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Dust often contains chemical airborne pollutants that might negatively affect human health. Polystyrene is one of the most widely used types of plastic. Bulk polystyrene exhibits no short-term cytotoxicity. However, during degradation of polystyrene, small nanoparticles are formed. Due to specific properties, such as the large surface to volume ratio, toxicity of nanoparticles might be different to that of the bulk material. Hence, particularly the surface chemistry is crucial for nanoparticle behaviour in biological environment. For this study, carboxyl(PS-COOH) and amino-functionalized (PS-NH2) nanoparticles were prepared by free-radical copolymerization in a direct (oil in water) miniemulsion system. We show that surface functionalization of polystyrene nanoparticles with amino groups (PS-NH2), but not with carboxyl groups (PS-COOH), induced inhibition of proliferation in a monocytic cell line and induce a specific cell death, apoptosis. In PS-NH2–treated cells, acidic vesicular organelles exhibited elevated pH and impaired processing of a lysosomal enzyme. Moreover, solely in PS-NH2-treated cells, but not in PS-COOHtreated cells, this was followed by permeabilization of acidic vesicular organelles and induction of cell death. These data indicate that surface charge of nanoplastics defines their effects on biological systems and can be used to predict environmental toxicity of nanoplastics.

Insulin dysregulation (ID) is associated with an increased risk of laminitis which often necessitates the need for clinical intervention. To test the contention that the prophylactic supplementation of nutraceuticals could mitigate ID in susceptible horses, 16 mature horses with a history of ID were supplemented with either the placebo ( n = 8) or nutraceutical ( n = 8) once daily. Horses were housed in dry lots with ad libitum access to grass hay and fed a concentrate twice daily to provide 0.5 g starch/kg BW/meal. A combined glucose-insulin tolerance test was performed on all horses before and after 4 weeks of treatment. Nutraceutical-supplemented horses had 61% greater ( p = 0.05) glucose clearance rates compared to the placebo group. This resulted in a shorter time in the positive phase of glucose clearance ( p = 0.03) for the nutraceutical group compared to the placebo group. Horses receiving the nutraceutical had lower ( p = 0.003) insulin concentrations at 75 min and lower ( p = 0.04) glucose concentrations at 45 min compared to the placebo. Prophylactic supplementation with nutraceuticals resulted in greater glucose clearance rates during a starch challenge, indicating that nutraceuticals can mitigate ID in susceptible horses consuming an excess of non-structural carbohydrate.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy., (© 2024. The Author(s).)

Reversible cerebral vasoconstriction syndrome (RCVS) is a condition defined by severe sudden-onset headaches, typically &lsquo;thunderclap&rsquo; headaches, caused by multifocal cerebral vasoconstriction. Various triggers have been described, including illegal substances, medication and infections. We observed a 27 year old man that suddenly developed severe headaches during admission to a psychiatric ward, where RCVS was diagnosed as most likely clinical cause. He was given nimodipine with rapid and full symptom remission. We aim to highlight this rare, but important, neurological syndrome and its various psychiatric risk factors.

The mechanisms by which antibodies confer protection vary across vaccines, ranging from simple neutralization to functions requiring innate immune recruitment via Fc-dependent mechanisms. The role of adjuvants in shaping the maturation of antibody-effector functions remains under investigated. Using systems serology, we compared adjuvants in licensed vaccines (AS01 B /AS01 E /AS03/AS04/Alum) combined with a model antigen. Antigen-naive adults received two adjuvanted immunizations followed by late revaccination with fractional-dosed non-adjuvanted antigen ( NCT00805389 ). A dichotomy in response quantities/qualities emerged post-dose 2 between AS01 B /AS01 E /AS03 and AS04/Alum, based on four features related to immunoglobulin titers or Fc-effector functions. AS01 B/E and AS03 induced similar robust responses that were boosted upon revaccination, suggesting that memory B-cell programming by the adjuvanted vaccinations dictated responses post non-adjuvanted boost. AS04 and Alum induced weaker responses, that were dissimilar with enhanced functionalities for AS04. Distinct adjuvant classes can be leveraged to tune antibody-effector functions, where selective vaccine formulation using adjuvants with different immunological properties may direct antigen-specific antibody functions., (© 2023. GSK.)

Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.

Objective: This is the first study to use a daily diary design to investigate the relationship between daily work-related rumination (WRR), daily well-being, and burnout symptoms among psychotherapeutic practitioners., Method: In total, N = 58 psychotherapeutic practitioners participated in the study. For 4 weeks, the participants received a daily evening prompt on weekdays asking about their WRR and well-being. The burnout level of the psychotherapists was assessed using Maslach Burnout Inventory (MBI) prior to the daily diary period and afterward. The MBI measures the level of work-related distress on three subscales: emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). Two main analyses were performed: Based on the hierarchical structure of the data we performed random intercept and slopes models. These models examined the association between daily WRR and daily well-being, and the relationship between pre-burnout and daily WRR and daily mood. Secondly, linear regressions with the post-MBI subscales as criterion and the daily diary variables as predictors were calculated to assess their contribution to post-burnout., Results: The compliance rate in our study was 76.8%. Daily WRR and pre-assessment EE were associated with all aspects of reduced daily well-being: bad mood, increased nervousness, and tiredness after work. Daily tiredness and nervousness played a differential role in predicting post-burnout., Conclusion: Our results indicated that daily rumination and pre-EE were associated with reduced daily well-being. As we are the first to present a daily diary study among psychotherapists, we examined the feasibility of the daily diary design in particular and ecological momentary assessment (EMA) in general in this population. Compliance rates compared well with other EMA studies, indicating that EMAs were a feasible assessment option for psychotherapeutic practitioners., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gossmann, Schmid, Loos, Orthmann, Rosner and Barke.)

Introduction and Purpose: Flat detector computed tomography (FD-CT) technology is becoming more widely available in the angiography suites of comprehensive stroke centers. In patients with acute ischemic stroke (AIS), who are referred for endovascular therapy (EVT), FD-CT generates cerebral pooled blood volume (PBV) maps, which might help in predicting the final infarct area. We retrospectively analyzed pre- and post-recanalization therapy quantitative PBV measurements in both the infarcted and hypoperfused brain areas of AIS patients referred for EVT., Materials and Methods: We included AIS patients with large vessel occlusion in the anterior circulation referred for EVT from primary stroke centers to our comprehensive stroke center. The pre- and post-recanalization FD-CT regional relative PBV (rPBV) values were measured between ipsilateral lesional and contralateral non-lesional areas based on final infarct area on post EVT follow-up cross-sectional imaging. Statistical analysis was performed to identify differences in PBV values between infarcted and non-infarcted, recanalized brain areas., Results: We included 20 AIS patients. Mean age was 63 years (ranging from 36 to 86 years). The mean pre- EVT rPBV value was 0.57 (±0.40) for infarcted areas and 0.75 (±0.43) for hypoperfusion areas. The mean differences (Δ) between pre- and post-EVT rPBV values for infarcted and hypoperfused areas were respectively 0.69 (±0.59) and 0.69 (±0.90). We found no significant differences (p > 0.05) between pre-EVT rPBV and ΔrPBV values of infarct areas and hypoperfusion areas., Conclusion: Angiographic PBV mapping is useful for the detection of cerebral perfusion deficits, especially in combination with the fill run images. However, we were not able to distinguish irreversibly infarcted tissue from potentially salvageable, hypoperfused brain tissue based on quantitative PBV measurement in AIS patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The visual-gestural modality affords its users simultaneous movement of several independent articulators and thus lends itself to simultaneous encoding of information. Much research has focused on the fact that sign languages coordinate two manual articulators in addition to a range of non-manual articulators to present different types of linguistic information simultaneously, from phonological contrasts to inflection, spatial relations, and information structure. Children and adults acquiring a signed language arguably thus need to comprehend and produce simultaneous structures to a greater extent than individuals acquiring a spoken language. In this paper, we discuss the simultaneous encoding that is found in emerging and established sign languages; we also discuss places where sign languages are unexpectedly sequential. We explore potential constraints on simultaneity in cognition and motor coordination that might impact the acquisition and use of simultaneous structures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Loos, German and Meier.)

The central nervous system (CNS) has emerged as a critical HIV reservoir. Thus, interventions aimed at controlling and eliminating HIV must include CNS-targeted strategies. Given the inaccessibility of the brain, efforts have focused on cerebrospinal fluid (CSF), aimed at defining biomarkers of HIV-disease in the CNS, including HIV-specific antibodies. However, how antibodies traffic between the blood and CNS, and whether specific antibody profiles track with HIV-associated neurocognitive disorders (HAND) remains unclear. Here, we comprehensively profiled HIV-specific antibodies across plasma and CSF from 20 antiretroviral therapy (ART) naive or treated persons with HIV. CSF was populated by IgG1 and IgG3 antibodies, with reduced Fc-effector profiles. While ART improved plasma antibody functional coordination, CSF profiles were unaffected by ART and were unrelated to HAND severity. These data point to a functional sieving of antibodies across the blood-brain barrier, providing previously unappreciated insights for the development of next-generation therapeutics targeting the CNS reservoir., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Drugs that target histone deacetylase (HDAC) entered the pharmacopoeia in the 2000s. However, some enigmatic phenotypes suggest off-target engagement. Here, we developed a quantitative chemical proteomics assay using immobilized HDAC inhibitors and mass spectrometry that we deployed to establish the target landscape of 53 drugs. The assay covers 9 of the 11 human zinc-dependent HDACs, questions the reported selectivity of some widely-used molecules (notably for HDAC6) and delineates how the composition of HDAC complexes influences drug potency. Unexpectedly, metallo-β-lactamase domain-containing protein 2 (MBLAC2) featured as a frequent off-target of hydroxamate drugs. This poorly characterized palmitoyl-CoA hydrolase is inhibited by 24 HDAC inhibitors at low nanomolar potency. MBLAC2 enzymatic inhibition and knockdown led to the accumulation of extracellular vesicles. Given the importance of extracellular vesicle biology in neurological diseases and cancer, this HDAC-independent drug effect may qualify MBLAC2 as a target for drug discovery., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua. Children protected from symptomatic infections had more anti-envelope (E) and anti-nonstructural protein 1 (NS1) total immunoglobulin G (IgG), IgG4, and greater Fc effector functions than those with symptoms. Fc effector functions were also associated with protection from hemorrhagic manifestations in the pre-symptomatic group. Furthermore, in vitro virological assays using these plasma samples revealed that protection mediated by antibody-dependent complement deposition was associated with both lysis of virions and DENV-infected cells. These data suggest that E- and NS1-specific Fc functions may serve as correlates of protection, which can be potentially applied toward the design and evaluation of dengue vaccines.

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient's pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection., (© 2021. The Author(s).)

A worldwide decline in stroke hospitalizations during the COVID-19 pandemic has been reported. Information on stroke care during the pandemic in Belgium is lacking. This study aims to analyze the impact of COVID-19 on acute stroke care in eight Belgian stroke centers. This Belgian study is part of an international observational and retrospective study in 70 countries and 457 stroke centers. We compared volumes of COVID-19 and stroke hospitalizations, intravenous thrombolysis and endovascular treatment rates, acute treatment time intervals and functional outcome at 90 days during the first wave of the pandemic to two control intervals (March-May 2019 and December-February 2020). From March 2020 to May 2020, 860 stroke patients were hospitalized. In the same time period, 2850 COVID-19 patients were admitted, of which 37 (1.3%) were diagnosed with a stroke. Compared to the months prior to the pandemic and the same time epoch one year earlier, stroke hospitalizations were reduced (relative difference 15.9% [p = 0.03] and 14.5% [p = 0.05], respectively). Despite a reduction in absolute volumes, there was no difference in the monthly proportion of thrombolysis or endovascular treatment provided to the overall stroke hospitalizations. Acute treatment time metrics did not change between COVID-19 pandemic and control time epochs. We found no difference in 90-day functional outcomes nor in mortality after stroke between patients admitted during the pandemic versus control periods. We found a decline in the volume of stroke hospitalizations during the first wave of the COVID-19 pandemic in Belgium. Stroke care quality parameters remained unchanged., (© 2021. Belgian Neurological Society.)

Recently approved vaccines have shown remarkable efficacy in limiting SARS-CoV-2-associated disease. However, with the variety of vaccines, immunization strategies, and waning antibody titers, defining the correlates of immunity across a spectrum of antibody titers is urgently required. Thus, we profiled the humoral immune response in a cohort of non-human primates immunized with a recombinant SARS-CoV-2 spike glycoprotein (NVX-CoV2373) at two doses, administered as a single- or two-dose regimen. Both antigen dose and boosting significantly altered neutralization titers and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were associated with distinct levels of protection in the upper and lower respiratory tract. Moreover, NVX-CoV2373 elicited antibodies that functionally targeted emerging SARS-CoV-2 variants. Collectively, the data presented here suggest that a single dose may prevent disease via combined Fc/Fab functions but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants., Competing Interests: N.P., M.G.-X., J.-H.T., B.Z., S.M., A.M.G., M.J.M., A.D.P., G.G., G.S., and L.E. are current or past employees of Novavax, Inc. and have stock options in the company. G.A. is the founder of SeromYx Systems, Inc. A.L.Z. is a current employee of Moderna, Inc. but conducted this work before employment. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. F.A. is also listed on the serological assay patent application as a co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Y.G.-G., R.C., M.J.G., C.A., K.M.P., C.L., D.Y., K.A.B., M.E.M., J.L., D.M., C.M., S.S., F.A., E.O.S, D.L., and M.B.F. declare no competing interest., (© 2021.)

Background: Development of an effective vaccine against the pathogenic blood-stage infection of human malaria has proved challenging, and no candidate vaccine has affected blood-stage parasitemia following controlled human malaria infection (CHMI) with blood-stage Plasmodium falciparum ., Methods: We undertook a phase I/IIa clinical trial in healthy adults in the United Kingdom of the RH5.1 recombinant protein vaccine, targeting the P. falciparum reticulocyte-binding protein homolog 5 (RH5), formulated in AS01 B adjuvant. We assessed safety, immunogenicity, and efficacy against blood-stage CHMI. Trial registered at ClinicalTrials.gov, NCT02927145., Findings: The RH5.1/AS01 B formulation was administered using a range of RH5.1 protein vaccine doses (2, 10, and 50 μg) and was found to be safe and well tolerated. A regimen using a delayed and fractional third dose, in contrast to three doses given at monthly intervals, led to significantly improved antibody response longevity over ∼2 years of follow-up. Following primary and secondary CHMI of vaccinees with blood-stage P. falciparum , a significant reduction in parasite growth rate was observed, defining a milestone for the blood-stage malaria vaccine field. We show that growth inhibition activity measured in vitro using purified immunoglobulin G (IgG) antibody strongly correlates with in vivo reduction of the parasite growth rate and also identify other antibody feature sets by systems serology, including the plasma anti-RH5 IgA1 response, that are associated with challenge outcome., Conclusions: Our data provide a new framework to guide rational design and delivery of next-generation vaccines to protect against malaria disease., Funding: This study was supported by USAID, UK MRC, Wellcome Trust, NIAID, and the NIHR Oxford-BRC., Competing Interests: A.D.D. and S.J.D. are named inventors on patent applications relating to RH5 and/or other malaria vaccines and immunization regimens. W.A.d.J. is an employee of and shareholder in ExpreS2ion Biotechnologies, which has developed and is marketing the ExpreS2 cell expression platform. A.R.N. is an employee of Leidos, Inc., which holds the MVDP prime contract (AID-OAA-C-15-00071). A.M.M. has an immediate family member who is an inventor on patents relating to RH5 and/or other malaria vaccines and immunization regimens., (© 2021 The Author(s).)

Echo phonology was originally proposed to account for obligatory coordination of manual and mouth articulations observed in several sign languages. However, previous research into the phenomenon lacks clear criteria for which components of movement can or must be copied when the articulators are so different. Nor is there discussion of which nonmanual articulators can echo manual movement. Given the prosodic properties of echoes (coordination of onset/offset and of dynamics such as speed) as well as general motoric coordination of various articulators in the human body, we expect that the mouth is not the only nonmanual articulator involved in echo phonology. In this study, we look at a fixed set of lexical items across 36 sign languages and establish that the head can echo manual movement with respect to timing and to the axis/axes of manual movement. We propose that what matters in echo phonology is the visual percept of temporally coordinated movement that repeats a salient movement property in such a way as to give the visual impression of a copy. Our findings suggest that echoes are not obligatory motor couplings of two or more articulators but may enhance phonological distinctions that are otherwise difficult to see., (© 2021 Cognitive Science Society, Inc.)

Importance: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines., Objective: To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses., Design, Setting, and Participants: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S., Interventions: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group)., Main Outcomes and Measures: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses., Results: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced., Conclusion and Relevance: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine., Trial Registration: ClinicalTrials.gov Identifier: NCT04436276.

Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n = 20) or not hospitalized (n = 40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4+ T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4+ T cells and antibodies targeting the S1 domain of spike among subjects who were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.