Which physical and/or biochemical markers correlate with COVID-19 infection severity?
Date First Published:
May 5, 2020
Last Updated:
June 3, 2020
Report by:
Ffion Barham (1) Thomas Roe (2) Jessica Crawford (2), Academic Emergency Medicine Trainee, Medical Students (1) Derriford Hospital, Plymouth 2) University of Plymouth 3) University of Bristol)
Three-Part Question:
[In adults with confirmed or suspected Covid-19 infection attending the Emergency Department], are [physical and biochemical parameters] able to [predict the requirement for hospital care]?
Clinical Scenario:
A 25 year old female attends your emergency department with fever and cough. She is streamed to the Amber area for assessment where you see her and diagnose probable COVID-19. Are there specific points from the history and specific blood test which would help you assess her risk of disease progression, and therefore influence your decision to admit or discharge?
Search Strategy:
On 17 Apr 2020, Pubmed and EMBASE databases searched (via HDAS)
Title and Abstract: (covid OR coronavirus OR SARS-CoV-2) AND (prognos* OR score OR decision OR predic*)
Title and Abstract: (covid OR coronavirus OR SARS-CoV-2) AND (prognos* OR score OR decision OR predic*)
Outcome:
Pubmed 451 + EMBASE 290 results published since 01 Jan 2019
118 titles selected for abstract review, 76 selected for full text review
1 systematic review was identified relevant to the three part question. Papers relevant to this BestBET were extracted and reviewed.
118 titles selected for abstract review, 76 selected for full text review
1 systematic review was identified relevant to the three part question. Papers relevant to this BestBET were extracted and reviewed.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| The value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2019 Rui et al. Apr-20 China | 119 confirmed COVID-19 and 45 healthy controls | Prospective observational | Progression to moderate, severe or critical disease | Urinary glucose and protein levels were associated with severity of disease, with more severe disease having significantly higher levels of glucose and protein. Urine tests can be used as a marker of kidney damage secondary to COVID. | Unbalanced number in case and control groups. Not necessarily a prognostic tool - authors suggest using as a confirmatory test. |
| Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China Dawei et al. Feb-20 China | 138 hospitalised confirmed COVID patients in Wuhan | Retrospective observational | Admission to intensive care unit | Those admitted to ITU had - higher D-dimer, CK, creat, WCC, neutrophils, were older and had more co-morbidities. Only age was a statistically significant finding. | Authors admit to higher chance of type 1 error given style of analysis. Follow up ceased before discharge. |
| Clinical Characteristics of Coronavirus Disease 2019 in China Wei-jie et al. Feb-20 China | 1099 confirmed COVID patients in mainland China | Retrospective observational | One or more of admission to ITU, mechanical ventilation, mortality | Severe cases (as defined by American Thoracic Society guidelines for community acquired pneumonia) were older, more likely to have co-morbidities, had more prominent laboratory abnormalities, and required ventilatory support. None of these findings were shown to be statistically significant. | Incomplete documentation of original case data. Selection bias for patients who present to hospital. Follow up ceased before discharge. |
| Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia Wang et al. Mar-20 China | 60 confirmed COVID-19 patients, compared with normal subjects |
Retrospective case-control study |
Correlation of severe disease with biomarkers | Compared with healthy controls, COVID-19 positive patients had significantly lower total lymphocytes, CD4+ cells, CD8 + cells, B cells, and NK cells with higher CRP and ESR. There was some correlation with disease severity. | Lymphocyte subset not routinely collected. |
| Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis Henry et al. Apr-20 USA | COVID-19 positive patients from China and Singapore | Meta-analysis of 24 articles | Correlation with severe disease and mortality with biomarkers. | Markedly increased white cell count (predominantly neutrophils), and reduced CD4+ and CD8+ T-cells, biomarkers of cardiac and muscle injury, LFTs, U+Es, coagulation tests, CRP, ferritin, IL-10 and IL-6 are indicative of severe disease and mortality. | No clear timing of blood tests. Variable definitions of severity across studies. Smaller sample size for mortality. |
Author Commentary:
Abnormalities in liver function, clotting, full blood count, and inflammatory markers correlate with disease severity. More extensive inflammatory and clotting abnormalities (including D-dimer) suggest more severe disease.
Chronic diseases (including COPD, diabetes and CKD) and increasing age also correlate with more severe disease.
Otherwise unexplained excess urine glucose and protein may indicate renal damage as part of the disease process.
Bottom Line:
Biochemical abnormalities and pre-existing co-morbidities are associated with more severe disease.
References:
- Rui et al. . The value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2019
- Dawei et al.. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China
- Wei-jie et al.. Clinical Characteristics of Coronavirus Disease 2019 in China
- Wang et al. . Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia
- Henry et al.. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis