Viral Load in COVID-19: Underestimated Clinical and Epidemiological Marker

Background. The viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the new coronavirus infection, is becoming increasingly important in clinical and epidemiological contexts. Despite this, there are significant complexities in the implementation of viral load quantitative measurement into clinical practice due to the limited approaches to its assessment.

The aim of this work was to develop an approach for SARS-CoV-2 viral load analysis by the value of sample threshold cycles (Ct) relative to the Ct of the internal control sample obtained in routine PCR diagnostics of the COVID-19, and to use this approach for quantitative monitoring of viral load in patients with first positive SARS-CoV-2 test from the Irkutsk region.

Materials and methods. Using regression models based on the least squares method, an approach to determine the number of copies of SARS-CoV-2 RNA in 1 ml of nasopharyngeal secretion was developed. The viral load of SARS-CoV-2 was assessed in nasopharyngeal and pharyngeal samples obtained from 1370 patients from Irkutsk and Angarsk with primary diagnosed positive PCR result in the period from July 1 to November 10, 2020.

Results. A tenfold increase in the average monthly viral load among patients in September-October 2020 was revealed. We assume that the change in the epidemiological pattern of the spread of the new coronavirus infection during this period is associated with an increase in the number of contacts in the population due to the school year beginning. Higher viral loads are observed in populations at risk for COVID-19 – among healthcare workers and adults/elderly patients.

Conclusion. The development of a standardized quantification of SARS-CoV-2 viral load in the nasopharyngeal samples can be a predictive clinical marker and a reliable tool for improving COVID-19 surveillance using the proposed approach to assess average viral load in a local population.

1. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798): 265-269. doi: 10.1038/s41586020-2008-3

2. World Health Organization. COVID-19 weekly epidemiological update 22. 2021. URL: https://www.who.int/docs/default-source/coronaviruse/situation-reports/weekly_epidemiological_update_22.pdf.

3. 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. 2020; 395(10229): 1054-1062. doi: 10.1016/S0140-6736(20)30566-3

4. Peckham H, de Gruijter NM, Raine C, Radziszewska A, Ciurtin C, Wedderburn LR, et al. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun. 2020; 11(1): 1-10. doi: 10.1038/s41467-020-19741-6

5. Li X, Xu S, Yu M, Wang K, Tao Y, Zhou Y. Risk factors for severity and mortality in adult COVID-19 in patients in Wuhan. J Allergy Clin Immunol. 2020; 146(1): 110-118. doi: 10.1016/j.jaci.2020.04.006

6. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area. JAMA. 2020; 323(20): 20522059. doi: 10.1001/jama.2020.6775

7. Cheng VCC, Hung IFN, Tang BSF, Chu CM, Wong MML, Chan KH, et al. Viral replication in the nasopharynx is associated with diarrhea in patients with severe acute respiratory syndrome. Clin Infect Dis. 2004; 38(4): 467-475. doi: 10.1086/382681

8. Hung IFN, Cheng VCC, Wu AKL, Tang BSF, Chan KH, Chu CM, et al.Viral loads in clinical specimens and SARS manifestations. Emerg Infect Dis. 2004; 10(9): 1550-1557. doi: 10.3201/eid1009.040058

9. To KKW, Tsang OTY, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020; 20(5): 565-574. doi: 10.1016/S1473-3099(20)30196-1

10. Xu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors associated with prolonged viral RNA shedding in patients with coronavirus disease 2019 (COVID-19). Clin Infect Dis. 2020; 71(15): 799-806. doi: 10.1093/cid/ciaa351

11. 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): 672-675. doi: 10.1038/s41591-020-0869-5

12. Wu JT, Leung K, Bushman M, Kishore N, Niehus R, de Salazar PM, et al. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nat Med. 2020; 26(4): 506-510. doi: 10.1038/s41591-020-0822-7

13. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382(18): 1708-1720. doi: 10.1056/NEJMoa2002032

14. Fajnzylber J, Regan J, Coxen K, Corry H, Wong C, Rosenthal A, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun. 2020; 11(1): 1-9. doi: 10.1038/s41467-020-19057-5

15. Das M, Chu PL, Santos GM, Scheer S, Vittinghoff E, McFarland W, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One. 2010; 5(6): e11068. doi: 10.1371/journal.pone.0011068

16. Tang YW, Schmitz JE, Persing DH, Stratton CW. Laboratory diagnosis of COVID-19: Current issues and challenges. J Clin Microbiol. 2020; 58(6): e00512-e00520. doi: 10.1128/JCM.00512-20

17. Tom MR, Mina MJ. To interpret the SARS-CoV-2 test, consider the cycle threshold value. Clin Infect Dis. 2020; 71(16): 2252-2254. doi: 10.1093/cid/ciaa619