The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of coronavirus disease 2019 (COVID-19), was declared a pandemic on March 11, 2020, by the World Health Organisation (WHO).
The severity of this infectious disease has strained healthcare resources to capacity in many parts of the world. Many healthcare systems have seen an inadequate number of intensive care unit (ICU) beds as well as mechanical ventilators available to treat the influx of patients the pandemic has wrought. The critically low supply of these vital resources underscores the need for clinicians to identify biomarkers that can predict factors such as ICU stay and mortality. This would help to allocate these lifesaving resources appropriately.
A team of researchers has conducted a systematic review to identify laboratory factors that can predict the risk of severe and critical COVID-19 as well as associated mortality rates. The team – from institutions in India and the USA – recently published their findings in the Journal of Clinical Medicine Research.
COVID-19 can be identified through a range of symptoms, and this allows clinicians to identify if patients have either asymptomatic, mild, moderate, severe or critical cases. Patients with asymptomatic and mild and, in some cases, even moderate clinical presentation can include a continuous dry cough, a sore throat, and fever, among others. These patients tend not to require hospitalization, usually clearing the within 2-14 days.
However, the clinical presentation of the infection, which usually includes evidence of lower respiratory infection, for those with severe and critical symptoms will require hospitalization – patients who develop critical COVID-19 exhibit the potentially fatal acute respiratory distress syndrome (ARDS) and multiple organ failure.
Biomarkers for investigation
The number of severe and critical patients who are admitted to the hospital can overwhelm the resources available, and this can lead to a lack of beds and ventilators. The systematic review investigated biomarkers such as hematological and cardiac markers as well as coagulation, inflammatory and renal and liver function indices. Identifying these laboratory markers would effectively predict the risk of severe infection and mortality rates of COVID-19, which can help to efficiently meet the needs of critically infected patients.
One study in the review, which compared patients with differing severities of COVID-19, found that there was an elevated level of D-dimer and fibrin-degradation products in severely ill patients as opposed to those experiencing milder symptoms. This elevated level was also reinforced by the findings of Tongji Hospital of Huazhong University of Science and Technology in Wuhan, which looked at 183 patients, when they investigated the levels of D-dimer and fibrin-degradation in non-survivors compared to survivors. These findings illustrate a need for further investigation of these elevated factors, which can aid the prognostication of severe coronavirus infections.
Other biomarkers which may require monitoring include hematological markers, as low platelet counts have also been associated with adverse outcomes of COVID-19. A study by Lippi et al. conducted a meta-analysis of nine studies with 1,779 patients and found that thrombocytopenia, which consists of a platelet count of lower than 150,000/mm3, had an association with higher mortality rates, which is five times higher in COVID-19 patients. Lymphocytopenia, which includes a lower number of lymphocytes than normal, is also a factor that can aid identification of poor coronavirus outcomes, with this condition found in 83.2% of the 1,099 patients admitted with COVID-19, which was studied by Guan et al.
Cardiac biomarkers can also help assist with the prognosis of coronavirus patients, with cardiac troponin (I) levels found significantly higher in patients with severe COVID-19 infections than non-severe patients. A study investigating 191 patients with COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospitals found that elevated cardiac troponin levels were recorded in 4.1% of all patients, 3% of survivors, but in one-fifth (22.1%) of non-survivors. This study found high sensitivity cardiac troponin levels to be a key predictor of death within hospitals, which illustrates the use of this factor as a biomarker for adverse outcomes of coronavirus.
Renal, inflammatory and liver function markers
Renal function indices are also found to be a significant marker for adverse outcomes for COVID-19, with higher serum creatinine levels being associated with higher mortality rates and in more severely infected patients. Other key markers which were identified by Narvel and Sayed et al. in their systematic review as being of importance for severe COVID-19 include inflammatory indices, such as lactate dehydrogenase levels and liver function indices like serum aspartate aminotransferase and alanine aminotransferase levels.
The investigation of these factors as markers that are associated with more severely ill COVID-19 patients is significant, as it can help to identify the patients who are more likely to be impacted by the virus. This can further inform healthcare professionals and aid with more effective triaging and, in turn, help them provide appropriate care and monitoring of patients who are in the early stages of having a severe infection based on the predictive biomarkers.
- Narvel, H., Sayed, A., Narvel, N., Yakkali, S. and Katchi, T., 2021. Do Certain Biomarkers Predict Adverse Outcomes in Coronavirus Disease 2019?. Journal of Clinical Medicine Research, 13(4), pp.195-203. DOI: https://doi.org/10.14740/jocmr4254, https://www.jocmr.org/index.php/JOCMR/article/view/4254