Post-COVID-19 syndrome. SARS-CoV-2 RNA detection in plasma, stool, and urine in patients with persistent symptoms after COVID-19
Authors: Tejerina Francisco , Catalan Pilar , Rodriguez-Grande Cristina , Adan Javier , Rodriguez-Gonzalez Carmen , Muñoz Patricia , Aldamiz Teresa , Diez Cristina , Perez Leire , Fanciulli Chiara , Garcia de Viedma Dario ,   Gregorio Marañon Microbiology ID COVID 19 Study Group, Alcalá Luis , Alonso Roberto , Álvarez Beatriz , Álvarez-Uría Ana , Arias Alexi , Arroyo Luis Antonio , Berenguer Juan , Bermúdez Elena , Bouza Emilio , Burillo Almudena , Candela Ana , Carrillo Raquel , Cercenado Emilia , Cobos Alejandro , Escribano Pilar , Estévez Agustín , Fernandez Silvia , Galar Alicia , García Mª Dolores , Gijón Paloma , González Adolfo , Guillén Helmuth , Guinea Jesús , Haces Laura Vanessa , Kestler Martha , López Juan Carlos , Losada Carmen Narcisa , Machado Marina , Marín Mercedes , Martín Pablo , Martín Paloma , Montilla Pedro , Moure Zaira , Muñoz Patricia , Olmedo María , Padilla Belén , Palomo María , Parras Francisco , Pérez-Granda María Jesús , Pérez Laura , Pescador Paula , Reigadas Elena , Rincón Cristina , Rodríguez Belén , Rodríguez Sara , Rojas Adriana , Ruiz-Serrano María Jesús , Sánchez Carlos , Sánchez Mar , Serrano Julia , Valerio Maricela , Veintimilla Mª Cristina , Vesperinas Lara , Vicente Teresa , de la Villa Sofía 
Published: March 2022

Abstract
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.