Try a new search

Format these results:

Searched for:

person:somav01

in-biosketch:true

Total Results:

14


Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents

Wolf, Joshua; Abzug, Mark J; Anosike, Brenda I; Vora, Surabhi B; Waghmare, Alpana; Sue, Paul K; Olivero, Rosemary M; Oliveira, Carlos R; James, Scott H; Morton, Theodore H; Maron, Gabriela M; Young, Jennifer L; Orscheln, Rachel C; Schwenk, Hayden T; Bio, Laura L; Willis, Zachary I; Lloyd, Elizabeth C; Hersh, Adam L; Huskins, Charles W; Soma, Vijaya L; Ratner, Adam J; Hayes, Molly; Downes, Kevin; Chiotos, Kathleen; Grapentine, Steven P; Wattier, Rachel L; Lamb, Gabriella S; Zachariah, Philip; Nakamura, Mari M
BACKGROUND:Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. METHODS:A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. RESULTS:The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. CONCLUSIONS:Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.
PMID: 35107571
ISSN: 2048-7207
CID: 5153602

Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents

Geva, Alon; Patel, Manish M; Newhams, Margaret M; Young, Cameron C; Son, Mary Beth F; Kong, Michele; Maddux, Aline B; Hall, Mark W; Riggs, Becky J; Singh, Aalok R; Giuliano, John S; Hobbs, Charlotte V; Loftis, Laura L; McLaughlin, Gwenn E; Schwartz, Stephanie P; Schuster, Jennifer E; Babbitt, Christopher J; Halasa, Natasha B; Gertz, Shira J; Doymaz, Sule; Hume, Janet R; Bradford, Tamara T; Irby, Katherine; Carroll, Christopher L; McGuire, John K; Tarquinio, Keiko M; Rowan, Courtney M; Mack, Elizabeth H; Cvijanovich, Natalie Z; Fitzgerald, Julie C; Spinella, Philip C; Staat, Mary A; Clouser, Katharine N; Soma, Vijaya L; Dapul, Heda; Maamari, Mia; Bowens, Cindy; Havlin, Kevin M; Mourani, Peter M; Heidemann, Sabrina M; Horwitz, Steven M; Feldstein, Leora R; Tenforde, Mark W; Newburger, Jane W; Mandl, Kenneth D; Randolph, Adrienne G
Background/UNASSIGNED:Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods/UNASSIGNED:We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Findings/UNASSIGNED: = 583; 19% labeled MIS-C) were younger (2·8 ± 2·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Interpretation/UNASSIGNED:Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.
PMCID:8405351
PMID: 34485878
ISSN: 2589-5370
CID: 5067082

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes

Son, Mary Beth F; Murray, Nancy; Friedman, Kevin; Young, Cameron C; Newhams, Margaret M; Feldstein, Leora R; Loftis, Laura L; Tarquinio, Keiko M; Singh, Aalok R; Heidemann, Sabrina M; Soma, Vijaya L; Riggs, Becky J; Fitzgerald, Julie C; Kong, Michele; Doymaz, Sule; Giuliano, John S; Keenaghan, Michael A; Hume, Janet R; Hobbs, Charlotte V; Schuster, Jennifer E; Clouser, Katharine N; Hall, Mark W; Smith, Lincoln S; Horwitz, Steven M; Schwartz, Stephanie P; Irby, Katherine; Bradford, Tamara T; Maddux, Aline B; Babbitt, Christopher J; Rowan, Courtney M; McLaughlin, Gwenn E; Yager, Phoebe H; Maamari, Mia; Mack, Elizabeth H; Carroll, Christopher L; Montgomery, Vicki L; Halasa, Natasha B; Cvijanovich, Natalie Z; Coates, Bria M; Rose, Charles E; Newburger, Jane W; Patel, Manish M; Randolph, Adrienne G
BACKGROUND:The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS:We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS:A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS:Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).
PMID: 34133855
ISSN: 1533-4406
CID: 4925592

Multisystem Inflammatory Syndrome in Children [Editorial]

Shust, Gail F; Soma, Vijaya L; Kahn, Philip; Ratner, Adam J
PMID: 34210761
ISSN: 1526-3347
CID: 4927192

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of COVID-19 in Children and Adolescents

Wolf, Joshua; Abzug, Mark J; Wattier, Rachel L; Sue, Paul K; Vora, Surabhi B; Zachariah, Philip; Dulek, Daniel E; Waghmare, Alpana; Olivero, Rosemary; Downes, Kevin J; James, Scott H; Pinninti, Swetha G; Yarbrough, April; Aldrich, Margaret L; MacBrayne, Christine E; Soma, Vijaya L; Grapentine, Steven P; Oliveira, Carlos R; Hayes, Molly; Kimberlin, David W; Jones, Sarah B; Bio, Laura L; Morton, Theodore H; Hankins, Jane S; MarÏŒn-Alfaro, Gabriella M; Timberlake, Kathryn; Young, Jennifer L; Orscheln, Rachel C; Schwenk, Hayden T; Goldman, David L; Groves, Helen E; Huskins, W Charles; Rajapakse, Nipunie S; Lamb, Gabriella S; Tribble, Alison C; Lloyd, Elizabeth E; Hersh, Adam L; Thorell, Emily A; Ratner, Adam J; Chiotos, Kathleen; Nakamura, Mari M
BACKGROUND:In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for two novel virus-neutralizing monoclonal antibody therapies, bamlanivimab, and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate COVID-19 in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. METHODS:A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. RESULTS:The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. CONCLUSIONS:Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence, and ensure implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.
PMID: 33388760
ISSN: 2048-7207
CID: 4738392

Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19

Feldstein, Leora R; Tenforde, Mark W; Friedman, Kevin G; Newhams, Margaret; Rose, Erica Billig; Dapul, Heda; Soma, Vijaya L; Maddux, Aline B; Mourani, Peter M; Bowens, Cindy; Maamari, Mia; Hall, Mark W; Riggs, Becky J; Giuliano, John S; Singh, Aalok R; Li, Simon; Kong, Michele; Schuster, Jennifer E; McLaughlin, Gwenn E; Schwartz, Stephanie P; Walker, Tracie C; Loftis, Laura L; Hobbs, Charlotte V; Halasa, Natasha B; Doymaz, Sule; Babbitt, Christopher J; Hume, Janet R; Gertz, Shira J; Irby, Katherine; Clouser, Katharine N; Cvijanovich, Natalie Z; Bradford, Tamara T; Smith, Lincoln S; Heidemann, Sabrina M; Zackai, Sheemon P; Wellnitz, Kari; Nofziger, Ryan A; Horwitz, Steven M; Carroll, Ryan W; Rowan, Courtney M; Tarquinio, Keiko M; Mack, Elizabeth H; Fitzgerald, Julie C; Coates, Bria M; Jackson, Ashley M; Young, Cameron C; Son, Mary Beth F; Patel, Manish M; Newburger, Jane W; Randolph, Adrienne G
Importance/UNASSIGNED:Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective/UNASSIGNED:To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants/UNASSIGNED:Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure/UNASSIGNED:SARS-CoV-2. Main Outcomes and Measures/UNASSIGNED:Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results/UNASSIGNED:Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance/UNASSIGNED:This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.
PMID: 33625505
ISSN: 1538-3598
CID: 4794702

Multicenter interim guidance on use of antivirals for children with COVID-19/SARS-CoV-2

Chiotos, Kathleen; Hayes, Molly; Kimberlin, David W; Jones, Sarah B; James, Scott H; Pinninti, Swetha G; Yarbrough, April; Abzug, Mark J; MacBrayne, Christine E; Soma, Vijaya L; Dulek, Daniel E; Vora, Surabhi B; Waghmare, Alpana; Wolf, Joshua; Olivero, Rosemary; Grapentine, Steven; Wattier, Rachel L; Bio, Laura; Cross, Shane J; Dillman, Nicholas O; Downes, Kevin J; Oliveira, Carlos R; Timberlake, Kathryn; Young, Jennifer; Orscheln, Rachel C; Tamma, Pranita D; Schwenk, Hayden T; Zachariah, Philip; Aldrich, Margaret L; Goldman, David L; Groves, Helen E; Rajapakse, Nipunie S; Lamb, Gabriella S; Tribble, Alison C; Hersh, Adam L; Thorell, Emily A; Denison, Mark R; Ratner, Adam J; Newland, Jason G; Nakamura, Mari M
BACKGROUND:Although Coronavirus Disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data evaluating agents with potential antiviral activity continue to expand, such that updated guidance is needed regarding use of these agents in children. METHODS:A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS:Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for non-invasive or invasive mechanical ventilation or extra-corporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or non-invasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS:Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.
PMID: 32918548
ISSN: 2048-7207
CID: 4592272

Multisystem inflammatory syndrome in children

Soma, Vijaya L; Shust, Gail F; Ratner, Adam J
PURPOSE OF REVIEW/OBJECTIVE:Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases. RECENT FINDINGS/RESULTS:Clinical presentation of MIS-C is dominated by significant inflammation. Fever, gastrointestinal symptoms, cardiac dysfunction, and hypotension are common features. Kawasaki disease-like findings are common, but epidemiologic data and recent mechanistic studies suggest that distinct inflammatory pathways mediate Kawasaki disease and MIS-C. A broad diagnostic approach is recommended, given overlapping presentations between MIS-C and many other disease processes. Current management of MIS-C is highly variable, depending on illness severity, and can range from supportive care to aggressive immune modulation. A multidisciplinary approach with early involvement of multiple pediatric subspecialists is recommended for complicated cases. SUMMARY/CONCLUSIONS:Several studies have described the clinical manifestations of MIS-C, but definitive diagnosis remains challenging. Robust information about long-term outcomes awaits further study, as do immunologic data to refine diagnostic and therapeutic strategies.
PMID: 33278107
ISSN: 1531-698x
CID: 4708332

Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2

Chiotos, Kathleen; Hayes, Molly; Kimberlin, David W; Jones, Sarah B; James, Scott H; Pinninti, Swetha G; Yarbrough, April; Abzug, Mark J; MacBrayne, Christine E; Soma, Vijaya L; Dulek, Daniel E; Vora, Surabhi B; Waghmare, Alpana; Wolf, Joshua; Olivero, Rosemary; Grapentine, Steven; Wattier, Rachel L; Bio, Laura; Cross, Shane J; Dillman, Nicholas O; Downes, Kevin J; Timberlake, Kathryn; Young, Jennifer; Orscheln, Rachel C; Tamma, Pranita D; Schwenk, Hayden T; Zachariah, Philip; Aldrich, Margaret; Goldman, David L; Groves, Helen E; Lamb, Gabriella S; Tribble, Alison C; Hersh, Adam L; Thorell, Emily A; Denison, Mark R; Ratner, Adam J; Newland, Jason G; Nakamura, Mari M
BACKGROUND:Although Coronavirus Disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develops severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS:A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS:Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS:Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare children who develop severe or critical disease, this guidance offer an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.
PMID: 32318706
ISSN: 2048-7207
CID: 4397102

Very low incidence of <i>Clostridioides difficile</i> infection in pediatric sickle cell disease patients

Lee, Philip; Sinha, Arpan A; Soma, Vijaya L; Cruz, Carlos; Wang, Tao; Aroniadis, Olga; Herold, Betsy C; Frenette, Paul S; Goldman, David L; Manwani, Deepa
PMID: 33054107
ISSN: 1592-8721
CID: 4641552