Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis
To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as marker...
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| description | To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19.
We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/μl and -123.6 (-170.6, -76.6) cells/μl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml).
Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19. |
| doi_str_mv | 10.1371/journal.pone.0239802 |
| format | Article |
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We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/μl and -123.6 (-170.6, -76.6) cells/μl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml).
Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0239802</identifier><identifier>PMID: 33002041</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive immunity ; Betacoronavirus ; Biological markers ; Biology and Life Sciences ; C-reactive protein ; C-Reactive Protein - analysis ; Calcium-binding protein ; CD4 antigen ; CD8 antigen ; Confidence intervals ; Coronavirus Infections - diagnosis ; Coronavirus Infections - pathology ; Coronaviruses ; COVID-19 ; Dehydrogenases ; Diabetes ; Diagnosis ; Dimers ; Dyspnea ; Epidemiology ; Fibrin Fibrinogen Degradation Products - analysis ; Health risks ; Humans ; Immune response ; Immune system ; Infections ; Innate immunity ; Intensive care ; Interleukin ; Interleukin 6 ; Interleukin-6 - blood ; Life Sciences ; Literature reviews ; Lymphocyte Count ; Lymphocytes ; Lymphocytes T ; Markers ; Medical laboratories ; Medical research ; Medicine and Health Sciences ; Meta-analysis ; Multiple organ dysfunction syndrome ; Observational Studies as Topic ; Oxygen saturation ; Pandemics ; Parameters ; Physical Sciences ; Pneumonia ; Pneumonia, Viral - diagnosis ; Pneumonia, Viral - pathology ; Pregnancy ; Public health ; Quality assessment ; Quality control ; Research and Analysis Methods ; Respiratory diseases ; Santé publique et épidémiologie ; SARS-CoV-2 ; Search engines ; Sepsis ; Severe acute respiratory syndrome coronavirus 2 ; Severity of Illness Index ; Systematic review ; Troponin ; Troponin I ; Troponin I - blood ; Ventilators ; Viral diseases ; Womens health ; Zoonoses</subject><ispartof>PloS one, 2020-10, Vol.15 (10), p.e0239802</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Moutchia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2020 Moutchia et al 2020 Moutchia et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c627t-53eaf7c0b47d51d300cb1798ad2febf630dfa0e941d0e331f95f0e357dbf82873</citedby><cites>FETCH-LOGICAL-c627t-53eaf7c0b47d51d300cb1798ad2febf630dfa0e941d0e331f95f0e357dbf82873</cites><orcidid>0000-0002-4892-9471</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/PMC7529271/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529271/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33002041$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://ehesp.hal.science/hal-03709890$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Simonin, Anna</contributor><creatorcontrib>Moutchia, Jude</creatorcontrib><creatorcontrib>Pokharel, Pratik</creatorcontrib><creatorcontrib>Kerri, Aldiona</creatorcontrib><creatorcontrib>McGaw, Kaodi</creatorcontrib><creatorcontrib>Uchai, Shreeshti</creatorcontrib><creatorcontrib>Nji, Miriam</creatorcontrib><creatorcontrib>Goodman, Michael</creatorcontrib><title>Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19.
We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/μl and -123.6 (-170.6, -76.6) cells/μl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml).
Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.</description><subject>Adaptive immunity</subject><subject>Betacoronavirus</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>C-reactive protein</subject><subject>C-Reactive Protein - analysis</subject><subject>Calcium-binding protein</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Confidence intervals</subject><subject>Coronavirus Infections - diagnosis</subject><subject>Coronavirus Infections - pathology</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Dehydrogenases</subject><subject>Diabetes</subject><subject>Diagnosis</subject><subject>Dimers</subject><subject>Dyspnea</subject><subject>Epidemiology</subject><subject>Fibrin Fibrinogen Degradation Products - analysis</subject><subject>Health risks</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Infections</subject><subject>Innate immunity</subject><subject>Intensive care</subject><subject>Interleukin</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - blood</subject><subject>Life Sciences</subject><subject>Literature reviews</subject><subject>Lymphocyte Count</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Markers</subject><subject>Medical laboratories</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Meta-analysis</subject><subject>Multiple organ dysfunction syndrome</subject><subject>Observational Studies as Topic</subject><subject>Oxygen saturation</subject><subject>Pandemics</subject><subject>Parameters</subject><subject>Physical Sciences</subject><subject>Pneumonia</subject><subject>Pneumonia, Viral - diagnosis</subject><subject>Pneumonia, Viral - pathology</subject><subject>Pregnancy</subject><subject>Public health</subject><subject>Quality assessment</subject><subject>Quality control</subject><subject>Research and Analysis Methods</subject><subject>Respiratory diseases</subject><subject>Santé publique et épidémiologie</subject><subject>SARS-CoV-2</subject><subject>Search engines</subject><subject>Sepsis</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Severity of Illness Index</subject><subject>Systematic review</subject><subject>Troponin</subject><subject>Troponin I</subject><subject>Troponin I - blood</subject><subject>Ventilators</subject><subject>Viral diseases</subject><subject>Womens health</subject><subject>Zoonoses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu2zAQFIoWTZr2D4qWQC_JwS4fkij2UMBwHwlgIJe2V2JFrWwakuiSsgP_Rr-4lK0EcRDwQGI5M7uzmCR5z-iUCck-r93Wd9BMN67DKeVCFZS_SM6ZEnyScypePnqfJW9CWFOaiSLPXydnQlDKacrOk3_zxnbWQEMaKJ2H3vk92YCHFnv0gUAIzljosSJ3tl-RgDv0SJwnxtv-QOzcDhtinHcd7KzfBlLZgBCQcMoUuZzf_rn5NmHq6guZkbAPPbYQmcTjzuIdga4isRlMILrZBxveJq9qaAK-G--L5PeP77_m15PF7c-b-WwxMTmX_SQTCLU0tExllbEqOjIlk6qAitdY1rmgVQ0UVcoqikKwWmV1fGSyKuuCF1JcJB-PupvGBT2uM2ieprIQNGcD4uaIqBys9cbbFvxeO7D6UHB-qcFHKw1qkYkMSi5TxooUa1kKA2WJIgWuMFcqan0du23LFiuDXe-hORE9_ensSi_dTsuMKy5ZFLg6Cqye0K5nCz3UqJBUFYruBuzl2My7v1sMvW5tMNg00KHbHjwWKS1EOnj89AT6_CZG1BKiWdvVLs5oBlE9y2MaOS0OHqfPoOKpsLUm5rS2sX5CSI8E410IHusHY4zqIeX3w-gh5XpMeaR9eLzLB9J9rMV_LYD55A</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Moutchia, Jude</creator><creator>Pokharel, Pratik</creator><creator>Kerri, Aldiona</creator><creator>McGaw, Kaodi</creator><creator>Uchai, Shreeshti</creator><creator>Nji, Miriam</creator><creator>Goodman, Michael</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4892-9471</orcidid></search><sort><creationdate>20201001</creationdate><title>Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis</title><author>Moutchia, Jude ; Pokharel, Pratik ; Kerri, Aldiona ; McGaw, Kaodi ; Uchai, Shreeshti ; Nji, Miriam ; Goodman, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c627t-53eaf7c0b47d51d300cb1798ad2febf630dfa0e941d0e331f95f0e357dbf82873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adaptive immunity</topic><topic>Betacoronavirus</topic><topic>Biological markers</topic><topic>Biology and Life Sciences</topic><topic>C-reactive protein</topic><topic>C-Reactive Protein - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moutchia, Jude</au><au>Pokharel, Pratik</au><au>Kerri, Aldiona</au><au>McGaw, Kaodi</au><au>Uchai, Shreeshti</au><au>Nji, Miriam</au><au>Goodman, Michael</au><au>Simonin, Anna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>15</volume><issue>10</issue><spage>e0239802</spage><pages>e0239802-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To date, several clinical laboratory parameters associated with Coronavirus disease 2019 (COVID-19) severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19.
We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] ×109 cells/L), and lower lymphocyte, CD4 and CD8 T cell counts with MMD (95% CI) of -0.39 (-0.47, -0.31) ×109 cells/L, -204.9 (-302.6, -107.1) cells/μl and -123.6 (-170.6, -76.6) cells/μl, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml).
Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33002041</pmid><doi>10.1371/journal.pone.0239802</doi><orcidid>https://orcid.org/0000-0002-4892-9471</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-10, Vol.15 (10), p.e0239802 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2447830617 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adaptive immunity Betacoronavirus Biological markers Biology and Life Sciences C-reactive protein C-Reactive Protein - analysis Calcium-binding protein CD4 antigen CD8 antigen Confidence intervals Coronavirus Infections - diagnosis Coronavirus Infections - pathology Coronaviruses COVID-19 Dehydrogenases Diabetes Diagnosis Dimers Dyspnea Epidemiology Fibrin Fibrinogen Degradation Products - analysis Health risks Humans Immune response Immune system Infections Innate immunity Intensive care Interleukin Interleukin 6 Interleukin-6 - blood Life Sciences Literature reviews Lymphocyte Count Lymphocytes Lymphocytes T Markers Medical laboratories Medical research Medicine and Health Sciences Meta-analysis Multiple organ dysfunction syndrome Observational Studies as Topic Oxygen saturation Pandemics Parameters Physical Sciences Pneumonia Pneumonia, Viral - diagnosis Pneumonia, Viral - pathology Pregnancy Public health Quality assessment Quality control Research and Analysis Methods Respiratory diseases Santé publique et épidémiologie SARS-CoV-2 Search engines Sepsis Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Systematic review Troponin Troponin I Troponin I - blood Ventilators Viral diseases Womens health Zoonoses |
| title | Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis |
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