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1.
Neurol Neuroimmunol Neuroinflamm ; 9(5)2022 09.
Article in English | MEDLINE | ID: covidwho-1892254

ABSTRACT

BACKGROUND AND OBJECTIVES: The biologic mechanisms underlying neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are incompletely understood. METHODS: We measured markers of neurologic injury (glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL]) and soluble markers of inflammation among a cohort of people with prior confirmed SARS-CoV-2 infection at early and late recovery after the initial illness (defined as less than and greater than 90 days, respectively). The primary clinical outcome was the presence of self-reported CNS PASC symptoms during the late recovery time point. We compared fold changes in marker values between those with and without CNS PASC symptoms using linear mixed-effects models and examined relationships between neurologic and immunologic markers using rank linear correlations. RESULTS: Of 121 individuals, 52 reported CNS PASC symptoms. During early recovery, those who went on to report CNS PASC symptoms had elevations in GFAP (1.3-fold higher mean ratio, 95% CI 1.04-1.63, p = 0.02), but not NfL (1.06-fold higher mean ratio, 95% CI 0.89-1.26, p = 0.54). During late recovery, neither GFAP nor NfL levels were elevated among those with CNS PASC symptoms. Although absolute levels of NfL did not differ, those who reported CNS PASC symptoms demonstrated a stronger downward trend over time in comparison with those who did not report CNS PASC symptoms (p = 0.041). Those who went on to report CNS PASC also exhibited elevations in interleukin 6 (48% higher during early recovery and 38% higher during late recovery), monocyte chemoattractant protein 1 (19% higher during early recovery), and tumor necrosis factor α (19% higher during early recovery and 13% higher during late recovery). GFAP and NfL correlated with levels of several immune activation markers during early recovery; these correlations were attenuated during late recovery. DISCUSSION: Self-reported neurologic symptoms present approximately 4 months after SARS-CoV-2 infection are associated with elevations in markers of neurologic injury and inflammation at earlier time points. Some inflammatory pathways seem to be involved months after acute infection. Additional work will be needed to better characterize these processes and to identify interventions to prevent or treat this condition.


Subject(s)
COVID-19 , Biomarkers , COVID-19/complications , Humans , Inflammation , SARS-CoV-2 , Self Report
2.
J Clin Immunol ; 42(2): 253-265, 2022 02.
Article in English | MEDLINE | ID: covidwho-1565436

ABSTRACT

Patients with primary antibody deficiency are at risk for severe and in many cases for prolonged COVID-19. Convalescent plasma treatment of immunocompromised individuals could be an option especially in countries with limited access to monoclonal antibody therapies. While studies in immunocompetent COVID19 patients have demonstrated only a limited benefit, evidence for the safety, timing, and effectiveness of this treatment in antibody-deficient patients is lacking. Here, we describe 16 cases with primary antibody deficiency treated with convalescent plasma in four medical centers. In our cohort, treatment was associated with a reduction in viral load and improvement of clinical symptoms, even when applied over a week after onset of infection. There were no relevant side effects besides a short-term fever reaction in one patient. Longitudinal full-genome sequencing revealed the emergence of mutations in the viral genome, potentially conferring an antibody escape in one patient with persistent viral RNA shedding upon plasma treatment. However, he resolved the infection after a second course of plasma treatment. Thus, our data suggest a therapeutic benefit of convalescent plasma treatment in patients with primary antibody deficiency even months after infection. While it appears to be safe, PCR follow-up for SARS-CoV-2 is advisable and early re-treatment might be considered in patients with persistent viral shedding.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Plasma/immunology , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Child , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , Virus Shedding/immunology , Young Adult
3.
J Infect Dis ; 224(11): 1839-1848, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1483458

ABSTRACT

BACKGROUND: The biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown. METHODS: We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (<90 days) and late (>90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods. RESULTS: During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor-α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01-1.28]; P = .028) and interferon-γ-induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01-1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98-1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11-1.86]; P < .001). These differences were more pronounced among those with a greater number of PASC symptoms. CONCLUSIONS: Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.


Subject(s)
COVID-19 , Inflammation , Biomarkers/blood , COVID-19/complications , COVID-19/immunology , Cytokines/blood , Disease Progression , Humans , Inflammation/blood , Inflammation/virology
4.
Clin Immunol ; 230: 108803, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322033

ABSTRACT

To better understand COVID-19 infection in patients receiving biologic and immunomodulatory therapies, we evaluated prevalence and outcomes for symptomatic cases of COVID-19 at a large therapeutic infusion center in New York City during the height of the pandemic. 2074 patients received treatment with biologic infusions at our center between March and May 2020, and 34 patients developed symptomatic COVID-19 infection, for an overall low rate of 1.64%. The majority of infections and deaths were in a small subset of patients with a primary immunodeficiency. Patients with inflammatory or autoimmune conditions requiring biologic therapies tended to have mild cases. Higher inflammatory responses were observed in patients who died.


Subject(s)
Ambulatory Care Facilities , Autoimmune Diseases/therapy , Biological Factors/administration & dosage , COVID-19/epidemiology , SARS-CoV-2 , Biomarkers , COVID-19/complications , COVID-19/mortality , Comorbidity , Female , Humans , Incidence , Inflammation/metabolism , Male , Middle Aged , New York City/epidemiology , Prevalence
5.
J Infect Dis ; 223(3): 403-408, 2021 02 13.
Article in English | MEDLINE | ID: covidwho-1082007

ABSTRACT

We performed a retrospective study of coronavirus disease 2019 (COVID-19) in people with human immunodeficiency virus (PWH). PWH with COVID-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin 6, interleukin 8, and tumor necrosis factor α were commonly elevated. In all, 19 of 72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of COVID-19 despite antiretroviral therapy and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.


Subject(s)
COVID-19/immunology , COVID-19/virology , HIV Infections/immunology , HIV Infections/virology , Aged , COVID-19/blood , COVID-19/mortality , Female , HIV Infections/blood , HIV Infections/mortality , HIV-1/isolation & purification , Hospitalization/statistics & numerical data , Humans , Inflammation/blood , Inflammation/immunology , Inflammation/virology , Inflammation Mediators/blood , Inflammation Mediators/immunology , Lymphocyte Count , Lymphopenia/virology , Male , Middle Aged , New York/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
8.
Am J Emerg Med ; 45: 185-191, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-718599

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (Covid-19) has led to unprecedented healthcare demand. This study seeks to characterize Emergency Department (ED) discharges suspected of Covid-19 that are admitted within 72 h. METHODS: We abstracted all adult discharges with suspected Covid-19 from five New York City EDs between March 2nd and April 15th. Those admitted within 72 h were then compared against those who were not using descriptive and regression analysis of background and clinical characteristics. RESULTS: Discharged ED patients returning within 72 h were more often admitted if suspected of Covid-19 (32.9% vs 12.1%, p < .0001). Of 7433 suspected Covid-19 discharges, the 139 (1.9%) admitted within 72 h were older (55.4 vs. 45.6 years, OR 1.03) and more often male (1.32) or with a history of obstructive lung disease (2.77) or diabetes (1.58) than those who were not admitted (p < .05). Additional associations included non-English preference, cancer, heart failure, hypertension, renal disease, ambulance arrival, higher triage acuity, longer ED stay or time from symptom onset, fever, tachycardia, dyspnea, gastrointestinal symptoms, x-ray abnormalities, and decreased platelets and lymphocytes (p < .05 for all). On 72-h return, 91 (65.5%) subjects required oxygen, and 7 (5.0%) required mechanical ventilation in the ED. Twenty-two (15.8%) of the study group have since died. CONCLUSION: Several factors emerge as associated with 72-h ED return admission in subjects suspected of Covid-19. These should be considered when assessing discharge risk in clinical practice.


Subject(s)
COVID-19/epidemiology , Emergency Service, Hospital/statistics & numerical data , Pandemics , Patient Discharge/statistics & numerical data , Risk Assessment/methods , COVID-19/therapy , Female , Humans , Male , Middle Aged , New York City/epidemiology , Respiration, Artificial/methods , Retrospective Studies , SARS-CoV-2
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