Search

Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19)., Methods: This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity., Results: aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways., Conclusions: Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers., Competing Interests: Potential conflicts of interest . S. A. has received honoraria for lectures and educational events from Gilead, AbbVie, MSD, and Biogen; and reports grants from Gilead and AbbVie. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection., Methods: In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARS-CoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659)., Findings: The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication., Interpretation: The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies., Funding: The present studies were supported by grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and Karolinska Institutet., Competing Interests: Declaration of interests PB has received honoraria from Takeda for educational lectures not directly relevant to this work. SM has received honoraria from Celgene/BMS, Novartis, Gilead/Kite, DNA Prime for lectures and educational events and as a member and/or head of data safety monitoring boards from Miltenyi and Immunicum not directly relevant to this work. CIES has received financial support from Moderna for work not directly relevant to this work. KL has received financial support from Moderna for work not directly relevant to this work. PL has received grants from Pfizer, MSD, and personal fees from Takeda, AiCuris, and OctaPharma, not directly relevant to the submitted work. SA has received honoraria for lectures and educational events, from Gilead, AbbVie, MSD, Biogen and Netdoktor, not directly related to this work, and reports grants from the Swedish Research Council on COVID-19 vaccination. HGL received honoraria from Sanofi for consultation not relevant to this work, and has served on the UK-CIC Oversight Committee, had led the Karolinska Institutet COVID-19 vaccine group, and is on the scientific advisory group for the International Vaccine Institute not directly relevant to this work, and reports grants from Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and Karolinska Institutet for studies on COVID-19 and COVID-19 vaccination. All other authors declare no potential or actual conflict of interest to the work presented in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite intensive research since the emergence of SARS-CoV-2, it has remained unclear precisely which components of the early immune response protect against the development of severe COVID-19. Here, we perform a comprehensive immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples obtained during the acute phase of infection with SARS-CoV-2. We find that soluble and transcriptional markers of systemic inflammation peak during the first week after symptom onset and correlate directly with upper airways viral loads (UA-VLs), whereas the contemporaneous frequencies of circulating viral nucleocapsid (NC)-specific CD4 + and CD8 + T cells correlate inversely with various inflammatory markers and UA-VLs. In addition, we show that high frequencies of activated CD4 + and CD8 + T cells are present in acutely infected nasopharyngeal tissue, many of which express genes encoding various effector molecules, such as cytotoxic proteins and IFN-γ. The presence of IFNG mRNA-expressing CD4 + and CD8 +  T cells in the infected epithelium is further linked with common patterns of gene expression among virus-susceptible target cells and better local control of SARS-CoV-2. Collectively, these results identify an immune correlate of protection against SARS-CoV-2, which could inform the development of more effective vaccines to combat the acute and chronic illnesses attributable to COVID-19., (© 2023. The Author(s).)

Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4 + and CD8 + T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4 + T cells and robust expansions of oligoclonal effector-memory CD45RA + CD8 + T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes., Competing Interests: Declaration of interests M.B. is a consultant for Oxford Immunotec. A.S. is a consultant for Gritstone, Flow Pharma, Arcturus, Immunoscape, CellCarta, Oxford Immunotech, and Avalia. A.S. has filed for patent protection for various aspects of T cell epitope and vaccine design work., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Immunodeficient individuals often rely on donor-derived immunoglobulin (Ig) replacement therapy (IGRT) to prevent infections. The passive immunity obtained by IGRT is limited and reflects the state of immunity in the plasma donor population at the time of donation. The objective of the current study was to describe how the potential of passive immunity to SARS-CoV-2 in commercial off-the-shelf Ig products used for IGRT has evolved during the pandemic. Samples were collected from all consecutive Ig batches (n = 60) from three Ig producers used at the Immunodeficiency Unit at Karolinska University Hospital from the start of the SARS-CoV-2 pandemic until January 2022. SARS-CoV-2 antibody concentrations and neutralizing capacity were assessed in all samples. In vivo relevance was assessed by sampling patients with XLA (n = 4), lacking endogenous immunoglobulin synthesis and on continuous Ig substitution, for plasma SARS-CoV-2 antibody concentration. SARS-CoV-2 antibody concentrations in commercial Ig products increased over time but remained inconsistently present. Moreover, Ig batches with high neutralizing capacity towards the Wuhan-strain of SARS-CoV-2 had 32-fold lower activity against the Omicron variant. Despite increasing SARS-CoV-2 antibody concentrations in commercial Ig products, four XLA patients on IGRT had relatively low plasma concentrations of SARS-CoV-2 antibodies with no potential to neutralize the Omicron variant in vitro. In line with this observation, three out the four XLA patients had symptomatic COVID-19 during the Omicron wave. In conclusion, 2 years into the pandemic the amounts of antibodies to SARS-CoV-2 vary considerably among commercial Ig batches obtained from three commercial producers. Importantly, in batches with high concentrations of antibodies directed against the original virus strain, protective passive immunity to the Omicron variant appears to be insufficient., (© 2022. The Author(s).)

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant of concern (VOC) has destabilized global efforts to control the impact of coronavirus disease 2019 (COVID-19). Recent data have suggested that B.1.1.529 can readily infect people with naturally acquired or vaccine-induced immunity, facilitated in some cases by viral escape from antibodies that neutralize ancestral SARS-CoV-2. However, severe disease appears to be relatively uncommon in such individuals, highlighting a potential role for other components of the adaptive immune system. We report here that SARS-CoV-2 spike-specific CD4 + and CD8 + T cells induced by prior infection or BNT162b2 vaccination provide extensive immune coverage against B.1.1.529. The median relative frequencies of SARS-CoV-2 spike-specific CD4 + T cells that cross-recognized B.1.1.529 in previously infected or BNT162b2-vaccinated individuals were 84% and 91%, respectively, and the corresponding median relative frequencies for SARS-CoV-2 spike-specific CD8 + T cells were 70% and 92%, respectively. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4 + and CD8 + T cells were functionally and phenotypically similar in response to the ancestral strain or B.1.1.529. Collectively, our data indicate that established SARS-CoV-2 spike-specific CD4 + and CD8 + T cell responses, especially after BNT162b2 vaccination, remain largely intact against B.1.1.529., (© 2022. The Author(s).)

Corona disease 2019 (COVID-19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID-19 severity. However, several questions pertain with respect to the metabolome in COVID-19. We performed an in-depth assessment of 1129 unique metabolites in 27 hospitalized COVID-19 patients and integrated results with large-scale proteomic and immunology data to capture multiorgan system perturbations. More than half of the detected metabolic alterations in COVID-19 were driven by patient-specific confounding factors ranging from comorbidities to xenobiotic substances. Systematically adjusting for this, a COVID-19-specific metabolic imprint was defined which, over time, underwent a switch in response to severe acute respiratory syndrome coronavirus-2 seroconversion. Integration of the COVID-19 metabolome with clinical, cellular, molecular, and immunological severity scales further revealed a network of metabolic trajectories aligned with multiple pathways for immune activation, and organ damage including neurological inflammation and damage. Altogether, this resource refines our understanding of the multiorgan system perturbations in severe COVID-19 patients., (© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C + NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021-000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1 ., (© 2022. The Author(s).)

We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1-13 of the pandemic. Sixty patients (median age 71 y, range 43-97) were identified. Median CIRS was eight (4-20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1-6 vs 7-13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls., Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection., Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively., Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity., Funding: Knut and Alice Wallenberg Foundation, the Swedish Research Council, Nordstjernan AB, Region Stockholm, Karolinska Institutet, and organizations for PID/CLL-patients in Sweden., Competing Interests: Declaration of Competing Interest SM received honoraria via his institution from Celgene/BMS, Novartis, Gilead/Kite, DNA Prime for lectures and educational events and as a member and/or head of data safety monitoring boards from Miltenyi and Immunicum outside the submitted work. SH has been taking part in a COVID-19 Strategic Consultancy Group and a Virtual Advisory Board, not related to the current study. KL reports grants from Knut and Alice Wallenberg Foundation for this study. HGL reports grants from Knut and Alice Wallenberg Foundation and Nordstjernan AB for studies on COVID-19, and has served on the UK-CIC Oversight Committee, is leading the Karolinska Institutet COVID-19 vaccine group, and has served on several Karolinska Institutet COVID-19 Task force and Reference groups. PL reports grants from Pfizer, grants from MSD, grants and personal fees from Takeda, personal fees from AiCuris, personal fees from OctaPharma, outside the submitted work. SA has received honoraria for lectures and educational events, not related to this work, from Gilead, AbbVie, MSD, Biogen and Netdoktor, and reports grants from Knut and Alice Wallenberg Foundation for this study., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Cross-reactive CD4 + T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2–reactive CD8 + T cells. However, large numbers of memory CD8 + T cells reside in tissues, feasibly harboring localized SARS-CoV-2–specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19 (coronavirus disease 2019). We found that SARS-CoV-2–specific memory CD4 + T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2–specific memory CD8 + T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2–specific memory CD8 + T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus–specific memory CD8 + T cells, but were functionally less potent than other virus-specific memory CD8 + T cell responses. The presence of preexisting tissue-resident memory CD8 + T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.

Numerous assays evaluating serological and cellular responses have been developed to characterize immune responses against SARS-CoV-2. Serological assays are both cost- and time-effective compared to cellular assays, but cellular immune responses may provide a diagnostic value to determine previous SARS-CoV-2 infection in seronegative individuals. However, potential cross-reactive T cell responses stemming from prior encounters with human coronaviruses (HCoVs) may affect assay specificity. In this study, we evaluated the specificity and sensitivity of a SARS-CoV-2 IFN-γ Release Assay (IGRA) based on the FluoroSpot method employing commercially available SARS-CoV-2-specific peptide pools, as well as an in-house designed SARS-CoV-2 peptide pool restricted to 5 amino acid stretches or less aligning with endemic HCoVs. Blood samples were obtained from healthcare workers (HCW) 5-6 months post SARS-CoV-2 spike (S) IgG and nucleocapsid (N) IgG dual seroconversion (n = 187) and HCW who had been S IgG and N IgG dual seronegative at repeated occasions, including the current sampling time point (n = 102). In addition, samples were obtained 4 to 5 months post infection from 55 polymerase chain reaction (PCR)-confirmed COVID-19 patients. Assay specificity and sensitivity were calculated with serology as a reference standard for HCW. The in-house generated peptide pool displayed a specificity of 96.1%, while the commercially available peptide pools displayed specificities of 80.4% and 85.3%, respectively. Sensitivity was higher in a cohort of previously hospitalized COVID-19 patients (96.4% and 84.0% for the commercially available peptide pools and 92.7% for the in-house generated peptide pool) compared to the HCW cohort (92.0% and 66.8% for the commercially available peptide pools and 76.0% for the in-house generated peptide pool). Based on these findings, the individual diagnostic value of T cell immune responses against SARS-CoV-2 currently appears to be limited but remain an important research tool ahead., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: PD is a paid employee of SciCross AB. SM is the Chief Development Officer of Ultimovacs AB and is the founder and board member of Immuneed AB, Vivologica AB and Strike pharma AB and holds stocks in the mentioned companies. MB is a consultant for Oxford Immunotec. ML and IL are founder and stock holders of Strike pharma AB. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Exceptional efforts have been undertaken to shed light into the biology of adaptive immune responses to SARS-CoV-2. T cells occupy a central role in adaptive immunity to mediate helper functions to different arms of the immune system and are fundamental to mediate protection, control, and clearance of most viral infections. Even though many questions remain unsolved, there is a growing literature linking specific T cell characteristics to differential COVID-19 severity and vaccine outcome. In this review, we summarize our current understanding of CD4 + and CD8 + T cell responses in acute and convalescent COVID-19. Further, we discuss the T cell literature coupled to pre-existing immunity and vaccines and highlight the need to look beyond blood to fully understand how T cells function in the tissue space., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tremendous progress has been made in understanding the role of T cell immunity in acute and convalescent COVID-19 infection. Here we shed light on the "known unknowns" of pre-existing and acquired T cell responses in relation to acute and convalescent SARS-CoV-2 infection., (Copyright © 2020, American Association for the Advancement of Science.)

T cells are critical for immune protection against severe COVID-19, but it has remained unclear whether repeated exposure to SARS-CoV-2 antigens delivered in the context of vaccination fuels T cell exhaustion or reshapes T cell functionality. Here, we sampled convalescent donors with a history of mild or severe COVID-19 before and after SARS-CoV-2 vaccination to profile the functional spectrum of hybrid T cell immunity. Using combined single-cell technologies and high-dimensional flow cytometry, we found that the frequencies and functional capabilities of spike-specific CD4+ and CD8+ T cells in previously infected individuals were enhanced by vaccination, despite concomitant increases in the expression of inhibitory receptors such as PD-1 and TIM3. In contrast, CD4+ and CD8+ T cells targeting non-spike proteins remained functionally static and waned over time, and only minimal effects were observed in healthy vaccinated donors experiencing breakthrough infections with SARS-CoV-2. Moreover, hybrid immunity was characterized by elevated expression of IFN-γ, which was linked with clonotype specificity in the CD8+ T cell lineage. Collectively, these findings identify a molecular hallmark of hybrid immunity and suggest that vaccination after infection is associated with cumulative immunological benefits over time, potentially conferring enhanced protection against subsequent episodes of COVID-19.

Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In highresponders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited. [ABSTRACT FROM AUTHOR]

The Karolinska KI/K COVID‐19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS‐CoV‐2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS‐CoV‐2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient‐groups as they presented with moderate and severe COVID‐19 disease. The present Resource Article describes how the Karolinska KI/K COVID‐19 Immune Atlas allows scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS‐CoV‐2 infection in an online setting. [ABSTRACT FROM AUTHOR]

Purpose: Limited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the results from vaccinating a single-center cohort of patients with common variable immunodeficiency (CVID). Methods: In a prospective, open-label clinical trial, 50 patients with CVID and 90 age-matched healthy controls (HC) were analyzed for SARS-CoV-2 spike antibody (Ab) production after one or two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Additionally, in selected patients, SARS-CoV-2 spike-specific T-cells were assessed. Results: A potent vaccine-induced anti-spike–specific IgG Ab response was observed in all the HC. In contrast, only 68.3% of the CVID patients seroconverted, with median titers of specific Ab being 83-fold lower than in HC. In fact, only 4/46 patients (8.6%) of patients who were seronegative at baseline reached the threshold for an optimal response (250 U/mL). Using the EUROclass definition, patients with either a reduced proportion, but not absolute counts, of switched memory B-cells or having an increased frequency of CD21low B-cells generally generated poor vaccine responses. Overall, CVID-patients had reduced spike-specific IFN-γ positive CD4+ T cell responses 2 weeks after the second dose, compared to HC. The total CD4 and CD4 central memory cell counts correlated with humoral immunity to the vaccine. Conclusions: CVID patients with low frequency of switched memory B-cells or an increased frequency of CD21low B-cells according to the EUROclass definition demonstrated poor responses to Pfizer-BioNTech BNT162b2 mRNA vaccination. Cellular immune responses were significantly affected, affirming that the defect in CVID is not limited to humoral immunity. [ABSTRACT FROM AUTHOR]

Infections with SARS‐CoV‐2 have been unduly severe in patients with haematological malignancies, in particular in those with chronic lymphocytic leukaemia (CLL). Based on a series of observations, we propose that an underlying mechanism for the aggressive clinical course of COVID‐19 in CLL is a paucity of plasmacytoid dendritic cells (pDCs) in these patients. Indeed, pDCs express Toll‐like receptor 7 (TLR7), which together with interferon‐regulatory factor 7 (IRF7), enables pDCs to produce large amounts of type I interferons, essential for combating COVID‐19. Treatment of CLL with Bruton's tyrosine kinase (BTK) inhibitors increased the number of pDCs, likely secondarily to the reduction in the tumour burden. [ABSTRACT FROM AUTHOR]

Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of CXCR3 , CXCR6 , and CCR5 and their respective ligands in BAL fluid. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza compared to COVID-19. Together, our results indicate a role for CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells that potentially migrate to the lungs in moderate COVID-19 and influenza patients, identifying common targets for future therapeutic interventions in respiratory viral infections. [ABSTRACT FROM AUTHOR]

Objectives: Humoral and cellular immunity to SARS‐CoV‐2 following COVID‐19 will likely contribute to protection from reinfection or severe disease. It is therefore important to characterise the initiation and persistence of adaptive immunity to SARS‐CoV‐2 amidst the ongoing pandemic. Methods: Here, we conducted a longitudinal study on hospitalised moderate and severe COVID‐19 patients from the acute phase of disease into convalescence at 5 and 9 months post‐symptom onset. Utilising flow cytometry, serological assays as well as B cell and T cell FluoroSpot assays, we assessed the magnitude and specificity of humoral and cellular immune responses during and after human SARS‐CoV‐2 infection. Results: During acute COVID‐19, we observed an increase in germinal centre activity, a substantial expansion of antibody‐secreting cells and the generation of SARS‐CoV‐2‐neutralising antibodies. Despite gradually decreasing antibody levels, we show persistent, neutralising antibody titres as well as robust specific memory B cell responses and polyfunctional T cell responses at 5 and 9 months after symptom onset in both moderate and severe COVID‐19 patients. Conclusion: Our findings describe the initiation and, importantly, persistence of cellular and humoral SARS‐CoV‐2‐specific immunological memory in hospitalised COVID‐19 patients long after recovery, likely contributing towards protection against reinfection. [ABSTRACT FROM AUTHOR]