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2.
World Neurosurg ; 2022 Jun 18.
Article in English | MEDLINE | ID: covidwho-1960086

ABSTRACT

OBJECTIVE: Changes to neurosurgical practices during the coronavirus disease 2019 (COVID-19) pandemic have not been thoroughly analyzed. We report the effects of operative restrictions imposed under variable local COVID-19 infection rates and health care policies using a retrospective multicenter cohort study and highlight shifts in operative volumes and subspecialty practice. METHODS: Seven academic neurosurgery departments' neurosurgical case logs were collected; procedures in April 2020 (COVID-19 surge) and April 2019 (historical control) were analyzed overall and by 6 subspecialties. Patient acuity, surgical scheduling policies, and local surge levels were assessed. RESULTS: Operative volume during the COVID-19 surge decreased 58.5% from the previous year (602 vs. 1449, P = 0.001). COVID-19 infection rates within departments' counties correlated with decreased operative volume (r = 0.695, P = 0.04) and increased patient categorical acuity (P = 0.001). Spine procedure volume decreased by 63.9% (220 vs. 609, P = 0.002), for a significantly smaller proportion of overall practice during the COVID-19 surge (36.5%) versus the control period (42.0%) (P = 0.02). Vascular volume decreased by 39.5% (72 vs. 119, P = 0.01) but increased as a percentage of caseload (8.2% in 2019 vs. 12.0% in 2020, P = 0.04). Neuro-oncology procedure volume decreased by 45.5% (174 vs. 318, P = 0.04) but maintained a consistent proportion of all neurosurgeries (28.9% in 2020 vs. 21.9% in 2019, P = 0.09). Functional neurosurgery volume, which declined by 81.4% (41 vs. 220, P = 0.008), represented only 6.8% of cases during the pandemic versus 15.2% in 2019 (P = 0.02). CONCLUSIONS: Operative restrictions during the COVID-19 surge led to distinct shifts in neurosurgical practice, and local infective burden played a significant role in operative volume and patient acuity.

3.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327776

ABSTRACT

COVID-19 convalescent plasma (CCP), a passive polyclonal antibody therapeutic, has exhibited mixed results in the treatment of COVID-19. Given that the therapeutic effect of CCP may extend beyond the ability of SARS-CoV-2-specific antibody binding and neutralization to influence the evolution of the endogenous antibody response, we took a systematic and comprehensive approach to analyze SARS-CoV-2 functional antibody profiles of participants in a randomized controlled trial of CCP treatment of individuals hospitalized with COVID-19 pneumonia where CCP was associated with both decreased mortality and improved clinical severity. Using systems serology, we found that the clinical benefit of CCP is related to a shift towards reduced inflammatory Spike (S) responses and enhanced Nucleocapsid (N) humoral responses. We found CCP had the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function, rather than S or N antibody levels or participant demographic features. Further, CCP induced immunomodulatory changes to recipient humoral profiles persisted for at least two months, marked by the selective evolution of anti-inflammatory Fc-glycan profiles and persistently expanded nucleocapsid-specific humoral immunity following CCP therapy. Together, our findings identify a novel mechanism of action of CCP, suggest optimal patient characteristics for CCP treatment, identify long-last immunomodulatory effects of CCP, and provide guidance for development of novel N-focused antibody therapeutics for severe COVID-19 hyperinflammation.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313773

ABSTRACT

The robust protection conferred by SARS-CoV-2 mRNA vaccines represents a critical milestone in the COVID-19 vaccine development. However, the emergence of variants has inspired renewed concern related to the protective efficacy of currently approved vaccines, which lose neutralizing potency against some variants. However, emerging data suggest that antibody functions, beyond neutralization, may contribute to protection from disease. Thus, here we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOC). While neutralizing antibody responses are affected by VOCs, antibodies generated after infection exhibited robust binding to VOCs but compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies bound robustly to VOCs and continued interacting with Fc-receptors and mediated antibody effector functions. These data point to a previously unappreciated resilience in the mRNA vaccine-induced humoral immune response that may continue to provide protection from SARS-CoV-2 VOCs independent of neutralization.Trial Registration: This work used samples from the phase 1, dose-escalation, open-labelclinical trial designed to determine the safety, reactogenicity, and immunogenicity of mRNA-1273 (mRNA-1273 ClinicalTrials.gov number, NCT04283461 mRNA-1273 study;DOI: 10.1056/NEJMoa2022483).Funding: We acknowledge support from the Ragon Institute of MGH, MIT, and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, CIVIC75N93019C00052), the Gates Foundation Global Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), Translational Research Institute for Space Health through NASA Cooperative Agreement (NNX16AO69A), and the Musk Foundation. This work used samples from the phase 1 mRNA-1273 study (NCT04283461;DOI: 10.1056/NEJMoa2022483). The mRNA-1273 phase 1 study was sponsored and primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD. This trial has been funded in part with federal funds from the NIAID under grant awards UM1AI148373, to Kaiser Washington;UM1AI148576, UM1AI148684, and NIH P51 OD011132, to Emory University;NIH AID AI149644, and contract award HHSN272201500002C, to Emmes. Funding for the manufacture of mRNA-1273 phase 1 material was provided by the Coalition for Epidemic Preparedness Innovation.Declaration of Interest: G.A. is a founder of Seromyx Systems Inc. A.C. is employee of Moderna Inc. D.D., P.M., A.S.M, and E.R.M. are employees of Space Exploration Technologies Corp. All other authors have declared that no conflict of interest exists.Ethical Approval: The MGH IRB reviewed the ethics protocol for secondary use under record 2020P004042 and the project was deemed Not Human Research.

5.
Immunity ; 55(2): 355-365.e4, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1611777

ABSTRACT

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.


Subject(s)
/immunology , Antibodies, Viral/immunology , COVID-19/metabolism , COVID-19/prevention & control , Receptors, Fc/metabolism , SARS-CoV-2/immunology , /administration & dosage , Adult , Antibodies, Neutralizing/immunology , Cross Reactions/immunology , Female , Host-Pathogen Interactions , Humans , Male , Middle Aged , Neutralization Tests , Protein Binding , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Young Adult
6.
Viruses ; 13(11)2021 11 06.
Article in English | MEDLINE | ID: covidwho-1502534

ABSTRACT

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.


Subject(s)
Antibodies, Viral/blood , COVID-19/complications , COVID-19/immunology , Obesity/complications , Obesity/immunology , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Age Factors , Body Mass Index , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , Young Adult
7.
Cell ; 184(3): 628-642.e10, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1385216

ABSTRACT

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Maternal-Fetal Exchange/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Trimester, Third/immunology , Receptors, IgG/immunology , THP-1 Cells
8.
Nat Med ; 27(3): 454-462, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319036

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Age of Onset , Aged , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/blood , Antibodies, Viral/analysis , Asymptomatic Infections , COVID-19/blood , COVID-19/pathology , Carrier State/blood , Carrier State/epidemiology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunity/physiology , Immunoglobulin A/blood , Immunoglobulin G/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Severity of Illness Index , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Young Adult
9.
Neurospine ; 18(2): 292-302, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1296238

ABSTRACT

OBJECTIVE: The use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations. METHODS: We identified a 12-member panel composed of spine surgeons, fellows, and senior residents at a single institution. We created an initial telehealth strength examination protocol based on published data and developed 10 agree/disagree statements summarizing the protocol. A blinded Delphi method was utilized to build consensus for each statement, defined as > 80% agreement and no significant disagreement using a 2-way binomial test (significance threshold of p < 0.05). Any statement that did not meet consensus was edited and iteratively resubmitted to the panel until consensus was achieved. In the final round, the panel was unblinded and the protocol was finalized. RESULTS: After the first round, 4/10 statements failed to meet consensus ( < 80% agreement, and p = 0.031, p = 0.031, p = 0.003, and p = 0.031 statistical disagreement, respectively). The disagreement pertained to grading of strength of the upper (3/10 statements) and lower extremities (1/10 statement). The amended statements clarified strength grading, achieved consensus ( > 80% agreement, p > 0.05 disagreement), and were used to create the final telehealth strength examination protocol. CONCLUSION: The resulting protocol was used in our clinic to standardize the telehealth strength examination. This protocol, as well as our summary of telehealth clinical practice, should aid neurosurgical clinics in integrating telemedicine modalities into their practice.

10.
JCO Oncol Pract ; 17(7): e427-e438, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278136

ABSTRACT

INTRODUCTION: The COVID-19 pandemic is an unprecedented global crisis profoundly affecting oncology care delivery. PURPOSE: This study will describe the occupational and personal consequences of the COVID-19 pandemic on oncologist well-being and patient care. MATERIALS AND METHODS: Four virtual focus groups were conducted with US ASCO member oncologists (September-November 2020). Inquiry and subsequent discussions centered on self-reported accounts of professional and personal COVID-19 experiences affecting well-being, and oncologist recommendations for well-being interventions that the cancer organization and professional societies (ASCO) might implement were explored. Qualitative interviews were analyzed using Framework Analysis. RESULTS: Twenty-five oncologists were interviewed: median age 44 years (range: 35-69 years), 52% female, 52% racial or ethnic minority, 76% medical oncologists, 64% married, and an average of 51.5 patients seen per week (range: 20-120). Five thematic consequences emerged: (1) impact of pre-COVID-19 burnout, (2) occupational or professional limitations and adaptations, (3) personal implications, (4) concern for the future of cancer care and the workforce, and (5) recommendations for physician well-being interventions. Underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment. Oncologists noted personal and familial stressors related to COVID-19 exposure fears and loss of social support. Many participants strongly considered working part-time or taking early retirement. Yet, opportunities arose to facilitate personal growth and rise above pandemic adversity, fostering greater resilience. Recommendations for organizational well-being interventions included psychologic or peer support resources, flexible time-off, and ASCO and state oncology societies involvement to develop care guidelines, well-being resources, and mental health advocacy. CONCLUSION: Our study suggests that the COVID-19 pandemic has adversely affected oncologist burnout, fulfillment, practice health, cancer care, and workforce. It illuminates where professional organizations could play a significant role in oncologist well-being.


Subject(s)
COVID-19 , Oncologists , Adult , Burnout, Psychological , Female , Humans , Male , Minority Groups , Pandemics , SARS-CoV-2
11.
Am Soc Clin Oncol Educ Book ; 41: e339-e353, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1249568

ABSTRACT

Optimizing the well-being of the oncology clinician has never been more important. Well-being is a critical priority for the cancer organization because burnout adversely impacts the quality of care, patient satisfaction, the workforce, and overall practice success. To date, 45% of U.S. ASCO member medical oncologists report experiencing burnout symptoms of emotional exhaustion and depersonalization. As the COVID-19 pandemic remains widespread with periods of outbreaks, recovery, and response with substantial personal and professional consequences for the clinician, it is imperative that the oncologist, team, and organization gain direct access to resources addressing burnout. In response, the Clinician Well-Being Task Force was created to improve the quality, safety, and value of cancer care by enhancing oncology clinician well-being and practice sustainability. Well-being is an integrative concept that characterizes quality of life and encompasses an individual's work- and personal health-related environmental, organizational, and psychosocial factors. These resources can be useful for the cancer organization to develop a well-being blueprint: a detailed start plan with recognized strategies and interventions targeting all oncology stakeholders to support a culture of community in oncology.


Subject(s)
Burnout, Professional/psychology , Medical Oncology/methods , Neoplasms/therapy , Oncologists/psychology , Stress, Psychological/prevention & control , Burnout, Psychological/prevention & control , Burnout, Psychological/psychology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Humans , Internet , Job Satisfaction , Medical Oncology/organization & administration , Neoplasms/diagnosis , Pandemics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Social Support , United States
12.
Surgeon ; 19(5): e310-e317, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1131837

ABSTRACT

BACKGROUND: In early 2020, the COVID-19 pandemic significantly altered management of surgical patients globally. International guidelines recommended that non-operative management be implemented wherever possible (e.g. in proven uncomplicated appendicitis) to reduce pressure on healthcare services and reduce risk of peri-operative viral transmission. We sought to compare our management and outcomes of appendicitis during lockdown vs a non-pandemic period. METHODS: All presentations to our department with a clinical diagnosis of acute appendicitis between 12/03/2020 and 30/06/2020 were compared to the same 110-day period in 2019. Quantity and severity of presentations, use of radiological investigations, rate of operative intervention and histopathological findings were variables collected for comparison. RESULTS: There was a reduction in appendicitis presentations (from 74 to 56 cases), and an increase in radiological imaging (from 70.27% to 89.29%) (P = 0.007) from 2019 to 2020. In 2019, 93.24% of patients had appendicectomy, compared to 71.42% in 2020(P < 0.001). This decrease was most pronounced in uncomplicated cases, whose operative rates dropped from 90.32% to 62.5% (P = 0.009). Post-operative histology confirmed appendicitis in 73.9% in 2019, compared to 97.5% in 2020 (P = 0.001). Normal appendiceal pathology was reported for 17 cases (24.64%) in 2019, compared to none in 2020 (P < 0.001) - a 0% negative appendicectomy rate (NAR). DISCUSSION: The 0% NAR in 2020 is due to a combination of increased CT imaging, a higher threshold to operate, and is impacted by increased disease severity due to delayed patient presentation. This study adds to growing literature promoting routine use of radiological imaging to confirm appendicitis diagnosis. As we enter a second lockdown, patients should be encouraged to avoid late presentations, and surgical departments should continue using radiological imaging more liberally in guiding appendicitis management.


Subject(s)
Appendectomy/statistics & numerical data , Appendicitis/epidemiology , Appendicitis/surgery , COVID-19/epidemiology , Communicable Disease Control , Adolescent , Adult , Aged , Aged, 80 and over , Appendicitis/diagnosis , COVID-19/prevention & control , COVID-19/transmission , Clinical Protocols , Female , Humans , Male , Middle Aged , Patient Selection , Practice Patterns, Physicians' , Retrospective Studies , Severity of Illness Index , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
13.
Nat Commun ; 12(1): 1018, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-1085426

ABSTRACT

Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity-defined by the level of antibodies-is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/blood , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin G/immunology , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Viral Vaccines/immunology , Young Adult
15.
JCI Insight ; 6(1)2021 01 11.
Article in English | MEDLINE | ID: covidwho-1066996

ABSTRACT

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross-SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection.


Subject(s)
Antibodies, Neutralizing/pharmacology , COVID-19/immunology , Immunity, Innate/drug effects , Immunoglobulin Fc Fragments/genetics , Immunoglobulin G/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Antibodies, Monoclonal , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , COVID-19/physiopathology , Cricetinae , Cross Reactions , Epitopes , Humans , Immunity, Innate/immunology , Immunoglobulin G/genetics , Immunoglobulin G/therapeutic use , Mesocricetus , Mice , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/immunology , Protein Engineering , Receptors, Fc/immunology , SARS Virus/drug effects , SARS Virus/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , THP-1 Cells , Viral Load/drug effects , Weight Loss/drug effects
17.
J Neurosurg Spine ; : 1-9, 2020 Oct 02.
Article in English | MEDLINE | ID: covidwho-1016048

ABSTRACT

OBJECTIVE: During the COVID-19 pandemic, quaternary-care facilities continue to provide care for patients in need of urgent and emergent invasive procedures. Perioperative protocols are needed to streamline care for these patients notwithstanding capacity and resource constraints. METHODS: A multidisciplinary panel was assembled at the University of California, San Francisco, with 26 leaders across 10 academic departments, including 7 department chairpersons, the chief medical officer, the chief operating officer, infection control officers, nursing leaders, and resident house staff champions. An epidemiologist, an ethicist, and a statistician were also consulted. A modified two-round, blinded Delphi method based on 18 agree/disagree statements was used to build consensus. Significant disagreement for each statement was tested using a one-sided exact binomial test against an expected outcome of 95% consensus using a significance threshold of p < 0.05. Final triage protocols were developed with unblinded group-level discussion. RESULTS: Overall, 15 of 18 statements achieved consensus in the first round of the Delphi method; the 3 statements with significant disagreement (p < 0.01) were modified and iteratively resubmitted to the expert panel to achieve consensus. Consensus-based protocols were developed using unblinded multidisciplinary panel discussions. The final algorithms 1) quantified outbreak level, 2) triaged patients based on acuity, 3) provided a checklist for urgent/emergent invasive procedures, and 4) created a novel scoring system for the allocation of personal protective equipment. In particular, the authors modified the American College of Surgeons three-tiered triage system to incorporate more urgent cases, as are often encountered in neurosurgery and spine surgery. CONCLUSIONS: Urgent and emergent invasive procedures need to be performed during the COVID-19 pandemic. The consensus-based protocols in this study may assist healthcare providers to optimize perioperative care during the pandemic.

18.
Cell ; 183(6): 1508-1519.e12, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-898562

ABSTRACT

The urgent need for an effective SARS-CoV-2 vaccine has forced development to progress in the absence of well-defined correlates of immunity. While neutralization has been linked to protection against other pathogens, whether neutralization alone will be sufficient to drive protection against SARS-CoV-2 in the broader population remains unclear. Therefore, to fully define protective humoral immunity, we dissected the early evolution of the humoral response in 193 hospitalized individuals ranging from moderate to severe. Although robust IgM and IgA responses evolved in both survivors and non-survivors with severe disease, non-survivors showed attenuated IgG responses, accompanied by compromised Fcɣ receptor binding and Fc effector activity, pointing to deficient humoral development rather than disease-enhancing humoral immunity. In contrast, individuals with moderate disease exhibited delayed responses that ultimately matured. These data highlight distinct humoral trajectories associated with resolution of SARS-CoV-2 infection and the need for early functional humoral immunity.


Subject(s)
COVID-19 , Immunity, Humoral , Immunoglobulin A/immunology , Immunoglobulin M/immunology , Receptors, IgG/immunology , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/mortality , Female , HL-60 Cells , Humans , Male
19.
Cell ; 183(6): 1496-1507.e16, 2020 12 10.
Article in English | MEDLINE | ID: covidwho-898561

ABSTRACT

Antibodies are key immune effectors that confer protection against pathogenic threats. The nature and longevity of the antibody response to SARS-CoV-2 infection are not well defined. We charted longitudinal antibody responses to SARS-CoV-2 in 92 subjects after symptomatic COVID-19. Antibody responses to SARS-CoV-2 are unimodally distributed over a broad range, with symptom severity correlating directly with virus-specific antibody magnitude. Seventy-six subjects followed longitudinally to ∼100 days demonstrated marked heterogeneity in antibody duration dynamics. Virus-specific IgG decayed substantially in most individuals, whereas a distinct subset had stable or increasing antibody levels in the same time frame despite similar initial antibody magnitudes. These individuals with increasing responses recovered rapidly from symptomatic COVID-19 disease, harbored increased somatic mutations in virus-specific memory B cell antibody genes, and had persistent higher frequencies of previously activated CD4+ T cells. These findings illuminate an efficient immune phenotype that connects symptom clearance speed to differential antibody durability dynamics.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , CD4-Positive T-Lymphocytes/immunology , COVID-19 , Immunoglobulin G/immunology , Lymphocyte Activation , Mutation , COVID-19/genetics , COVID-19/immunology , Humans , SARS-CoV-2/genetics , SARS-CoV-2/immunology
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