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Oropharyngeal persistence of SARS-CoV-2: Influence of viral load
Persistencia orofaríngea de SARS-CoV-2: influencia de la carga viral
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Nuria Puentea, Marina Fayosa, Daniel Pablo-Marcosb, Carmen Valero Díaz de Lamadrida,b,
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mirvdc@humv.es

Corresponding author.
a Departamento de Medicina Interna, Hospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain
b Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla, Santander, Spain
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Dear Editor:

Several clinical factors have been associated with oropharyngeal persistence of SARS-CoV-2.1 Our study included the viral load determination by quantitative PCR (Exact Diagnostics SARS-CoV-2 Standard; Bio-Rad, Texas, USA) of 33 COVID-19 patients with persistent PCR in nasopharyngeal samples > 4 weeks and 33 controls, adjusted for age and sex, who tested negative before. Values are expressed as Log10 mean viral load (N and R genes) and cycle threshold (Ct) values. The Clinical Research Ethics Committee (CREC) of Cantabria approved the study. Student's t-test or Mann–Whitney U were used to compare quantitative variables, and chi-square or Fisher’s test for qualitative variables. All analyses were performed using SPSS 23.0 software (Chicago, IL, USA). A p value < 0.05 was considered statistically significant.

The viral load of COVID-19 patients with mild disease (outpatients) and persistent SARS-CoV-2 was significantly higher than that of their controls in copies/ml (Log10: 7.04 ± 1.81 copies/ml vs. 5.15 ± 2.14 copies/ml; p = 0.018) and Ct of the N gene (25.7 ± 5.6 versus 31.3 ± 6.7 in controls; p = 0.02). Their clinical profile showed no peculiarities (Table 1). Hospitalized patients with persistent SARS-CoV-2 (49 ± 20 days) had the same viral load as their controls (Log10: 6.21 ± 2.06 copies/ml vs. 5.98 ± 1.97 copies/ml; p = 0.73 and Ct values of the N and R genes) and there were no differences in terms of their clinical characteristics (Table 1).

Table 1.

COVID-19 patients.

Outpatients  Persistent SARS-CoV-2, N = 15  Controls, N = 15 
Age (years)  57 (20)  56 (20)  0.85 
Sex, n (%)  2 (13%)  2 (13)  0.64 
Days until negative PCR  45 (9)  18 (5)  < 0.001 
Smoking, n (%)  1 (7)  1 (7)  0.05 
ACE or ARB, n (%)  2 (13)  1 (7)  0.55 
Comorbidities, n (%)
Hypertension  3 (20)  1 (7)  0.35 
Dyslipidemia  3 (20)  3 (20)  0.60 
Diabetes mellitus  0 (0)  1 (7)  0.46 
Asthma  0 (0)  0 (0)  – 
Atrial fibrillation  1 (7)  1 (7)  0.72 
Neoplasm  1 (7)  0 (0)  0.53 
COPD  0 (0)  0 (0)  – 
Symptomatic, n (%)  11 (73)  7 (47)  0.18 
Duration of symptoms, (days)  15 (8)  12 (9)  0.48 
Chest x-ray, n (%)  3 (20)  1 (7)  0.42 
Pulmonary infiltrates, n (%)  2/3 (66)  0/1 (0)  0.36 
Viral load       
Log10 (copies/ml)  7.0 (1.8)  5.1 (2.1)  0.018 
N gene Ct  25.7 (5.6)  31.3 (6.7)  0.020 
R gene Ct  25.1 (7.0)  29.8 (7.9)  0.12 
Hospitalized  Persistent SARS-CoV-2, N = 18  Controls, N = 18 
Age (years)  71 (16)  72 (13)  0.78 
Sex, n (%)  7 (40)  7 (40)  0.63 
Days until negative PCR  49 (20)  16 (9)  < 0.001 
Smoking, n (%)  0 (0)  4 (22)  0.10 
ACEI or ARBs, n (%)  8 (44)  4 (22)  0.14 
Comorbidities, n (%)
Hypertension  11 (61)  7 (39)  0.15 
Dyslipidemia  7 (39)  10 (56)  0.25 
Diabetes mellitus  2 (11)  2 (11)  0.64 
Asthma  1 (5.6)  0 (0)  0.50 
Atrial fibrillation  0 (0)  2 (11)  0.24 
Neoplasm  0 (0)  1 (5)  0.50 
COPD  1 (5.6)  3 (17)  0.30 
Duration of symptoms (days)  14 (7)  16 (10)  0.49 
Chest x-ray n (%)  18 (100)  18 (100)  – 
Pulmonary infiltrates n (%)  12 (67)  17 (94)  0.10 
Viral load
Log10 (copies/ml)  6.21 (2.06)  5.98 (1.97)  0.73 
N gene Ct  28.0 (6.6)  28.9 (6.1)  0.67 
R gene Ct  27.3 (7.1)  26.8 (5.6)  0.82 

Mean (SD) or n (%).

ARBs: angiotensin receptor blockers; COPD: chronic obstructive pulmonary disease; ACEI: ACE inhibitors.

Viral shedding in respiratory samples varies from 2 to 3 weeks after the onset of symptoms, but it has been reported up to 83 days later.2 Various clinical factors are related to this fact, including male gender, age over 65, the use of invasive mechanical ventilation, the presence of immunodeficiency or diabetes.2 Some studies find that persistence is more common in seriously ill hospitalised patients with high comorbidity3; however, others associate it with asymptomatic cases.2 The use of corticosteroids and lopinavir/ritonavir also seems to be associated.4,5 Our study has the limitations of observational studies and we do not know the clinical translation of the persistence of SARS-CoV-2; however, we consider it important to continue analysing the problem of prolonged shedding and fluctuations of the virus.

Conflicts of interest

The authors declare that they have no conflicts of interest.

References
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K. Xu, Y. Chen, J. Yuan, P. Yi, C. Ding, W. Wu, et al.
Factors associated with prolonged viral RNA shedding in patients with COVID-19.
Clin Infect Dis, 71 (2020), pp. 799-806
[2]
S.M. Kim, Y.J. Hwang, Y. Kwak.
Prolonged SARS-CoV-2 detection and reversed RT-PCR results in mild or asymptomatic patients.
Infect Dis (Lond), 53 (2021), pp. 31-37
[3]
Z. Yongchen, H. Shen, X. Wang, X. Shi, Y. Li, J. Yan.
Different longitudinal patterns of nucleic acid and serology testing results based on disease severity of COVID-19 patients.
Emerg Microbes Infect, 9 (2020), pp. 833-836
[4]
Z. Hu, S. Li, A. Yang, W. Li, X. Xiong, J. Hu, et al.
Delayed hospital admission and high-dose corticosteroids potentially prolong SARS-CoV-2 RNA detection duration of patients with COVID-19.
Eur J Clin Microbiol Infect Dis, 40 (2021), pp. 841-848
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S. Yan, X.Y. Liu, Y.N. Zhu, L. Huang, B.T. Dan, G.J. Zhang, et al.
Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection.

Please cite this article as: Puente N, Fayos M, Pablo-Marcos D, Valero Díaz de Lamadrid C. Persistencia orofaríngea de SARS-CoV-2: influencia de la carga viral. Med Clin (Barc). 2022;158:494–495.

Copyright © 2021. Elsevier España, S.L.U.. All rights reserved
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