Antibody Response Against Sars-Cov-2 in Convalescent Plasma Donors: Preliminary Results from a Single Center in Midwest Brazil

In March 2020, COVID-19 was declared a pandemic by the WHO. Since then, efforts have been made to increase our knowledge of the disease. The convalescent plasma (CP) donation involves a series of criteria for donor eligibility, such as pre-donation and serological tests. Currently, the antibody response against SARS-CoV-2 remains poorly understood and the usefulness of serological tests is unclear (Long, et al. Nature Medicine, 2020). Based on donor eligibility, one can better assess the antibody response to SARS-CoV-2 from post-infection candidates. This is an observational, prospective study, without intervention. From 06/26/2020 to 07/31/2020, serological data of candidates for CP donation were collected. Recovered COVID-19 patients who had been previously tested were interviewed. RT-PCR and serological test (chemiluminescence immunoassays) for SARS-CoV-2 were carried out to verify their eligibility for CP collection. The data were related to the time of the onset of symptoms and the collection of the material. Subjects with non-detectable RT-PCR and reagent IgG were considered eligible. Reference values were IgM > 1.2 AU/mL and IgG > 1.4 AU/mL. The characteristics of the candidates are summarized in Table 1. Of 234 interviewed subjects, 70 were screened for pre-collection tests, 49 were male. The average age was 36 (20 - 57). After serological screening, 44/70 (62.8%) were considered eligible for CP donation. The reasons for ineligibility were: 17/70 (24.3%) non-reagent IgG, 4/70 (5.7%) with detectable RT-PCR and 5/70 (7.1%) due to reasons in clinical screening. The median between the onset of symptoms and the serology sample collection was 32.5 (21 - 77) days, (IQR 28.75 to 37.25). Those who were more likely to be eligible to donate were the subjects who had a longer time interval between the symptoms onset and the sample collection (p <0.012). Although viral clearance in the upper airways is expected from the 10th day of symptom onset, only 50% of patients will have an undetectable test (Özçürümez, et al. J Allergy Clin Immunol. 2020). In our sample, 5.7% (4/70) of the subjects had detectable RT-PCR, which can represent residual viral genome and not active infection. We observed that 20% of the subjects samples were non-reagent. Those who were tested up to the 21st of the onset of symptoms might not have had seroconversion yet. For those tested after the 28th day, we can infer that the antibodies had already been cleared. Some authors state that patients who had mild infections may react with less antibodies (Özçürümez, et al. J Allergy Clin Immunol. 2020), which could explain this fact. Likewise, it was not possible to relate serological titers to the severity of the disease, as this was not one of the selection criteria.In 40/70 donors (57.2%) IgM remained above 1.2 AU / mL after the 21st day of symptom onset. Interestingly, 2 of these had only reagent IgM after the 36th day of symptom onset. Most subjects who had reagent IgM after the 21st of symptoms also had reagent IgG. We inferred that they were in a vigorous convalescence phase. In addition, 75.7% of the subjects presented reagent IgG regardless of the date of onset of symptoms. Most of them had both reagent IgM and IgG. Only one donor's (1.4%) IgM and IgG were non-reagent 21 days after the onset of symptoms. As we did not collect serial samples, we could not verify the average amount of days for seroconversion to take place. Some authors recommend that the single collection should occur at least 21 days after the onset of symptoms, so seroconversion is observed (Deeks, et al., Cochrane Database Syst Rev. 2020). In our sample, 4 donors (5%) collected the samples on the 21st day after the symptom onset. Of these, 3 had seroconversion, 2 with IgM and IgG, 1 with IgG and 1 with reagent IgM. The values suggest that the subjects who could donate CP were those that presented a longer time interval between the onset of symptoms and the blood sample collection, in comparison to those who could not (p=0,012 and 0,409, respectively). The median of days between symptom onset and serology testing was also higher in the non-eligible group. Besides, the eligible group had a higher average concentration of IgM and IgG compared to the non-eligible one. In conclusion, regarding the serological criteria, about 25% of the studied population could not donate CP. Although a single serology sample collection after the 21st day of symptom onset is recommended, only 1 candidate did not show seroconversion. Disclosures No relevant conflicts of interest to declare.

mSphere of Influence: Frameshift—a Vision for Human Microbiome Research

ABSTRACT Ariangela J. Kozik studies the respiratory microbiome as it relates to asthma. In this mSphere of Influence article, she reflects on how two papers, “Time’s up to adopt a biopsychosocial model to address racial and ethnic disparities in asthma outcomes” (E. C. Matsui, A. S. Adamson, and R. D. Peng, Allergy Clin Immunol 143:2024–2025, 2019, https://doi.org/10.1016/j.jaci.2019.03.015) and “Health disparities and the microbiome” (K. Findley, D. R. Williams, E. A. Grice, and V. L. Bonham, Trends Microbiol 24:847–850, 2016, https://doi.org/10.1016/j.tim.2016.08.001), shape her approach to human microbiome research.

BCG Moreau Vaccine Safety Profile and NK Cells—Double Protection Against Disseminated BCG Infection in Retrospective Study of BCG Vaccination in 52 Polish Children with Severe Combined Immunodeficiency

Objectives The aim of the study was to estimate the rate of adverse reactions to live BCG Moreau vaccine, manufactured by Biomed in Poland, in severe combined immunodeficiency (SCID) patients. Material The profiles of 52 SCID patients vaccinated at birth with BCG, hospitalized in Children’s Memorial Health Institute, Warsaw (CMHI), in the years 1980–2015 were compared with those of 349 BCG-vaccinated SCID patients from other countries analyzed by Beatriz E. Marciano et al. in a retrospective study (Marciano et al. J Allergy Clin Immunol. 2014;133(4):1134–1141). Results Significantly less disseminated BCG infections (10 out of 52 SCID, 19%) occurred in comparison with Marciano study—119 out of 349, 34% (p = 0.0028), with no death in patients treated with SCID anti-TB drug, except one in lethal condition. In our study, disseminated BCG infection was observed only in SCID with T-B+NK- phenotype and significantly lower NK cell counts (p = 0.0161). NK cells do not influence on the frequency of local BCG reaction. A significantly higher number of hematopoietic stem cells transplantations (HSCT) were performed in CMHI study (p = 0.0001). Anti-TB treatment with at least two medicines was provided. Conclusion The BCG Moreau vaccine produced in Poland, with well-documented genetic characteristics, seems to be safer than other BCG substrains used in other regions of the world. Importantly, NK cells seem to play a role in protecting SCID patients against disseminated BCG complications, which NK- SCID patients are more prone to. HSCT and TB therapy could be relevant due to the patients’ survival and the fact that they protect against BCG infection.

Icatibant is not helpful for the treatment of ACE inhibitor-induced angioedema

<p>A critical appraisal and clinical application of Sinert R, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. <em>J Allergy Clin Immunol Pract</em>. 2017; 5(5): 1402-1409. doi: <a href="https://doi.org/10.1016/j.jaip.2017.03.003">10.1016/j.jaip.2017.03.003</a>.</p>

Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions

Previous studies have demonstrated that resistance to infection is decreased in Swiss Webster female mice maintained in the hindlimb-unloading model (Aviles H, Belay T, Fountain K, Vance M, and Sonnenfeld G. J Appl Physiol 95: 73–80, 2003; Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 110: 262–268, 2002). This is a model of some of the aspects of spaceflight conditions, including lack of load bearing on hindlimbs and a fluid shift to the head. Active hexose correlated compound (AHCC), extracted from Basidiomycete mushrooms, has been shown to induce enhancement of immune responses, including enhanced natural killer activity. In the present study, AHCC was orally administered to mice to determine whether the treatment could decrease immunosuppression and mortality of mice maintained in the hindlimb-unloaded model and infected with Klebsiella pneumoniae. The results of the present study showed that administration of AHCC by gavage for 1 wk (1 g/kg body wt) before suspension and throughout the 10-day suspension period yielded significant beneficial effects for the hindlimb-unloaded group, including 1) decreased mortality, 2) increased time to death, and 3) increased ability to clear bacteria. The results suggest that AHCC can decrease the deleterious effects of the hindlimb-unloading model on immunity and resistance to infection.

Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions

It has been reported that spaceflight conditions alter the immune system and resistance to infection [Belay T, Aviles H, Vance M, Fountain K, and Sonnenfeld G. J Allergy Clin Immunol 170: 262–268, 2002; Hankins WR and Ziegelschmid JF. In: Biomedical Results of Apollo. Washington, DC: NASA, 1975, p. 43–81 . (NASA Spec. Rep. SP-368)]. Ground-based models, including the hindlimb-unloading model, have become important tools for increasing understanding of how spaceflight conditions can influence physiology. The objective of the present study was to determine the effect of hindlimb unloading on the susceptibility of mice to Pseudomonas aeruginosa infection. Hindlimb-unloaded and control mice were subcutaneously infected with 1 LD50 of P. aeruginosa. Survival, bacterial organ load, and antibody and corticosterone levels were compared among the groups. Hindlimb unloading had detrimental effects for infected mice. Animals in the hindlimb-unloaded group, compared with controls, 1) showed significantly increased mortality and reduced time to death, 2) had increased levels of corticosterone, and 3) were much less able to clear bacteria from the organs. These results suggest that hindlimb unloading may induce the production of corticosterone, which may play a critical role in the modulation of the immune system leading to increased susceptibility to P. aeruginosa infection.

SURVEY OF FATALITIES FROM SKIN TESTING AND IMMUNOTHERAPY, 1985 TO 1989

Purpose of the Study. This study was a survey of fatalities from skin testing and immunotherapy performed by the American Academy of Allergy and Immunology (AAAI) for the period 1985 to 1989. (An initial study dating from 1959 to 1984 was reported by Lockey in 1987 (J Allergy Clin Immunol. 1987;79:660).) Methods. Questionnaires were sent to all members of the AAAI and ACAI requesting reports of any fatalities known to have been associated with skin testing or immunotherapy. An extensive clinical history of these fatalities was obtained and reviewed. Findings. Seventeen fatalities were associated with immunotherapy from 1985 to 1989 (in this same period, no fatalities were reported with skin testing). The mean age of the patients who died was 36 years; 69% were female. Of note, four patients were 18 years of age or younger. Of the patients who died, 76% had asthma, and most were reported to have had factors associated with increased severity. High allergic sensitivity was reported by 71%; 36% reported prior systemic reactions. Additional factors associated with fatalities were: changing to a new vial of extract (5), dosing error or inappropriate dose adjustment (5), allergen season (3), symptoms before injection (4), no waiting after injection (2), and home injection (1). The authors note that the annual fatality rate for administration of allergen extracts in the United States remains low: one fatality per 2 million doses, but that additional educational efforts to reduce the fatality rate are needed. Reviewer's Comments. The observation that 76% of the fatalities occurred in patients with asthma is similar to the observation that patients who die from stinging insect hypersensitivity and food-induced anaphylaxis are more likely asthmatics.