Performance of Rapid Antigen Tests and Inflammatory Markers in SARS-CoV-2: Lessons for Future Respiratory Pandemics
Keywords:
SARS-CoV-2, Inflammatory biomarkers, Healthcare workers, Diagnostic performance, Resource-limited settings, Pandemic preparedness.Abstract
OBJECTIVE: To evaluate the diagnostic performance of rapid antigen tests (RATs) and the utility of inflammatory biomarkers in symptomatic and asymptomatic SARS-CoV-2 cases among healthcare workers and the general population in Punjab, Pakistan.
METHODOLOGY: This cross-sectional study enrolled 1,500 participants (734 symptomatic; 766 asymptomatic), including healthcare workers (HCWs) and the general population (GP), across three cities in Punjab, Pakistan, between November 2021 and July 2022 at the Institute of Microbiology, Government College University, Faisalabad, Pakistan. Participants underwent parallel RT-PCR and Rapid antigen testing (RAT) from nasopharyngeal swabs. Serum/plasma biomarkers (LDH, D-dimer, CRP, IL-6) were quantified using standardized assays.
RESULTS: Symptomatic individuals showed significantly higher SARS-CoV-2 positivity than asymptomatic individuals by PCR (92.3% vs. 38.8%), RAT (89.8% vs. 4.0%), and IgG serology (82.2% vs. 59.7%) (all p<0.0001). Symptomatic cases exhibited markedly elevated biomarkers (e.g., LDH: 394 U/L vs. 195 U/L; CRP: 29 mg/L vs. 0.81 mg/L; all p<0.001). HCWs had higher PCR positivity (68.0% vs. 62.6%; p=0.041) and higher levels of LDH, CRP, and IL-6 (p<0.001) than GP. RAT sensitivity was high in symptomatic cases (97.3%) but low in asymptomatic individuals (10.2%).
CONCLUSION: Rapid antigen tests excel at detecting symptomatic SARS-CoV-2 infections but are unreliable for asymptomatic infections. Biomarkers robustly indicate systemic inflammation and clinical risk in symptomatic individuals and HCWs. Context-based strategies are essential. For example, using RATs to control the spread among people with symptoms while using biomarkers to assess disease severity in high-risk groups, especially in low-resource settings, can improve the pandemic response.
References
1. He X, Lau EHY, Wu P, Deng X, Wang J, Hao X et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med. 2020; 26(5): 672-5.
2. Ozawa T, Chubachi S, Namkoong H, Nemoto S, Ikegami R, Asakura T et al. Predicting coronavirus disease 2019 severity using explainable artificial intelligence techniques. Scientif Rprts. 2025; 15(1): 9459.
3. Dinnes J, Sharma P, Berhane S, van Wyk SS, Nyaaba N, Domen J et al. Rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. Cochrane Database System Rev. 2022; 7(7): Cd013705.
4. Fernandes RS, de Oliveira Silva J, Gomes KB, Azevedo RB, Townsend DM, de Paula Sabino A et al. Recent advances in point of care testing for COVID-19 detection. Biomed Pharmacother. 2022; 153: 113538.
5. Schuit E, Veldhuijzen IK, Venekamp RP, van den Bijllaardt W, Pas SD, Lodder EB et al. Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross-sectional study. BMJ (Clin Res ed). 2021; 374: n1676.
6. Statsenko Y, Al Zahmi F, Habuza T, Gorkom KN, Zaki N. Prediction of COVID-19 severity using laboratory findings on admission: informative values, thresholds, ML model performance. BMJ Open. 2021; 11(2): e044500.
7. Saricaoglu EM, Coskun B, Ayhan M, Akinci E, Kayaaslan B, Aypak A et al. A New Laboratory Tool for COVID-19 Severity Prediction, CENIL Score. Diagnostics (Basel, Switzerland). 2024; 14(22):2557.
8. Zeng H, Ma Y, Zhou Z, Liu W, Huang P, Jiang M, et al. Spectrum and Clinical Characteristics of Symptomatic and Asymptomatic Coronavirus Disease 2019 (COVID-19) With and Without Pneumonia. Front Med. 2021; 8: 645651.
9. Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020; 588(7837): 315-20.
10. Wu J, Liu X, Zhou D, Qiu G, Dai M, Yang Q et al. Identification of RT-PCR-Negative Asymptomatic COVID-19 Patients via Serological Testing. Front Public Health. 2020; 8: 267.
11. Al-Rifai RH, Acuna J, Al Hossany FI, Aden B, Al Memari SA, Al Mazrouei SK et al. Epidemiological characterization of symptomatic and asymptomatic COVID-19 cases and positivity in subsequent RT-PCR tests in the United Arab Emirates. PloS One. 2021; 16(2): e0246903.
12. Badawy ER, Ezz El-Din AM, El Zohne RA. Evaluation of diagnostic performance of a rapid antigen test in diagnosing COVID-19. Egypt J Immunol. 2023; 30(1): 14-9.
13. Wertenauer C, Dressel A, Wieland E, Wertenauer HJ, Braitmaier H, Straub A et al. Diagnostic performance of rapid antigen testing for SARS-CoV-2: the COVid-19 AntiGen (COVAG) extension study. Front Med. 2024; 11: 1352633.
14. Winkel B, Schram E, Gremmels H, Debast S, Schuurman R, Wensing A, et al. Screening for SARS-CoV-2 infection in asymptomatic individuals using the Panbio COVID-19 antigen rapid test (Abbott) compared with RT-PCR: a prospective cohort study. BMJ Open. 2021; 11(10): e048206.
15. Pray IW, Ford L, Cole D, Lee C, Bigouette JP, Abedi GR et al. Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020. MMWR Morb Mortal Wkly Rep. 2021; 69(5152): 1642-7.
16. Ko JH, Joo EJ, Park SJ, Baek JY, Kim WD, Jee J et al. Neutralizing Antibody Production in Asymptomatic and Mild COVID-19 Patients, in Comparison with Pneumonic COVID-19 Patients. J Clin Med. 2020; 9(7):2268.
17. Serwanga J, Ankunda V, Sembera J, Kato L, Oluka GK, Baine C et al. Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months. Front Immunol. 2023; 14: 1152522.
18. Ebrahimpur M, Hajilooi M, Solgi G, Rastegari-Pouyani M. Serum Levels of IL-21 and IL-27 Do not Reflect differential Avidity of Anti-SARS-CoV-2 IgG Antibodies in Symptomatic and Asymptomatic COVID-19 Patients. Iran J Allergy Asthma Immunol. 2025; 24(3): 396-402.
19. Efrati S, Catalogna M, Abu Hamed R, Hadanny A, Bar-Chaim A, Benveniste-Levkovitz P et al. Early and long-term antibody kinetics of asymptomatic and mild disease COVID-19 patients. Scientif Rprts. 2021; 11(1): 13780.
20. Kumar D, Burma A, Mandal AK, Joshy V. A Comparative Analysis of COVID-19 IgG Antibody Level and Socio-Demographic Status in Symptomatic and Asymptomatic Population of South Andaman, India. Cureus. 2022; 14(2): e22398.
21. Mahdi DS, Al-Shawk RS, Hamid ZA, Abed SM. Comparison Study of the Inflammatory Biomarkers and Cytokine Levels in COVID-19 Patients. Mustansiriya Med J. 2024; 23(1): 7-11.
22. Chaudhary R, Garg J, Houghton DE, Murad MH, Kondur A, Chaudhary R, et al. Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients. Mayo Clinic proceedings Innovations, Quality & Outcomes. 2021; 5(2): 388-402.
23. Paranga TG, Pavel-Tanasa M, Constantinescu D, Plesca CE, Petrovici C, Miftode IL et al. Comparison of C-reactive protein with distinct hyperinflammatory biomarkers in association with COVID-19 severity, mortality and SARS-CoV-2 variants. Front Immunol. 2023; 14: 1213246.
24. Lampart M, Zellweger N, Bassetti S, Tschudin-Sutter S, Rentsch KM, Siegemund M, et al. Clinical utility of inflammatory biomarkers in COVID-19 in direct comparison to other respiratory infections: A prospective cohort study. PloS One. 2022; 17(5): e0269005.
25. Semiz S. COVID-19 biomarkers: What did we learn from systematic reviews? Front Cell Infect Microbiol. 2022; 12: 1038908.
26. Weidmann MD, Ofori K, Rai AJ. Laboratory Biomarkers in the Management of Patients With COVID-19. Am J Clin Pathol. 2021; 155(3): 333-42.
27. Kermali M, Khalsa RK, Pillai K, Ismail Z, Harky A. The role of biomarkers in diagnosis of COVID-19: A systematic review. Life Sci. 2020; 254: 117788.
28. Nguyen LH, Drew DA, Graham MS, Joshi AD, Guo CG, Ma W et al. Risk of COVID-19 among frontline healthcare workers and the general community: a prospective cohort study. Lancet Public Health. 2020; 5(9): e475-e83.
29. Lai X, Wang M, Qin C, Tan L, Ran L, Chen D et al. Coronavirus Disease 2019 (COVID-2019) Infection Among Health Care Workers and Implications for Prevention Measures in a Tertiary Hospital in Wuhan, China. JAMA Network Open. 2020; 3(5): e209666.
30. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020; 130(5): 2620-9.
31. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (Lond, Engl). 2020; 395(10223): 497-506.
32. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (Lond Engl). 2020; 395(10229): 1054-62.
33. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020; 323(11): 1061-9.
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