Coronavirus disease (COVID-19), identified first in December 2019, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an enveloped, positive-sense, single-stranded RNA virus belonging to the Betacoronavirus genus of the Orthocoronavirinae subfamily in the Coronaviridae family. Six types of coronaviruses (CoV-229, CoV-OC43, CoV-NL63, CoV-HKU1, SARS-CoV, and MERS-CoV) can cause human respiratory tract infection (1). The primary mode of transmission is person-to-person via direct contact and respiratory droplets. COVID-19 symptoms range from mild or undetectable symptoms to highly severe symptoms, including death (2). Disease severity and mortality rates are closely associated with comorbidities such as advanced age, diabetes, hypertension, and cardiovascular diseases (3). Several inflammation markers, including cytokines, nitrogen species, and mediators, have been documented to predict severity (4), and these markers widely use C-reactive protein (CRP) and high-sensitivity CRP (hsCRP) (5–7). Elevated levels of acute-phase proteins are associated with various cytokines, which indicate inflammation. Worse COVID-19 clinical outcomes are caused by cytokine storms and the formation of widespread microthrombi among multiple organ systems (8). Novel biomarkers are being investigated to predict clinical outcomes (9). The hsCRP test is widely used to assess cardiovascular disease risk or monitor inflammation in patients because hsCRP is more sensitive than CRP detection, which detects vessel inflammation. Theoretically, the COVID-19 virus can damage respiratory and vascular tissues. Several studies have demonstrated that elevated hsCRP levels are correlated with worse clinical outcomes in patients with COVID-19 infection, suggesting that hsCRP might be a valuable biomarker for predicting the severity of clinical outcomes (8, 10). However, the correlation between hsCRP and hospitalization is not fully understood. The dynamics of hsCRP levels in patients with COVID-19 infection are still being investigated. We hypothesized that hsCRP is associated with worse clinical outcomes among hospitalized COVID-19 patients. This study analyzed clinical data from two hospitals in Thailand to explore the association of hsCRP levels with all-cause mortality and the likelihood of hospital discharge.

Of the 184 hospitalized patients who tested positive for the SARS-CoV-2 virus between 2021 and 2023, 87 (47.3%) cases had high hsCRP levels (median = 11.20; [IQR = 7.03–18.31]). The median age of patients with high hsCRP was 61.0 [IQR = 52.0–72.0]. Patients with normal hsCRP were younger (median age, 55.0 [39.0–69.0] versus 61.0 [IQR = 51.0–72.0] years; p = 0.009) and had a lower incidence of type 2 diabetes (18.6% versus 34.5%, p = 0.014). The top four clinical presentations were fever (89.1%), cough (77.2%), dyspnea (67.4%), and sore throat (18.5%). Only dyspnea (p = 0.003) showed a statistically significant difference between patients with elevated and normal hsCRP levels at admission. Patients with elevated hsCRP level at admission had leukocytosis (7.27 [5.41–9.43] x 10⁶/L versus 6.24 [5.27–7.78] x 10⁶/L; p = 0.017), high absolute neutrophil count (ANC) (5,641 [4,011–8,307] cells/μL versus 4,349 [3,058–5,667] cell/μL), low absolute lymphocyte count (ALC) (1,128 [760–1,368] cells/μL versus 1,485 [942–1,960] cells/μL), high NLR (5.39 [3.49–8.47] versus 2.66 [1.71–4.86], elevated liver function test [ALT, AST], high D-dimer (1.22 [0.73–2.93] mg/L versus 0.66 [0.40–1.94] mg/L), high ferritin (1,657 [766–2,930] ng/dL versus 298 [128–954] ng/dL), high procalcitonin (0.2 [0.2–0.8] versus 0.1 [0–0.1], high LDH (513 [398–681] U/L versus 266 [213–357] U/L, low albumin (3.5 [3.2–3.7] g/dL versus 3.8 [3.5–4.1] g/dL), and low eGFR (72.0 [47.0–94.0] ml/min/1.73 m² versus 95.0 [70.0–106.0] mL/min/1.73 m²) (p < 0.001 for each; Table 1).

Adult hospitalized with COVID-19 infection at two hospitals in Bangkok, Thailand, 47.3% had an elevated hsCRP level. Those patients with initially elevated hsCRP showed a 2-fold increased risk of ICU admission requirement. Interestingly, of serial hsCRP during hospitalization, those who tested for hsCRP on day 5 were associated with a 4-fold increased risk of acute kidney injury events. To the best of our knowledge, this study is the first to investigate the impact of dynamic hsCRP among patients with COVID-19 infection. Serial follow-up hsCRP levels within 5 days after hospitalization also showed an independent association with the increased requirement of an intensive hospital setting as well as death. The requirement for intensive care and mortality exhibited a dose-dependent correlation with the third hsCRP measurement in these patients. This finding is similar to the study of CRP concentration to show the association between respiratory failure and cardiovascular dysfunctions (13, 14). The patients were followed and categorized two times high hsCRP levels; those patients also showed between 4- and 7-fold increased ICU setting requirements. Patients with high hsCRP had a 3- to 4-fold increased risk of mortality (7). Our findings might be used to triage patients for immediate treatment and tailor treatment plans to individual patient needs. Interestingly, patients with high hsCRP levels had shorter survival rates, especially those with a high viral load. The present study suggests the association between patients with either high hsCRP or SAR-CoV-2 viral loads and high mortality due to high viral burden and high inflammation conditions (15–18). Therefore, the hsCRP level might guide the physician in estimating a prognosis and identifying poor prognosis patients with COVID-19 infection, especially new variants. The top four clinical presentations were fever, cough, dyspnea, and sore throat. The study by Lacobucci G et al. also showed that the omicron variant of COVID-19 had four common symptoms at admission (19). This epidemic data correlated with demographic data on the spread of COVID-19 in Thailand during 2021–2022 (20). As the survey results showed, the omicron variant of COVID-19 was a major species during this period. Thus, this omicron variant of COVID-19 affects patients with mild to moderate severity (21). Hospitalized patients might be undelegated admissions because of the decreasing severity of the disease. Tacoo et al. demonstrated that the number of required hospital beds declined during this situation (22). Similar to our study, 20% of hospitalized patients had severe forms, and 27% of patients occupied an ICU setting. Except for patients with elevated hsCRP levels, they were predominately transferred from the ward to the ICU. Patients with elevated hsCRP levels may need close monitoring. This study also showed that serial follow-up hsCRP is beneficial in patients with persistently elevated hsCRP levels within 5 days of hospitalization. Independently related to poor outcomes, hsCRP can persist within 72 h if the COVID-19 virus is damaged and related to a cytokine storm. Similar to Widasari N et al. they demonstrated that high hsCRP and neutrophil-to-lymphocyte ratio (NLR) correlated with high post-COVID-19 syndrome (23). NLR, neutrophil, and lymphocyte have been established markers significantly discriminating against COVID-19 patients with different progression and survival outcomes. This study adds to this evidence by demonstrating that hsCRP levels at admission possess similar discriminatory ability, suggesting its potential utility as a readily available and cost-effective marker. Most studies that used CRP demonstrated that this test is related to increased mortality rates due to the viral destruction of the vascular injury process. HsCRP is one of the most popular tests related to vascular complications. Our patient also had high acute kidney injury within 5 days after admission, which was explained by vascular injury events (14). However, small thrombotic events have been documented, especially in patients with preexisting diabetes and liver disease (24, 25). This is a limitation of the COVID-19 patient’s autopsy investigation because it is a highly contagious disease.

The limitation of this study was that it was a retrospective study, and the hsCRP test was not routinely and continuously performed in all patients. Some patients were excluded during data collection. Second, cardiovascular events depend on the diagnosis conducted by the attending physicians. However, our data were validated by two independent physicians. The bias or discordance is unknown. Third, no autopsy was performed because of the easy spread of viral properties. This may miss some data on death causes. Finally, we did not assess subsequent cardiovascular injury events among discharge patients.

This study adds to the growing evidence that elevated hsCRP levels measured at admission significantly differentiate COVID-19 patients with poor clinical outcomes, such as needing ICU care or dying. Additionally, rising hsCRP levels within 5 days of hospitalization independently predicted these poor outcomes, even when accounting for vascular injury events like acute kidney injury. Notably, patients with high hsCRP and exceptionally high viral loads had shorter life expectancies. These findings support the potential of using hsCRP as an additional biomarker to represent a direct correlation with the severity of COVID-19 infection and predict patient outcomes.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving humans were approved by the Ethics Committee of Rajavithi Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because this is a retrospective study.

KI-a: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Validation, Visualization, Writing – original draft, Writing – review & editing. SC: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. PT: Conceptualization, Data curation, Investigation, Project administration, Validation, Visualization, Writing – review & editing. AC: Data curation, Investigation, Methodology, Project administration, Validation, Visualization, Writing – review & editing. CN: Investigation, Methodology, Validation, Visualization, Writing – review & editing. TS: Investigation, Methodology, Project administration, Validation, Visualization, Writing – review & editing. TU: Conceptualization, Data curation, Investigation, Project administration, Supervision, Validation, Visualization, Writing – review & editing.