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1.
Front Immunol ; 13: 834988, 2022.
Article in English | MEDLINE | ID: covidwho-1817941

ABSTRACT

Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibited higher basal levels of activation measured by P-selectin surface expression and had poor functional reserve upon in vitro stimulation. To investigate this question in more detail, we developed an assay to assess the capacity of plasma from COVID-19 patients to activate platelets from healthy donors. Platelet activation was a common feature of plasma from COVID-19 patients and correlated with key measures of clinical outcome including kidney and liver injury, and APACHEIII scores. Further, we identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with in vitro platelet activation. Mechanistically, blocking the signaling of the FcγRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect.


Subject(s)
Blood Platelets/immunology , COVID-19/immunology , Complement C5a/metabolism , Receptor, Anaphylatoxin C5a/metabolism , Receptors, IgG/metabolism , SARS-CoV-2/physiology , Thromboembolism/immunology , Adult , Aminopyridines/pharmacology , Cells, Cultured , Female , Hospitalization , Humans , Male , Morpholines/pharmacology , Platelet Activation , Pyrimidines/pharmacology , Severity of Illness Index , Signal Transduction , Syk Kinase/antagonists & inhibitors
2.
Cell ; 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1778028

ABSTRACT

We examined antibody and memory B cell responses longitudinally for ∼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330895

ABSTRACT

Background: Disparate COVID-19 outcomes have been observed between Hispanic, Non-Hispanic Black, and White patients. The underlying causes for these disparities are not fully understood. Methods: : This was a retrospective study utilizing electronic medical record data from five hospitals within a single academic health system based in New York City. Multivariable logistic regression models were used to identify demographic, clinical, and lab values associated with in-hospital mortality. Results: : 3,086 adult patients with self-reported race/ethnicity information presenting to the emergency department and hospitalized with COVID-19 up to April 13, 2020 were included in this study. While older age (multivariable OR 1.06, 95% CI 1.05-1.07) and baseline hypoxia (multivariable OR 2.71, 95% CI 2.17-3.36) were associated with increased mortality overall and across all races/ethnicities, Non-Hispanic Black (median age 67, IQR 58-76) and Hispanic (median age 63, IQR 50-74) patients were younger and had different comorbidity profiles compared to Non-Hispanic White patients (median age 73, IQR 62-84;p<0.05 for both comparisons). Among inflammatory markers associated with COVID-19 mortality, there was a significant interaction between the Non-Hispanic Black population and interleukin-1-beta (interaction p-value 0.04). Conclusions: : This analysis of a multi-ethnic cohort highlights the need for inclusion and consideration of diverse popualtions in ongoing COVID-19 trials targeting inflammatory cytokines.

4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327778

ABSTRACT

Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for ~9-10 months after the primary 2-dose mRNA vaccine series, as well as for ~3 months after a 3rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and ~40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3rd dose. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.

5.
J Infect Dis ; 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1672211

ABSTRACT

Some risk factors for severe COVID-19 have been identified, including age, race, and obesity. However, 20-50% of severe cases occur in the absence of these factors. Cytomegalovirus (CMV) is a herpes virus that infects ~50% of all individuals worldwide and is one of the most significant non-genetic determinants of immune system. We hypothesized that latent CMV infection might influence the severity of COVID-19. Our analyses demonstrate that CMV seropositivity associates with more than twice the risk of hospitalization due to SARS-CoV-2 infection. Immune profiling of blood and CMV DNA qPCR in a subset of patients for whom respiratory tract samples were available revealed altered T cell activation profiles in absence of extensive CMV replication in the upper respiratory tract. These data suggest a potential role for CMV-driven immune perturbations in affecting the outcome of SARS-CoV-2 infection and may have implications for the discrepancies in COVID-19 severity between different human populations.

6.
Nat Med ; 27(11): 1990-2001, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526094

ABSTRACT

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Subject(s)
COVID-19 Vaccines/therapeutic use , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, CD20/immunology , COVID-19/prevention & control , Case-Control Studies , Chlorocebus aethiops , HEK293 Cells , Humans , Immunity, Cellular , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Immunotherapy/methods , Longitudinal Studies , Multiple Sclerosis/blood , RNA, Messenger/immunology , RNA, Viral/immunology , Rituximab/pharmacology , Rituximab/therapeutic use , SARS-CoV-2/genetics , Vaccination , Vero Cells
7.
Non-conventional in English | MEDLINE, Grey literature | ID: grc-750509

ABSTRACT

Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.

8.
Science ; 374(6572): abm0829, 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1467659

ABSTRACT

The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2­naïve and ­recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.


Subject(s)
COVID-19 Vaccines/immunology , Immunologic Memory , SARS-CoV-2/genetics , SARS-CoV-2/immunology , /immunology , Humans
9.
Immunity ; 54(9): 2133-2142.e3, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1433401

ABSTRACT

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Th1 Cells/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunization, Secondary , Immunologic Memory , Lectins, C-Type/metabolism , Lymphocyte Activation , Male , Middle Aged , Peptides/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Young Adult
10.
Nat Med ; 27(11): 1990-2001, 2021 11.
Article in English | MEDLINE | ID: covidwho-1410406

ABSTRACT

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Subject(s)
COVID-19 Vaccines/therapeutic use , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, CD20/immunology , COVID-19/prevention & control , Case-Control Studies , Chlorocebus aethiops , HEK293 Cells , Humans , Immunity, Cellular , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Immunotherapy/methods , Longitudinal Studies , Multiple Sclerosis/blood , RNA, Messenger/immunology , RNA, Viral/immunology , Rituximab/pharmacology , Rituximab/therapeutic use , SARS-CoV-2/genetics , Vaccination , Vero Cells
11.
Sci Immunol ; 6(58)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1349998

ABSTRACT

Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19 Vaccines , COVID-19/immunology , SARS-CoV-2/immunology , Vaccines, Synthetic , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Female , Humans , Male , Middle Aged , RNA, Messenger , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Young Adult
12.
Nat Med ; 27(7): 1280-1289, 2021 07.
Article in English | MEDLINE | ID: covidwho-1238011

ABSTRACT

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Hematologic Neoplasms/immunology , Neoplasms/immunology , Aged , Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19/complications , COVID-19/mortality , Cohort Studies , Female , Hematologic Neoplasms/complications , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunophenotyping , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasms/complications , Proportional Hazards Models , Prospective Studies , SARS-CoV-2 , Survival Rate
13.
Sci Immunol ; 6(57)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1115087

ABSTRACT

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8+ T cells that correlated with the use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct from one another and implicate CD8+ T cells in the clinical presentation and trajectory of MIS-C.


Subject(s)
COVID-19/immunology , Lymphocyte Activation , Systemic Inflammatory Response Syndrome/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Aging/immunology , Child , Child, Preschool , Female , Flow Cytometry , Humans , Leukopenia/immunology , Male , Young Adult
14.
Cell ; 184(7): 1858-1864.e10, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1071140

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the coronavirus disease 2019 (COVID-19) pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 431 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 251 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼20% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but they were boosted upon SARS-CoV-2 infection.


Subject(s)
Alphacoronavirus/immunology , Antibodies, Viral , Betacoronavirus/immunology , COVID-19/immunology , Adolescent , Adult , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19 Serological Testing , Child , Child, Preschool , Chlorocebus aethiops , Cross Protection , Cross Reactions , Disease Susceptibility , HEK293 Cells , Humans , Infant , Infant, Newborn , Vero Cells
15.
Science ; 369(6508)2020 09 04.
Article in English | MEDLINE | ID: covidwho-981641

ABSTRACT

Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.


Subject(s)
B-Lymphocytes/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Adaptive Immunity , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , B-Lymphocyte Subsets/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Cytokines/blood , Female , Humans , Immunologic Memory , Lymphocyte Activation , Male , Middle Aged , Pandemics , Plasma Cells/immunology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Helper-Inducer/immunology , Time Factors , Young Adult
16.
medRxiv ; 2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-807631

ABSTRACT

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8 T cells that correlated with use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct and implicate CD8 T cells in clinical presentation and trajectory of MIS-C.

17.
Sci Immunol ; 5(49)2020 07 29.
Article in English | MEDLINE | ID: covidwho-690482

ABSTRACT

Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important for determining SARS-CoV-2 exposures within both individuals and populations. We validated a SARS-CoV-2 spike receptor binding domain serological test using 834 pre-pandemic samples and 31 samples from COVID-19 recovered donors. We then completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate exposure to SARS-CoV-2 within the community.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Health Status Disparities , Pneumonia, Viral/epidemiology , Pregnancy Complications, Infectious/epidemiology , Adult , African Americans/statistics & numerical data , Antibodies, Viral/immunology , Betacoronavirus/immunology , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/statistics & numerical data , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Pandemics , Philadelphia/epidemiology , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Protein Domains/immunology , SARS-CoV-2 , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology , Young Adult
18.
medRxiv ; 2020 Jul 10.
Article in English | MEDLINE | ID: covidwho-663600

ABSTRACT

Limited data are available for pregnant women affected by SARS-CoV-2. Serological tests are critically important to determine exposure and immunity to SARS-CoV-2 within both individuals and populations. We completed SARS-CoV-2 serological testing of 1,293 parturient women at two centers in Philadelphia from April 4 to June 3, 2020. We tested 834 pre-pandemic samples collected in 2019 and 15 samples from COVID-19 recovered donors to validate our assay, which has a ~1% false positive rate. We found 80/1,293 (6.2%) of parturient women possessed IgG and/or IgM SARS-CoV-2-specific antibodies. We found race/ethnicity differences in seroprevalence rates, with higher rates in Black/non-Hispanic and Hispanic/Latino women. Of the 72 seropositive women who also received nasopharyngeal polymerase chain reaction testing during pregnancy, 46 (64%) were positive. Continued serologic surveillance among pregnant women may inform perinatal clinical practices and can potentially be used to estimate seroprevalence within the community.

19.
Sci Immunol ; 5(49)2020 07 15.
Article in English | MEDLINE | ID: covidwho-646575

ABSTRACT

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.


Subject(s)
B-Lymphocyte Subsets/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Neutrophils/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Aged , COVID-19 , Clonal Selection, Antigen-Mediated/immunology , Coronavirus Infections/pathology , Cytokines/metabolism , Female , Humans , Immunity, Innate/immunology , Immunologic Memory/immunology , Lymphocyte Activation/immunology , Lymphocyte Count , Male , Middle Aged , Pandemics , Pneumonia, Viral/pathology , SARS-CoV-2
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