Risk factors for long coronavirus disease 2019 (long COVID) among healthcare personnel, Brazil, 2020-2022.

OBJECTIVE: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP). METHODS: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. RESULTS: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID. CONCLUSIONS: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

Corrigendum: Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: a case report.

[This corrects the article DOI: 10.3389/fmed.2022.1008585.].

Cognitive impairment in long-COVID and its association with persistent dysregulation in inflammatory markers.

Objective: To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19. Methods: We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive battery, as well as a psychiatric, clinical and laboratory evaluation. A large set of inferential statistical methods was used to predict potential variables associated with any long-term cognitive impairment, with a focus on a panel of 28 cytokines and other blood inflammatory and disease severity markers. Results: Concerning the subjective assessment of cognitive performance, 36.1% reported a slightly poorer overall cognitive performance, and 14.6% reported being severely impacted, compared to their pre-COVID-19 status. Multivariate analysis found sex, age, ethnicity, education, comorbidity, frailty and physical activity associated with general cognition. A bivariate analysis found that G-CSF, IFN-alfa2, IL13, IL15, IL1.RA, EL1.alfa, IL45, IL5, IL6, IL7, TNF-Beta, VEGF, Follow-up C-Reactive Protein, and Follow-up D-Dimer were significantly (p<.05) associated with general cognition. However, a LASSO regression that included all follow-up variables, inflammatory markers and cytokines did not support these findings. Conclusion: Though we identified several sociodemographic characteristics that might protect against cognitive impairment following SARS-CoV-2 infection, our data do not support a prominent role for clinical status (both during acute and long-stage of COVID-19) or inflammatory background (also during acute and long-stage of COVID-19) to explain the cognitive deficits that can follow COVID-19 infection.

Monitoring Multiple U.S. Government-Supported Covid-19 Vaccine Trials

Operation Warp Speed was a partnership created to accelerate the development of Covid-19 vaccines. The National Institutes of Health oversaw one data and safety monitoring board to review/monitor all Operation Warp Speed trials. This article describes the challenges faced in monitoring these trials and provides ideas for future similar endeavors.

ZnO-Based Electrochemical Immunosensor to Assess Vaccine-Induced Antibody-Mediated Immunity against Wild-Type and Gamma SARS-CoV-2 Strains.

The evaluation of serological responses to COVID-19 is crucial for population-level surveillance, developing new vaccines, and evaluating the efficacy of different immunization programs. Research and development of point-of-care test technologies remain essential to improving immunity assessment, especially for SARS-CoV-2 variants that partially evade vaccine-induced immune responses. In this work, an impedimetric biosensor based on the immobilization of the recombinant trimeric wild-type spike protein (S protein) on zinc oxide nanorods (ZnONRs) was employed for serological evaluation. We successfully assessed its applicability using serum samples from spike-based COVID-19 vaccines: ChAdOx1-S (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech). Overall, the ZnONRs/ spike-modified electrode displayed accurate results for both vaccines, showing excellent potential as a tool for assessing and monitoring seroprevalence in the population. A refined outcome of this technology was achieved when the ZnO immunosensor was functionalized with the S protein from the P.1 linage (Gamma variant). Serological responses against samples from vaccinated individuals were acquired with excellent performance. Following studies based on traditional serological tests, the ZnONRs/spike immunosensor data reveal that ChAdOx1-S vaccinated individuals present significantly less antibody-mediated immunity against the Gamma variant than the BNT162b2 vaccine, highlighting the great potential of this point-of-care technology for evaluating vaccine-induced humoral immunity against different SARS-CoV-2 strains.

Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape.

Introduction: Considering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information. Methods: We used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals. Results: We found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity. Discussion: This peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Follow-up of young adult monozygotic twins after simultaneous critical coronavirus disease 2019: A case report

Background The influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins. Case presentation and methods Here we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing. Conclusion Although the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.

Time-dependent contraction of the SARS-CoV-2-specific T-cell responses in convalescent individuals.

Background: Adaptive immunity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is decisive for disease control. Delayed activation of T cells is associated with a worse outcome in coronavirus disease 2019 (COVID-19). Although convalescent individuals exhibit solid T-cell immunity, to date, long-term immunity to SARS-CoV-2 is still under investigation. Objectives: We aimed to characterize the specific T-cell response on the basis of the in vitro recall of IFN-γ-producing cells to in silico-predicted peptides in samples from SARS-CoV-2 convalescent individuals. Methods: The sequence of the SARS-CoV-2 genome was screened, leading to the identification of specific and promiscuous peptides predicted to be recognized by CD4+ and CD8+ T cells. Next, we performed an in vitro recall of specific T cells from PBMC samples from the participants. The results were analyzed according to clinical features of the cohort and HLA diversity. Results: Our results indicated heterogeneous T-cell responsiveness among the participants. Compared with patients who exhibited mild symptoms, hospitalized patients had a significantly higher magnitude of response. In addition, male and older patients showed a lower number of IFN-γ-producing cells. Analysis of samples collected after 180 days revealed a reduction in the number of specific circulating IFN-γ-producing T cells, suggesting decreased immunity against viral peptides. Conclusion: Our data are evidence that in silico-predicted peptides are highly recognized by T cells from convalescent individuals, suggesting a possible application for vaccine design. However, the number of specific T cells decreases 180 days after infection, which might be associated with reduced protection against reinfection over time.

Worsening of asthma control after COVID-19

Background SARS-CoV-2 enters lung cells via angiotensin-converting enzyme 2 (ACE2) receptor. Several studies suggest that interleukin-13, an important cytokine involved in T2 inflammation, reduces ACE2 expression, and therefore, asthma would not be a significant risk factor for the development of severe COVID-19. However, several asthma-related risk factors should be valued during the concurrent occurrence of asthma and COVID-19. The purpose of this study was to compare the evolution of asthma in patients who had COVID-19 with those who did not have the disease. Methods This was an observational and retrospective study involving asthmatic patients followed up at a tertiary center. Patients were assessed for severity of asthma, atopy, comorbidities, and COVID-19. Worsening of asthma was considered when, during the period of Sept 2020 to Oct 2021, patients referred an increasing of asthma symptoms and a need to increment their maintenance therapy. Results This study included 208 asthmatic patients, the mean age was 52.75 years, 79.81% were atopic asthmatics, and 59 (28.37%) had laboratory-confirmed coronavirus disease. Of all patients infected with the SARS-CoV-2, eleven (18.64%) needed hospitalization and required oxygen supply with an O2 mask. Comparing the worsening of asthma between patients who had COVID-19 and those who had not the disease, there was a statistically significant difference, 33.90 vs. 11.41%, respectively (p < 0.001). There was no statistical significance regarding asthma comorbidities. Conclusion This study assessed a group of asthmatic patients that had COVID-19, and that although the respiratory symptoms related to COVID-19 were mild to moderate, a subgroup of these asthmatic patients evolved with a chronic worsening of their asthma requiring an increment in asthma medication to control the disease.

Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein.

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.

COVID19: uncovering interindividual variability for tailoring appropriate therapeutic interventions / COVID19: a variabilidade individual da resposta imunoinflamatória

The severity of SARS-CoV2 infection, Covid19 disease, should account for the diversity of human individual immu-noinflammatory responses. Serum immunological markers during Covid19 illness may lead to individualized thera-peutics with better outcomes. Efficient treatment for Covid19 may require: 1) early disease detection, 2) combined drug therapy for 3) targeting the virus replication cycle, and 4) individualized drug treatment for specific immu-noinflammatory human profile responses administered in a 5) timely manner. Covid19 is unlikely to be the last emergent human disease with fast pandemic potential. Gathering knowledge on the individual human host profiles of immunoinflammatory responses is an opportunity that could lead us to understand individual differences in re-sponse to infection at the individual and population level, paving the way to faster, more efficient strategies to tack-le upcoming infectious diseases. This is a position paper based on an integrative non-exhaustive literature revision (AU)

A diversidade das respostas imunoinflamatórias individuais humanas muito provavelmente tem papel na gravidade da doença Covid19 causada pela infecção pelo vírus SARS-CoV2. Marcadores imunológicos séricos durante a Covid19 po-dem guiar a escolha de terapias individualizadas com melhores resultados. O tratamento eficiente para Covid19 pode exigir: 1) detecção precoce da doença, 2) terapia medicamentosa combinada com alvo ao 3) ciclo de replicação do ví-rus e 4) terapia anti-inflamatória individualizada para perfis de respostas imunoinflamatórias humanas, administradas em tempo hábil. É improvável que a Covid19 seja a última doença humana emergente com potencial de alastramento veloz pandêmico. Reunir conhecimento sobre perfis de respostas imunoinflamatórias individuais dos hospedeiros humanos é uma oportunidade ímpar que pode nos levar a entender as diferenças dessas respostas entre indivíduos, abrindo caminho para estratégias terapêuticas mais rápidas e eficientes no combate à futuras epidemias (AU)

Federation of Clinical Immunology Societies Goes South 2021: advanced course on molecular and cellular translational immunology.

The Federation of Clinical Immunology Societies (FOCIS) regularly organizes scientific meetings to foster advances in immunology. A new event of this type is FOCIS Goes South, a course and workshop organized by FOCIS Centers of Excellence (FCEs) from across Latin America, which consists of a course on advanced immunology, a flow cytometry workshop and seminars on cutting-edge research in autoimmunity, tolerance, cancer, infectious diseases and vaccines. Due to the COVID-19 pandemic, the second version of FOCIS Goes South, hosted by the Millennium Institute on Immunology and Immunotherapy in Chile, took place virtually from 15 to 18 November 2021, with more than 950 registered participants. The present article summarizes the key findings and insights discussed at FOCIS Goes South 2021.