In this post, a part of our COVID-19 series, we discuss several meta-analyses that confirm biomarker patterns for severe COVID-19.
Meta-analysis of data for 4663 COVID-19 patients indicated that elevated LDH and elevated CRP (the most prevalent finding), and decreased lymphocytes were associated significantly with the severity of COVID-19. Elevations in erythrocyte sedimentation rate (ESR) and IL-6, and decreased levels of albumin and eosinophils were also associated with severe disease.[i]
A 20-study meta-analysis confirmed that those with more severe disease displayed higher WBCs, ALT, AST, total bilirubin, CRP, procalcitonin, LDH, creatine kinase, and D-dimer and lower albumin values than less severe COVID-19. [ii]
Meta-analysis of 10 studies indicated that trends in blood chemistry marker patterns associated with COVID-19 include: [iii]
A 40-study meta-analysis of 5872 COVID-19 patients revealed that severe disease was associated with significantly: [iv]
Meta-analysis of 2401 patients found that of those who died of COVID-19:[v]
Meta-analysis of 13 studies, comprising 3027 cases of SARS-CoV-2 infection, revealed laboratory characteristics of disease progression: [vi]
| AST | greater than 40 U/L |
| Creatinine | 5 mg/dL (133 umol/L) or greater |
| Hs-troponin | greater than 28 pg/mL |
| Procalcitonin | greater than 0.5 ng/mL |
| LDH | greater than 245 U/L |
| D-dime | greater than 0.5 mg/L |
| WBC total | greater than 4 × 109/L |
| When Tested |
non-critically ill |
Critically ill |
Death |
P |
|
|
ALT (median (IQR)) |
At admission |
21.00 (14.00, 37.00) |
25.00 (15.00, 40.00) |
28.00 (18.00, 43.00) |
<0.001 |
|
Second test |
24.00 (16.00, 42.00) |
28.00 (17.00, 46.00) |
27.00 (17.00, 44.00) |
<0.001 |
|
|
AST (median (IQR)) |
At admission |
24.00 (18.00, 34.00) |
33.00 (23.00, 49.00) |
41.00 (28.25, 60.50) |
<0.001 |
|
Second test |
21.00 (16.00, 29.00) |
25.00 (18.00, 37.00) |
35.00 (24.00, 53.50) |
<0.001 |
|
|
GGT (median (IQR)) |
At admission test |
27.00 (18.00, 46.00) |
37.00 (22.00, 70.00) |
39.00 (25.00, 70.00) |
<0.001 |
|
Second test |
29.00 (19.00, 49.00) |
38.00 (22.00, 78.00) |
43.00 (26.00, 75.50) |
<0.001 |
|
|
ALT/AST (median (IQR)) |
At admission test |
0.71 (0.56, 0.93) |
0.67 (0.60, 1.08) |
0.60 (0.53, 0.77) |
0.558 |
|
Second test |
0.97 (0.66, 1.38) |
1.05 (0.70, 1.33) |
0.56 (0.56, 0.56) |
0.455 |
|
|
TBIL (median (IQR)) |
At admission test |
8.30 (6.20, 11.40) |
10.00 (7.30, 14.50) |
12.20 (8.60, 17.60) |
<0.001 |
|
Second test |
8.20 (6.30, 11.30) |
10.50 (7.62, 14.57) |
13.70 (9.35, 20.30) |
<0.001 |
|
|
DBIL (median (IQR)) |
At admission test |
3.60 (2.60, 4.80) |
4.70 (3.45, 6.70) |
5.85 (4.20, 9.22) |
<0.001 |
|
Second test |
3.40 (2.60, 4.60) |
4.70 (3.50, 7.00) |
6.90 (4.50, 11.00) |
<0.001 |
|
|
IBIL (median (IQR)) |
At admission test |
4.70 (3.40, 6.70) |
5.10 (3.58, 7.73) |
5.75 (4.10, 8.33) |
<0.001 |
|
Second test |
4.80 (3.60, 6.70) |
5.50 (3.90, 7.80) |
6.20 (3.88, 9.62) |
<0.001 |
Data are shown as median (IQR). P values were calculated by Kruskal-Wallis rank-sum test. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), AST/ALT, total bilirubin (TBil), direct bilirubin (DBil), and indirect Bilirubin (IBiL) on admission and after admission were compared among non-critically ill, critically ill, and death groups. If the values of biomarkers were below the lower reference limit, half of the lower reference value was used.
Source: Huang, Wei et al. “Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases.” Science China. Life sciences vol. 63,11 (2020): 1678-1687. doi:10.1007/s11427-020-1733-4. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
In the retrospective study of 413 COVID-19 patients (346 severe, 67 critical), significant differences in biomarker values were observed. When comparing the two groups, critically ill patients had significantly higher total WBCs, neutrophils, D-dimer, pro-calcitonin, CRP, IL-6, IL-10, urea nitrogen, and albumin/globulin ratio. Critically ill patients also had significantly lower lymphocytes, platelets, albumin, and prealbumin.[viii]
A study of 105 PCR-positive versus 102 PCR-negative for SARS-CoV-2 was conducted to compare routine blood test results. COVID positive individuals had:[ix]
The following patterns were observed in emergency room patients, 105 of whom were COVID-19 positive versus 102 of whom were COVID-19 negative: [x]
A retrospective study of 227 pneumonia patients and 97 hospitalized COVID-19 patients found that 71.7% of those with COVID-19 had decreased eosinophils, a finding significant when compared to non-COVID-19 pneumonia patients. The association was strengthened when the neutrophil/lymphocyte ratio (NLR) was considered, with an NLR cutoff value for COVID-19 of 2.425. [xi]
Low levels of eosinophils on admission were associated with a greater incidence of fatigue, fever, shortness of breath, chest CT lesions, extended hospital stay, and disease course. An increase to normal levels of eosinophils occurred before PCR tests for COVID-19 converted to negative.
In a small study of 28 adults with mild and 15 patients with severe COVID-19, those with severe disease had significantly higher IL-6, glucose, fibrinogen, CRP, D-dimer, and thrombin time. The cutoff for IL-6 was 24.3 ug/L.[xii] Notably, six out of seven patients with diabetes had severe versus mild COVID-19.
In a study of 9 ICU versus 58 non-ICU COVID-19 patients, those in the ICU had significantly lower lymphocytes and monocytes, and significantly higher neutrophils and peak LDH levels than non-ICU patients.[xiii]
In COVID-19 patients with ocular complications such as conjunctivitis and increased secretions, levels of WBCs, neutrophils, CRP, LDH, and procalcitonin were higher than in COVID-19 patients without ocular involvement. Researchers suggest that the virus may be transmitted via the eyes.[xiv]
In patients who recover from COVID-19, specific antibodies to SARS-CoV-2 are present, while CD4+ and CD8+ T cells, B cells, natural killer cells, and exhaustion markers on cytotoxic lymphocytes normalize.[xv]
Awareness of the biomarker patterns associated with COVID-19 will help clinicians assess, monitor, and mitigate the immune and metabolic abnormalities associated with this insidious disease.
Next Up - COVID-19: Blood Biomarkers - Neutrophils
[i] Zhang, Zu-Li et al. “Laboratory findings of COVID-19: a systematic review and meta-analysis.” Scandinavian journal of clinical and laboratory investigation vol. 80,6 (2020): 441-447. doi:10.1080/00365513.2020.1768`587
[ii] Xu, Lizhen et al. “Risk factors for 2019 novel coronavirus disease (COVID-19) patients progressing to critical illness: a systematic review and meta-analysis.” Aging vol. 12,12 (2020): 12410-12421. doi:10.18632/aging.103383
[iii] Deng, Xiaoling et al. “Blood biochemical characteristics of patients with coronavirus disease 2019 (COVID-19): a systemic review and meta-analysis.” Clinical chemistry and laboratory medicine vol. 58,8 (2020): 1172-1181. doi:10.1515/cclm-2020-0338
[iv] Ou, Mingchun et al. “Risk factors of severe cases with COVID-19: a meta-analysis.” Epidemiology and infection vol. 148 e175. 12 Aug. 2020, doi:10.1017/S095026882000179X
[v] Qiu, Peishan et al. “Clinical characteristics, laboratory outcome characteristics, comorbidities, and complications of related COVID-19 deceased: a systematic review and meta-analysis.” Aging clinical and experimental research vol. 32,9 (2020): 1869-1878. doi:10.1007/s40520-020-01664-3
[vi] Zheng, Zhaohai et al. “Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis.” The Journal of infection vol. 81,2 (2020): e16-e25. doi:10.1016/j.jinf.2020.04.021
[vii] Huang, Wei et al. “Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases.” Science China. Life sciences vol. 63,11 (2020): 1678-1687. doi:10.1007/s11427-020-1733-4
[viii] Zhao, Xiaobo et al. “Evaluation of Nutrition Risk and Its Association With Mortality Risk in Severely and Critically Ill COVID-19 Patients.” JPEN. Journal of parenteral and enteral nutrition, 10.1002/jpen.1953. 1 Jul. 2020, doi:10.1002/jpen.1953
[ix] Ferrari, Davide et al. “Routine blood tests as a potential diagnostic tool for COVID-19.” Clinical chemistry and laboratory medicine vol. 58,7 (2020): 1095-1099. doi:10.1515/cclm-2020-0398).
[x] Ferrari, Davide et al. “Routine blood tests as a potential diagnostic tool for COVID-19.” Clinical chemistry and laboratory medicine vol. 58,7 (2020): 1095-1099. doi:10.1515/cclm-2020-0398).
[xi] Xie, Guogang et al. “The role of peripheral blood eosinophil counts in COVID-19 patients.” Allergy, 10.1111/all.14465. 20 Jun. 2020, doi:10.1111/all.14465
[xii] Gao, Yong et al. “Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19.” Journal of medical virology vol. 92,7 (2020): 791-796. doi:10.1002/jmv.25770
[xiii] Fan, Bingwen Eugene, et al. "Hematologic parameters in patients with COVID‐19 infection." American journal of hematology 95.6 (2020): E131-E134.
[xiv] Wu, Ping et al. “Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China.” JAMA ophthalmology vol. 138,5 (2020): 575-578. doi:10.1001/jamaophthalmol.2020.1291
[xv] Cao, Xuetao. “COVID-19: immunopathology and its implications for therapy.” Nature reviews. Immunology vol. 20,5 (2020): 269-270. doi:10.1038/s41577-020-0308-3