scholarly journals Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience

Author(s):  
Michael J Joyner ◽  
Jonathon W Senefeld ◽  
Stephen A Klassen ◽  
John R Mills ◽  
Patrick W Johnson ◽  
...  

Importance: Passive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. Objective: To explore potential signals of efficacy of COVID-19 convalescent plasma. Design: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma. Setting: Multicenter, including 2,807 acute care facilities in the US and territories. Participants: Adult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. Intervention: Transfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. Results: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. Conclusions and Relevance: The relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma. Trial Registration: ClinicalTrials.gov Identifier: NCT04338360

2021 ◽  
Vol 7 (8) ◽  
pp. 595
Author(s):  
Helmut J. F. Salzer ◽  
Isabel Massango ◽  
Nilesh Bhatt ◽  
Emelva Machonisse ◽  
Maja Reimann ◽  
...  

Background: Chronic pulmonary aspergillosis (CPA) is a life-threatening sequel in patients with pulmonary tuberculosis (PTB). Aspergillus-specific IgG antibody is a useful diagnostic biomarker supporting CPA diagnosis, especially in countries with limited health recourses. Methods: We conducted a prospective pilot study to assess the seroprevalence of Aspergillus-specific IgG antibodies among 61 Mozambican tuberculosis patients before, during, and after the end of TB treatment. Aspergillus-specific IgG antibody levels were measured using the ImmunoCAP®. Results: In this study, 3 out of 21 HIV-negative PTB patients had a positive Aspergillus-specific IgG antibody level before, during, and after the end of TB treatment. Antibody levels were 41.1, 45.5, and 174 mg/L at end of treatment (EOT), respectively. Additionally, two HIV-negative PTB patients with negative Aspergillus-specific IgG antibody levels at baseline became seropositive at EOT (41.9 and 158 mg/L, respectively). Interestingly, none of the HIV-positive PTB patients (40/61) had a positive Aspergillus-specific IgG antibody level at any time, neither at baseline nor at EOT. Probable CPA was diagnosed in one HIV-negative patient (5%; 1/20). Conclusion: Seroprevalence of Aspergillus-specific IgG antibody may differ between HIV-negative and HIV-positive Mozambican PTB patients. Future studies evaluating post-tuberculosis lung disease should integrate CPA as a life-threatening sequel to PTB.


1988 ◽  
Vol 101 (2) ◽  
pp. 405-410 ◽  
Author(s):  
R. C. H Lau

SUMMARYEnzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components were 34.2% (with 3 components), 34.4% (2 components), and 78.1% (1 component). It appears the immunization strategy for diphtheria and tetanus is satisfactory for herd immunity in New Zealand children. However, the current pertussis strategy may not be providing adequate immunity to 5-year-olds in this country.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew D. Moura ◽  
Hernan H. M. da Costa ◽  
Victor A. Correa ◽  
Ana K. de S. Lima ◽  
José A. L. Lindoso ◽  
...  

AbstractSARS-CoV-2 is considered a global emergency, resulting in an exacerbated crisis in the health public in the world. Although there are advances in vaccine development, it is still limited for many countries. On the other hand, an immunological response that mediates protective immunity or indicates that predict disease outcome in SARS-CoV-2 infection remains undefined. This work aimed to assess the antibody levels, avidity, and subclasses of IgG to RBD protein, in symptomatic patients with severe and mild forms of COVID-19 in Brazil using an adapted in-house RBD-IgG ELISA. The RBD IgG-ELISA showed 100% of specificity and 94.3% of sensibility on detecting antibodies in the sera of hospitalized patients. Patients who presented severe COVID-19 had higher anti-RBD IgG levels compared to patients with mild disease. Additionally, most patients analyzed displayed low antibody avidity, with 64.4% of the samples of patients who recovered from the disease and 84.6% of those who died in this avidity range. Our data also reveals an increase of IgG1 and IgG3 levels since the 8th day after symptoms onset, while IgG4 levels maintained less detectable during the study period. Surprisingly, patients who died during 8–14 and 15–21 days also showed higher anti-RBD IgG4 levels in comparison with the recovered (P < 0.05), suggesting that some life-threatening patients can elicit IgG4 to RBD antibody response in the first weeks of symptoms onset. Our findings constitute the effort to clarify IgG antibodies' kinetics, avidity, and subclasses against SARS-CoV-2 RBD in symptomatic patients with COVID-19 in Brazil, highlighting the importance of IgG antibody avidity in association with IgG4 detection as tool laboratory in the follow-up of hospitalized patients with more significant potential for life-threatening.


2002 ◽  
Vol 128 (3) ◽  
pp. 491-502 ◽  
Author(s):  
K. GLASS ◽  
J. L. N. WOOD ◽  
J. A. MUMFORD ◽  
D. JESSET ◽  
B. T. GRENFELL

This paper demonstrates that a simple stochastic model can capture the features of an epidemic of equine influenza in unvaccinated horses. When the model is modified to consider vaccinated horses, we find that vaccination dramatically reduces the incidence and size of epidemics. Although occasional larger outbreaks can still occur, these are exceptional. We then look at the effects of vaccination on a yard of horses, and in particular at the relationship between pre-challenge antibody level and quantity of virus shed when challenged with the virus. While on average, a high antibody level implies that less virus will be shed during the infectious period, we identify a high degree of heterogeneity in the response of horses with similar pre-challenge antibody levels. We develop a modified model that incorporates some heterogeneity in levels of infectivity, and compare this with the simpler model.


2012 ◽  
Vol 19 (10) ◽  
pp. 1561-1566 ◽  
Author(s):  
Mohamed Khalil ◽  
Yagob Al-Mazrou ◽  
Helen Findlow ◽  
Helen Chadha ◽  
Valerie Bosch Castells ◽  
...  

ABSTRACTSaudi Arabian children respond poorly to 2 doses of meningococcal quadrivalent polysaccharide vaccine (MPSV4) when given before 2 years of age. This study examined whether such children were able to respond to 1 dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MCV4) when they were older. Saudi Arabian children 5 to 8 years of age who had previously been vaccinated with 2 doses of MPSV4 when they were under 2 years of age (termed the prior-MPSV4 group) were enrolled in a controlled, open-label, multicenter study. In the prior-MPSV4 group, children (n= 153) received 1 dose of MCV4, as did a group of age-matched meningococcal vaccine-naïve children (n= 85). Blood samples collected prevaccination and 28 days postvaccination were measured for serogroup-specific serum bactericidal antibody (SBA) levels in the presence of baby rabbit complement (rSBA) and for IgG antibody levels. Vaccine tolerability and safety were also evaluated. For all of the measured serogroups (A, C, Y, and W-135), the meningococcal vaccine-naïve participants achieved higher postvaccination rSBA geometric mean titers (GMTs) than did those in the prior-MPSV4 group. This was statistically significant for serogroup C (512 versus 167). Percentages of participants with postvaccination titers of ≥8 and with ≥4-fold increases in prevaccination to postvaccination titers appeared to be quite similar in the 2 groups. No worrisome safety signals were detected. MCV4 induced robust immune responses and was well tolerated in Saudi Arabian children who previously received 2 doses of MPSV4 as well as in those who were previously meningococcal vaccine naïve.


Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 101
Author(s):  
Ching-Ju Shen ◽  
Yi-Chen Fu ◽  
Yen-Pin Lin ◽  
Ching-Fen Shen ◽  
Der-Ji Sun ◽  
...  

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy could result in adverse perinatal outcome. Clinical data on the assessment of the immune response in vaccinated pregnant women and subsequent transplacental antibody transfer are quite limited. Objective: To assess maternal and neonatal neutralizing antibody levels against both wildtype and Delta (B.1.617.2) variants after maternal mRNA vaccination. Study Design: This cohort study was conducted 29 pregnant women who were vaccinated at least one dose of Moderna (mRNA-1273) vaccine. Both neutralizing antibody (wildtype and Delta variant) and S1 receptor binding domain IgG antibody levels were evaluated in maternal and cord blood on the day of delivery. Results: Superiority of antibody level was significant in fully vaccinated women compared with the one-dose group (maternal sera, median, 97.46%; cord sera, median, 97.37% versus maternal sera, median, 4.01%; cord sera, median, 1.44%). No difference in antibody level was noted in relation to interval of second immunization to delivery in the two-dose group (95.99% in 0–2 weeks, 97.45% in 2–4 weeks, 97.48% in 4–8 weeks, 97.72% in 8–10 weeks). The most pronounced reduction was observed for the Delta variant. The wildtype neutralizing antibody level of full-vaccinated women was not influenced by the pertussis vaccination. Conclusion: The data underscore the importance of full vaccination in pregnancy and support the recommendation of COVID-19 immunization for pregnant women. The lower level of vaccine-induced neutralizing antibodies for the Delta variant indicates insufficient protection for mother and newborn and highlights the need for development of effective vaccine strategies.


2021 ◽  
Author(s):  
Andrew Moura ◽  
Hernan H. da Costa ◽  
Victor Correa ◽  
Ana K. Lima ◽  
José A. Lindoso ◽  
...  

Abstract SARS-CoV-2 is considered a global emergency, resulting in an exacerbated crisis in the health public in the world. Although there are advances in vaccine development, it is still not available for many countries. On the other hand, an immunological response that mediates protective immunity or indicates that predict disease outcome in SARS-CoV-2 infection remains undefined. This work aimed to assess the antibody levels, avidity, and subclasses of IgG to RBD protein, in symptomatic patients with severe and mild forms of COVID-19 in Brazil using an adapted in-house RBD-IgG ELISA. The RDB IgG-ELISA showed 100% of specificity and 94.3% of sensibility on detecting antibodies in the sera of hospitalized patients. Patients who presented severe COVID-19 had higher anti-RBD IgG levels compared to patients with mild disease. Additionally, most patients analyzed displayed low antibody avidity, with 64.4% of the samples of patients who recovered from the disease and 84.6% of those who died in this avidity range. Our data also reveals an increase of IgG1 and IgG3 levels since the 8th day after symptoms onset, while IgG4 levels maintained less detectable during the study period. Surprisingly, patients who died during 8-14 and 15-21 days also showed higher anti-RBD IgG4 levels in comparison with the recovered (P < 0.05), suggesting that some life-threatening patients can elicit IgG4 to RBD antibody response in the first weeks of symptoms onset. Our findings constitute the effort to clarify IgG antibodies' kinetics, avidity, and subclasses against SARS-CoV-2 RDB in symptomatic patients with COVID-19 in Brazil, highlighting the importance of IgG antibody avidity in association with IgG4 detection as tool laboratory in the follow-up of hospitalized patients with more significant potential for life-threatening.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ahmad Faudzi Yusoff ◽  
Zatil Zahidah Mohd Sharani ◽  
Chee Cheong Kee ◽  
Nuur Hafizah Md Iderus ◽  
Ahmed Syahmi Syafiq Md Zamri ◽  
...  

Abstract Background Despite high childhood immunization coverage, sporadic cases of diphtheria have been reported in Malaysia in recent years. This study aims to evaluate the seroprevalence of diphtheria among the Malaysian population. Methods A total of 3317 respondents age 2 years old to 60 years old were recruited in this study from August to November 2017. Enzyme-linked immunosorbent assay (ELISA) was used to measure the level of IgG antibody against the toxoid of C. diphtheriae in the blood samples of respondents. We classified respondent antibody levels based on WHO definition, as protective (≥0.1 IU/mL) and susceptible (< 0.1 IU/mL) to C. diphtheriae infection. Results Among the 3317 respondents, 57% were susceptible (38.1% of children and 65.4% of adults) and 43% (61.9% of children and 34.6% of adults) had protective antibody levels against diphtheria. The mean antibody level peaked among individuals aged 1–2 years old (0.59 IU/mL) and 6–7 years old (0.64 IU/mL) but generally decreased with age, falling below 0.1 IU/mL at around 4–6 years old and after age 20 years old. There was a significant association between age [Children: χ2 = 43.22(df = 2),p < 0.001)], gender [Adults: χ2 = 5.58(df = 1),p = 0.018] and ethnicity [Adults: χ2 = 21.49(df = 5),p = 0.001] with diphtheria toxoid IgG antibody level. Conclusions About 57% of the Malaysian population have inadequate immunity against diphtheria infection. This is apparently due to waning immunity following childhood vaccination without repeated booster vaccination in adults. Children at age 5–6 years old are particularly vulnerable to diphtheria infection. The booster vaccination dose normally given at 7 years should be given earlier, and an additional booster dose is recommended for high-risk adults.


2018 ◽  
Vol 29 (10) ◽  
pp. 2458-2470 ◽  
Author(s):  
Fouad T. Chebib ◽  
Ronald D. Perrone ◽  
Arlene B. Chapman ◽  
Neera K. Dahl ◽  
Peter C. Harris ◽  
...  

In the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Li ◽  
Chianru Tan ◽  
Jia Zeng ◽  
Chen Luo ◽  
Shi Hu ◽  
...  

Abstract Background COVID-19 has caused a global pandemic and the death toll is increasing. However, there is no definitive information regarding the type of clinical specimens that is the best for SARS-CoV-2 detection, the antibody levels in patients with different duration of disease, and the relationship between antibody level and viral load. Methods Nasopharyngeal swabs, anal swabs, saliva, blood, and urine specimens were collected from patients with a course of disease ranging from 7 to 69 days. Viral load in different specimen types was measured using droplet digital PCR (ddPCR). Meanwhile, anti-nucleocapsid protein (anti-N) IgM and IgG antibodies and anti-spike protein receptor-binding domain (anti-S-RBD) IgG antibody in all serum samples were tested using ELISA. Results The positive detection rate in nasopharyngeal swab was the highest (54.05%), followed by anal swab (24.32%), and the positive detection rate in saliva, blood, and urine was 16.22%, 10.81%, and 5.41%, respectively. However, some patients with negative nasopharyngeal swabs had other specimens tested positive. There was no significant correlation between antibody level and days after symptoms onset or viral load. Conclusions Other specimens could be positive in patients with negative nasopharyngeal swabs, suggesting that for patients in the recovery period, specimens other than nasopharyngeal swabs should also be tested to avoid false negative results, and anal swabs are recommended. The antibody level had no correlation with days after symptoms onset or the viral load of nasopharyngeal swabs, suggesting that the antibody level may also be affected by other factors.


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