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1.
Ann Allergy Asthma Immunol ; 2022 Jun 16.
Article in English | MEDLINE | ID: covidwho-1959282

ABSTRACT

OBJECTIVE: To update clinicians on current evidence regarding the immunogenicity and safety of coronavirus disease 2019 (COVID-19) vaccines in patients with inborn errors of immunity (IEI). DATA SOURCES: Peer-reviewed, published studies in PubMed, clinical trials listed on ClinicalTrials.gov, and professional organization and governmental guidelines. STUDY SELECTIONS: Literature searches on PubMed and ClinicalTrials.gov were performed using a combination of the following keywords: primary immunodeficiency, COVID-19, SARS-CoV-2, and vaccination. RESULTS: A total of 26 studies met the criteria and were included in this review. Overall, antibody responses to COVID-19 vaccination were found in 72% of study subjects, with stronger responses observed after messenger RNA vaccination. Neutralizing antibodies were detected in patients with IEI, though consistently at lower levels than healthy controls. Risk factors for poor antibody responses included diagnosis of common variable immunodeficiency, presence of autoimmune comorbidities, and use of rituximab. T cell responses were detectable in most patients with IEI, with poorer responses often found in patients with common variable immunodeficiency. Safety of COVID-19 vaccines in patients with IEI was acceptable with high rates of reactogenicity but very few serious adverse events, including in patients with immune dysregulation. CONCLUSION: COVID-19 vaccines are safe in patients with IEI and seem to be immunogenic in most individuals, with stronger responses found after messenger RNA vaccinations.

2.
J Int Dev ; 34(4): 823-860, 2022 May.
Article in English | MEDLINE | ID: covidwho-1929865

ABSTRACT

This study assesses the economic costs of COVID-19 and the state of emergency implemented by the Government of Mozambique. We use a social accounting matrix multiplier analysis to estimate the effects of the pandemic on the economy. Our simulations suggest that the Mozambican economy lost 3.6 percentage points of GDP growth in 2020 and that employment was 1.9 percentage points down. These losses were primarily driven by export shocks, the most heavily affected sectors being trade and accommodation and mining. Mozambique faces a critical challenge of how to promote economic diversification and reduce vulnerability to foreign shocks.

3.
Mol Ther Methods Clin Dev ; 25: 439-447, 2022 Jun 09.
Article in English | MEDLINE | ID: covidwho-1815002

ABSTRACT

Adoptive T cell immunotherapy has been used to restore immunity against multiple viral targets in immunocompromised patients after bone-marrow transplantation and has been proposed as a strategy for preventing coronavirus 2019 (COVID-19) in this population. Ideally, expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-virus-specific T cells (CSTs) should demonstrate marked cell expansion, T cell specificity, and CD8+ T cell skewing prior to adoptive transfer. However, current methodologies using IL-4 + IL-7 result in suboptimal specificity, especially in CD8+ cells. Using a microexpansion platform, we screened various cytokine cocktails (IL-4 + IL-7, IL-15, IL-15 + IL-4, IL-15 + IL-6, and IL-15 + IL-7) for the most favorable culture conditions. IL-15 + IL-7 optimally balanced T cell expansion, polyfunctionality, and CD8+ T cell skewing of a final therapeutic T cell product. Additionally, the transcriptomes of CD4+ and CD8+ T cells cultured with IL-15 + IL-7 displayed the strongest induction of antiviral type I interferon (IFN) response genes. Subsequently, microexpansion results were successfully translated to a Good Manufacturing Practice (GMP)-applicable format where IL-15 + IL-7 outperformed IL-4 + IL-7 in specificity and expansion, especially in the desirable CD8+ T cell compartment. These results demonstrate the functional implications of IL-15-, IL-4-, and IL-7-containing cocktails for therapeutic T cell expansion, which could have broad implication for cellular therapy, and pioneer the use of RNA sequencing (RNA-seq) to guide viral-specific T cell (VST) product manufacturing.

4.
Ann Intern Med ; 174(9): 1240-1251, 2021 09.
Article in English | MEDLINE | ID: covidwho-1789654

ABSTRACT

BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.


Subject(s)
COVID-19/mortality , Hospitalization/statistics & numerical data , Adrenal Cortex Hormones/therapeutic use , Adult , COVID-19/therapy , Critical Care/statistics & numerical data , Female , Hospital Bed Capacity/statistics & numerical data , Hospital Mortality , Humans , Male , Odds Ratio , Respiration, Artificial , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Survival Rate , United States/epidemiology
5.
Medsurg Nursing ; 31(2):105-109, 2022.
Article in English | ProQuest Central | ID: covidwho-1781872

ABSTRACT

Keywords post-traumatic stress disorder, men and women Veterans, smells, triggers, odors, autobiographical-memory, olfactory, Proust phenomenon, military sexual trauma, traumatic brain injury, amyotrophic lateral sclerosis, migraines, coping strategies, neurologic - nervous system, psychosocial and behavioral, assessment "For some inexplicable reason the sense of smell does not hold the high position it deserves among its sisters. The amygdala and hippocampus interaction also contributes emotional stimulation and relationship (conditional fear, anxiety, attention) to the odor-evoked memories, producing people, place, and event reminders. Reduced smell recognition, tolerance, and differentiation have been noted in women ages 45-60 with fibromyalgia, with imaging studies documenting smaller olfactory bulb volume (Blanco et al., 2018). During the COVID-19 pandemic, when patients complained of olfactory and gustatory loss with nasal-limited congestion, health providers were encouraged to suspect viral infection affecting the nasal passage neurons (Holbrook & Meyers, 2020;Moein et al., 2020;Xydakis et al., 2020).

6.
Crit Care Med ; 50(7): 1051-1062, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1752195

ABSTRACT

OBJECTIVES: Prior research has hypothesized the Sequential Organ Failure Assessment (SOFA) score to be a poor predictor of mortality in mechanically ventilated patients with COVID-19. Yet, several U.S. states have proposed SOFA-based algorithms for ventilator triage during crisis standards of care. Using a large cohort of mechanically ventilated patients with COVID-19, we externally validated the predictive capacity of the preintubation SOFA score for mortality prediction with and without other commonly used algorithm elements. DESIGN: Multicenter, retrospective cohort study using electronic health record data. SETTING: Eighty-six U.S. health systems. PATIENTS: Patients with COVID-19 hospitalized between January 1, 2020, and February 14, 2021, and subsequently initiated on mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 15,122 mechanically ventilated patients with COVID-19, SOFA score alone demonstrated poor discriminant accuracy for inhospital mortality in mechanically ventilated patients using the validation cohort (area under the receiver operating characteristic curve [AUC], 0.66; 95% CI, 0.65-0.67). Discriminant accuracy was even poorer using SOFA score categories (AUC, 0.54; 95% CI, 0.54-0.55). Age alone demonstrated greater discriminant accuracy for inhospital mortality than SOFA score (AUC, 0.71; 95% CI, 0.69-0.72). Discriminant accuracy for mortality improved upon addition of age to the continuous SOFA score (AUC, 0.74; 95% CI, 0.73-0.76) and categorized SOFA score (AUC, 0.72; 95% CI, 0.71-0.73) models, respectively. The addition of comorbidities did not substantially increase model discrimination. Of 36 U.S. states with crisis standards of care guidelines containing ventilator triage algorithms, 31 (86%) feature the SOFA score. Of these, 25 (81%) rely heavily on the SOFA score (12 exclusively propose SOFA; 13 place highest weight on SOFA or propose SOFA with one other variable). CONCLUSIONS: In a U.S. cohort of over 15,000 ventilated patients with COVID-19, the SOFA score displayed poor predictive accuracy for short-term mortality. Our findings warrant reappraisal of the SOFA score's implementation and weightage in existing ventilator triage pathways in current U.S. crisis standards of care guidelines.


Subject(s)
COVID-19 , Organ Dysfunction Scores , Algorithms , Delivery of Health Care , Electronic Health Records , Hospital Mortality , Humans , Intensive Care Units , Prognosis , ROC Curve , Retrospective Studies , Triage , Ventilators, Mechanical
7.
Blood ; 140(3): 208-221, 2022 07 21.
Article in English | MEDLINE | ID: covidwho-1724390

ABSTRACT

Patients with blood disorders who are immune suppressed are at increased risk for infection with severe acute respiratory syndrome coronavirus 2. Sequelae of infection can include severe respiratory disease and/or prolonged duration of viral shedding. Cellular therapies may protect these vulnerable patients by providing antiviral cellular immunity and/or immune modulation. In this recent review of the field, phase 1/2 trials evaluating adoptive cellular therapies with virus-specific T cells or natural killer cells are described along with trials evaluating the safety, feasibility, and preliminary efficacy of immune modulating cellular therapies including regulatory T cells and mesenchymal stromal cells. In addition, the immunologic basis for these therapies is discussed.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , Humans , Immunity, Cellular , SARS-CoV-2 , Virus Shedding
8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-322039

ABSTRACT

While most studies describing COVID-19 vaccine responses have focused on antibodies, there is increasing evidence that T cells play a critical role. Here we evaluated T cell responses in seronegative donors before and after vaccination to define responses to SARS-CoV-2 reference strain, as well as to mutations in the variant strains B.1.1.7 and B.1.351. We observed enhanced T cell responses to reference and variant Spike strains post vaccination.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308745

ABSTRACT

Background: Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. The cause of these differences in presentation may relate to differences in the host response to infection between adults and children. We thus set out to measure the SARS-CoV-2-specific T cell (CST) response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection.Methods: CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay.Findings: Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses were significantly increased in adults versus children with uncomplicated SARS-CoV-2 infection (P=0.008), while children with MIS-C displayed a CST response that was similar to convalescent adults.Interpretation: Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults. Children with MIS-C have T cell immunity to SARS-CoV-2 that is similar to convalescent adults and greater than children with uncomplicated SARS-CoV-2, despite near uniform seropositivity.Funding: This study was funded by the Board of Visitors of Children’s National Hospital, the Connor Family Foundation, the Katzen Foundation, the National Institute of Allergy and Infectious Diseases, and the National Institute of Dental and Craniofacial Research.Declaration of Interest: C.M.B. is a co-founder and on the scientific advisory boards for Catamaran Bio and Mana Therapeutics with stock and/or ownership, is on the Board of Directors for Caballeta Bio with stock options and has stock in Neximmune and Repertoire Immune Medicines. M.D.K. is on a scientific advisory panel for Enzyvant. The other authors declare that there are no conflicts of interest.Ethical Approval: Peripheral blood mononuclear cells (PBMCs) were obtained from participants recruited from Children’s National Hospital (Washington, DC) and the National Institutes of Health under informed consent approved by the Institutional Review Board of both institutions in accordance with the Declaration of Helsinki.

10.
Front Immunol ; 12: 793197, 2021.
Article in English | MEDLINE | ID: covidwho-1674334

ABSTRACT

Background: Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection. Methods: CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay. Findings: Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults. Interpretation: Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.


Subject(s)
COVID-19/complications , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Antibodies, Viral/immunology , COVID-19/immunology , Child , Child, Preschool , Convalescence , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Infant , Male , Middle Aged , Phosphoproteins/immunology , Spike Glycoprotein, Coronavirus/immunology
11.
Pediatr Hematol Oncol ; : 1-9, 2022 Feb 09.
Article in English | MEDLINE | ID: covidwho-1671873

ABSTRACT

Recipients of anti-CD19 targeted therapies such as chimeric antigen receptor (CAR)-T cell are considered at high risk for complicated Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection due to prolonged B cell aplasia and immunosuppression. These patients represent a unique cohort and so far, immune responses to SARS-CoV-2 have not been well characterized in this setting. We report a pediatric patient with B-cell acute lymphoblastic leukemia (B-ALL) who had asymptomatic SARS-CoV-2 infection while receiving blinatumomab, followed by lymphodepletion (LD) and tisagenlecleucel, a CD19 targeting CAR-T therapy. The patient had a complete response to tisagenlecleucel, did not develop cytokine release syndrome, or worsening of SARS-CoV-2 during therapy. The patient had evidence of ongoing persistence of IgG antibody responses to spike and nucleocapsid after LD followed by tisagenlecleucel despite the B-cell aplasia. Further we were able to detect SARS-CoV-2 specific T-cells recognizing multiple viral structural proteins for several months following CAR-T. The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.

12.
J Int Dev ; 34(4): 771-802, 2022 May.
Article in English | MEDLINE | ID: covidwho-1664413

ABSTRACT

This study assesses the impact of COVID-19 on household consumption poverty. To predict changes in income and the associated effects on poverty, we rely on existing estimated macroeconomic impacts. We assume two main impact channels: direct income/wage and employment losses. Our simulations suggest that consumption decreased by 7.1%-14.4% and that poverty increased by 4.3-9.9 percentage points in 2020. This points to a reversal of the positive poverty reduction trend observed in previous years. Poverty most certainly increased in the pre-COVID period due to other shocks, so Mozambique finds itself in a deepening struggle against poverty.

13.
J Heart Lung Transplant ; 41(4): 458-466, 2022 04.
Article in English | MEDLINE | ID: covidwho-1587721

ABSTRACT

BACKGROUND: As a marker of underlying lung allograft injury, donor-derived cell-free DNA (dd-cfDNA) may be used to identify episodes of acute allograft injury in lung transplant recipients. We investigated the utility of dd-cfDNA to monitor subjects at risk of acute rejection or infection in routine clinical practice. METHODS: This multicenter, retrospective cohort study collected data from lung transplant recipients within 3 years of transplant at 4 centers between March 24, 2020 and September 1, 2020. During this period, as part of routine care during the COVID-19 pandemic, these centers implemented a home-based surveillance program using plasma dd-cfDNA in preference to surveillance bronchoscopy. Dd-cfDNA was used to detect acute lung allograft dysfunction (ALAD) - a composite endpoint of acute rejection and infection. dd-cfDNA levels in patients with ALAD were compared to stable patients. The performance characteristics of dd-cfDNA ≥ 1.0% to detect ALAD were estimated. RESULTS: A total of 175 patients underwent 380 dd-cfDNA measurements, of which 290 were for routine surveillance purposes. dd-cfDNA was higher in patients with ALAD than stable patients (Median (IQR) 1.7% (0.63, 3.1) vs 0.35% (0.22, 0.79), p < 0.001). As an indication of underlying ALAD during surveillance testing, the estimated sensitivity of dd-cfDNA ≥1% was 73.9%, specificity of 87.7%, positive predictive value of 43.4% and negative predictive value of 96.5%. CONCLUSIONS: dd-cfDNA identified acute lung allograft dysfunction in asymptomatic lung transplant patients that may not have been identified by using a clinically indicated biopsy strategy alone. dd-cfDNA <1.0% may be useful in ruling out acute rejection and infection, supporting its use as a potential noninvasive marker for surveillance monitoring.


Subject(s)
COVID-19 , Cell-Free Nucleic Acids , Kidney Transplantation , Allografts , Graft Rejection/genetics , Humans , Lung , Pandemics , Retrospective Studies
14.
15.
J Clin Immunol ; 41(6): 1146-1153, 2021 08.
Article in English | MEDLINE | ID: covidwho-1384523

ABSTRACT

Immunocompromised patients, including those with inborn errors of immunity (IEI), may be at increased risk for severe or prolonged infections with SARS-CoV-2 (Zhu et al. N Engl J Med. 382:727-33, 2020; Guan et al. 2020; Minotti et al. J Infect. 81:e61-6, 2020). While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity has not yet been characterized in patients with antibody deficiency (Grifoni et al. Cell. 181:1489-1501 e1415, 2020; Burbelo et al. 2020; Long et al. Nat Med. 26:845-8, 2020; Braun et al. 2020). Herein, we describe the clinical course, antibody, and T cell responses to SARS-CoV-2 structural proteins in a cohort of adult and pediatric patients with antibody deficiencies (n = 5) and controls (related and unrelated) infected with SARS-CoV-2. Five patients within the same family (3 with antibody deficiency, 2 immunocompetent controls) showed antibody responses to nucleocapsid and spike proteins, as well as SARS-CoV-2 specific T cell immunity at days 65-84 from onset of symptoms. No significant difference was identified between immunocompromised patients and controls. Two additional unrelated, adult patients with common variable immune deficiency were assessed. One did not show antibody response, but both demonstrated SARS-CoV-2-specific T cell immunity when evaluated 33 and 76 days, respectively, following SARS-CoV-2 diagnosis. This report is the first to show robust T cell activity and humoral immunity against SARS-CoV-2 structural proteins in some patients with antibody deficiency. Given the reliance on spike protein in most candidate vaccines (Folegatti et al. Lancet. 396:467-78, 2020; Jackson et al. N Engl J Med. 383:1920-31, 2020), the responses are encouraging. Additional studies will be needed to further define the timing of onset of immunity, longevity of the immune response, and variability of response in immunocompromised patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Common Variable Immunodeficiency/immunology , SARS-CoV-2/physiology , T-Lymphocytes/immunology , Adolescent , Adult , Carrier State , Cells, Cultured , Child , Female , Humans , Immunity, Humoral , Lymphocyte Activation , Male , Middle Aged , Mutation/genetics , Pedigree , Transmembrane Activator and CAML Interactor Protein/genetics , Whole Exome Sequencing , Young Adult
16.
Cytotherapy ; 24(1): 10-15, 2022 01.
Article in English | MEDLINE | ID: covidwho-1385878

ABSTRACT

Although most studies describing coronavirus disease 2019 vaccine responses have focused on antibodies, there is increasing evidence that T cells play a critical role. Here the authors evaluated T-cell responses in seronegative donors before and after vaccination to define responses to the severe acute respiratory syndrome coronavirus 2 reference strain as well as to mutations in the variant strains Alpha/B.1.1.7 and Beta/B.1.351. The authors observed enhanced T-cell responses to reference and variant spike strains post-vaccination.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Spike Glycoprotein, Coronavirus/genetics , T-Lymphocytes , Vaccination
17.
J Allergy Clin Immunol ; 148(5): 1192-1197, 2021 11.
Article in English | MEDLINE | ID: covidwho-1385788

ABSTRACT

BACKGROUND: SARS-CoV-2 vaccination is recommended in patients with inborn errors of immunity (IEIs); however, little is known about immunogenicity and safety in these patients. OBJECTIVE: We sought to evaluate the impact of genetic diagnosis, age, and treatment on antibody response to COVID-19 vaccine and related adverse events in a cohort of patients with IEIs. METHODS: Plasma was collected from 22 health care worker controls, 81 patients with IEIs, and 2 patients with thymoma; the plasma was collected before immunization, 1 to 6 days before the second dose of mRNA vaccine, and at a median of 30 days after completion of the immunization schedule with either mRNA vaccine or a single dose of Johnson & Johnson's Janssen vaccine. Anti-spike (anti-S) and anti-nucleocapsid antibody titers were measured by using a luciferase immunoprecipitation systems method. Information on T- and B-cell counts and use of immunosuppressive drugs was extracted from medical records, and information on vaccine-associated adverse events was collected after each dose. RESULTS: Anti-S antibodies were detected in 27 of 46 patients (58.7%) after 1 dose of mRNA vaccine and in 63 of 74 fully immunized patients (85.1%). A lower rate of seroconversion (7 of 11 [63.6%]) was observed in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Previous use of rituximab and baseline counts of less than 1000 CD3+ T cells/mL and less than 100 CD19+ B cells/mL were associated with lower anti-S IgG levels. No significant adverse events were reported. CONCLUSION: Vaccinating patients with IEIs is safe, but immunogenicity is affected by certain therapies and gene defects. These data may guide the counseling of patients with IEIs regarding prevention of SARS-CoV-2 infection and the need for subsequent boosts.


Subject(s)
Age Factors , B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Polyendocrinopathies, Autoimmune/immunology , SARS-CoV-2/physiology , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Antibodies, Viral/blood , Antibody Formation , COVID-19/drug therapy , COVID-19/genetics , Cohort Studies , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunization, Secondary , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunosuppressive Agents/therapeutic use , Lymphocyte Count , Male , Middle Aged , Phosphoproteins/immunology , Polyendocrinopathies, Autoimmune/drug therapy , Polyendocrinopathies, Autoimmune/genetics , Rituximab/therapeutic use , Seroconversion , Spike Glycoprotein, Coronavirus/immunology , Young Adult
18.
Ann Intern Med ; 174(9): 1240-1251, 2021 09.
Article in English | MEDLINE | ID: covidwho-1296184

ABSTRACT

BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.


Subject(s)
COVID-19/mortality , Hospitalization/statistics & numerical data , Adrenal Cortex Hormones/therapeutic use , Adult , COVID-19/therapy , Critical Care/statistics & numerical data , Female , Hospital Bed Capacity/statistics & numerical data , Hospital Mortality , Humans , Male , Odds Ratio , Respiration, Artificial , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Survival Rate , United States/epidemiology
19.
J Clin Immunol ; 41(6): 1146-1153, 2021 08.
Article in English | MEDLINE | ID: covidwho-1226229

ABSTRACT

Immunocompromised patients, including those with inborn errors of immunity (IEI), may be at increased risk for severe or prolonged infections with SARS-CoV-2 (Zhu et al. N Engl J Med. 382:727-33, 2020; Guan et al. 2020; Minotti et al. J Infect. 81:e61-6, 2020). While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity has not yet been characterized in patients with antibody deficiency (Grifoni et al. Cell. 181:1489-1501 e1415, 2020; Burbelo et al. 2020; Long et al. Nat Med. 26:845-8, 2020; Braun et al. 2020). Herein, we describe the clinical course, antibody, and T cell responses to SARS-CoV-2 structural proteins in a cohort of adult and pediatric patients with antibody deficiencies (n = 5) and controls (related and unrelated) infected with SARS-CoV-2. Five patients within the same family (3 with antibody deficiency, 2 immunocompetent controls) showed antibody responses to nucleocapsid and spike proteins, as well as SARS-CoV-2 specific T cell immunity at days 65-84 from onset of symptoms. No significant difference was identified between immunocompromised patients and controls. Two additional unrelated, adult patients with common variable immune deficiency were assessed. One did not show antibody response, but both demonstrated SARS-CoV-2-specific T cell immunity when evaluated 33 and 76 days, respectively, following SARS-CoV-2 diagnosis. This report is the first to show robust T cell activity and humoral immunity against SARS-CoV-2 structural proteins in some patients with antibody deficiency. Given the reliance on spike protein in most candidate vaccines (Folegatti et al. Lancet. 396:467-78, 2020; Jackson et al. N Engl J Med. 383:1920-31, 2020), the responses are encouraging. Additional studies will be needed to further define the timing of onset of immunity, longevity of the immune response, and variability of response in immunocompromised patients.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Common Variable Immunodeficiency/immunology , SARS-CoV-2/physiology , T-Lymphocytes/immunology , Adolescent , Adult , Carrier State , Cells, Cultured , Child , Female , Humans , Immunity, Humoral , Lymphocyte Activation , Male , Middle Aged , Mutation/genetics , Pedigree , Transmembrane Activator and CAML Interactor Protein/genetics , Whole Exome Sequencing , Young Adult
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