Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19

Abstract

Este estudio describe una cohorte de pacientes con síndrome post-COVID-19 que presentaban síntomas persistentes al menos cuatro semanas después de la infección aguda por SARS-CoV-2, con distintos grados de limitación funcional. Se evaluaron 29 pacientes mediante análisis clínicos, funcionales y microbiológicos, incluyendo RT-PCR para SARS-CoV-2 en plasma, heces y orina. El 45% de los pacientes presentó detección de ARN viral en plasma y el 51,7% en al menos una muestra extrapulmonar, con una mediana de 55 días desde el diagnóstico inicial. La mayoría de los pacientes había cursado una COVID-19 leve o moderada. Los síntomas más frecuentes fueron fatiga, mialgias, disnea y taquicardia inapropiada, con limitación funcional moderada o grave en una proporción significativa. Un grupo de pacientes recibió tratamiento antiviral compasivo, observándose una mejoría funcional más marcada, aunque el diseño observacional impide establecer causalidad. Los resultados sugieren la posible persistencia o recurrencia intermitente de viremia por SARS-CoV-2 en pacientes con síndrome post-COVID-19 y apoyan la necesidad de estudios controlados para evaluar estrategias terapéuticas específicas.

Background: There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation.

Methods: We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use).

Results: We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39-67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01).

Conclusions: In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.