Insulin sensitivity is not decreased in adult patients with hypopituitarism without growth hormone replacement

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fatmass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR10CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSem informaçã

Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer

We studied MET alterations in 474 advanced non-small-cell lung cancer (NSCLC) patients by nCounter, an RNA-based technique. We identified 3% with MET Δex14 mRNA and 3.5% with very-high MET mRNA expression, a surrogate of MET amplification. MET alterations identified by nCounter correlated with clinical benefit from MET inhibitors. Quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies. MET inhibitors have shown activity in non-small-cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect, and thus, response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA-based technique, together with next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with MET Δex14 and 15 patients (3.5%) with very-high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally coexist with other drivers. For MET Δex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very-high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very-high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies

Metabolic syndrome in patients with Pan-hypopituitarism : clinical-laboratory characterization

Orientadores: Denise Engelbrecht Zantut Wittmann, Heraldo Mendes GarmesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução O Hipopituitarismo (HP) é uma doença que tem como condição básica a deficiência na produção ou na ação de qualquer um dos hormônios da adeno-hipófise. Quando isto ocorre em dois ou mais hormônios, é denominado Pan-hipopituitarismo (PH). O HP é conhecidamente associado ao aumento da prevalência de Síndrome metabólica (SM), principalmente em pacientes com deficiência grave de hormônio de crescimento (GH). Apesar da suposta relação entre HP e síndrome metabólica, poucos estudos avaliaram a prevalência da SM e suas características clínico-laboratoriais nos pacientes com PH, geralmente ressaltando apenas a relação com a falência de GH. Objetivos Neste sentido, devido à escassez de informações na literatura, realizamos um estudo em pacientes com Pan-hipopituitarismo investigando as características e as frequências da SM e esteatose hepática (EH), assim como os perfis glicêmico, lipídico e de marcadores inflamatórios e de RI comparados a um grupo controle pareados pela idade, sexo e IMC. Metodologia Estudo transversal em que foram avaliados 41 pacientes com diagnóstico de PH e 37 indivíduos com função hipofisária normal pareados pela idade, sexo e índice de massa corporal. Avaliaram-se dados clínicos, antropométricos, ultrassonográficos (para EH), concentrações séricas de proteína C reativa (PCR) bem como exames laboratoriais que refletem os perfis lipídico, glicêmico e de RI. Resultados As frequências de SM e EH foram 65,9% e 78% nos pacientes com PH, e de 59,5% e 64,9% nos indivíduos do grupo de controle respetivamente. No entanto a frequência do diagnostico de dislipidemia (DLP) foi maior nos pacientes com PH (75,6% vs 51,4%; p=0,026). Os valores de Índice cintura quadril (ICQ) (p<0,001), glicemia (Gli) (p=0,010), insulina (p<0,001), e do índice indicativo de resistência à insulina (Homeostatic Model Assessment, HOMA-IR) (p<0,001) foram maiores nos indivíduos do grupo de controle. Por outro lado as concentrações séricas de PCR (p=0,011) foram maiores nos pacientes com PH. Na comparação entre os pacientes e indivíduos controle com SM, apresentaram-se valores significativamente superiores no grupo de indivíduos com SM, em relação à Gli (p=0,043), hemoglobina glicada (HBGli) (p=0,030), insulina (p<0,001), HOMA-IR (p<0,001), ICQ ( p=0,001). No entanto, os pacientes com PH e SM apresentaram maior frequência do diagnóstico de DLP (P=0,012) e concentrações significativamente superiores de PCR (P=0,028). O índice de massa corporal (IMC), idade e sexo feminino foram fatores de risco independentes para o desenvolvimento de SM nos pacientes com pan-hipopituitarismo, e a hemoglobina glicada nos indivíduos do grupo controle. Conclusões As frequências de síndrome metabólica e esteatose hepática foram semelhantes em pacientes com PH e nos indivíduos controle, por outro lado a frequência do diagnóstico de DLP foi maior nos pacientes com PH. Os indivíduos controle com SM apresentaram maior RI quando comparados aos pacientes com PH e SM. No entanto, os pacientes com PH e SM apresentaram maiores concentrações de PCR, e maior frequência do diagnóstico de DLP. O IMC, idade e sexo feminino foram os fatores de risco independentes para o desenvolvimento da SM nos pacientes com PH e a hemoglobina glicada nos indivíduos do grupo de controleAbstract: Introduction Hypopituitarism (HP) is a disease that is characterized by the deficiency in secretion or action of any of the anterior pituitary hormones. When it occurs in two or more hormonal axis it is denominated pan-hypopituitarism (PH). PH is associated to and increased prevalence of metabolic syndrome (MS), especially in patients with severe growth hormone (GH) deficiency. Despite the supposed relation of MS and PH, few studies have assessed the prevalence of MS and its clinical and laboratorial characteristics in patients with PH, often only highlighting the association with GH deficiency. Objectives Thus, due to the paucity of information in the literature, we conducted a study in patients with PH investigating the characteristics and the frequencies of MS and hepatic steatosis (HS), as well as fasting glycaemia, lipid profile and inflammatory and insulin resistance markers compared to a control group paired by age, sex and body mass index (BMI). Methodology This was a cross study evaluating 41 patients with PH and 37 individuals with normal pituitary function paired by age, sex and BMI. We evaluated clinical, anthropometric and ultrassonographic (for HS) data as well as serum levels of C-reactive protein (CRP), fasting glycaemia, lipid profile and insulin resistance index. Results The frequencies of MS and HS were 65.9% and 78% in patients with PH and 59.5% and 64.9% in control group individuals, respectively. However, the frequency of dyslipidemia diagnosis was higher in patients with PH (75.6% vs 51.4%; p=0.026). Waist to hip ratio (WHR) (p<0.001), fasting glycemia (p=0.01), fasting insulin (p<0.001) and the HOMA (Homeostatic Model Assessment ¿ HOMA IR) (p<0.001) were higher in control group individuals. On the other hand, CRP (p=0.011) levels were higher in patients with PH. Comparing control group individuals with MS and patients with PH and MS, fasting glycaemia (p=0.043), HbA1c (p=0.03), fasting insulin (p<0.001), HOMA IR (p<0.001) and WHR (p=0.001) were higher in the control group. Patients with PH and MS presented higher frequency of dyslipidemia diagnosis (p=0.012) and CRP levels (p=0.028). Body mass index, age and female sex were independent risk factors for MS in patients with PH, whereas the only significant factor in the control group was HbA1c. Conclusions The frequencies of MS and HS were similar in patients with PH and control group individuals. However, the frequency of dyslipidemia was higher in patients with PH. Control group individuals with MS showed increased insulin resistance when compared to patients with PH and MS. Patients with PH and MS had higher serum concentrations of CRP, and higher frequency of dyslipidemia diagnosis. Body mass index, age and female sex were independent risk factors for MS development in patients with PH whereas only HbA1c was a significant risk factor for MS in control group individualsMestradoClinica MedicaMestre em Clinica Medic

Hypopituitarism without growth hormone replacement in the adult patients : evaluation of insulin sensitivity and body composition

Orientadores: Heraldo Mendes Garmes, Denise Engelbrecht Zantut WittmannTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: Hipopituitarismo sem reposição de GH (HP-SRGH) no paciente adulto é frequentemente associado a alterações da composição corporal (CC) como o aumento da massa gorda (MG) e diminuição da massa magra (MM) assim como à diminuição da sensibilidade à insulina (SI). Em relação a este último aspecto, existem estudos com resultados conflitantes na literatura. Objetivos: Avaliar as características clínicas, demográficas, da SI e de CC em uma população de pacientes adultos com HP-SRGH e comparar a indivíduos de um grupo de controle (GC) pareados por idade, sexo e indice de massa corporal (IMC), Metodología: Estudo transversal onde avaliamos 15 pacientes adultos com diagnóstico prévio de HP-SRGH, em tratamento de reposição hormonal convencional e 15 indivíduos de um GC com função hipofisária normal pareados por idade, sexo e IMC. Avaliaram-se as características clínicas, demográficas, de SI por intermédio do clamp euglicêmico hiperinsulinêmico, além da glicemia de jejum (GJ) e insulina de jejum (IJ) para o cálculo do HOMA-IR. Adicionalmente foi avaliada a CC por intermédio da bioimpedanciometria elétrica determinando-se o peso da massa gorda (PMG), peso da massa magra (PMM), porcentagem de massa gorda (POMG), porcentagem de massa magra (POMM) e a taxa metabólica basal (TMB). Resultados: Quando comparados os pacientes com HP-SRGH e os indivíduos do GC, observamos que a SI foi semelhante nos dois grupos (p=0.0890). Por outro lado encontramos nos pacientes menores valores de IGF-1 (p<0.0001), GJ (p=0.0128), IJ (p=0.0007), HOMA-IR (p=0.009), PMM (p=0.0421), POMM (p= 0.0381) e TMB (p=0.0421), além de maiores valores de POMG (p=0.0381). No grupo de pacientes uma melhor SI correlacionou-se com menores valores de IMC, PMM, PMG, POMG e menores níveis de GJ, e com maiores valores de POMM. Além disso a melhor SI associou-se com o PH de início na infância (HP-SRGH-II). Na comparação de acordo com a presença de obesidade e de início do HP na etapa adulta (HP-SRGH-IEA), só foi significativo a presença de menores valores de IGF-1 no grupo HP-SRGH em cada caso. Já de acordo com a ausência obesidade observamos que os pacientes apresentaram uma melhor SI (p=0.0452), menores valores de IGF-1, GJ, IJ, HOMA-IR, PMM, POMM, e TMB, além de maiores valores de PMG e de POMG. Além disso na comparação dos pacientes com HP-II com seus indivíduos do GC pareados observamos que, os HP-II além de apresentar menores valores de IGF-1, GJ, IJ, HOMA-IR, PMM, POMM, TMB, e maiores valores de PMG e de POMG, os mesmos apresentaram melhor SI. Conclusões: Este estudo evidenciou que não houve diminuição da SI nos pacientes com HP-SRGH apesar de apresentar maior quantidade de MG e menor quantidade de MM. Demonstramos no grupo de pacientes que a SI tem uma correlação negativa com o IMC, PMM, PMG, POMG e a GJ e positiva com a POMM e o HP-II. Verificamos também que os pacientes com HP-SRGH não obesos e os HP-SRGH-II apresentaram melhor SI do que seus controles pareados apesar de apresentar quantidade maior de MG e menor de MMAbstract: Introduction: Hypopituitarism without GH replacement (HP-WGHR) in adults is often associated with alterations in body composition (BC) such as the increment in the fat mass (FM) and decrease in the lean mass (LM) as well as a decrease in insulin sensitivity (IS). Regarding the last aspect, there are contradictory studies in the literature about these topics. Objective: To evaluate the clinical, demographic, IS and BC characteristics in adult patients with HP-WGHR and compared to a control group (CG) paired by age, sex and body mass index (BMI). METHODOLOGY: A cross-sectional study was carried out to 15 adult patients with a previous diagnosis of HP-WGHR, in a conventional hormone replacement treatment, and 15 individuals of a CG with normal pituitary function were matched by age, sex and BMI. The clinical, demographic and IS characteristics were evaluated through the euglicemic hyperinsulinemic clamp. In addition, fasting glycemia (FG) and fasting insulin (FI) were considered for calculating HOMA-IR. On the other hand, the CC was evaluated by means of the electrical bioimpedanciometry determining the fat mass weight (FMW), lean mass weight (LMW), percentage of fat mass (PFM), percentage of lean mass (PLM) and basal metabolic rate (BMR). Results: When comparing patients with HP-WGHR and individuals in the CG, it was observed that IS was similar in both groups (p=0.0890). On the other hand, we found the lowest values of IGF-1 (p<0.0001), FG (p=0.0128), FI (p=0.0007), HOMA-IR (p=0.009), LMW (p=0.0381) and BMR (p=0.0421), and higher values of PFM (p=0.0381). In the patients group a better IS was correlated with lower values of BMI, LMW, FMW, PFM and lower values of FG, and higher values of PLM. The highest IS was associated with early childhood HP (HP-ECHIL). In the comparison, according to the presence of obesity and onset of PH in the adult stage (HP-AS), only the presence of lower values of IGF-1 in the HP-WGHR group in each case was significant. According to the absence of obesity, it was observed that the patients had a better IS (p=0.0452), lower values of IGF-1, FG, FI, HOMA-IR, LMW, PLM and BMR, and higher values of FMW and PFM. While comparing patients with HP-ECHIL with their paired CG, it was observed that HP-ECHIL apart from presenting lower values of IGF-1, FG, FI, HOMA-IR, LMW, PLM, BMR and higher values of FMW and PFM, they presented better sensibility to IS. Conclusions: This study demonstrated that there was no decrease in IS in adult patients with HP-WGHR, despite of the fact that there is more fat mass and less lean mass. It was revealed in the patients group that the IS had a negative correlation with BMI, LMW, FMW, PFM and FG and positive with PLM and HP-ECHIL. It was also verified that non-obese patients and HP-ECHIL presented better IS than their matched controls despite of an increase in the fat mass and a decrease in the lean massDoutoradoClinica MedicaDoutor em Ciências140829/2015-6CNP

Ritmos circadiano, circaseptano y circanual en el infarto agudo del miocardio

Se realizó un estudio descriptivo y transversal de 64 pacientes con infarto agudo del miocardio, atendidos en el Hospital Clinicoquirúrgico Docente "Dr. Joaquín Castillo Duany" de Santiago de Cuba, durante el 2008, a fin de determinar la variabilidad en el tiempo de los eventos cardiovasculares, con distribución irregular de los episodios de isquemia miocárdica, en relación con horas del día, semana o meses del año. En la casuística predominaron los hombres mayores de 45 años. Los episodios isquémicos prevalecieron durante el día, en los 2 primeros días de la semana, así como en el segundo trimestre del año. La citada afección presentó variaciones circadianas, circaseptanas, circanuales y su incidencia fue mayor a medida que aumentó la edad

Caracterización clinicoepidemiológica de pacientes con infarto agudo del miocardio egresados de una unidad de cuidados intensivos Clinical epidemiological characterization of patients with acute myocardial infarction discharged from an intensive care unit

Se realizó un estudio descriptivo y transversal, a fin de caracterizar 64 pacientes diagnosticados con infarto agudo del miocardio, los cuales egresaron de la Unidad de Cuidados Intensivos del Hospital Clinicoquirúrgico Docente "Dr. Joaquín Castillo Duany" de Santiago de Cuba, desde enero hasta diciembre del 2008. En la casuística predominaron el sexo masculino y el grupo etario de 55-64 años. Asimismo mientras mayor fue el tiempo prehospitalario hubo más complicaciones, siendo estas menos frecuentes en los afectados con trombolisis, a pesar de que en más de la mitad de los pacientes no se cumplió con el tratamiento trombolítico. Se demostró que el mayor número de pacientes que egresó precozmente fue sometido a este tratamiento.<br>ABSTRACT A descriptive and cross-sectional study was conducted in order to characterize 64 patients diagnosed with acute myocardial infarction, who were discharged from the Intensive Care Unit of "Dr. Joaquín Castillo Duany" Clinical Surgical Hospital of Santiago de Cuba, from January to December, 2008. Males and age group of 55-64 years prevailed in the case material. Also, the greater prehospital time was the more complications were, which were less frequent in those with thrombolysis, although in more than half of patients thrombolytic treatment was not administered. It was demonstrated that the higher number of patients that were early discharged received this treatment

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: &minus;0.8214, p = 0.0234 and rs: &minus;0.3639, p &lt; 0.0344), while this correlation was not observed with COGHD (rs: &minus;0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD

Correction to: RIC in COVID-19—a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19 : RIC in COVID-19—a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19 (Cardiovascular Drugs and Therapy, (2021), 10.1007/s10557-021-07221-y)

Publisher Copyright: © 2021, Springer Science+Business Media, LLC, part of Springer Nature.The original article has been corrected. Author “Dereks M. Yellon” should be “Derek M. Yellon.”

RIC in COVID-19—a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19

Funding for this study was provided by grants from the Thompson Family Trust, The Hatter Cardiovascular Institute, Mancherje-Potash Foundation, and the Fundação de Apoio a Pesquisa do Estado de São Paulo (FAPESP). Publisher Copyright: © 2021, The Author(s).Purpose: Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. “RIC in COVID-19” is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. Methods: A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. Conclusions: The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. Trial Registration: NCT04699227, registered January 7th, 2021.Peer reviewe

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols