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In September 2020, we tested 13,398 persons in Portugal for antibodies against severe acute respiratory syndrome coronavirus 2 by using a quota sample stratified by age and population density. We found a seroprevalence of 2.2%, 3–4 times larger than the official number of cases at the end of the first wave of the pandemic.

Long-term solutions against SARS-CoV-2 infections require understanding of immune protection induced by different vaccine COVID-19 formulations. We investigated humoral and cellular immunity induced by Sinopharm (BBIBP-CorV) in a region of high SARS-CoV-2 seroprevalence.Levels of IgG antibodies to SARS-CoV-2 spike protein and its receptor-binding domain (RBD) were determined 24-weeks. Cellular immunity was investigated using a commercially available IFN-γ release assay to SARS-CoV-2 spike (Ag1 and 2) and extended genome antigens (Ag3).Increasing IgG seropositivity to Spike protein and RBD was observed post-vaccination. Seropositivity was reduced in those over 50 years and raised in females and those with prior COVID-19. After 20 weeks post-vaccination, only one third of participants had positive T cell responses to SARS-CoV-2 antigens. Prior COVID-19 impacted IFNγ responses, with reactivity enhanced in those infected earlier. The frequency of IFNγ responses was highest to extended genome antigen set.Overall, BBIBP-CorV- induced antibody responses were impacted by age, gender and prior COVID-19. Cellular immunity was present in a limited number of individuals after 20 weeks but was enhanced by prior infection. This suggests the need for booster vaccinations in older individuals. BBIBP-CorV-induced cellular activation is broader than to spike, requiring further study to understand how to monitor vaccine effectiveness.

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point the control of COVID-19 would be achieved for each scenario., G.R., J.V., A.N., M.C.G. were supported by Fundação para a Ciência e a Tecnologia (FCT) project reference 131_596787873, awarded to G.R. M.V. was supported by the European Union H2020 ERA project (No. 667824 - EXCELLtoINNOV). The contribution of C.H.v.D. was under the auspices of the US Department of Energy (contract number 89233218CNA000001) and supported by the National Institutes of Health (grant number R01-OD011095). MK acknowledges support from the Netherlands Organization for Health Research and Development (ZonMw) Grant no. 10430022010001.

Introduction Sinopharm (BBIBP-CorV) inactivated virus vaccination for COVID-19 has been administered widely in Pakistan. We investigated the dynamics of BBIBP-CorV -induced antibody responses over a 24 week period in a region with a high seroprevalence. Methods Study subjects (n = 312) were followed up over a 24-week period between May and August 2021. Sera were tested for IgG antibodies to spike and the receptor binding domain (RBD). Results Study subjects were 62% female. Twenty-two percent had a prior history of COVID-19. At 4-, 8- 16- and 24-weeks post-vaccination, the rate of IgG antibodies positive to spike was 57%, 87%, 66% and 90% of individuals, compared with to RBD which was 48%, 62%, 68% and 85% of subjects, respectively,. IgG to spike and RBD showed a positive correlation at each interval (rho > 0.6, p

Key Points PI3Kδ is required for the maintenance of normal Treg cell development and function. PI3Kα contributes to maintaining Treg cell function in context of neuroinflammation. Loss of PI3Kα and PI3Kδ in Treg cells leads to spontaneous peripheral neuropathy., Class I PI3K enzymes are critical for the maintenance of effective immunity. In T cells, PI3Kα and PI3Kδ are activated by the TCR and costimulatory receptors, whereas PI3Kγ is activated by G protein–coupled chemokine receptors. PI3Kδ is a key regulator of regulatory T (Treg) cell function. PI3K isoform-selective inhibitors are in development for the treatment of diseases associated with immune dysregulation, including chronic inflammatory conditions, cancer, and autoimmune diseases. Idelalisib (PI3Kδ), alpelisib (PI3Kα), duvelisib (PI3Kδ/γ), and copanlisib (pan-PI3K) have recently been approved for use in cancer treatment. Although effective, these therapies often have severe side effects associated with immune dysregulation and, in particular, loss of Treg cells. Therefore, it is important to gain a better understanding of the relative contribution of different PI3K isoforms under homeostatic and inflammatory conditions. Experimental autoimmune encephalitis is a mouse model of T cell–driven CNS inflammation, in which Treg cells play a key protective role. In this study, we show that PI3Kδ is required to maintain normal Treg cell development and phenotype under homeostatic conditions but that loss of PI3Kδ alone in Treg cells does not lead to autoimmunity. However, combined loss of PI3Kα and PI3Kδ signaling resulted in increased experimental autoimmune encephalitis disease severity. Moreover, mice lacking PI3Kα and PI3Kδ in Treg cells developed spontaneous peripheral nerve inflammation. These results show a key role for PI3K signaling in Treg cell–mediated protection against CNS inflammation.

In order to identify risk factors for SARS-CoV-2 infection as well as for severe/critical COVID-19 in rheumatic and musculoskeletal diseases (RMDs) patients, we conducted a multicentre observational nationwide study of adult patients prospectively-followed in the Rheumatic Diseases Portuguese Register – Reuma.pt – during the first 6 months of the pandemic. We further evaluated the development of IgG antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in patients with RMDs. We used multivariate logistic regression to compare patients with COVID-19 (COVID-19+) with those who did not develop the disease (COVID-19-) and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. COVID-19+ patients were asked to collect a blood sample for IgG testing ≥ 3 months after infection and results were compared with age-, sex- and sampling date-matched controls. Overall, 179 cases of COVID-19 were registered in Reuma.pt in the period of interest (median age 55 (IQR 20); 76.5% females) in a total of 6404 registered appointments. We found that patients treated with TNF inhibitors had reduced odds of infection (OR=0.16, 95%CI 0.10-0.26, p

Introduction One million cases of COVID-19 have been reported in Pakistan until August 1, 2021. However, SARS-CoV-2 PCR testing capacity is limited, and the true level of SARS-CoV-2 infections is unknown. Most individuals have asymptomatic or mild COVID-19 and remain undiagnosed. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure. We determined COVID-19 seroprevalence during the second pandemic wave in Karachi. Materials and Methods We enrolled 558 healthy blood donors at the Aga Khan University Hospital blood bank between December 2020 and February 2021. Serum IgG reactivity were measured to spike and receptor binding domain (RBD) proteins. Clinical history was taken from individuals with a positive IgG result. Results Of the 558 study subjects, 553 (99.1%) were males and 5 (0.9%) were females with a mean (± SD) age of 29.0 ± 7.4 years (range 17–53 years). Positive IgG responses to spike were detected in 298/558 blood donors (53.4%). Of the spike IgG positive cases, 93/298 individuals (31.2%) had IgG antibodies to RBD. Clinical information was available for 63.7% of spike IgG positive cases. Of these, 37% had flu-like symptoms, 25% had travelled, individuals had contact with COVID-19 suspected (18%) or confirmed (15%) cases. Within the year prior to blood donation, 29% of individuals had laboratory confirmed COVID-19. Conclusions The seroprevalence of 53.4% of IgG antibodies to spike and 31.2% of IgG to RBD of SARS-CoV-2 in healthy blood donors indicates high rates of exposure and gives insights into protective immunity in the population.

Introduction An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure in the population. We determined COVID-19 seroprevalence during the second pandemic wave in Karachi in donors without known infections or symptoms in 4 weeks prior to enrollment. Materials and methods We enrolled 558 healthy blood donors at the Aga Khan University Hospital between December 2020 and February 2021. ABO blood groups were determined. Serum IgG reactivity were measured to spike and receptor binding domain (RBD) proteins. Results Study subjects were predominantly males (99.1%) with a mean age of 29.0±7.4 years. Blood groups were represented by; B (35.8%), O (33.3%), A (23.8%) and AB (7%). Positive IgG responses to spike were detected in 53.4% (95% CI, 49.3–37.5) of blood donors. Positive IgG antibodies to RBD were present in 16.7% (95% CI; 13.6–19.8) of individuals. No significant difference was found between the frequency of IgG antibodies to spike or RBD across age groups. Frequencies of IgG to Spike and RBD antibodies between December 2020 and February 2021 were found to be similar. Seropositivity to either antigen between individuals of different blood groups did not differ. Notably, 31.2% of individuals with IgG antibodies to spike also had IgG antibodies to RBD. Amongst donors who had previously confirmed COVID-19 and were seropositive to spike, 40% had IgG to RBD. Conclusions Our study provides insights into the seroprevalence of antibodies to COVID-19 in a healthy cohort in Karachi. The differential dynamics of IgG to spike and RBD likely represent both exposure to SARS-CoV-2 and associate with protective immunity in the population.

T cells located in non-lymphoid tissues have come to prominence in recent years. CD8+ tissue-resident memory (Trm) cells are important for tissue immune surveillance, provide an important line of defence against invading pathogens and show promise in cancer therapies. These cells differ in phenotype from other memory populations, are adapted to the tissue they home to where they found their cognate antigen and have different metabolic requirements for survival and activation. CD4+ Foxp3+ regulatory T (Treg) cells also consist of specialised populations, found in non-lymphoid tissues, with distinct transcriptional programmes. These cells have equally adapted to function in the tissue they made their home. Both Trm and Treg cells have functions beyond immune defence, involving tissue homeostasis, repair and turnover. They are part of a multicellular communication network. Intriguingly, occupying the same niche, Treg cells are important in the establishment of Trm cells, which may have implications to harness the immune surveillance and tissue homeostasis properties of Trm cells for future therapies.

During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, six months after the initial moderate wave. Here we show the seroprevalence changes six months later, up to the second week of March 2021, shortly following the third wave, which was one of the most severe in the world, and two months following the start of the vaccination campaign. A longitudinal epidemiological study was conducted, with a stratified quota sample of the Portuguese population. Serological testing was performed, including ELISA determination of antibody class and titres. The proportion of seropositives, which was 2.2% in September 2020, rose sharply to 17.3% (95% CI: 15.8% – 18.8%) in March 2021. Importantly, circulating IgG and IgA antibody levels were very stable six months after the initial determination and up to a year after initial infection, indicating long-lasting natural immunity against SARS-CoV-2. Moreover, vaccinated people had higher IgG levels from 3 weeks post-vaccination when compared with previously infected people at the same times post-infection.

© 2021 AlphaMed Press., Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with cancer show worse outcomes compared with patients without cancer. The humoral immune response (HIR) of patients with cancer against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized patients with cancer infected with SARS-CoV-2. Materials and methods: This was a unicentric, retrospective study enrolling adult patients with SARS-CoV-2 admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptor-binding domain or spike protein IgM, IgG, and IgA antibodies. The aims of the study were to assess the HIR to SARS-CoV-2; correlate it with different cancer types, stages, and treatments; clarify the interplay between the HIR and clinical outcomes of patients with cancer; and compare the HIR of SARS-CoV-2-infected patients with and without cancer. Results: We included 72 SARS-CoV-2-positive subjects (19 with cancer, 53 controls). About 90% of controls revealed a robust serological response. Among patients with cancer, a strong response was verified in 57.9%, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among patients with cancer. No significant differences in outcomes were observed between patients with strong and weak responses. All IgG, IgM, IgA, and total Ig antibody titers were significantly lower in patients with cancer compared with those without. Conclusion: A significant portion of patients with cancer develop a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among patients with cancer. Patients with cancer have a weaker SARS-CoV-2 antibody response compared with those without cancer. Implications for practice: These results place the spotlight on patients with cancer, particularly those actively treated with chemotherapy. These patients may potentially be more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, so it is important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining, or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected patients with cancer in accordance with cancer type, stage and prognosis, treatment agents, treatment setting, and SARS-CoV-2 infection risks., LtoINNOV), the Fundação para a Ciência e a Tecnologia (SFRH/BD/131605/2017), and research4COVID19 (231_596873172, generating SARS-CoV-2 seroconversion assay), with additional support by Sociedade Francisco Manuel dos Santos.

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point control of COVID-19 would be achieved for each scenario.

All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point control of COVID-19 would be achieved for each scenario.

The work was supported by the following grants: NIH-AG045223 and NIH-AI137198 to L.S.; the Swiss National Science Foundation, grant 310030_182528 to C.H.; Telethon GGP17094 and the Associazione Italiana per la Ricerca sul Cancro (AIRC; 19903) to F.F.; Sigrid Juselius Foundation to K.A.; NIH T32 DK007110 to S.C.; NIH-AI103338 and NIH-AI138552 to G.L.; NIH K12 GM102779/BETTR program to R.F.; Associazione Italiana per la Ricerca sul Cancro (AIRC 2019-23084) to U.G.; The Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases ZIG AR041181-11) to W.L.T. and M.G. European Union H2020 ERA project (No. 667824 -EXCELLtoINNOV) to M.V., Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance., Swiss National Science Foundation (SNSF), European Commission 310030_182528, Fondazione Telethon GGP17094, Fondazione AIRC per la ricerca sul cancro 19903, Sigrid Juselius Foundation, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA T32 DK007110 K12 GM102779, Fondazione AIRC per la ricerca sul cancro AIRC 2019-23084, National Institutes of Health (NIH) - USA, NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) ZIG AR041181-11, European Union H2020 ERA project 667824 NIH-AG045223 NIH-AI137198 NIH-AI103338 NIH-AI138552

© The Author(s). 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we explore its role in this tissue. Results: Specific deletion of Smarcad1 in the mouse intestinal epithelium leads to colitis resistance and substantial changes in gene expression, including a striking increase of expression of several genes linked to innate immunity. Absence of Smarcad1 leads to changes in chromatin accessibility and significant changes in histone H3K9me3 over many sites, including genes that are differentially regulated upon Smarcad1 deletion. We identify candidate members of the gut microbiome that elicit a Smarcad1-dependent colitis response, including members of the poorly understood TM7 phylum. Conclusions: Our study sheds light onto the role of the chromatin remodeling machinery in intestinal epithelial cells in the colitis response and shows how a highly conserved chromatin remodeling factor has a distinct role in anti-microbial defense. This work highlights the importance of the intestinal epithelium in the colitis response and the potential of microbial species as pharmacological and probiotic targets in the context of inflammatory diseases., This work was supported by BBSRC Institute Strategic Programme Grants (BBS/E/B/000C0404, BBS/E/B/000C0405), a MRC project grant to PVW and MV (MR/N009398/1), a BBSRC-Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP-Brazil Pump-priming award (BB/N013565/1,FAPESP#2015/50379-1), and a Newton Advanced Fellowship from the Royal Society to MARV and PVW (NAF\R1\180116).

© 2020 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., SARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia-COVID-19-but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed. We quantified IgM, IgG, and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of 6 months following COVID-19 onset. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff, and 198 post-COVID-19 volunteers. Anti-SARS-CoV-2 antibody responses follow a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce subsequently, the ability to detect anti-SARS-CoV-2 IgG antibodies remained robust with confirmed neutralization activity for up to 6 months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Importantly, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2., We like to acknowledge the funding from the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV) and the Fundação para a Ciência e a Tecnologia (FCT) to P.F‐C. (SFRH/BD/131605/2017), PTDC/MED‐IMU/28003/2017, and research4COVID19 (no. 231_596873172, Generating SARS‐CoV2 seroconversion assay and no. 729, High‐throughput SARS‐CoV2 neutralizing antibodies assessment), with additional support by Sociedade Francisco Manuel dos Santos.

SARS-CoV-2 has emerged as a novel human pathogen, causing clinical signs, from fever to pneumonia – COVID-19 – but may remain mild or even asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed and have been setup around the world. We quantified immunoglobulin M (IgM), IgG and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of five months following COVID-19 disease onset or in previously SARS-CoV-2 PCR-positive volunteers. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff and 187 post-COVID19 volunteers, and assessing titres for IgM, IgG and IgA. Anti-SARS-CoV-2 antibody responses followed a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce from approximately four weeks, the ability to detect SARS-CoV-2 antibodies remained robust for five months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Moreover, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2, at least up to five months after infection.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., AhR is a ligand-activated transcription factor that plays an important role in the innate and adaptive immune responses. In infection models, it has been associated with host responses that promote or inhibit disease progression. In pulmonary paracoccidioidomycosis, a primary fungal infection endemic in Latin America, immune protection is mediated by Th1/Th17 cells and disease severity with predominant Th2/Th9/Treg responses. Because of its important role at epithelial barriers, we evaluate the role of AhR in the outcome of a pulmonary model of paracoccidioidomycosis. AhR-/- mice show increased fungal burdens, enhanced tissue pathology and mortality. During the infection, AhR-/- mice have more pulmonary myeloid cells with activated phenotype and reduced numbers expressing indoleamine 2,3 dioxygenase 1. AhR-deficient lungs have altered production of cytokines and reduced numbers of innate lymphoid cells (NK, ILC3 and NCR IL-22). The lungs of AhR-/- mice showed increased presence Th17 cells concomitant with reduced numbers of Th1, Th22 and Foxp3+ Treg cells. Furthermore, treatment of infected WT mice with an AhR-specific antagonist (CH223191) reproduced the main findings obtained in AhR-/- mice. Collectively our data demonstrate that in pulmonary paracoccidioidomycosis AhR controls fungal burden and excessive tissue inflammation and is a possible target for antifungal therapy., This work was supported by a grant from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-grant to VLGC 2011/51258-2 and 2016/23189-0; fellowship to EFA 2014/18668-2; grant to FVL 2018/14762-3; fellowship to NWP 2019-09278-8), European Union H2020 ERA project (No 667824 – EXCELLtoINNOV) to MV and Conselho Nacional de Pesquisas (CNPq).

© The Author(s), under exclusive licence to Springer Nature America, Inc. 2020, Tissue-resident memory T (TRM) cells, functionally distinct from circulating memory T cells, have a critical role in protective immunity in tissues, are more efficacious when elicited after vaccination and yield more effective antitumor immunity, yet the signals that direct development of TRM cells are incompletely understood. Here we show that type 1 regulatory T (Treg) cells, which express the transcription factor T-bet, promote the generation of CD8+ TRM cells. The absence of T-bet-expressing type 1 Treg cells reduces the presence of TRM cells in multiple tissues and increases pathogen burden upon infectious challenge. Using infection models, we show that type 1 Treg cells are specifically recruited to local inflammatory sites via the chemokine receptor CXCR3. Close proximity with effector CD8+ T cells and Treg cell expression of integrin-β8 endows the bioavailability of transforming growth factor-β in the microenvironment, thereby promoting the generation of CD8+ TRM cells., The project leading to these results has received funding from the European Union H2020 ERA project (no. 667824, EXCELLtoINNOV), Fundo iMM-Laço and ‘la caixa’ Foundation (ID 100010434) under agreement LCF/PR/HR19/52160005 for work in the Veldhoen laboratory, with additional funding from the Fundação para a Ciência e a Tecnologia to P.F.-C. (SFRH/BD/131605/2017), to L.B. (PD/BD/138847/2018) and to A.B. (SFRH/BD/138900/2018). In addition, the work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) SFB1366 (project no. 394046768-SFB 1366; C02) and by SPP 1937 (CE 140/2-1) to A.C and SFB1292 (TP13) and TR156 (TPB02) to H.C.P. A.L. was supported by Ligue Nationale Contre le Cancer. Other grants supporting this study: Foncer Contre le Cancer (JCM) and EL-2016 LNCC Labelisation Ligue Nationale Contre Cancer.

Adaptive immunity critically depends on cell migration combined with clonal selection and rapid expansion of rare lymphocytes recognising their cognate antigen in secondary lymphoid organs. It has since become apparent that large populations of T cells are maintained in tissues, which do not migrate throughout the body and do not require clonal expansion. Murine intraepithelial lymphocytes (IELs), located in the skin and small intestines, are maintained in a state of semi-activation, in marked contrast to the quiescent condition naive and memory lymphocytes are kept in. The poised activation state of IELs, their location in the top layers of barrier organs and close bidirectional interactions with epithelial cells suggests IELs are part of a sophisticated strategy of immune-surveillance and compartmentalisation of immune responses. Recent murine studies have reemphasised the influence of metabolism in T-cell activation and differentiation, with different metabolic make up of naive, effector and memory T cells. Here we highlight and discuss some of the current insights on immunometabolism of IELs, with emphasis on novel data contrasting how IELs may be maintained in a semi-activated state and may become fully functional compared with conventional T cells.

The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs., Histone post-translational modifications are known key regulators of gene expression. Here, the authors characterize histone crotonylation at histone H3 lysine 18 in intestinal epithelia and find that it is a highly dynamic cell cycle regulated mark under the regulation of the HDAC deacetylases.

Copyright: © 2021 Abidi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Background: Individuals recovering from COVID-19 are known to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability although they may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 neutralizing assays for the determination of virus-neutralizing activity in sera of individuals. Here we describe a PCR-based micro-neutralization assay that can be used to evaluate the viral neutralization titers of serum from SARS-CoV-2 infected individuals. Methods: The SARS-CoV-2 strain used was isolated from a nasopharyngeal specimen of a COVID-19 case. The limiting dilution method was used to obtain a 50% tissue culture infective dose (TCID50) of Vero cells. For the micro-neutralization assay, 19 serum samples, with positive IgG titers against Spike Receptor-Binding Domain (RBD) were tested. After 24 hours, infected cells were inspected for the presence of a cytopathic effect, lysed and RNA RT-PCR conducted for SARS-CoV-2. PCR target Ct values were used to calculate percent neutralization/inhibition of SARS-CoV-2. Results: Out of 19 samples, 13 samples gave 100% neutralization at all dilutions, 1 sample showed neutralization at the first dilution, 4 samples showed neutralization at lower dilutions, while one sample did not demonstrate any neutralization. The RBD ODs and neutralization potential percentages were found to be positively correlated. Conclusion: We describe a rapid RT-PCR-based SARS-CoV-2 microneutralization assay for the detection of neutralizing antibodies. This can effectively be used to test the antiviral activity of serum antibodies for the investigation of both disease-driven and vaccine-induced responses., This study received funding support through a grant from the Provosts Academic Priorities Fund, The Aga Khan University. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV).

Copyright © 2021, Springer Nature Limited, COVID-19 vaccinations have started. They will stop the pandemic. Citing recent data that are in line with immunological knowledge and predictions, combined with insights of common cold coronaviruses, we here set out the case that the maintenance of population immunity will not depend on continued vaccinations but on the endemic presence of SARS-CoV-2.

Tissue-resident memory T (T

Copyright © 2018 The Authors; exclusive licensee Bio-protocol LLC., Eimeria vermiformis is a tissue specific, intracellular protozoan that infects the murine small intestinal epithelia, which has been widely used as a coccidian model to study mucosal immunology. This mouse infection model is valuable to investigate the mechanisms of host protection against primary and secondary infection in the small intestine. Here, we describe the generation of an E. vermiformis stock solution, preparation of sporulated E. vermiformis to infect mice and determination of oocysts burden. This protocol should help to establish a highly reproducible natural infection challenge model to study immunity in the small intestine. The information obtained from using this mouse model can reveal fundamental mechanisms of interaction between the pathogen and the immune response, e.g., provided by intraepithelial lymphocytes (IEL) at the basolateral site of epithelial cells but also a variety of other immune cell populations present in the gut., This work was supported by the European Union H2020 ERA project (No. 667824– EXCELLtoINNOV) for work in the Veldhoen laboratory and Fundação para a Ciência e a Tecnologia (FCT) Studentship SFRH/BD/131605/2017 to P.F-C.

Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses.