WHO, Weekly epidemiological covid-19-6 july 2021 edition 47. https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19%2D%2D-6-july-2021. (Published Date 6 July 2021, Accessed Date 11 July 2021).
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239.
Article
CAS
PubMed
Google Scholar
Santesmasses D, Castro JP, Zenin AA, Shindyapina AV, Gerashchenko MV, Zhang B, et al. COVID‐19 is an emergent disease of aging. Aging Cell. 2020;19:e13230.
Holmes KV. SARS-associated coronavirus. N Engl J Med. 2003;348:1948–51.
Article
PubMed
Google Scholar
de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14:523–34.
Article
PubMed
PubMed Central
Google Scholar
Zhong N, Zheng B, Li Y, Poon L, Xie Z, Chan K, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s republic of China, in February, 2003. Lancet. 2003;362:1353–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Meftahi GH, Jangravi Z, Sahraei H, Bahari Z. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of “inflame-aging.”. Inflamm Res. 2020;69:825–39.
Article
CAS
PubMed
PubMed Central
Google Scholar
Genebat M, Tarancón-Díez L, de Pablo-Bernal R, Calderón A, Muñoz-Fernández MÁ, Leal M. Coronavirus disease (COVID-19): a perspective from Immunosenescence. Aging Dis. 2021;12:3.
Article
PubMed
PubMed Central
Google Scholar
Du Toit A. Outbreak of a novel coronavirus. Nat Rev Microbiol. 2020;18:123.
Article
PubMed
PubMed Central
Google Scholar
Bogoch II, Watts A, Thomas-Bachli A, Huber C, Kraemer MUG, Khan K. Pneumonia of unknown aetiology in Wuhan, China: potential for international spread via commercial air travel. J Travel Med. 2020;27:taaa008.
Article
PubMed
Google Scholar
Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433.
Article
CAS
PubMed
PubMed Central
Google Scholar
Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;181:281–292.e6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280.e8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Song X, Hu W, Yu H, Zhao L, Zhao Y, Zhao X, et al. Little to no expression of angiotensin‐converting enzyme‐2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytometry A. 2020;1:10.
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of Covid-19 in the Young. N Engl J Med. 2020;382:e60.
Article
PubMed
Google Scholar
Gu J, Han B, Wang J. COVID-19: Gastrointestinal Manifestations and Potential Fecal–Oral Transmission. Gastroenterology. 2020;158:1518–9.
Article
CAS
PubMed
Google Scholar
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323:1061.
Article
CAS
PubMed
PubMed Central
Google Scholar
Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease 2019. Crit Care Med. 2020;48:1358–64.
Article
CAS
PubMed
Google Scholar
Franchini M, Marano G, Cruciani M, Mengoli C, Pati I, Masiello F, et al. COVID-19-associated coagulopathy. Diagnosis. 2020;7:357–63.
Article
CAS
PubMed
Google Scholar
Leentjens J, van Haaps TF, Wessels PF, Schutgens REG, Middeldorp S. COVID-19-associated coagulopathy and antithrombotic agents—lessons after 1 year. Lancet Haematol. 2021;8:e524–33.
Article
PubMed
PubMed Central
Google Scholar
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. N Engl J Med. 2020;382:1199–207.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol. 2020;92:441–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lee P-I, Hu Y-L, Chen P-Y, Huang Y-C, Hsueh P-R. Are children less susceptible to COVID-19? J Microbiol Immunol Infect. 2020;53:371–2.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cevik M, Kuppalli K, Kindrachuk J, Peiris M. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ. 2020;371:m3862.
Reddy R, Asante I, Liu S, Parikh P, Liebler J, Borok Z, et al. Circulating angiotensin peptides levels in acute respiratory distress syndrome correlate with clinical outcomes: a pilot study. PLoS One. 2019;14:e0213096.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24:422.
Article
PubMed
PubMed Central
Google Scholar
Lee SH, Yim SJ, Kim HC. Aging of the respiratory system. Kosin Med J. 2016;31:11–8.
Article
Google Scholar
Bickler SW, Cauvi DM, Fisch KM, Prieto JM, Sykes AG, Thangarajah H, et al. Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease. BMC Med Genet. 2021;14:138.
CAS
Google Scholar
Bunyavanich S, Do A, Vicencio A. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults. JAMA. 2020;323:2427.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chen J, Jiang Q, Xia X, Liu K, Yu Z, Tao W, et al. Individual variation of the SARS‐CoV‐2 receptor ACE2 gene expression and regulation. Aging cell. 2020;19:e13168.
AlGhatrif M, Cingolani O, Lakatta EG. The dilemma of coronavirus disease 2019, aging, and cardiovascular disease: insights from cardiovascular aging science. JAMA Cardiol. 2020;5:747.
Article
PubMed
Google Scholar
Li M-Y, Li L, Zhang Y, Wang X-S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020;9:45.
Article
PubMed
PubMed Central
Google Scholar
Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20:669–77.
Article
CAS
PubMed
PubMed Central
Google Scholar
Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bennett JM, Reeves G, Billman GE, Sturmberg JP. Inflammation–Nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front Med. 2018;5:316.
Article
Google Scholar
Netea MG, Balkwill F, Chonchol M, Cominelli F, Donath MY, Giamarellos-Bourboulis EJ, et al. A guiding map for inflammation. Nat Immunol. 2017;18:826–31.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nathan C. Points of control in inflammation. Nature. 2002;420:846–52.
Article
CAS
PubMed
Google Scholar
Serhan CN, Chiang N, Dalli J, Levy BD. Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol. 2015;7:a016311.
Article
PubMed Central
Google Scholar
Weyand CM, Goronzy JJ. The immunology of rheumatoid arthritis. Nat Immunol. 2021;22:10–8.
Article
CAS
PubMed
Google Scholar
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging: an evolutionary perspective on Immunosenescence. Ann N Y Acad Sci. 2006;908:244–54.
Article
Google Scholar
Ershler WB. Interleukin-6: a cytokine for Gerontolgists. J Am Geriatr Soc. 1993;41:176–81.
Article
CAS
PubMed
Google Scholar
Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33:127–48.
Article
CAS
PubMed
Google Scholar
Hager K, Machein U, Krieger S, Platt D, Seefried G, Bauer J. Interleukin-6 and selected plasma proteins in healthy persons of different ages. Neurobiol Aging. 1994;15:771–2.
Article
CAS
PubMed
Google Scholar
Wei J, Xu H, Davies JL, Hemmings GP. Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci. 1992;51:1953–6.
Article
CAS
PubMed
Google Scholar
Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and age-related diseases: role of inflammation triggers and cytokines. Front Immunol. 2018;9:586.
Article
PubMed
PubMed Central
Google Scholar
Swanson KV, Deng M, Ting JP-Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19:477–89.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bauernfeind F, Niepmann S, Knolle PA, Hornung V. Aging-associated TNF production primes Inflammasome activation and NLRP3-related metabolic disturbances. JI. 2016;197:2900–8.
CAS
Google Scholar
Brahadeeswaran S, Sivagurunathan N, Calivarathan L. Inflammasome signaling in the aging brain and age-related neurodegenerative diseases. Mol Neurobiol. 2022;59:2288–304.
Article
CAS
PubMed
Google Scholar
Gritsenko A, Green JP, Brough D, Lopez-Castejon G. Mechanisms of NLRP3 priming in inflammaging and age related diseases. Cytokine Growth Factor Rev. 2020;55:15–25.
Article
CAS
PubMed
PubMed Central
Google Scholar
NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice - PubMed. https://pubmed.ncbi.nlm.nih.gov/31625260/. Accessed 16 Jun 2022.
Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, et al. The origins of age-related proinflammatory state. Blood. 2005;105:2294–9.
Article
CAS
PubMed
Google Scholar
Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr. 2006;83:447S–55S.
Article
CAS
PubMed
Google Scholar
Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14:877–82.
Article
PubMed
Google Scholar
Gangemi S, Basile G, Merendino RA, Minciullo PL, Novick D, Rubinstein M, et al. Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity? Exp Gerontol. 2003;38:669–72.
Article
CAS
PubMed
Google Scholar
Magalhães CA, Ferreira CN, Loures CMG, Fraga VG, Chaves AC, Oliveira ACR, et al. Leptin, hsCRP, TNF-α and IL-6 levels from normal aging to dementia: relationship with cognitive and functional status. J Clin Neurosci. 2018;56:150–5.
Article
PubMed
Google Scholar
Lakoski SG, Liu Y, Brosnihan KB, Herrington DM. Interleukin-10 concentration and coronary heart disease (CHD) event risk in the estrogen replacement and atherosclerosis (ERA) study. Atherosclerosis. 2008;197:443–7.
Article
CAS
PubMed
Google Scholar
Didion SP, Kinzenbaw DA, Schrader LI, Chu Y, Faraci FM. Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction. Hypertension. 2009;54:619–24.
Article
CAS
PubMed
Google Scholar
Kinzenbaw DA, Chu Y, Silva RAP, Didion SP, Faraci FM. Interleukin-10 protects against aging-induced endothelial dysfunction. Physiol Rep. 2013;1:e00149.
Tominaga K, Suzuki HI. TGF-β signaling in cellular senescence and aging-related pathology. IJMS. 2019;20:5002.
Article
CAS
PubMed Central
Google Scholar
Blaney Davidson E, Scharstuhl A, Vitters E, van der Kraan P, van den Berg W. Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity. Arthritis Res Ther. 2005;7:R1338.
Article
CAS
PubMed
PubMed Central
Google Scholar
Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128:92–105.
Article
CAS
PubMed
Google Scholar
Dall’Olio F, Vanhooren V, Chen CC, Slagboom PE, Wuhrer M, Franceschi C. N-glycomic biomarkers of biological aging and longevity: a link with inflammaging. Ageing Res Rev. 2013;12:685–98.
Article
PubMed
Google Scholar
Biagi E, Candela M, Franceschi C, Brigidi P. The aging gut microbiota: new perspectives. Ageing Res Rev. 2011;10:428–9.
Article
PubMed
Google Scholar
Wiley CD, Campisi J. The metabolic roots of senescence: mechanisms and opportunities for intervention. Nat Metab. 2021;3:1290–301.
Article
CAS
PubMed
PubMed Central
Google Scholar
Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM. Aging of the innate immune system. Curr Opin Immunol. 2010;22:507–13.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fredman G, Hellmann J, Proto JD, Kuriakose G, Colas RA, Dorweiler B, et al. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nat Commun. 2016;7:12859.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rong Y-D, Bian A-L, Hu H-Y, Ma Y, Zhou X-Z. Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10. BMC Geriatr. 2018;18:308.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ma L, Sha G, Zhang Y, Li Y. Elevated serum Il-6 and adiponectin levels are associated with frailty and physical function in Chinese older adults. CIA. 2018;13:2013–20.
Article
CAS
Google Scholar
Beavers DP, Kritchevsky SB, Gill TM, Ambrosius WT, Anton SD, Fielding RA, et al. Elevated IL-6 and CRP levels are associated with incident self-reported major mobility disability: a pooled analysis of older adults with slow gait speed. J Gerontol A Biol Sci Med Sci. 2021;76:2293–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Il’yasova D, Colbert LH, Harris TB, Newman AB, Bauer DC, Satterfield S, et al. Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomark Prev. 2005;14:2413–8.
Article
Google Scholar
Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement (N Y). 2018;4:575–90.
Article
Google Scholar
Lu Y, Tan CTY, Nyunt MSZ, Mok EWH, Camous X, Kared H, et al. Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies. Oncotarget. 2016;7:28783–95.
Article
PubMed
PubMed Central
Google Scholar
Gao Q, Camous X, Lu Y-X, Lim M-L, Larbi A, Ng T-P. Novel inflammatory markers associated with cognitive performance: Singapore longitudinal ageing studies. Neurobiol Aging. 2016;39:140–6.
Article
CAS
PubMed
Google Scholar
Guan W-J, Liang W-H, Zhao Y, Liang H-R, Chen Z-S, Li Y-M, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J. 2020;55:2000547.
Article
CAS
PubMed
PubMed Central
Google Scholar
Posso M, Comas M, Román M, Domingo L, Louro J, González C, et al. Comorbidities and mortality in patients with COVID-19 aged 60 years and older in a University Hospital in Spain. Arch Bronconeumol. 2020;56:756–8.
Article
PubMed
PubMed Central
Google Scholar
Coronavirus disease (COVID-19) – World Health Organization. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed 17 Jun 2022.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180:934–43.
Article
CAS
PubMed
Google Scholar
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.
Article
CAS
PubMed
PubMed Central
Google Scholar
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384:693–704.
Article
Google Scholar
Lei J, Li J, Li X, Qi X. CT imaging of the 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology. 2020;295:18.
Article
PubMed
Google Scholar
Tizazu AM, Nyunt MSZ, Cexus O, Suku K, Mok E, Xian CH, et al. Metformin monotherapy downregulates diabetes-associated inflammatory status and impacts on mortality. Front Physiol. 2019;10:572.
Article
PubMed
PubMed Central
Google Scholar
Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; what we know so far. Front Immunol. 2020;11:1446.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383:2255–73.
Article
CAS
PubMed
PubMed Central
Google Scholar
Flatt T. A new definition of aging? Front Genet. 2012;3:148.
Article
PubMed
PubMed Central
Google Scholar
Kirkwood TBL. Understanding the odd science of aging. Cell. 2005;120:437–47.
Article
CAS
PubMed
Google Scholar
Effros RB. Roy Walford and the immunologic theory of aging. Immun Ageing. 2005;2:7.
Article
PubMed
PubMed Central
Google Scholar
Cheung HT, Twu JS, Richardson A. Mechanism of the age-related decline in lymphocyte proliferation: role of IL-2 production and protein synthesis. Exp Gerontol. 1983;18:451–60.
Article
CAS
PubMed
Google Scholar
Ciabattini A, Nardini C, Santoro F, Garagnani P, Franceschi C, Medaglini D. Vaccination in the elderly: the challenge of immune changes with aging. Semin Immunol. 2018;40:83–94.
Article
PubMed
Google Scholar
Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391:1285–300.
Article
PubMed
Google Scholar
Vadasz Z, Haj T, Kessel A, Toubi E. Age-related autoimmunity. BMC Med. 2013;11:1–4.
Article
Google Scholar
Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol. 2012;24:331–41.
Article
CAS
PubMed
Google Scholar
Schultze JL, Aschenbrenner AC. COVID-19 and the human innate immune system. Cell. 2021;184:1671–92.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369:718–24.
Article
CAS
PubMed
PubMed Central
Google Scholar
Galani I-E, Rovina N, Lampropoulou V, Triantafyllia V, Manioudaki M, Pavlos E, et al. Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nat Immunol. 2021;22:32–40.
Article
CAS
PubMed
Google Scholar
Borregaard N. Neutrophils, from marrow to microbes. Immunity. 2010;33:657–70.
Article
CAS
PubMed
Google Scholar
Kumar V, Sharma A. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol. 2010;10:1325–34.
Article
CAS
PubMed
Google Scholar
Gasparoto TH, Dalboni TM, Amôr NG, Abe AE, Perri G, LARA VS, et al. Fcγ receptors on aging neutrophils. J Appl Oral Sci. 2021;29:e20200770.
Simell B, Vuorela A, Ekström N, Palmu A, Reunanen A, Meri S, et al. Aging reduces the functionality of anti-pneumococcal antibodies and the killing of Streptococcus pneumoniae by neutrophil phagocytosis. Vaccine. 2011;29:1929–34.
Article
CAS
PubMed
Google Scholar
Fortin CF, McDonald PP, Lesur O, Fülöp T. Aging and neutrophils: there is still much to do. Rejuvenation Res. 2008;11:873–82.
Article
CAS
PubMed
Google Scholar
Silvin A, Chapuis N, Dunsmore G, Goubet A-G, Dubuisson A, Derosa L, et al. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell. 2020;182:1401–1418.e18.
Article
CAS
PubMed
PubMed Central
Google Scholar
Middleton EA, He X-Y, Denorme F, Campbell RA, Ng D, Salvatore SP, et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136:1169–79.
Article
CAS
PubMed
Google Scholar
Reusch N, De Domenico E, Bonaguro L, Schulte-Schrepping J, Baßler K, Schultze JL, et al. Neutrophils in COVID-19. Front Immunol. 2021;12:652470.
Article
CAS
PubMed
PubMed Central
Google Scholar
Jakubzick CV, Randolph GJ, Henson PM. Monocyte differentiation and antigen-presenting functions. Nat Rev Immunol. 2017;17:349–62.
Article
CAS
PubMed
Google Scholar
Zhang C, Yang M, Ericsson AC. Function of macrophages in disease: current understanding on molecular mechanisms. Front Immunol. 2021;12:620510.
Article
CAS
PubMed
PubMed Central
Google Scholar
Novak ML, Koh TJ. Macrophage phenotypes during tissue repair. J Leukoc Biol. 2013;93:875–81.
Article
CAS
PubMed
PubMed Central
Google Scholar
Trombetta AC, Soldano S, Contini P, Tomatis V, Ruaro B, Paolino S, et al. A circulating cell population showing both M1 and M2 monocyte/macrophage surface markers characterizes systemic sclerosis patients with lung involvement. Respir Res. 2018;19:186.
Article
PubMed
PubMed Central
Google Scholar
Wong KL, Yeap WH, Tai JJY, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41–57.
Article
CAS
PubMed
Google Scholar
Ong S-M, Hadadi E, Dang T-M, Yeap W-H, Tan CT-Y, Ng T-P, et al. The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence. Cell Death Dis. 2018;9:266.
Article
PubMed
PubMed Central
Google Scholar
van Duin D, Mohanty S, Thomas V, Ginter S, Montgomery RR, Fikrig E, et al. Age-associated defect in human TLR-1/2 function. J Immunol. 2007;178:970–5.
Article
PubMed
Google Scholar
Qian F, Montgomery RR. Quantitative imaging of lineage-specific Toll-like receptor-mediated signaling in monocytes and dendritic cells from small samples of human blood. J Vis Exp. 2012;62:3741.
De Maeyer RPH, Chambers ES. The impact of ageing on monocytes and macrophages. Immunol Lett. 2021;230:1–10.
Article
PubMed
Google Scholar
Chua RL, Lukassen S, Trump S, Hennig BP, Wendisch D, Pott F, et al. COVID-19 severity correlates with airway epithelium–immune cell interactions identified by single-cell analysis. Nat Biotechnol. 2020;38:970–9.
Article
CAS
PubMed
Google Scholar
Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, et al. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26:842–4.
Article
CAS
PubMed
Google Scholar
Li D, Chen Y, Liu H, Jia Y, Li F, Wang W, et al. Immune dysfunction leads to mortality and organ injury in patients with COVID-19 in China: insights from ERS-COVID-19 study. Signal Transduct Target Ther. 2020;5:62.
Article
PubMed
PubMed Central
Google Scholar
Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7:998–1002.
Article
PubMed
PubMed Central
Google Scholar
Schulte-Schrepping J, Reusch N, Paclik D, Baßler K, Schlickeiser S, Zhang B, et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell. 2020;182:1419–1440.e23.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus; 2020. p. 2020.02.12.945576.
Google Scholar
Dress RJ, Ginhoux F. Monocytes and macrophages in severe COVID-19 – friend, foe or both? Immunol Cell Biol. 2021. https://doi.org/10.1111/imcb.12464.
Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV. Myeloid dendritic cells: development, functions, and role in atherosclerotic inflammation. Immunobiology. 2015;220:833–44.
Article
CAS
PubMed
Google Scholar
Zhou R, To KK-W, Wong Y-C, Liu L, Zhou B, Li X, et al. Acute SARS-CoV-2 infection impairs dendritic cell and T cell responses. Immunity. 2020;53:864–877.e5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sánchez-Cerrillo I, Landete P, Aldave B, Sánchez-Alonso S, Sánchez-Azofra A, Marcos-Jiménez A, et al. COVID-19 Severity Associates With Pulmonary Redistribution of CD1c+ DCs and Inflammatory Transitional and Nonclassical Monocytes. J Clin Invest. 2020;130:6290–300.
Saichi M, Ladjemi MZ, Korniotis S, Rousseau C, Ait Hamou Z, Massenet-Regad L, et al. Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity. Nat Cell Biol. 2021;23:538–51.
Article
CAS
PubMed
Google Scholar
Arunachalam PS, Wimmers F, Mok CKP, Perera RAPM, Scott M, Hagan T, et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science. 2020;369:1210–20.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kiessling R, Klein E, Wigzell H. “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol. 1975;5:112–7.
Article
CAS
PubMed
Google Scholar
Gounder SS, Abdullah BJJ, Radzuanb NEIBM, Zain FDBM, Sait NBM, Chua C, et al. Effect of Aging on NK Cell Population and Their Proliferation at Ex Vivo Culture Condition. Anal Cell Pathol (Amst). 2018;2018:7871814.
Google Scholar
Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013;12:1069–78.
Article
CAS
PubMed
PubMed Central
Google Scholar
Masselli E, Vaccarezza M, Carubbi C, Pozzi G, Presta V, Mirandola P, et al. NK cells: a double edge sword against SARS-CoV-2. Adv Biol Regul. 2020;77:100737.
Article
CAS
PubMed
PubMed Central
Google Scholar
Arthur L, Esaulova E, Mogilenko DA, Tsurinov P, Burdess S, Laha A, et al. Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging. Nat Aging. 2021;1:535–49.
Article
Google Scholar
Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17:533–5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ, McKechnie JL, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020;26:1070–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Pawelec G. Hallmarks of human “immunosenescence”: adaptation or dysregulation? Immun Ageing. 2012;9:15.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rydyznski Moderbacher C, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell. 2020;183:996–1012.e19.
Article
CAS
PubMed
PubMed Central
Google Scholar
Mejia-Ramirez E, Florian MC. Understanding intrinsic hematopoietic stem cell aging. Haematologica. 2020;105:22–37.
Article
CAS
PubMed
PubMed Central
Google Scholar
Beerman I, Rossi DJ. Epigenetic control of stem cell potential during homeostasis, aging, and disease. Cell Stem Cell. 2015;16:613–25.
Article
CAS
PubMed
PubMed Central
Google Scholar
Young K, Borikar S, Bell R, Kuffler L, Philip V, Trowbridge JJ. Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging. J Exp Med. 2016;213:2259–67.
Article
CAS
PubMed
PubMed Central
Google Scholar
Min H, Montecino-Rodriguez E, Dorshkind K. Effects of aging on the common lymphoid progenitor to pro-B cell transition. J Immunol. 2006;176:1007–12.
Article
CAS
PubMed
Google Scholar
Chandel NS, Jasper H, Ho TT, Passegué E. Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing. Nat Cell Biol. 2016;18:823–32.
Article
CAS
PubMed
Google Scholar
De Silva NS, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol. 2015;15:137–48.
Article
PubMed
PubMed Central
Google Scholar
Sanz I, Wei C, Jenks SA, Cashman KS, Tipton C, Woodruff MC, et al. Challenges and Opportunities for Consistent Classification of Human B Cell and Plasma Cell Populations. Front Immunol. 2019;10:2458.
Ma S, Wang C, Mao X, Hao Y. B Cell Dysfunction Associated With Aging and Autoimmune Diseases. Front Immunol. 2019;10:318.
Ademokun A, Wu Y-C, Dunn-Walters D. The ageing B cell population: composition and function. Biogerontology. 2010;11:125–37.
Article
PubMed
Google Scholar
Chong Y, Ikematsu H, Yamaji K, Nishimura M, Nabeshima S, Kashiwagi S, et al. CD27(+) (memory) B cell decrease and apoptosis-resistant CD27(−) (naive) B cell increase in aged humans: implications for age-related peripheral B cell developmental disturbances. Int Immunol. 2005;17:383–90.
Article
CAS
PubMed
Google Scholar
Son NH, Joyce B, Hieatt A, Chrest FJ, Yanovski J, Weng N. Stable telomere length and telomerase expression from naïve to memory B-lymphocyte differentiation. Mech Ageing Dev. 2003;124:427–32.
Article
CAS
PubMed
Google Scholar
Colonna-Romano G, Bulati M, Aquino A, Pellicanò M, Vitello S, Lio D, et al. A double-negative (IgD-CD27-) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev. 2009;130:681–90.
Article
CAS
PubMed
Google Scholar
Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013;14:428–36.
Article
CAS
PubMed
PubMed Central
Google Scholar
Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol. 2005;175:3262–7.
Article
CAS
PubMed
Google Scholar
Kogut I, Scholz JL, Cancro MP, Cambier JC. B cell maintenance and function in aging. Semin Immunol. 2012;24:342–9.
Article
CAS
PubMed
Google Scholar
Frasca D, Landin AM, Lechner SC, Ryan JG, Schwartz R, Riley RL, et al. Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol. 2008;180:5283–90.
Article
CAS
PubMed
Google Scholar
Tabibian-Keissar H, Hazanov L, Schiby G, Rosenthal N, Rakovsky A, Michaeli M, et al. Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues. Eur J Immunol. 2016;46:480–92.
Article
CAS
PubMed
Google Scholar
Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B, Wang JH, et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol. 2020;5:eabe5511.
Article
PubMed
PubMed Central
Google Scholar
Lenti MV, Aronico N, Pellegrino I, Boveri E, Giuffrida P, Borrelli de Andreis F, et al. Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19. Sci Rep. 2020;10:20836.
Article
CAS
PubMed
PubMed Central
Google Scholar
Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020;369:eabc8511.
Article
CAS
PubMed
PubMed Central
Google Scholar
Anderson EM, Goodwin EC, Verma A, Arevalo CP, Bolton MJ, Weirick ME, et al. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell. 2021;184:1858–1864.e10.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gilbert PB, Montefiori DC, McDermott A, Fong Y, Benkeser D, Deng W, et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science. 2022;375:43–50.
Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, et al. Waning immune humoral response to BNT162b2 Covid-19 vaccine over 6 months. N Engl J Med. 2021;385:e84.
Article
CAS
PubMed
Google Scholar
Müller L, Andrée M, Moskorz W, Drexler I, Walotka L, Grothmann R, et al. Age-dependent immune response to the Biontech/Pfizer BNT162b2 coronavirus disease 2019 vaccination. Clin Infect Dis. 2021;73:2065–72.
Article
PubMed
Google Scholar
Röltgen K, Boyd SD. Antibody and B cell responses to SARS-CoV-2 infection and vaccination. Cell Host Microbe. 2021;29:1063–75.
Article
PubMed
PubMed Central
Google Scholar
Li Y, Yin Y, Mariuzza RA. Structural and biophysical insights into the role of CD4 and CD8 in T cell activation. Front Immunol. 2013;4:206.
Seo W, Taniuchi I. Transcriptional regulation of early T-cell development in the thymus. Eur J Immunol. 2016;46:531–8.
Article
CAS
PubMed
Google Scholar
Kumar BV, Connors TJ, Farber DL. Human T cell development, localization, and function throughout life. Immunity. 2018;48:202–13.
Article
CAS
PubMed
PubMed Central
Google Scholar
Geginat J, Paroni M, Maglie S, Alfen JS, Kastirr I, Gruarin P, et al. Plasticity of human CD4 T cell subsets. Front Immunol. 2014;5:630.
Pellicci DG, Koay H-F, Berzins SP. Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge. Nat Rev Immunol. 2020;20:756–70.
Article
CAS
PubMed
Google Scholar
Hale JS, Boursalian TE, Turk GL, Fink PJ. Thymic output in aged mice. Proc Natl Acad Sci U S A. 2006;103:8447–52.
Article
CAS
PubMed
PubMed Central
Google Scholar
den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mögling R, de Boer AB, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012;36:288–97.
Article
Google Scholar
Czesnikiewicz-Guzik M, Lee W-W, Cui D, Hiruma Y, Lamar DL, Yang Z-Z, et al. T cell subset-specific susceptibility to aging. Clin Immunol. 2008;127:107–18.
Article
CAS
PubMed
PubMed Central
Google Scholar
Xu W, Larbi A. Markers of T cell senescence in humans. Int J Mol Sci. 2017;18:E1742.
Article
PubMed
Google Scholar
Johnson PLF, Yates AJ, Goronzy JJ, Antia R. Peripheral selection rather than thymic involution explains sudden contraction in naive CD4 T-cell diversity with age. Proc Natl Acad Sci U S A. 2012;109:21432–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tsukamoto H, Huston GE, Dibble J, Duso DK, Swain SL. Bim dictates naive CD4 T cell lifespan and the development of age-associated functional defects. J Immunol. 2010;185:4535–44.
Article
CAS
PubMed
Google Scholar
Nikolich-Žugich J, Li G, Uhrlaub JL, Renkema KR, Smithey MJ. Age-related changes in CD8 T cell homeostasis and immunity to infection. Semin Immunol. 2012;24:356–64.
Article
PubMed
PubMed Central
Google Scholar
Daniels MA, Teixeiro E. TCR signaling in T cell memory. Front Immunol. 2015;6:617.
Article
PubMed
PubMed Central
Google Scholar
Hwang J-R, Byeon Y, Kim D, Park S-G. Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development. Exp Mol Med. 2020;52:750–61.
Article
CAS
PubMed
PubMed Central
Google Scholar
Goronzy JJ, Li G, Yu M, Weyand CM. Signaling pathways in aged T cells – a reflection of T cell differentiation, cell senescence and host environment. Semin Immunol. 2012;24:365–72.
Article
CAS
PubMed
PubMed Central
Google Scholar
Larbi A, Pawelec G, Wong SC, Goldeck D, Tai JJ-Y, Fulop T. Impact of age on T cell signaling: a general defect or specific alterations? Ageing Res Rev. 2011;10:370–8.
Article
CAS
PubMed
Google Scholar
Pawelec G. Immunosenenescence: role of cytomegalovirus. Exp Gerontol. 2014;54:1–5.
Article
CAS
PubMed
Google Scholar
Tan AT, Linster M, Tan CW, Le Bert N, Chia WN, Kunasegaran K, et al. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep. 2021;34:108728.
Article
CAS
PubMed
PubMed Central
Google Scholar
Schulien I, Kemming J, Oberhardt V, Wild K, Seidel LM, Killmer S, et al. Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells. Nat Med. 2021;27:78–85.
Article
CAS
PubMed
Google Scholar
Moss P. The T cell immune response against SARS-CoV-2. Nat Immunol. 2022;23:186–93.
Article
CAS
PubMed
Google Scholar
Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020;181:1489–1501.e15.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wu F, Wang A, Liu M, Wang Q, Chen J, Xia S, et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. medRxiv; 2020. (https://www.medrxiv.org/content/10.1101/2020.03.30.20047365v2). preprint.
Mannick JB, Morris M, Hockey H-UP, Roma G, Beibel M, Kulmatycki K, et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med. 2018;10:eaaq1564.
Article
PubMed
Google Scholar
Bramante CT, Ingraham NE, Murray TA, Marmor S, Hovertsen S, Gronski J, et al. Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis. Lancet Healthy Longev. 2021;2:e34–41.
Sargiacomo C, Sotgia F, Lisanti MP. COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Aging (Albany NY). 2020;12:6511–7.
Article
CAS
Google Scholar