Establishment of an infrastructure for rapid pandemic response at the Frederick National Laboratory

The sudden onset of the 2019 SARS-CoV-2 pandemic required agile development of standards and efficient validation of assays to assess prevalence of infection as well as immune responses to infection and vaccination. Leveraging their experience in HPV serology and standards, the Vaccine, Immunity and Cancer Directorate (VICD) at the Frederick National Laboratory for Cancer Research (FNCLR) pivoted to address this unmet need in SARS-Co-V2 serology clinical testing and research. This standardization effort required the collection and processing of large volumes of blood from SARS-Co-V2 infected and uninfected individuals into serum and peripheral blood mononuclear cells (PBMCs). Collaborations with specimen collection sites across the United States were established. Following qualification for anti-SARS-CoV-2 IgG and IgM levels in independent laboratories, VICD assembled reference evaluation panels, which were used to assist the FDA's performance evaluation of commercial assays submitted for EUA approval. To date, 185 different shipments of the standard or validation panel have been sent to both domestic and international labs. These materials are also available to the SARS-CoV-2 serology community for assay calibration and performance evaluation which greatly facilitates assay data harmonization. In addition, the NCI Serological Sciences Network (SeroNet) was born from this initiative and expertise, resulting in the establishment of Capacity Building Centers (CBCs) for sample collection from different healthy, cancer and immunocompromised cohorts at Mount Sinai, Arizona State University, the University of Minnesota, and Northwell Feinstein. The NCI and FNLCR simultaneously collaborated to develop a network of investigators focused on advancing research on the immune response to SARS-CoV-2 infection and vaccination among diverse and vulnerable populations, including cancer patients. Their research has resulted in over 326 peer-reviewed publications. The CBC's have enrolled patients in longitudinal studies, resulting in a centralized collection of annotated, well characterized serum, PBMCs and clinical data. Numerous cancer cohorts, but predominantly Multiple Myeloma, are included. Furthermore, technology development was supported at the CBC's. Based upon this success, the VICD in collaboration with NCI is pursuing an even more innovative effort in pandemic preparedness to establish a Center for Serology and Data Emergency Preparedness (CESDEP);a global network able to activate and pivot to address pandemic-level threats, while continuing to expand the development of immunological assays that can inform clinical decisions for cancer and other immunocompromised patients.

Trajectories of respiratory recovery after severe SARSCoV-2 infection (RE2COVERI): a pragmatic, longitudinal cohort study

Background: Severe COVID-19 survivors may exhibit functional impairment, radiological sequelae and persistent symptoms at short to mid-term follow-up. Aim(s): To determine the trajectories of respiratory recovery after severe COVID-19, and factors that could influence it. Method(s): Prospective, multicentre, longitudinal cohort study of adult patients hospitalized for severe COVID-19 (LOS >= 7d, oxygen flow >= 3L), evaluated at 3 months from hospital discharge with conditional follow-up at 6 and 12 months. Result(s): 486 participants from 13 French hospitals were included (median age 61y;female sex 27%): 173 needed oxygen only, 96 required non invasive ventilatory support and 217 were intubated. 454 (93%) patients were evaluated at 3 months, whereas 294 (60%) and 163 (34%) were followed up at 6 and 12 months, respectively. At 3- months assessment, a restrictive lung defect, an altered diffusion capacity and significant radiological abnormalities were observed in 33%, 71% and 57% of the cases, respectively. In case of extended follow-up, FVC (% pred.) increased by 4 points at M6 and by 7 points at M12, in mean;DLCO (% pred.) by 5 and 7 points, respectively. Age, sex, obesity, immunodepression, chronic cardiac or respiratory disease, initial extension of pneumonia and mechanical ventilation over 14 days were associated with lung function at 3 months but not with respiratory trajectories from this time point. Conclusion(s): A systematic follow-up seems justified after a severe COVID-19, especially in patients with extensive radiological lesions during acute illness. Pulmonary function and residual radiological abnormalities may improve up to 1-year after hospital discharge. Covid-19 A.

Trajectoires de recuperation respiratoire apres une infection COVID-19 severe (RE2COVERI) : resultats d'une etude pragmatique de suivi jusqu'a 1 an

Introduction: Les survivants de formes severes a critiques de COVID-19 peuvent presenter des sequelles fonctionnelles et radiologiques et des symptomes persistants a distance de l'episode aigu justifiant un suivi prolonge. L'objectif de l'etude est de determiner les trajectoires de recuperation respiratoire apres un COVID-19 severe, et les facteurs qui pourraient l'influencer. Methodes: Etude de cohorte prospective, multicentrique, longitudinale de patients adultes hospitalises pour COVID-19 severe (duree d'hospitalisation >= 7 j, debit d'oxygene >= 3 L) ou critique (intubation), evalues (clinique, TDM, EFR, test de marche, questionnaires de symptomes et de qualite de vie) 3 mois apres leur sortie de l'hopital, avec un suivi ulterieur conditionnel a 6 et 12 mois. Resultats: Au total, 486 participants ont ete inclus dans 13 hopitaux francais (age median : 61 ans;sexe feminin : 27 %) : 173 avaient necessite de l'oxygene seul, 96 un support ventilatoire non invasif (CPAP, OHD ou VNI) et 217 avaient ete intubes. Au total, 454 patients (93 %) ont ete evalues a 3 mois, 294 (60 %) et 163 (34 %) ont ete suivis respectivement jusqu'a 6 et 12 mois. Une dyspnee d'effort, un syndrome restrictif, un trouble de la diffusion et des anomalies radiologiques significatives ont ete observees respectivement dans 62 %, 33 %, 71 % et 57 % des cas a M3. En cas de suivi prolonge, la DLCO (% theo.) et la CVF (% theo.) augmentaient en moyenne de +4 points a M6 et respectivement de +6 points et +7 points a M12. Le sexe, l'indice de masse corporelle, les maladies cardiovasculaires ou respiratoires chroniques, l'immunodepression, l'etendue de la pneumonie pendant la phase aigue de la maladie et la duree prolongee (> 14 j) de ventilation mecanique invasive etaient associes a la DLCO a M3, mais pas a sa trajectoire ulterieure. Parmi 476 patients (97,9 %) ayant eu au moins une TDM thoracique au cours du suivi, 196 (41 %) avaient des sequelles significatives sur leur derniere imagerie. Le sexe, l'etendue de la pneumonie a la phase aigue, la duree de la ventilation mecanique invasive et la DLCO a M3 etaient independamment associes au resume des composantes physiques du SF-36, tandis que seul l'age etait associe au resume des composantes mentales du SF-36. Conclusion(s): Bien que la fonction respiratoire s'ameliore et que les anomalies radiologiques residuelles regressent jusqu'a 1 an apres l'episode aigu, une proportion importante des survivants de formes severes ou critiques de COVID-19 ont des sequelles radiologiques et fonctionnelles importantes et des symptomes residuels pouvant affecter leur qualite de vie et justifiant un tel suivi. Copyright © 2022

SARS-COV-2 INFECTION AND VACCINATION PATTERNS DETERMINE LONG-TERM ANTIBODY RESPONSES IN NURSING HOME RESIDENTS: DATA FROM NH-COVAIR

Background: Older Nursing Home Residents (NHRs) are at greatest risk of morbidity and mortality from SARS-CoV-2, particularly in the context of both waning vaccine efficacy and the emergence of Variants-of-Concern (VOCs). However, the determinants of long-term vaccine-induced protective antibody responses are yet to be determined in this group. Methods: NH-COVAIR recruited older NHRs for comprehensive clinical and frailty (NH-FRAIL) assessment. Blood samples were obtained pre-vaccination, at 6-weeks and 6-months following primary vaccination and 6-months following booster vaccination. Antibody titres were measured using both an electrochemiluminescence assay and a custom bead-based array (Luminex™) to measure antibody titre and avidity for Wuhan strain/major VOC antigens. Stepwise adjusted linear regression (log-transformed) assessed longitudinal determinants of vaccine-induced antibody responses. Results: Of 86 participants (81.1 ± 10.8 years;65% female), just under half (45.4%) had evidence of previous SARS-CoV-2 infection. All NHRs mounted a significant antibody-response to vaccination at 5 weeks followed by a significant decrease in antibody titre by 6 months. Previous SARS-CoV-2 infection was the strongest predictor of antibody waning at all timepoints (β: 3.59;2.89, 4.28;P < 0.001 for 6-months). Independent of infection history, both age (β: –0.05;–0.08, –0.02;p<0.001) and frailty (β: –0.22;–0.33, –0.11;p<0.001) were associated with faster antibody waning at 6-months. Cross-reactivity and avidity were significantly lower for Beta (B.1.351) and Gamma (P.1) VOC strains (all p<0.001). Additionally, there was faster antibody waning and significantly reduced antibody avidity to Beta and Gamma VOCs in SARS-CoV-2 naïve NHRs. Conclusion: Older NHRs are capable of mounting protective antibody responses to SARS-CoV-2 vaccination. Responses were more durable, with a greater cross-reactivity to and avidity for VOCs in those with previous SARS-CoV-2 infection. Increasing age and greater frailty in NHRs was associated with faster antibody waning. Our findings support ongoing serological surveillance and use of additional vaccine doses in older NHRs, particularly in those without previous SARS-CoV-2 exposure.

First outbreak of COVID-19 in Cuban pediatric patients

Introduction: Until June 11, 2020, 10.4% of the total positive cases of SARS-CoV-2 in Cuba corresponded to patients under 18 years of age. Clinical manifestations in children affected by SARS-CoV-2 are usually mild and few deaths occur compared to other age groups. Objective: Characterize from the clinical, epidemiological and immunological point of view the Cuban pediatric patients infected by SARS-CoV-2 until June 11, 2020. Methods: Observational, cross-sectional study in 137 pediatric patients infected with COVID-19, who were epidemiologically discharged. Results: 56.9 % of the patients presented asymptomatic form of the disease. Havana was the most affected province and the average age was 11.3 years. The most frequent symptoms were: fever, cough and diarrhea and occurred more frequently in patients with black skin (Odd Ratio = 3.40). Antibody concentrations for tetanus and Haemophilus influenzae type b provided protection in 92.7% to 100% of children, while for diphtheria 24.8% had no reliable protection. Of the symptomatic patients, 62.5% developed specific total antibodies against SARS-CoV-2. Conclusions: Patients in pediatric ages can contribute significantly to the transmission dynamics. Reliable protection for specific vaccines, the development of total antibodies to SAR-Cov-2, and general favorable prognosis without complications require continued research to identify biological and immunological differences between children and other age groups. © 2021, Editorial Ciencias Medicas. All rights reserved.

Clinical-epidemiological characteristics of patients affected by COVID-19 residing in Havana

Introduction: Havana city was the most complex territory at the national level facingthe first outbreak of COVID-19. Its condition of capital, the population density, the limited geographical delimitation between its municipalities, the high inter-municipal and inter-provincial flow of people, added to the fact that it is the province that receives the largest number of travelers from abroad, conferred particularities on this territory. Objective: To determine the main clinical-epidemiological characteristics of patients affected by COVID-19 living in Havana. Methods: An observational, analytical, cross-sectional study was carried out. The sample contained 431 patients, older than one year, with epidemiological discharge from the SARS-CoV-2 infection. To collect information, a questionnaire was applied through an interview. Results: The average age of the sample was 45 years. More than half of the cases evolved in a symptomatic way (not serious or serious). Fever was the most frequent clinical manifestation. The individuals included in the sample, with blood group O or with a background of asthma, showed less risk of presenting symptomatic forms of the disease. Conclusions: The results suggest that age is the main risk factor for developing symptomatic forms (not severe or severe) of COVID-19. On the contrary, blood group O and a history of asthma are protective factors for these forms of clinical evolution. © 2021, Editorial Ciencias Medicas. All rights reserved.

The role of tumor necrosis factor alpha − 308A > G polymorphism on the clinical states of SARS-CoV-2 infection

Background: Tumor necrosis factor-alpha (TNFɑ) is a cytokine that manages the host defense mechanism, which may play a role in the pathogenesis of COVID-19 patients. Several single-nucleotide polymorphisms, described in the promoter region of the TNFα gene, have a significant role on its transcriptional activity. These include the − 308A > G polymorphism which increases the TNFα levels with the expression of the A allele. The aim of this study was to explore whether the TNFα.− 308A > G polymorphism affects the clinical state of COVID-19 patients. The study included a total of 1028 individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which were distributed in 3 groups: asymptomatic, mild symptomatic and severe symptomatic patients. The amplification-refractory mutation system was used to determine the genotype of the TNFα.− 308A > G polymorphism. Results: Results show a higher tendency of being asymptomatic in individuals carrying the GG genotype (336 of 411;OR 1.24, 95% CI 0.91–1.70). The development of a severe form of SARS-CoV-2 infection was not found in subjects with the A allele compared to those with the G allele (OR 0.96, 95% CI 0.51–1.79), except in the eastern region of the country where the risk increased (OR 4.41, 95% CI 1.14–17.05). However, the subjects carrying the A allele had a higher chance of developing symptoms (OR 1.24, 95% CI 0.91–1.70) compared to those with the G allele. Conclusion: The TNFα.− 308A allele has an influence on developing symptoms of COVID-19 in Cuban patients, and that it particularly increases the risk of presenting severe forms of the disease in the eastern region of the country. © 2022, The Author(s).