Lymphocyte subsets early predict mortality in a large series of hospitalized COVID‐19 patients in Spain
Disbalanced lymphocyte subpopulations are early markers of mortality in our series of 701 SARS‐CoV‐2 infected patients, when severe lymphopenia has yet to develop. If available, the study of lymphocyte subsets by flow cytometry is recommended to identify high‐risk COVID‐19 patients at hospital admis...
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| Veröffentlicht in: | Clinical and experimental immunology 2021-03, Vol.203 (3), p.424-432 |
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| creator | Cantenys‐Molina, S. Fernández‐Cruz, E. Francos, P. Lopez Bernaldo de Quirós, J. C. Muñoz, P. Gil‐Herrera, J. |
| description | Disbalanced lymphocyte subpopulations are early markers of mortality in our series of 701 SARS‐CoV‐2 infected patients, when severe lymphopenia has yet to develop. If available, the study of lymphocyte subsets by flow cytometry is recommended to identify high‐risk COVID‐19 patients at hospital admission.
Summary
The role of lymphocytes and their main subsets as prognostic factors of death in SARS‐CoV‐2‐infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)‐confirmed consecutive patients by lysed–no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3‐month follow‐up. The 112 patients who died were older and had significantly higher frequencies of known co‐morbidities than survivor COVID‐19 patients. A significant reduction in total lymphocytes, CD3+, CD4+, CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P |
| doi_str_mv | 10.1111/cei.13547 |
| format | Article |
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Summary
The role of lymphocytes and their main subsets as prognostic factors of death in SARS‐CoV‐2‐infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)‐confirmed consecutive patients by lysed–no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3‐month follow‐up. The 112 patients who died were older and had significantly higher frequencies of known co‐morbidities than survivor COVID‐19 patients. A significant reduction in total lymphocytes, CD3+, CD4+, CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+/CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in‐hospital death associated to age [odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9–3·0 P < 0·001]; CD4+ T counts ≤ 500 cells/μl, (OR = 2·79, 95% CI = 1·1–6·7, P = 0·021); CD8+ T counts ≤ 100 cells/μl, (OR = 1·98, 95% CI = 1·2–3·3) P = 0·009) and CD56+/CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1–3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co‐morbidities, with area under the curve 0·85 (95% CI = 0·81–0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID‐19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in‐hospital mortality.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/cei.13547</identifier><identifier>PMID: 33187018</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Age Factors ; Aged ; Aged, 80 and over ; Antigens, CD - blood ; CD16 antigen ; CD19 antigen ; CD3 antigen ; CD4 antigen ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - metabolism ; CD56 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - metabolism ; COVID-19 ; COVID-19 - blood ; COVID-19 - mortality ; Death ; Electronic medical records ; Female ; Flow cytometry ; Follow-Up Studies ; Hospital Mortality ; Humans ; lymphocyte subsets ; Lymphocytes ; Lymphocytes T ; Lymphopenia ; Male ; Middle Aged ; Mortality ; Natural killer cells ; organization ; Original ; Patients ; Peripheral blood ; Polymerase chain reaction ; Predictive Value of Tests ; prognosis ; SARS-CoV-2 - metabolism ; Severe acute respiratory syndrome coronavirus 2 ; Spain ; Statistical analysis ; T-Lymphocyte Subsets - metabolism</subject><ispartof>Clinical and experimental immunology, 2021-03, Vol.203 (3), p.424-432</ispartof><rights>2020 The Authors. published by John Wiley & Sons Ltd on behalf of British Society for Immunology</rights><rights>2020 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4717-75a0e842950166dd85068ea514743ebd263ba9478b0bcabe7618cf51074bda763</citedby><cites>FETCH-LOGICAL-c4717-75a0e842950166dd85068ea514743ebd263ba9478b0bcabe7618cf51074bda763</cites><orcidid>0000-0002-2297-9665 ; 0000-0001-6054-1069</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753314/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753314/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33187018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cantenys‐Molina, S.</creatorcontrib><creatorcontrib>Fernández‐Cruz, E.</creatorcontrib><creatorcontrib>Francos, P.</creatorcontrib><creatorcontrib>Lopez Bernaldo de Quirós, J. C.</creatorcontrib><creatorcontrib>Muñoz, P.</creatorcontrib><creatorcontrib>Gil‐Herrera, J.</creatorcontrib><title>Lymphocyte subsets early predict mortality in a large series of hospitalized COVID‐19 patients in Spain</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Disbalanced lymphocyte subpopulations are early markers of mortality in our series of 701 SARS‐CoV‐2 infected patients, when severe lymphopenia has yet to develop. If available, the study of lymphocyte subsets by flow cytometry is recommended to identify high‐risk COVID‐19 patients at hospital admission.
Summary
The role of lymphocytes and their main subsets as prognostic factors of death in SARS‐CoV‐2‐infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)‐confirmed consecutive patients by lysed–no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3‐month follow‐up. The 112 patients who died were older and had significantly higher frequencies of known co‐morbidities than survivor COVID‐19 patients. A significant reduction in total lymphocytes, CD3+, CD4+, CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+/CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in‐hospital death associated to age [odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9–3·0 P < 0·001]; CD4+ T counts ≤ 500 cells/μl, (OR = 2·79, 95% CI = 1·1–6·7, P = 0·021); CD8+ T counts ≤ 100 cells/μl, (OR = 1·98, 95% CI = 1·2–3·3) P = 0·009) and CD56+/CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1–3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co‐morbidities, with area under the curve 0·85 (95% CI = 0·81–0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID‐19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in‐hospital mortality.</description><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, CD - blood</subject><subject>CD16 antigen</subject><subject>CD19 antigen</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD56 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>COVID-19</subject><subject>COVID-19 - blood</subject><subject>COVID-19 - mortality</subject><subject>Death</subject><subject>Electronic medical records</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Follow-Up Studies</subject><subject>Hospital Mortality</subject><subject>Humans</subject><subject>lymphocyte subsets</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphopenia</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Natural killer cells</subject><subject>organization</subject><subject>Original</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Polymerase chain reaction</subject><subject>Predictive Value of Tests</subject><subject>prognosis</subject><subject>SARS-CoV-2 - metabolism</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spain</subject><subject>Statistical analysis</subject><subject>T-Lymphocyte Subsets - metabolism</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp1kcFOHCEch4nR6Nb24AsYEi_2MAozDDAXk2ZrdZNNPGh7JQzzXxczM4wwUzM99RH6jH0S0V03aiIXQvj4-MEPoQNKTmgcpwbsCc1yJrbQhGY8T9KUFdtoQggpkoIStoc-hXAXl5zzdBftZRmVglA5QXY-Nt3SmbEHHIYyQB8waF-PuPNQWdPjxvle17YfsW2xxrX2txEFbyFgt8BLFzr7BPyBCk-vfs2-___7jxa4072FNtriqetO2_Yz2lnoOsCX9byPfv44v5leJvOri9n02zwxTFCRiFwTkCwtckI5ryqZEy5B55QJlkFZpTwrdcGELElpdAmCU2kWOSWClZUWPNtHZytvN5QNVCaG8LpWnbeN9qNy2qq3O61dqlv3WwmRx39hUXC8Fnh3P0DoVWODgbrWLbghqJRxEu_JiIjo0Tv0zg2-jc-LlBSCSZqSSH1dUca7EDwsNmEoUU8Fqligei4wsoev02_Il8YicLoCHmwN48cmNT2frZSPphml_Q</recordid><startdate>202103</startdate><enddate>202103</enddate><creator>Cantenys‐Molina, S.</creator><creator>Fernández‐Cruz, E.</creator><creator>Francos, P.</creator><creator>Lopez Bernaldo de Quirós, J. C.</creator><creator>Muñoz, P.</creator><creator>Gil‐Herrera, J.</creator><general>Oxford University Press</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2297-9665</orcidid><orcidid>https://orcid.org/0000-0001-6054-1069</orcidid></search><sort><creationdate>202103</creationdate><title>Lymphocyte subsets early predict mortality in a large series of hospitalized COVID‐19 patients in Spain</title><author>Cantenys‐Molina, S. ; Fernández‐Cruz, E. ; Francos, P. ; Lopez Bernaldo de Quirós, J. 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C.</creatorcontrib><creatorcontrib>Muñoz, P.</creatorcontrib><creatorcontrib>Gil‐Herrera, J.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cantenys‐Molina, S.</au><au>Fernández‐Cruz, E.</au><au>Francos, P.</au><au>Lopez Bernaldo de Quirós, J. C.</au><au>Muñoz, P.</au><au>Gil‐Herrera, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lymphocyte subsets early predict mortality in a large series of hospitalized COVID‐19 patients in Spain</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2021-03</date><risdate>2021</risdate><volume>203</volume><issue>3</issue><spage>424</spage><epage>432</epage><pages>424-432</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><abstract>Disbalanced lymphocyte subpopulations are early markers of mortality in our series of 701 SARS‐CoV‐2 infected patients, when severe lymphopenia has yet to develop. If available, the study of lymphocyte subsets by flow cytometry is recommended to identify high‐risk COVID‐19 patients at hospital admission.
Summary
The role of lymphocytes and their main subsets as prognostic factors of death in SARS‐CoV‐2‐infected patients remains unclear, with no information obtained from patients outside China. We aimed to assess whether measuring lymphocyte subpopulations added clinical value to the total lymphocyte counting regarding mortality when they were simultaneously tested at hospital admission. Peripheral blood was analysed in 701 polymerase chain reaction (PCR)‐confirmed consecutive patients by lysed–no washed flow cytometry. Demographic and clinical features were registered in electronic medical records. Statistical analysis was performed after a 3‐month follow‐up. The 112 patients who died were older and had significantly higher frequencies of known co‐morbidities than survivor COVID‐19 patients. A significant reduction in total lymphocytes, CD3+, CD4+, CD8+ and CD19+ counts and CD3+ percentage was found in the group of deceased patients (P < 0·001), while the percentage of CD56+/CD16+ natural killer (NK) cells was significantly higher (P < 0·001). Multivariate logistic regression analysis showed a significantly increased risk of in‐hospital death associated to age [odds ratio (OR) = 2·36, 95% confidence interval (CI) = 1·9–3·0 P < 0·001]; CD4+ T counts ≤ 500 cells/μl, (OR = 2·79, 95% CI = 1·1–6·7, P = 0·021); CD8+ T counts ≤ 100 cells/μl, (OR = 1·98, 95% CI = 1·2–3·3) P = 0·009) and CD56+/CD16+ NK ≥ 30%, (OR = 1·97, 95% CI = 1·1–3·1, P = 0·002) at admission, independent of total lymphocyte numbers and co‐morbidities, with area under the curve 0·85 (95% CI = 0·81–0·88). Reduced counts of CD4+ and CD8+ T cells with proportional expansion of NK lymphocytes at admission were prognostic factors of death in this Spanish series. In COVID‐19 patients with normal levels of lymphocytes or mild lymphopenia, imbalanced lymphocyte subpopulations were early markers of in‐hospital mortality.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33187018</pmid><doi>10.1111/cei.13547</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2297-9665</orcidid><orcidid>https://orcid.org/0000-0001-6054-1069</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Factors Aged Aged, 80 and over Antigens, CD - blood CD16 antigen CD19 antigen CD3 antigen CD4 antigen CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - metabolism CD56 antigen CD8 antigen CD8-Positive T-Lymphocytes - metabolism COVID-19 COVID-19 - blood COVID-19 - mortality Death Electronic medical records Female Flow cytometry Follow-Up Studies Hospital Mortality Humans lymphocyte subsets Lymphocytes Lymphocytes T Lymphopenia Male Middle Aged Mortality Natural killer cells organization Original Patients Peripheral blood Polymerase chain reaction Predictive Value of Tests prognosis SARS-CoV-2 - metabolism Severe acute respiratory syndrome coronavirus 2 Spain Statistical analysis T-Lymphocyte Subsets - metabolism |
| title | Lymphocyte subsets early predict mortality in a large series of hospitalized COVID‐19 patients in Spain |
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