINE | ID: covidwho-663795

ABSTRACT

Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

20.
J Hematol Oncol ; 13(1): 94, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-647080

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the USA. Our institution has treated over 2000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York. METHODS: We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020, and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics including the persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. RESULTS: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (> 70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-White race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. The median time to PCR negativity was 43 (range 19-68) days from initial positive PCR. CONCLUSIONS: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia was associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to the identification of vulnerable MM patients who need early intervention to improve outcomes in future outbreaks of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Multiple Myeloma/complications , Pneumonia, Viral/complications , Tertiary Care Centers , Agammaglobulinemia/mortality , Agammaglobulinemia/pathology , Aged , COVID-19 , Cohort Studies , Coronavirus Infections/mortality , Female , Humans , Immunocompromised Host , Inflammation/mortality , Inflammation/pathology , Male , Middle Aged , Multiple Myeloma/immunology , New York City/epidemiology , Pandemics , Pneumonia, Viral/mortality , Retrospective Studies , Risk Factors , SARS-CoV-2
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