{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:26:56Z","timestamp":1792121216169,"version":"4.4.0"},"reference-count":86,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IFARHU-SENACYT doctoral fellowship","award":["270-2020-117"],"award-info":[{"award-number":["270-2020-117"]}]},{"name":"SNI grants","award":["270-2020-117"],"award-info":[{"award-number":["270-2020-117"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact on global health, with nearly 800 million cases reported in the Americas alone. The clinical presentation of the disease is highly variable, with approximately half of all patients experiencing severe symptoms. This variability confounds the complex interplay between immune responses and disease severity. Severe cases are often characterized by elevated levels of inflammatory cytokines. Over 88% of COVID-19 patients have multiple comorbidities; factors such as age and pre-existing conditions further modulate immune responses and contribute to the severity of the disease. While some studies have reported differences in cytokine profiles between severity groups, larger, well-designed cohorts are needed to clarify these relationships. Natural Killer cells, which are critical for the innate immune response against SARS-CoV-2, are often impaired and contribute to immune exhaustion. In addition, SARS-CoV-2 evades innate immune defenses through accessory proteins that inhibit interferon signaling and exacerbate cytokine storms and inflammation. This integrative review aims to synthesize findings from 2020 onward and provide insights into the innate immune responses induced by SARS-CoV-2 and their contributions to disease pathogenesis. Understanding cytokine dynamics, NK cell behaviors, and viral immune evasion strategies is critical for advancing therapeutic approaches.<\/jats:p>","DOI":"10.3390\/cells14110763","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T10:24:45Z","timestamp":1747909485000},"page":"763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dynamics of Innate Immunity in SARS-CoV-2 Infections: Exploring the Impact of Natural Killer Cells, Inflammatory Responses, Viral Evasion Strategies, and Severity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1951-3594","authenticated-orcid":false,"given":"Juan C.","family":"Batista","sequence":"first","affiliation":[{"name":"Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama City 0816-02593, Panama"},{"name":"MD-PhD Program on Clinical and Biomedical Research, Faculty of Medicine, Universidad de Panam\u00e1, Panama City 0830-00929, Panama"},{"name":"Caja de Seguro Social, Panama City 0816-06808, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2586-4115","authenticated-orcid":false,"given":"Rodrigo","family":"DeAntonio","sequence":"additional","affiliation":[{"name":"MD-PhD Program on Clinical and Biomedical Research, Faculty of Medicine, Universidad de Panam\u00e1, Panama City 0830-00929, Panama"},{"name":"Centro de Vacunaci\u00f3n e Investigaci\u00f3n CEVAXIN, Panama City 0830-00507, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1106-8479","authenticated-orcid":false,"given":"Sandra","family":"L\u00f3pez-Verg\u00e8s","sequence":"additional","affiliation":[{"name":"Department of Research in Virology and Biotechnology, Gorgas Memorial Institute of Health Studies, Panama City 0816-02593, Panama"},{"name":"MD-PhD Program on Clinical and Biomedical Research, Faculty of Medicine, Universidad de Panam\u00e1, Panama City 0830-00929, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shah, V.K., Firmal, P., Alam, A., Ganguly, D., and Chattopadhyay, S. (2020). Overview of Immune Response During SARS-CoV-2 Infection: Lessons from the Past. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01949"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mattoo, S.-U., Kim, S.-J., Ahn, D.-G., and Myoung, J. (2022). Escape and Over-Activation of Innate Immune Responses by SARS-CoV-2: Two Faces of a Coin. Viruses, 14.","DOI":"10.3390\/v14030530"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101533","DOI":"10.1016\/j.smim.2021.101533","article-title":"Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity","volume":"55","author":"Mengist","year":"2021","journal-title":"Semin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104454","DOI":"10.1016\/j.cellimm.2021.104454","article-title":"SARS-CoV-2 peptides bind to NKG2D and increase NK cell activity","volume":"371","author":"Kim","year":"2022","journal-title":"Cell Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00277-021-04735-1","article-title":"Hemophagocytosis, hyper-inflammatory responses, and multiple organ damages in COVID-19-associated hyperferritinemia","volume":"101","author":"Dong","year":"2022","journal-title":"Ann. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Seery, V., Raiden, S.C., Algieri, S.C., Grisol\u00eda, N.A., Filippo, D., De Carli, N., Di Lalla, S., Cairoli, H., Chiolo, M.J., and Meregalli, C.N. (2021). Blood neutrophils from children with COVID-19 exhibit both inflammatory and anti-inflammatory markers. EBioMedicine, 67.","DOI":"10.1016\/j.ebiom.2021.103357"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ling, L., Chen, Z., Lui, G., Wong, C.K., Wong, W.T., Ng, R.W.Y., Tso, E.Y.K., Fung, K.S.C., Chan, V., and Yeung, A.C.M. (2021). Longitudinal Cytokine Profile in Patients with Mild to Critical COVID-19. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.763292"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Inmunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cytogfr.2021.06.001","article-title":"SARS-CoV-2 Mutations and their Viral Variants","volume":"63","author":"Cosar","year":"2022","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zulu, M.Z., Sureshchandra, S., Pinski, A.N., Doratt, B., Shen, W., and Messaoudi, I. (2021). Obesity Correlates with Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.760288"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11684-020-0776-7","article-title":"Innate immune responses in RNA viral infection","volume":"15","author":"Xu","year":"2021","journal-title":"Front. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/j.molcel.2020.11.028","article-title":"Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2","volume":"80","author":"Hekman","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Young, B.E., Wei, W.E., Fong, S.-W., Mak, T.-M., Anderson, D.E., Chan, Y.-H., Pung, R., Heng, C.S., Ang, L.W., and Zheng, A.K.E. (2021). Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study. EBioMedicine, 66.","DOI":"10.1016\/j.ebiom.2021.103319"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1002\/jmv.28000","article-title":"The deciphering of the immune cells and marker signature in COVID-19 pathogenesis: An update","volume":"94","author":"Jasim","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fionda, C., Ruggeri, S., Scium\u00e8, G., Laffranchi, M., Quinti, I., Milito, C., Palange, P., Menichini, I., Sozzani, S., and Frati, L. (2022). Age-dependent NK cell dysfunctions in severe COVID-19 patients. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1039120"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1159\/000328005","article-title":"Immunosenescence of human natural killer cells","volume":"3","author":"Gayoso","year":"2011","journal-title":"J. Innate Immun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Biasizzo, M., and Kopitar-Jerala, N. (2020). Interplay Between NLRP3 Inflammasome and Autophagy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.591803"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00281-020-00793-1","article-title":"Infection-induced epigenetic changes and their impact on the pathogenesis of diseases","volume":"42","author":"Fischer","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12985-022-01783-5","article-title":"The molecular mechanism of SARS-CoV-2 evading host antiviral innate immunity","volume":"19","author":"Gu","year":"2022","journal-title":"Virol. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nagaoka, K., Kawasuji, H., Murai, Y., Kaneda, M., Ueno, A., Miyajima, Y., Fukui, Y., Morinaga, Y., and Yamamoto, Y. (2022). Circulating Type I Interferon Levels in the Early Phase of COVID-19 Are Associated with the Development of Respiratory Failure. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.844304"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sun, X., Gao, C., Zhao, K., Yang, Y., Rassadkina, Y., Fajnzylber, J., Regan, J., Li, J.Z., Lichterfeld, M., and Yu, X.G. (2022). Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.984553"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Della-Torre, E., Lanzillotta, M., Campochiaro, C., Cavalli, G., De Luca, G., Tomelleri, A., Boffini, N., De Lorenzo, R., Ruggeri, A., and Rovere-Querini, P. (2021). Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients with Severe Pneumonia and Hyper-Inflammation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.675678"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2003408","DOI":"10.1183\/13993003.03408-2020","article-title":"A profile of a retrospective cohort of 22 patients with COVID-19 and active\/treated tuberculosis","volume":"56","author":"Gupta","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Vassiliou, A.G., Keskinidou, C., Jahaj, E., Gallos, P., Dimopoulou, I., Kotanidou, A., and Orfanos, S.E. (2021). ICU admission levels of endothelial biomarkers as predictors of mortality in critically ill COVID-19 patients. Cells, 10.","DOI":"10.3390\/cells10010186"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.ymthe.2022.02.014","article-title":"The battle between host and SARS-CoV-2: Innate immunity and viral evasion strategies","volume":"30","author":"Zhang","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1182\/blood-2023-178100","article-title":"Understanding Netosis Priming and Induction through Nucleosome Changes and Real-Time Monitoring in Isolated Neutrophils and in an Ex-Vivo Model","volume":"142","author":"Cayford","year":"2023","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e12828","DOI":"10.15252\/emmm.202012828","article-title":"Humanized COVID-19 decoy antibody effectively blocks viral entry and prevents SARS-CoV-2 infection","volume":"13","author":"Huang","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Latreille, E., and Lee, W.L. (2021). Interactions of Influenza and SARS-CoV-2 with the Lung Endothelium: Similarities, Differences, and Implications for Therapy. Viruses, 13.","DOI":"10.3390\/v13020161"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jakobs, K., Reinshagen, L., Puccini, M., Friebel, J., Wilde, A.-C.B., Alsheik, A., Rroku, A., Landmesser, U., Haghikia, A., and Kr\u00e4nkel, N. (2022). Disease Severity in Moderate-to-Severe COVID-19 Is Associated with Platelet Hyperreactivity and Innate Immune Activation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.844701"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e23583","DOI":"10.1016\/j.heliyon.2023.e23583","article-title":"The immune inflammation factors associated with disease severity and poor prognosis in patients with COVID-19: A retrospective cohort study","volume":"10","author":"Kang","year":"2024","journal-title":"Heliyon"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nasrollahi, H., Talepoor, A.G., Saleh, Z., Vakili, M.E., Heydarinezhad, P., Karami, N., Noroozi, M., Meri, S., and Kalantar, K. (2023). Immune responses in mildly versus critically ill COVID-19 patients. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1077236"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Liu, S., Wang, X., She, F., Zhang, W., Liu, H., and Zhao, X. (2021). Effects of Neutrophil-to-Lymphocyte Ratio Combined with Interleukin-6 in Predicting 28-Day Mortality in Patients with Sepsis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.639735"},{"key":"ref_33","first-page":"1075","article-title":"Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19","volume":"52","author":"Bao","year":"2020","journal-title":"J. Peking Univ. (Health Sci.)"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hutcheon, C., Paulvannan, P., and Subramanian, N. (2016). Cytoplasmic Sensing in Innate Immunity. Encyclopedia of Cell Biology, Elsevier Inc.","DOI":"10.1016\/B978-0-12-394447-4.30108-0"},{"key":"ref_35","first-page":"138","article-title":"NLRP3 inflammasome activation and SARS-CoV-2-mediated hyperinflammation, cytokine storm and neurological syndromes","volume":"14","author":"Dutta","year":"2022","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ku\u015bnierz-Cabala, B., Maziarz, B., Dumnicka, P., Dembi\u0144ski, M., Kapusta, M., Boci\u0105ga-Jasik, M., Winiarski, M., Garlicki, A., Grodzicki, T., and Kukla, M. (2021). Diagnostic Significance of Serum Galectin-3 in Hospitalized Patients with COVID-19-A Preliminary Study. Biomolecules, 11.","DOI":"10.3390\/biom11081136"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"L\u00e9cuyer, D., Nardacci, R., Tannous, D., Gutierrez-Mateyron, E., Nathan, A.D., Subra, F., Di Primio, C., Quaranta, P., Petit, V., and Richetta, C. (2023). The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1270081"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12985-024-02506-8","article-title":"Aggravating mechanisms from COVID-19","volume":"21","author":"Lee","year":"2024","journal-title":"Virol. J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ulrich, C., Wildgrube, S., Fiedler, R., Seibert, E., Kneser, L., Fick, S., Sch\u00e4fer, C., Markau, S., Trojanowicz, B., and Girndt, M. (2020). NLRP3 Inflammasome Activation in Hemodialysis and Hypertensive Patients with Intact Kidney Function. Toxins, 12.","DOI":"10.3390\/toxins12110675"},{"key":"ref_40","first-page":"545","article-title":"Role of inflammasome NLRP3 in the pathophysiology of viral infections: A focus on SARS-CoV-2 infection","volume":"38","author":"Chemarin","year":"2022","journal-title":"Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/JLB.3COVA0820-410RRR","article-title":"Cytokine release syndrome in COVID-19: Innate immune, vascular, and platelet pathogenic factors differ in severity of disease and sex","volume":"109","author":"Petrey","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"167","DOI":"10.52403\/ijshr.20240225","article-title":"Role of Interleukin-6 as a Predictor in Assessing Severity of COVID-19 Patients: A Hospital Based Cross-Sectional Study","volume":"9","author":"Afrin","year":"2024","journal-title":"Int. J. Sci. Healthc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, L., Li, J., Gao, M., Fan, H., Wang, Y., Xu, X., Chen, C., Liu, J., Kim, J., and Aliyari, R. (2021). Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.602395"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2147\/JIR.S275570","article-title":"Serum and urine interleukin-6 and interleukin-8 levels do not differentiate acute pyelonephritis from lower urinary tract infections in children","volume":"13","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e177896","DOI":"10.1172\/JCI177896","article-title":"Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome","volume":"134","author":"Yehya","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2217\/fmb-2024-0010","article-title":"JN.1: Ongoing considerations of the shifting landscape of SARS-CoV-2 variants","volume":"19","author":"Basu","year":"2024","journal-title":"Future Microbiol."},{"key":"ref_47","first-page":"70","article-title":"ANALYSIS OF IMMUNE CELLS AND IMMUNOLOGICAL PROCESSES IN COVID-19","volume":"4","author":"Zaripov","year":"2024","journal-title":"Int. J. Med. Sci. Clin. Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kempaiah, P., Libertin, C.R., Chitale, R.A., Naeyma, I., Pleqi, V., Sheele, J.M., Iandiorio, M.J., Hoogesteijn, A.L., Caulfield, T.R., and Rivas, A.L. (2024). Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040871"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lionetto, L., Ulivieri, M., Capi, M., De Bernardini, D., Fazio, F., Petrucca, A., Pomes, L.M., De Luca, O., Gentile, G., and Casolla, B. (2021). Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study. Biochim. Biophys. Acta Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2020.166042"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eabe3024","DOI":"10.1126\/sciadv.abe3024","article-title":"Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm","volume":"6","author":"Mudd","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.55730\/1300-0144.5686","article-title":"Alterations in B and NK cells highly correlate with disease severity in children with COVID-19","volume":"53","author":"Topyildiz","year":"2023","journal-title":"Turk. J. Med. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Park, B.K., Kim, D., Park, S., Maharjan, S., Kim, J., Choi, J.-K., Akauliya, M., Lee, Y., and Kwon, H.-J. (2021). Differential signaling and virus production in Calu-3 cells and vero cells upon SARS-CoV-2 infection. Biomol. Ther., 29.","DOI":"10.4062\/biomolther.2020.226"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Park, J., Dean, L.S., Jiyarom, B., Gangcuangco, L.M., Shah, P., Awamura, T., Ching, L.L., Nerurkar, V.R., Chow, D.C., and Igno, F. (2023). Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1151780"},{"key":"ref_54","first-page":"100215","article-title":"Persistence of circulating CD169+monocytes and HLA-DR downregulation underline the immune response impairment in PASC individuals: The potential contribution of different COVID-19 pandemic waves","volume":"6","author":"Fanelli","year":"2024","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e13038","DOI":"10.15252\/emmm.202013038","article-title":"Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID-19 in type 2 diabetes","volume":"12","author":"Alzaid","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kennedy, A.E., Cook, L., Breznik, J.A., Cowbrough, B., Wallace, J.G., Huynh, A., Smith, J.W., Son, K., Stacey, H., and Ang, J. (2021). Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections. Viruses, 13.","DOI":"10.1101\/2021.09.25.21264117"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102512","DOI":"10.1016\/j.jaut.2020.102512","article-title":"Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab","volume":"114","author":"Morrison","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.humimm.2020.08.006","article-title":"Characteristics of immune cells and cytokines in patients with coronavirus disease 2019 in Guangzhou, China","volume":"81","author":"Chen","year":"2020","journal-title":"Hum. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Moin, A.S.M., Sathyapalan, T., Diboun, I., Atkin, S.L., and Butler, A.E. (2021). Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85760-y"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e13102","DOI":"10.1111\/sji.13102","article-title":"Perforin, COVID-19 and a possible pathogenic auto-inflammatory feedback loop","volume":"94","author":"Cunningham","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s12931-020-01546-2","article-title":"Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients\u2019 performance: A prospective observational cohort study","volume":"21","author":"Sonnweber","year":"2020","journal-title":"Respir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40164-021-00199-1","article-title":"Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients","volume":"10","author":"Bao","year":"2021","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12979-024-00426-3","article-title":"Changes in the innate immune response to SARS-CoV-2 with advancing age in humans","volume":"21","author":"Agrawal","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s13238-020-00762-2","article-title":"A human circulating immune cell landscape in aging and COVID-19","volume":"11","author":"Zheng","year":"2020","journal-title":"Protein Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1038\/s41590-023-01560-8","article-title":"Defining the role of natural killer cells in COVID-19","volume":"24","author":"Lee","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/jleuko\/qiad031","article-title":"NK cells in COVID-19-from disease to vaccination","volume":"114","author":"Hammer","year":"2023","journal-title":"J. Leukoc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1016\/j.immuni.2021.09.002","article-title":"Early IFN-\u03b1 signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19","volume":"54","author":"Knoll","year":"2021","journal-title":"Immunity"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113872","DOI":"10.1016\/j.celrep.2024.113872","article-title":"Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer","volume":"43","author":"Chen","year":"2024","journal-title":"Cell Rep."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Njiomegnie, G.F., Read, S.A., Fewings, N., George, J., McKay, F., and Ahlenstiel, G. (2020). Immunomodulation of the natural killer cell phenotype and response during HCV infection. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041030"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e20211381","DOI":"10.1084\/jem.20211381","article-title":"TIM3+ TRBV11-2 T cells and IFN\u03b3 signature in patrolling monocytes and CD16+ NK cells delineate MIS-C","volume":"219","author":"Hoste","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5942","DOI":"10.1172\/JCI141113","article-title":"Distinct clinical and immunological features of SARS\u2013CoV-2\u2013induced multisystem inflammatory syndrome in children","volume":"130","author":"Lee","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e1151","DOI":"10.1097\/CCM.0000000000005093","article-title":"Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children with Shock","volume":"49","author":"Borgel","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Casado, J.L., Moraga, E., Vizcarra, P., Velasco, H., Mart\u00edn-Hondarza, A., Haemmerle, J., G\u00f3mez, S., Quereda, C., and Vallejo, A. (2022). Expansion of cd56dim cd16neg nk cell subset and increased inhibitory kirs in hospitalized COVID-19 patients. Viruses, 14.","DOI":"10.3390\/v14010046"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Masselli, E., Vaccarezza, M., Carubbi, C., Pozzi, G., Presta, V., Mirandola, P., and Vitale, M. (2020). NK cells: A double edge sword against SARS-CoV-2. Adv. Biol. Regul., 77.","DOI":"10.1016\/j.jbior.2020.100737"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zandi, M., Shafaati, M., Kalantar-Neyestanaki, D., Pourghadamyari, H., Fani, M., Soltani, S., Kaleji, H., and Abbasi, S. (2022). The role of SARS-CoV-2 accessory proteins in immune evasion. Biomed. Pharmacother., 156.","DOI":"10.1016\/j.biopha.2022.113889"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e2208525120","DOI":"10.1073\/pnas.2208525120","article-title":"SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to down-regulate MHC-I surface expression","volume":"120","author":"Arshad","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zhang, J., Hom, K., Zhang, C., Nasr, M., Gerzanich, V., Zhang, Y., Tang, Q., Xue, F., Simard, J.M., and Zhao, R.Y. (2024). SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects. Pathogens, 13.","DOI":"10.3390\/pathogens13010075"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41435-020-00120-6","article-title":"Evolutionary and structural analysis of SARS-CoV-2 specific evasion of host immunity","volume":"21","author":"Hussain","year":"2020","journal-title":"Genes Immun."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Low, Z.Y., Zabidi, N.Z., Yip, A.J.W., Puniyamurti, A., Chow, V.T.K., and Lal, S.K. (2022). SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion. Viruses, 14.","DOI":"10.3390\/v14091991"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41392-021-00703-3","article-title":"Differential immune responses in pregnant patients recovered from COVID-19","volume":"6","author":"Chen","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.medj.2021.04.016","article-title":"Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface","volume":"2","author":"Chavan","year":"2021","journal-title":"Med"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Farias-Jofre, M., Romero, R., Xu, Y., Levenson, D., Tao, L., Kanninen, T., Galaz, J., Arenas-Hernandez, M., Liu, Z., and Miller, D. (2023). Differential immunophenotype of circulating monocytes from pregnant women in response to viral ligands. BMC Pregnancy Childbirth, 23.","DOI":"10.1186\/s12884-023-05562-0"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5","DOI":"10.20538\/1682-0363-2024-2-5-13","article-title":"Effect of COVID-19 infection in the third trimester of pregnancy on innate immunity parameters, association with obstetric and perinatal outcomes","volume":"23","author":"Andrievskaya","year":"2024","journal-title":"Bull. Sib. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e13828","DOI":"10.1111\/aji.13828","article-title":"Pregnant individuals with uncomplicated pregnancies display pro-inflammatory immune changes when exposed to the COVID-19 pandemic","volume":"91","author":"Bernier","year":"2024","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chambers, C.D., Song, J., Antunes, R.d.S., Sette, A., and Franco, A. (2024). T Cell Responses in Pregnant Women Who Received mRNA-Based Vaccination to Prevent COVID-19 Revealed Unknown Exposure to the Natural Infection and Numerous SARS-CoV-2-Specific CD4- CD8- Double Negative T Cells and Regulatory T Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042031"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Aziz, N.H.A., Salker, M.S., Lankapalli, A.K., Shafiee, M.N., Kocak, E., Sekhar Pal, S., Khalid, O., Kasim, N.M., Kalok, A., and Fuad, N.A. (2022). Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cell in recovered COVID-19 pregnant women. bioRxiv.","DOI":"10.1101\/2022.08.18.504053"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/11\/763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:38:34Z","timestamp":1760031514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/11\/763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":86,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cells14110763"],"URL":"https:\/\/doi.org\/10.3390\/cells14110763","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,22]]}}}