Activated CD8+CD38+ Cells Are Associated With Worse Clinical Outcome in Hospitalized COVID-19 Patients

. 2022 ; 13 () : 861666. [epub] 20220314

Jazyk angličtina Země Švýcarsko Médium electronic-ecollection

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid35392095

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, NK cells, CD4+CD45RO+), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8+CD38+ cells and significantly lower proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8+CD38+cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.

Zobrazit více v PubMed

Worldometer . COVID-19 Coronavirus Pandemic (2022). Available at: https://www.worldometers.info/coronavirus/ (Accessed January 14, 2022).

Kwok KO, McNeil EB, Tsoi MTF, Wei VWI, Wong SYS, Tang JWT. Will Achieving Herd Immunity be a Road to Success to End the COVID-19 Pandemic? J Infect (2021) 83(3):381–412. doi: 10.1016/j.jinf.2021.06.007 PubMed DOI PMC

Heaton PM. Herd Immunity: The Journey Is as Important as the Destination. J Infect Dis (2021) 224(6):931–3. doi: 10.1093/infdis/jiab234 PubMed DOI PMC

Jung J. A Long Way to the Recovery: COVID-19 Will Not Disappear. J Korean Med Sci (2021) 36(32):e231. doi: 10.3346/jkms.2021.36.e231 PubMed DOI PMC

National Institute of Health . Clinical Spectrum of SARS-CoV-2 Infection (2021). Available at: https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/ (Accessed January 14 2022).

Siddiqi HK, Mehra MR. COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal. J Heart Lung Transplant (2020) 39(5):405–7. doi: 10.1016/j.healun.2020.03.012 PubMed DOI PMC

Gao YD, Ding M, Dong X, Zhang JJ, Kursat Azkur A, Azkur D, et al. . Risk Factors for Severe and Critically Ill COVID-19 Patients: A Review. Allergy (2021) 76(2):428–55. doi: 10.1111/all.14657 PubMed DOI

Malik P, Patel U, Mehta D, Patel N, Kelkar R, Akrmah M, et al. . Biomarkers and Outcomes of COVID-19 Hospitalisations: Systematic Review and Meta-Analysis. BMJ Evid Based Med (2021) 26(3):107–8. doi: 10.1136/bmjebm-2020-111536 PubMed DOI PMC

Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers Associated With COVID-19 Disease Progression. Crit Rev Clin Lab Sci (2020) 57(6):389–99. doi: 10.1080/10408363.2020.1770685 PubMed DOI PMC

Baranovicova E, Bobcakova A, Vysehradsky R, Dankova Z, Halasova E, Nosal V, et al. . The Ability to Normalise Energy Metabolism in Advanced COVID-19 Disease Seems to Be One of the Key Factors Determining the Disease Progression – A Metabolomic NMR Study on Blood Plasma. Appl Sci (2021) 11(9):4231. doi: 10.3390/app11094231 DOI

Bobcakova A, Petriskova J, Vysehradsky R, Kocan I, Kapustova L, Barnova M, et al. . Immune Profile in Patients With COVID-19: Lymphocytes Exhaustion Markers in Relationship to Clinical Outcome. Front Cell Infect Microbiol (2021) 11:646688. doi: 10.3389/fcimb.2021.646688 PubMed DOI PMC

Jesenak M, Brndiarova M, Urbancikova I, Rennerova Z, Vojtkova J, Bobcakova A, et al. . Immune Parameters and COVID-19 Infection - Associations With Clinical Severity and Disease Prognosis. Front Cell Infect Microbiol (2020) 10:364. doi: 10.3389/fcimb.2020.00364 PubMed DOI PMC

Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. . Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol (2020) 11:827. doi: 10.3389/fimmu.2020.00827 PubMed DOI PMC

Huang W, Berube J, McNamara M, Saksena S, Hartman M, Arshad T, et al. . Lymphocyte Subset Counts in COVID-19 Patients: A Meta-Analysis. Cytometry A (2020) 97(8):772–6. doi: 10.1002/cyto.a.24172 PubMed DOI PMC

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. . Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis (2020) 71(15):762–8. doi: 10.1093/cid/ciaa248 PubMed DOI PMC

Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. . Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia. J Infect Dis (2020) 221(11):1762–9. doi: 10.1093/infdis/jiaa150 PubMed DOI PMC

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(6508):eabc8511. doi: 10.1126/science.abc8511 PubMed DOI PMC

Liu K, Yang T, Peng XF, Lv SM, Ye XL, Zhao TS, et al. . A Systematic Meta-Analysis of Immune Signatures in Patients With COVID-19. Rev Med Virol (2021) 31(4):e2195. doi: 10.1002/rmv.2195 PubMed DOI PMC

European Centre for Disease Prevention and Control . SARS-CoV-2 Variants of Concern as of 10 February 2022 (2022). Available at: https://www.ecdc.europa.eu/en/covid-19/variants-concern (Accessed February 10, 2022).

Úrad verejného zdravotníctva Slovenskej republiky . Výsledky Sekvenovania Pozitívnych Vzoriek (2021). Available at: www.uvzsr.sk (Accessed February 10, 2022).

Rahman A, Niloofa R, Jayarajah U, De Mel S, Abeysuriya V, Seneviratne SL. Hematological Abnormalities in COVID-19: A Narrative Review. Am J Trop Med Hyg (2021) 104(4):1188–201. doi: 10.4269/ajtmh.20-1536 PubMed DOI PMC

Lippi G, Plebani M, Henry BM. Thrombocytopenia Is Associated With Severe Coronavirus Disease 2019 (COVID-19) Infections: A Meta-Analysis. Clin Chim Acta (2020) 506:145–8. doi: 10.1016/j.cca.2020.03.022 PubMed DOI PMC

Yang X, Yang Q, Wang Y, Wu Y, Xu J, Yu Y, et al. . Thrombocytopenia and Its Association With Mortality in Patients With COVID-19. J Thromb Haemost (2020) 18(6):1469–72. doi: 10.1111/jth.14848 PubMed DOI PMC

Sun S, Cai X, Wang H, He G, Lin Y, Bi L, et al. . Abnormalities of Peripheral Blood System in Patients With COVID-19 in Wenzhou, China. Clin Chim Acta (2020) 507:174–80. doi: 10.1016/j.cca.2020.04.024 PubMed DOI PMC

Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases With Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis (2020) 71(15):769–77. doi: 10.1093/cid/ciaa272 PubMed DOI PMC

Li YX, Wu W, Yang T, Zhou W, Fu YM, Feng QM, et al. . Characteristics of Peripheral Blood Leukocyte Differential Counts in Patients With COVID-19. Zhonghua Nei Ke Za Zhi (2020) 59(5):372–4. doi: 10.3760/cma.j.cn112138-20200221-00114 PubMed DOI

Jesenak M, Banovcin P, Diamant Z. COVID-19, Chronic Inflammatory Respiratory Diseases and Eosinophils-Observations From Reported Clinical Case Series. Allergy (2020) 75(7):1819–22. doi: 10.1111/all.14353 PubMed DOI

Liu F, Xu A, Zhang Y, Xuan W, Yan T, Pan K, et al. . Patients of COVID-19 may Benefit From Sustained Lopinavir-Combined Regimen and the Increase of Eosinophil may Predict the Outcome of COVID-19 Progression. Int J Infect Dis (2020) 95:183–91. doi: 10.1016/j.ijid.2020.03.013 PubMed DOI PMC

Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. . Clinical Characteristics of 140 Patients Infected With SARS-CoV-2 in Wuhan, China. Allergy (2020) 75(7):1730–41. doi: 10.1111/all.14238 PubMed DOI

Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. . Clinical Features of 85 Fatal Cases of COVID-19 From Wuhan. A Retrospective Observational Study. Am J Respir Crit Care Med (2020) 201(11):1372–9. doi: 10.1164/rccm.202003-0543OC PubMed DOI PMC

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(7):934–43. doi: 10.1001/jamainternmed.2020.0994 PubMed DOI PMC

Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. . Clinical Characteristics of Refractory Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis (2021) 73(11):e4208–13. doi: 10.1093/cid/ciaa270 PubMed DOI PMC

Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, et al. . Clinical Features and Treatment of COVID-19 Patients in Northeast Chongqing. J Med Virol (2020) 92(7):797–806. doi: 10.1002/jmv.25783 PubMed DOI PMC

He R, Lu Z, Zhang L, Fan T, Xiong R, Shen X, et al. . The Clinical Course and Its Correlated Immune Status in COVID-19 Pneumonia. J Clin Virol (2020) 127:104361. doi: 10.1016/j.jcv.2020.104361 PubMed DOI PMC

Liu K, Yang T, Peng XF, Lv SM, Ye XL, Zhao TS, et al. . A Systematic Meta-Analysis of Immune Signatures in Patients With COVID-19. Rev Med Virol (2021) 31(4):e2195. doi: 10.1002/rmv.2195 PubMed DOI PMC

Lippi G, Henry BM. Eosinophil Count in Severe Coronavirus Disease 2019. QJM (2020) 113(7):511–2. doi: 10.1093/qjmed/hcaa137 PubMed DOI PMC

Shaw AC, Goldstein DR, Montgomery RR. Age-Dependent Dysregulation of in- Nate Immunity. Nat Rev Immunol (2013) 13(12):875–87. doi: 10.1038/nri3547 PubMed DOI PMC

Kapustova L, Petrovicova O, Banovcin P, Antosova M, Bobcakova A, Urbancikova I, et al. . COVID-19 and the Differences in Physiological Background Between Children and Adults and Their Clinical Consequences. Physiol Res (2021) 70(S2):S209–25. doi: 10.33549/physiolres.934759 PubMed DOI PMC

Wang F, Hou H, Luo Y, Tang G, Wu S, Huang M, et al. . The Laboratory Tests and Host Immunity of COVID-19 Patients With Different Severity of Illness. JCI Insight (2020) 5(10):e137799. doi: 10.1172/jci.insight.137799 PubMed DOI PMC

Barnova M, Bobcakova A, Urdova V, Kosturiak R, Kapustova L, Dobrota D, et al. . Inhibitory Immune Checkpoint Molecules and Exhaustion of T Cells in COVID-19. Physiol Res (2021) 70(S2):S227–47. doi: 10.33549/physiolres.934757 PubMed DOI PMC

Ely KH, Matsuoka M, DeBerge MP, Ruby JA, Liu J, Schneider MJ, et al. . Tissue-Protective Effects of NKG2A in Immune-Mediated Clearance of Virus Infection. PloS One (2014) 9(9):e108385. doi: 10.1371/journal.pone.0108385 PubMed DOI PMC

Braud VM, Allan DS, O’Callaghan CA, Söderström K, D’Andrea A, Ogg GS, et al. . HLA-E Binds to Natural Killer Cell Receptors CD94/NKG2A. Nature (1998) 391(6669):795–9. doi: 10.1038/35869 PubMed DOI

Haanen JB, Cerundolo V. NKG2A, A New Kid on the Immune Checkpoint Block. Cell (2018) 175(7):1720–2. doi: 10.1016/j.cell.2018.11.048 PubMed DOI

Zhang C, Wang XM, Li SR, Twelkmeyer T, Wang WH, Zhang SY, et al. . NKG2A Is a NK Cell Exhaustion Checkpoint for HCV Persistence. Nat Commun (2019) 10(1):1507. doi: 10.1038/s41467-019-09212-y PubMed DOI PMC

Rapaport AS, Schriewer J, Gilfillan S, Hembrador E, Crump R, Plougastel BF, et al. . The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8+ T Cells in Response to a Lethal Poxvirus Infection. Immunity (2015) 43(6):1112–24. doi: 10.1016/j.immuni.2015.11.005 PubMed DOI PMC

Gonzalez SM, Taborda NA, Rugeles MT. Role of Different Subpopulations of CD8+ T Cells During HIV Exposure and Infection. Front Immunol (2017) 8:936. doi: 10.3389/fimmu.2017.00936 PubMed DOI PMC

Lindgren T, Ahlm C, Mohamed N, Evander M, Ljunggren HG, Björkström NK. Longitudinal Analysis of the Human T Cell Response During Acute Hantavirus Infection. J Virol (2011) 85(19):10252–60. doi: 10.1128/JVI.05548-11 PubMed DOI PMC

Du J, Wei L, Li G, Hua M, Sun Y, Wang D, et al. . Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19. Front Immunol (2021) 12:735125. doi: 10.3389/fimmu.2021.735125 PubMed DOI PMC

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(5):533–5. doi: 10.1038/s41423-020-0402-2 PubMed DOI PMC

Antonioli L, Fornai M, Pellegrini C, Blandizzi C. NKG2A and COVID-19: Another Brick in the Wall. Cell Mol Immunol (2020) 17(6):672–4. doi: 10.1038/s41423-020-0450-7 PubMed DOI PMC

Martín-Quirós A, Maroun-Eid C, Avendaño-Ortiz J, Lozano-Rodríguez R, Valentín Quiroga J, Terrón V, et al. . Potential Role of the Galectin-9/TIM-3 Axis in the Disparate Progression of SARS-CoV-2 in a Married Couple: A Case Report. BioMed Hub (2021) 6(1):48–58. doi: 10.1159/000514727 PubMed DOI PMC

Herrmann M, Schulte S, Wildner NH, Wittner M, Brehm TT, Ramharter M, et al. . Analysis of Co-Inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium Falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease. Front Immunol (2020) 11:1870. doi: 10.3389/fimmu.2020.01870 PubMed DOI PMC

Varchetta S, Mele D, Oliviero B, Mantovani S, Ludovisi S, Cerino A, et al. . Unique Immunological Profile in Patients With COVID-19. Cell Mol Immunol (2021) 18(3):604–12. doi: 10.1038/s41423-020-00557-9 PubMed DOI PMC

Kong Y, Wang Y, Wu X, Han J, Li G, Hua M, et al. . Storm of Soluble Immune Checkpoints Associated With Disease Severity of COVID-19. Signal Transduct Target Ther (2020) 5(1):192. doi: 10.1038/s41392-020-00308-2 PubMed DOI PMC

Zheng HY, Zhang M, Yang CX, Zhang N, Wang XC, Yang XP, et al. . Elevated Exhaustion Levels and Reduced Functional Diversity of T Cells in Peripheral Blood may Predict Severe Progression in COVID-19 Patients. Cell Mol Immunol (2020) 17(5):541–3. doi: 10.1038/s41423-020-0401-3 PubMed DOI PMC

Schultheiß C, Paschold L, Simnica D, Mohme M, Willscher E, von Wenserski L, et al. . Next-Generation Sequencing of T and B Cell Receptor Repertoires From COVID-19 Patients Showed Signatures Associated With Severity of Disease. Immunity (2020) 53(2):442–455.e4. doi: 10.1016/j.immuni.2020.06.024 PubMed DOI PMC

Li M, Guo W, Dong Y, Wang X, Dai D, Liu X, et al. . Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease. Front Immunol (2020) 11:580237. doi: 10.3389/fimmu.2020.580237 PubMed DOI PMC

Rendeiro AF, Casano J, Vorkas CK, Singh H, Morales A, DeSimone RA, et al. . Profiling of Immune Dysfunction in COVID-19 Patients Allows Early Prediction of Disease Progression. Life Sci Alliance (2020) 4(2):e202000955. doi: 10.26508/lsa.202000955 PubMed DOI PMC

Zelinskyy G, Myers L, Dietze KK, Gibbert K, Roggendorf M, Liu J, et al. . Virus-Specific CD8+ T Cells Upregulate Programmed Death-1 Expression During Acute Friend Retrovirus Infection But Are Highly Cytotoxic and Control Virus Replication. J Immunol (2011) 187(7):3730–7. doi: 10.4049/jimmunol.1101612 PubMed DOI PMC

Legat A, Speiser DE, Pircher H, Zehn D, Fuertes Marraco SA. Inhibitory Receptor Expression Depends More Dominantly on Differentiation and Activation Than “Exhaustion” of Human CD8 T Cells. Front Immunol (2013) 4:455. doi: 10.3389/fimmu.2013.00455 PubMed DOI PMC

Horenstein AL, Faini AC, Malavasi F. CD38 in the Age of COVID-19: A Medical Perspective. Physiol Rev (2021) 101(4):1457–86. doi: 10.1152/physrev.00046.2020 PubMed DOI PMC

Sandalova E, Laccabue D, Boni C, Tan AT, Fink K, Ooi EE, et al. . Contribution of Herpesvirus Specific CD8 T Cells to Anti-Viral T Cell Response in Humans. PloS Pathog (2010) 6(8):e1001051. doi: 10.1371/journal.ppat.1001051 PubMed DOI PMC

Fox A, Le NM, Horby P, van Doorn HR, Nguyen VT, Nguyen HH, et al. . Severe Pandemic H1N1 2009 Infection Is Associated With Transient NK and T Deficiency and Aberrant CD8 Responses. PloS One (2012) 7(2):e31535. doi: 10.1371/journal.pone.0031535 PubMed DOI PMC

Chandele A, Sewatanon J, Gunisetty S, Singla M, Onlamoon N, Akondy RS, et al. . Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients From India. J Virol (2016) 90(24):11259–78. doi: 10.1128/JVI.01424-16 PubMed DOI PMC

Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, et al. . Breadth of Concomitant Immune Responses Prior to Patient Recovery: A Case Report of Non-Severe COVID-19. Nat Med (2020) 26(4):453–5. doi: 10.1038/s41591-020-0819-2 PubMed DOI PMC

Song JW, Zhang C, Fan X, Meng FP, Xu Z, Xia P, et al. . Immunological and Inflammatory Profiles in Mild and Severe Cases of COVID-19. Nat Commun (2020) 11(1):3410. doi: 10.1038/s41467-020-17240-2 PubMed DOI PMC

Zohar T, Loos C, Fischinger S, Atyeo C, Wang C, Slein MD, et al. . Compromised Humoral Functional Evolution Tracks With SARS-CoV-2 Mortality. Cell (2020) 183(6):1508–19.e12. doi: 10.1016/j.cell.2020.10.052 PubMed DOI PMC

Yates JL, Ehrbar DJ, Hunt DT, Girardin RC, Dupuis AP, 2nd, Payne AF, et al. . Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated With COVID-19 Disease Severity. Cell Rep Med (2021) 2(7):100329. doi: 10.1016/j.xcrm.2021.100329 PubMed DOI PMC

Chouaki Benmansour N, Carvelli J, Vivier E. Complement Cascade in Severe Forms of COVID-19: Recent Advances in Therapy. Eur J Immunol (2021) 51(7):1652–9. doi: 10.1002/eji.202048959 PubMed DOI PMC

Sinkovits G, Mező B, Réti M, Müller V, Iványi Z, Gál J, et al. . Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection. Front Immunol (2021) 12:663187. doi: 10.3389/fimmu.2021.663187 PubMed DOI PMC

Soresina A, Moratto D, Chiarini M, Paolillo C, Baresi G, Focà E, et al. . Two X-Linked Agammaglobulinemia Patients Develop Pneumonia as COVID-19 Manifestation But Recover. Pediatr Allergy Immunol (2020) 31(5):565–9. doi: 10.1111/pai.13263 PubMed DOI PMC

Quinti I, Lougaris V, Milito C, Cinetto F, Pecoraro A, Mezzaroma I, et al. . A Possible Role for B Cells in COVID-19? Lesson From Patients With Agammaglobulinemia. J Allergy Clin Immunol (2020) 146(1):211–213.e4. doi: 10.1016/j.jaci.2020.04.013 PubMed DOI PMC

Husain-Syed F, Vadász I, Wilhelm J, Walmrath HD, Seeger W, Birk HW, et al. . Immunoglobulin Deficiency as an Indicator of Disease Severity in Patients With COVID-19. Am J Physiol Lung Cell Mol Physiol (2021) 320(4):L590–9. doi: 10.1152/ajplung.00359.2020 PubMed DOI PMC

Pan P, Du X, Zhou Q, Cui Y, Deng X, Liu C. Characteristics of Lymphocyte Subsets and Cytokine Profiles of Patients With COVID-19. In: ResearchSquare. Available at: https://www.researchsquare.com/article/rs-729194/v1. PubMed PMC

National Institute of Health . Coronavirus Disease 2019 (COVID-19) Treatment Guidelines (2022). Available at: https://www.covid19treatmentguidelines.nih.gov (Accessed on 11 February 2022). PubMed

Biancofiore A, Mirijello A, Puteo MA, Di Viesti MP, Labonia M, Copetti M, et al. . Remdesivir Significantly Reduces SARS-CoV-2 Viral Load on Nasopharyngeal Swabs in Hospitalized Patients With COVID-19: A Retrospective Case-Control Study. J Med Virol (2022) 1–6. doi: 10.1002/jmv.27598 PubMed DOI PMC

Cour M, Simon M, Argaud L, Monneret G, Venet F. Effects of Dexamethasone on Immune Dysfunction and Ventilator-Associated Pneumonia in COVID-19 Acute Respiratory Distress Syndrome: An Observational Study. J Intensive Care (2021) 9(1):64. doi: 10.1186/s40560-021-00580-6 PubMed DOI PMC

Fanhøe U, Ronit A, Berg RMG, Jørgensten SE, Mogensen TH, Underwood AP, et al. . A Unique Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients. medRxiv doi: 10.1101/2022.01.12.22269048v1 PubMed DOI PMC

Bronte V, Ugel S, Tinazzi E, Vella A, De Sanctis F, Canè S, et al. . Baricitinib Restrains the Immune Dysregulation in Patients With Severe COVID-19. J Clin Invest (2020) 130(12):6409–16. doi: 10.1172/JCI141772 PubMed DOI PMC

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...