SARS-CoV-2 Viral Persistence Based on Cycle Threshold Value and Liver Injury in Patients With COVID-19

Grace Lai-Hung Wong; Terry Cheuk-Fung Yip; Vincent Wai-Sun Wong; Yee-Kit Tse; David Shu-Cheong Hui; Shui-Shan Lee; Eng-Kiong Yeoh; Henry Lik-Yuen Chan; Grace Chung-Yan Lui

doi:10.1093/ofid/ofab205

SARS-CoV-2 Viral Persistence Based on Cycle Threshold Value and Liver Injury in Patients With COVID-19

Open Forum Infect Dis. 2021 Apr 23;8(6):ofab205. doi: 10.1093/ofid/ofab205. eCollection 2021 Jun.

Authors

Grace Lai-Hung Wong^{1

2

3}, Terry Cheuk-Fung Yip^{1

2

3}, Vincent Wai-Sun Wong^{1

2

3}, Yee-Kit Tse^{1

2

3}, David Shu-Cheong Hui^{1

2

4}, Shui-Shan Lee⁴, Eng-Kiong Yeoh⁵, Henry Lik-Yuen Chan^{2

6}, Grace Chung-Yan Lui^{1

2

4}

Affiliations

¹ Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
² Medical Data Analytic Centre (MDAC), Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
³ Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁴ Stanley Ho Centre for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁵ Centre for Health Systems and Policy Research, Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁶ Union Hospital, Hong Kong SAR, China.

Abstract

Background: Liver injury in patients with coronavirus disease 2019 (COVID-19) is common and prognostic. Direct viral tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for angiotensin-converting enzyme 2 receptors in hepatocytes may be one of the mechanisms of liver injury. We aimed to determine the role of viral persistence of SARS-CoV-2, based on cycle threshold (Ct) value, in liver injury in COVID-19.

Methods: This was a territory-wide retrospective cohort study of all public hospitals in Hong Kong. Laboratory-confirmed COVID-19 was identified. Serial liver biochemistries and Ct values of SARS-CoV-2 RNA were analyzed.

Results: We identified 7622 COVID-19 patients (mean age, 47 years; 48.2% male) diagnosed from March 24 to January 1, 2021, who had serial liver biochemistries and Ct values. A total of 1363 (17.9%) COVID-19 patients had alanine transferase (ALT)/aspartate aminotransferase (AST) elevations with 2 temporal patterns-early (within first 14 days of symptom onset) and late (>14 days from symptom onset). COVID-19 patients with ALT/AST elevations had a lower Ct value at admission (23 vs 25; P < .001), day 5 (24 vs 26; P < .001), and day 20 (31 vs 32; P < .001) after admission, compared with those without ALT/AST elevations. COVID-19 patients with ALT/AST elevations had a longer duration from first positive to first negative reverse transcription polymerase chain reaction test for SARS-CoV-2 (13 vs 9 days; P < .001). ALT/AST elevation and presence of diabetes were independent risk factors of viral persistence.

Conclusions: Liver injury in COVID-19 is linked to a higher SARS-CoV-2 viral load during the early phase of infection, signifying a possible direct viral injury to the liver. Prolonged viral persistence of SARS-CoV-2 is associated with liver injury.

Keywords: COVID-19; SARS-CoV-2; cycle threshold value; liver injury; viral persistence.