scholarly journals EFFECT OF CONVALESCENT PLASMA ON MORTALITY IN PATIENTS WITH COVID-19 PNEUMONIA

2020 ◽  
Author(s):  
Martín R. Salazar ◽  
Soledad E. González ◽  
Lorena Regairaz ◽  
Noelia S. Ferrando ◽  
Veronica V. González Martínez ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Neutralizing Antibodies ◽  
Protective Factor ◽  
Viral Infections ◽  
Preliminary Evidence ◽  
Buenos Aires Province ◽  
List Type ◽  
Bed Management ◽  
Key Points ◽  
Epidemiological Characteristics

AbstractBackgroundConvalescent plasma, widely utilized in viral infections that induce neutralizing antibodies, has been proposed for COVID-19, and preliminary evidence shows that it might have beneficial effect. Our objective was to compare epidemiological characteristics and outcomes between patients who received convalescent plasma for COVID-19 and those who did not, admitted to hospitals in Buenos Aires Province, Argentina, throughout the pandemic.MethodsThis is a multicenter, retrospective cohort study of 2-month duration beginning on June 1, 2020, including unselected, consecutive adult patients with diagnosed COVID-19, admitted to 215 hospitals with pneumonia. Epidemiological and clinical variables were registered in the Provincial Hospital Bed Management System. Convalescent plasma was supplied as part of a centralized, expanded access program.ResultsWe analyzed 3,529 patients with pneumonia, predominantly male, aged 62±17, with arterial hypertension and diabetes as main comorbidities; 51.4% were admitted to the ward, 27.1% to the Intensive Care Unit (ICU), and 21.7% to the ICU with mechanical ventilation requirement (ICU-MV). 28-day mortality was 34.9%; and was 26.3%, 30.1% and 61.4% for ward, ICU and ICU-MV patients. Convalescent plasma was administered to 868 patients (24.6%); their 28-day mortality was significantly lower (25.5% vs. 38.0%, p<0.001). No major adverse effects occurred.Logistic regression analysis identified age, ICU admission with and without MV requirement, diabetes and preexistent cardiovascular disease as independent predictors of 28-day mortality, whereas convalescent plasma administration acted as a protective factor.ConclusionsOur study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with decreased mortality.Key PointsPreliminary evidence showed that convalescent plasma might be beneficial in COVID-19.In a cohort of 3,529 patients with pneumonia due to COVID-19, convalescent plasma was administered to 868 patients, without major adverse effects.Convalescent plasma was independently associated with decreased mortality.

scholarly journals Risk factors for COVID-19 mortality: The effect of convalescent plasma administration

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250386
Author(s):  
Martín R. Salazar ◽  
Soledad E. González ◽  
Lorena Regairaz ◽  
Noelia S. Ferrando ◽  
Verónica V. González Martínez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neutralizing Antibodies ◽  
Protective Factor ◽  
Viral Infections ◽  
Preliminary Evidence ◽  
Buenos Aires Province ◽  
Bed Management ◽  
Expanded Access Program ◽  
Improved Outcomes ◽  
Access Program

Background Convalescent plasma, widely utilized in viral infections that induce neutralizing antibodies, has been proposed for COVID-19, and preliminary evidence shows that it might have beneficial effect. Our objective was to determine the risk factors for 28-days mortality in patients who received convalescent plasma for COVID-19 compared to those who did not, who were admitted to hospitals in Buenos Aires Province, Argentina, throughout the pandemic. Methods This is a multicenter, retrospective cohort study of 2-month duration beginning on June 1, 2020, including unselected, consecutive adult patients with diagnosed COVID-19, admitted to 215 hospitals with pneumonia. Epidemiological and clinical variables were registered in the Provincial Hospital Bed Management System. Convalescent plasma was supplied as part of a centralized, expanded access program. Results We analyzed 3,529 patients with pneumonia, predominantly male, aged 62±17, with arterial hypertension and diabetes as main comorbidities; 51.4% were admitted to the ward, 27.1% to the Intensive Care Unit (ICU), and 21.7% to the ICU with mechanical ventilation requirement (ICU-MV). 28-day mortality was 34.9%; and was 26.3%, 30.1% and 61.4% for ward, ICU and ICU-MV patients. Convalescent plasma was administered to 868 patients (24.6%); their 28-day mortality was significantly lower (25.5% vs. 38.0%, p<0.001). No major adverse effects occurred. Logistic regression analysis identified age, ICU admission with and without MV requirement, diabetes, and preexistent cardiovascular disease as independent predictors of 28-day mortality, whereas convalescent plasma administration acted as a protective factor. Conclusions Our study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with improved outcomes.

scholarly journals Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation

Blood ◽  
2015 ◽  
Vol 125 (26) ◽  
pp. 4103-4113 ◽  
Author(s):  
Xiaoou Zhou ◽  
Gianpietro Dotti ◽  
Robert A. Krance ◽  
Caridad A. Martinez ◽  
Swati Naik ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Adverse Effects ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Viral Infections ◽  
Suicide Gene ◽  
Immune Recovery ◽  
Caspase 9 ◽  
Key Points

Key PointsAlloreplete iC9-T cells can promote immune recovery posttransplant and protect patients against viral infections. iC9-T cells can be eliminated from both peripheral blood and CNS by administration of AP1903 leading to a rapid resolution of GVHD.

scholarly journals Detection of acute ventilatory problems via magnetic induction in a newborn animal model

2021 ◽  
Author(s):  
Sabrina C. Behr ◽  
Christopher Platen ◽  
Pascal Vetter ◽  
Nicole Heussen ◽  
Steffen Leonhardt ◽  
...  
Keyword(s):  
Early Detection ◽  
Magnetic Induction ◽  
Side Information ◽  
Pulmonary Ventilation ◽  
Critical Role ◽  
Preliminary Evidence ◽  
List Type ◽  
Newborn Animal ◽  
Newborn Piglets ◽  
Patient Side

Abstract Background Magnetic induction measurement (MIM) is a noninvasive method for the contactless registration of respiration in newborn piglets by using measurement coils positioned at the bottom of an incubator. Acute pulmonary problems may be determinants of poor neurological and psychomotor outcomes in preterm infants. The current study tested the detection of pulmonary ventilation disorders via MIM in 11 newborn piglets. Methods Six measurement coils determined changes in magnetic induction, depending on the ventilation of the lung, in comparison with flow resistance. Contactless registration of induced acute pulmonary ventilation disorders (apnea, atelectasis, pneumothorax, and aspiration) was detected by MIM. Results All pathologies except aspiration were detected by MIM. Significant changes occurred after induction of apnea (three coils), malposition of the tube (one coil), and pneumothorax (three coils) (p ≤ 0.05). No significant changes occurred after induction of aspiration (p = 0.12). Conclusions MIM seems to have some potential to detect acute ventilation disorders in newborn piglets. The location of the measurement coil related to the animal’s position plays a critical role in this process. In addition to an early detection of acute pulmonary problems, potential information pointing to a therapeutic intervention, for example, inhalations or medical respiratory analepsis, may be conceivable with MIM in the future. Impact MIM seems to be a method in which noncontact ventilation disorders of premature and mature infants can be detected. This study is an extension of the experimental setup to obtain preliminary evidence for detection of respiratory activity in neonatal piglets. For the first time, MIM is used to register acute ventilation problems of neonates. The possibility of an early detection of acute ventilation problems via MIM may provide an opportunity to receive patient-side information for therapeutical interventions like inhalations or medical respiratory analepsis.

scholarly journals Neutralizing Antibodies Titers and Side Effects in Response to BNT162b2 Vaccine in Healthcare Workers with and without Prior SARS-CoV-2 Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 742
Author(s):  
José Javier Morales-Núñez ◽  
José Francisco Muñoz-Valle ◽  
Carlos Meza-López ◽  
Lin-Fa Wang ◽  
Andrea Carolina Machado Sulbarán ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Adverse Effects ◽  
Antibody Production ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Vaccination Program ◽  
Expected Result ◽  
Neutralizing Capacity ◽  
The Usa

The main expected result of a vaccine against viruses is the ability to produce neutralizing antibodies. Currently, several vaccines against SARS-CoV-2 are being applied to prevent mortal complications, being Pfizer-BioNTech (BNT162b2) one of the first to be authorized in the USA and Mexico (11 December 2020). This study evaluated the efficacy of this vaccine on antibody production with neutralizing capacity and its side effects in healthcare workers with and without prior SARS-CoV-2 infection and in a group of unvaccinated individuals with prior COVID-19. The main findings are the production of 100% neutralizing antibodies in both groups after the second dose, well-tolerated adverse effects, the possible presence of immunosenescence, and finally, we support that a single dose of this vaccine in individuals with prior COVID-19 would be sufficient to achieve an immunization comparable to people without prior COVID-19 with a complete vaccination program (2 doses).

scholarly journals The Epidemiological Characteristics of the COVID-19 Pandemic in Europe: Focus on Italy

2021 ◽  
Vol 18 (6) ◽  
pp. 2942
Author(s):  
Giovanni Gabutti ◽  
Erica d’Anchera ◽  
Francesco De Motoli ◽  
Marta Savio ◽  
Armando Stefanati
Keyword(s):  
Social Structures ◽  
World Population ◽  
European Continent ◽  
Key Points ◽  
Reporting Systems ◽  
The World ◽  
Definition Of ◽  
Epidemiological Characteristics ◽  
The Impact ◽  
Epidemiological Situation

Starting from December 2019, SARS-CoV-2 has forcefully entered our lives and profoundly changed all the habits of the world population. The COVID-19 pandemic has violently impacted the European continent, first involving only some European countries, Italy in particular, and then spreading to all member states, albeit in different ways and times. The ways SARS-CoV-2 spreads are still partly unknown; to quantify and adequately respond to the pandemic, various parameters and reporting systems have been introduced at national and European levels to promptly recognize the most alarming epidemiological situations and therefore limit the impact of the virus on the health of the population. The relevant key points to implement adequate measures to face the epidemic include identifying the population groups most involved in terms of morbidity and mortality, identifying the events mostly related to the spreading of the virus and recognizing the various viral mutations. The main objective of this work is to summarize the epidemiological situation of the COVID-19 pandemic in Europe and Italy almost a year after the first reported case in our continent. The secondary objectives include the definition of the epidemiological parameters used to monitor the epidemic, the explanation of superspreading events and the description of how the epidemic has impacted on health and social structures, with a particular focus on Italy.

scholarly journals Virus-Neutralizing Monoclonal Antibody Expressed in Milk of Transgenic Mice Provides Full Protection against Virus-Induced Encephalitis

2001 ◽  
Vol 75 (6) ◽  
pp. 2803-2809 ◽  
Author(s):  
Andreas F. Kolb ◽  
Lecia Pewe ◽  
John Webster ◽  
Stanley Perlman ◽  
C. Bruce A. Whitelaw ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Neutralizing Antibodies ◽  
Defense Mechanism ◽  
Viral Infections ◽  
Hepatitis Virus ◽  
Recombinant Antibody ◽  
Lethal Dose ◽  
Neutralizing Antibody ◽  
Murine Hepatitis Virus

ABSTRACT Neutralizing antibodies represent a major host defense mechanism against viral infections. In mammals, passive immunity is provided by neutralizing antibodies passed to the offspring via the placenta or the milk as immunoglobulin G and secreted immunoglobulin A. With the long-term goal of producing virus-resistant livestock, we have generated mice carrying transgenes that encode the light and heavy chains of an antibody that is able to neutralize the neurotropic JHM strain of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactating mammary gland by using the ovine β-lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of recombinant antibody/ml. In vitro analysis of milk derived from different transgenic lines revealed a linear correlation between antibody expression and virus-neutralizing activity, indicating that the recombinant antibody is the major determinant of MHV-JHM neutralization in murine milk. Offspring of transgenic and control mice were challenged with a lethal dose of MHV-JHM. Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas litters suckling transgenic dams were fully protected against challenge, irrespective of whether they were transgenic. This demonstrates that a single neutralizing antibody expressed in the milk of transgenic mice is sufficient to completely protect suckling offspring against MHV-JHM-induced encephalitis.

scholarly journals Distinct cellular immune signatures in acute Zika virus infection are associated with high or low persisting neutralizing antibody titers

2021 ◽  
Author(s):  
Elizabeth E. McCarthy ◽  
Pamela M. Odorizzi ◽  
Emma Lutz ◽  
Carolyn P. Smullin ◽  
Iliana Tenvooren ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Immune Cell ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Natural Immunity ◽  
Zikv Infection ◽  
Antibody Titers ◽  
Cellular Immune

Although the formation of a durable neutralizing antibody response after an acute viral infection is a key component of protective immunity, little is known about why some individuals generate high versus low neutralizing antibody titers to infection or vaccination. Infection with Zika virus (ZIKV) during pregnancy can cause devastating fetal outcomes, and efforts to understand natural immunity to this infection are essential for optimizing vaccine design. In this study, we leveraged the high-dimensional single-cell profiling capacity of mass cytometry (CyTOF) to deeply characterize the cellular immune response to acute and convalescent ZIKV infection in a cohort of blood donors in Puerto Rico incidentally found to be viremic during the 2015-2016 epidemic in the Americas. During acute ZIKV infection, we identified widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated innate immune subsets, as well as activated follicular helper CD4+ T cells and proliferating CD27-IgD- B cells, during acute infection were associated with high titers of ZIKV neutralizing antibodies at 6 months post-infection. On the other hand, low titers of ZIKV neutralizing antibodies were associated with immune features that suggested a cytotoxic-skewed immune "set-point." Our study offers insight into the cellular coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials for ZIKV and other acute viral infections aimed at inducing high titers of neutralizing antibodies.

scholarly journals Magnitude, change over time, demographic characteristics and geographic distribution of excess deaths among nursing home residents during the first wave of COVID-19 in France: a nationwide cohort study

2021 ◽  
Author(s):  
Florence Canouï-Poitrine ◽  
Antoine Rachas ◽  
Martine Thomas ◽  
Laure Carcaillon-Bentata ◽  
Roméo Fontaine ◽  
...  
Keyword(s):  
Nursing Home ◽  
General Population ◽  
Excess Mortality ◽  
Nursing Home Residents ◽  
Primary Objective ◽  
List Type ◽  
Key Points ◽  
Standardized Mortality Ratios ◽  
Using Data ◽  
Excess Deaths

AbstractImportanceNursing home (NH) residents are particularly vulnerable to SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19) lethality. However, excess deaths in this population have rarely been documented.ObjectivesThe primary objective was to assess the number of excess deaths among NH residents during the first wave of the COVID-19 pandemic in France. The secondary objectives were to determine the number of excess deaths as a proportion of the total excess deaths in the general population and determine whether a harvesting effect was present.DesignWe studied a cohort of 494,753 adults (as of March 1st, 2020) aged 60 and over in 6,515 NHs in mainland France. This cohort was exposed to the first wave of the COVID-19 pandemic (from March 1st to May 31st, 2020) and was compared with the corresponding, reference cohorts from 2014 to 2019 (using data from the French National Health Data System).Main outcome and measuresThe main outcome was all-cause death. Weekly excess deaths and standardized mortality ratios (SMRs) were estimated.ResultThere were 13,505 excess deaths among NH residents. Mortality increased by 43% (SMR: 1.43). The mortality excess was higher among males than among females (SMR: 1.51 and 1.38, respectively) and decreased with age (SMRs in females: 1.61 in the 60-74 age group, 1.58 for 75-84, 1.41 for 85-94, and 1.31 for 95 or over; Males: SMRs: 1.59 for 60-74, 1.69 for 75-84, 1.47 for 85-94, and 1.41 for 95 or over). We did not observe a harvesting effect (up until August 30th, 2020). By extrapolating to all NH residents nationally (N=570,003), the latter accounted for 51% of the total excess deaths in the general population (N=15,114 out of 29,563).ConclusionNH residents accounted for about half of the total excess deaths in France during the first wave of the COVID-19 pandemic. The excess death rate was higher among males than females and among younger residents than among older residents. We did not observe a harvesting effect. A real-time mortality surveillance system and the identification of individual and environmental risk factors might help to design the future model of care for older dependent adults.Key pointsDuring the first wave of the COVID-19 pandemic in France, the mortality among nursing home residents increased by 43%.Nursing home residents accounted for 51% of the total excess deaths in France.The excess mortality was higher among younger residents than among older residents.The excess mortality was higher among males than among females.We did not observe a harvesting effect during the study period (ending on August 30th, 2020, i.e., three months after the end of the first wave).

scholarly journals Mapping densely distributed membrane receptors in blood platelets with expansion microscopy

2021 ◽  
Author(s):  
Hannah S. Heil ◽  
Max Aigner ◽  
Sophia Maier ◽  
Vanessa Göb ◽  
Charly Kusch ◽  
...  
Keyword(s):  
Blood Platelets ◽  
Super Resolution ◽  
Membrane Receptors ◽  
List Type ◽  
Platelet Receptor ◽  
Key Points ◽  
Major Vessel ◽  
Integrin Clustering ◽  
Receptor Interactions ◽  
3D Scenarios

AbstractInterrogating small platelets and their densely packed, highly abundant receptor landscape is key to understand platelet clotting. Blot clots can save lives when stopping blood loss after an injury, but also kill when blocking a major vessel. The highly abundant and densely distributed GPIIb/IIIa receptors are one reason why the underlying key distributions and interactions, in particular the relevance of integrin clustering, are not fully understood. Such dense receptor scenarios are difficult to assess even by super-resolution fluorescence microscopy. Here, we quantify various receptor interactions, and demonstrate that expansion microscopy can pinpoint such challenging interactions where conventional methods fail in such dense 3D scenarios with highly abundant receptors. We successfully combine dual-color expansion and confocal microscopy with colocalization analysis and assess platelet receptor organization without the need of a super-resolution microscope. We reveal that GPIIb/IIIa receptors are organized in pre-formed clusters in resting platelets – a pattern that orchestrates platelet clotting. We show that 4x expansion is most straight-forward for platelet imaging, while 10x expansion provides highest precision which turned out to be absolutely necessary for the most difficult of the scenarios described here.Graphical AbstractNonstandard Abbreviations and AcronymsGPIX: glycoprotein IXExM: expansion microscopyKey PointsMapping of the very dense, highly abundant platelet receptor landscape requires 10x Expansion MicroscopyExM reveals that GPIIb/IIIa receptors are organized in pre-formed clusters in resting platelets.

ANTIBODY RESPONSES OF YOUNG INFANTS TO NATURALLY OCCURRING VIRAL INFECTIONS

PEDIATRICS ◽  
1966 ◽  
Vol 38 (4) ◽  
pp. 564-570
Author(s):  
Hugh L. Moffet ◽  
Henry G. Cramblett
Keyword(s):  
Neutralizing Antibodies ◽  
Virus Isolation ◽  
Viral Infections ◽  
Low Frequency ◽  
Severity Of Illness ◽  
Antibody Responses ◽  
Older Children ◽  
Young Infants ◽  
Naturally Occurring ◽  
Significant Difference

A fourfold rise in neutralizing antibodies was demonstrated for 45% of infants 1 through 6 months of age compared to 63% of older children or adults from whom an adenovirus or an enterovirus was recovered. This difference appeared to be related to severity of illness rather than to age, as there was no significant difference between young infants and older patients when only clinically severe illnesses were analyzed. The isolation of virus from more than one specimen increased the probability of a significant response in either age group. Infants with minor symptoms had a low frequency of significant fourfold antibody responses after virus isolation, but this was not significantly different from older children with minor symptoms. Failure to develop an increase in antibody titer could not be related to the presence of maternal antibodies.

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