Early Cytokine Signatures of Hospitalized Mild and Severe COVID-19 Patients: A Prospective Observational Study

Abstract

Background

The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test.

Methods

This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines.

Results

The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-ɣ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.

Conclusion

CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.

Keywords:

• SARS-CoV-2
• early inflammation
• asymptomatic patient
• proinflammatory cytokines
• regulatory cytokines

Ethics Statement

The Institutional Review Board, College of Medicine, King Saud University, Riyadh, Saudi Arabia reviewed and authorized the investigations involving human subjects. The patients gave written informed consent to participate in the study. The study was conducted according to the Declaration of Helsinki.

Acknowledgment

We would like to acknowledge the services, of Ms. Heba Mohammed, Ms. Salini Scaria Joy, Ms. Teena George Puthiyaparampil, Ms. Nourhan Mohamed, Ms. Tahany Mossa Edrees, and Ms. Faiza Abood from the Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia for data collection and encoding respectively. Ms. Deema Althagabi and Dr. Mohammad Al Wetidy from the College of Medicine Research Center, King Saud University, Riyadh, Saudi Arabia for patient consenting, clinical data collection, and coordination with the clinical laboratory and the services of Mr. Saud Alanazi, and Mr. Hossam Ayed Algohani from the Strategic Center for Diabetes Research, and Ms. Amina Fallata, and Mr. Kenneth Domero from the Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia for assisting in phlebotomy and sample collection are appreciated.

Author Contributions

All authors made substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit it to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This Work was funded by the National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, grant to the Strategic Center for Diabetes Research.