Oropharyngeal persistence of SARS-CoV-2: Influence of viral load

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	p
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	P
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.