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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">From December 31&#44; 2019&#44; when the detection of 27 cases of pneumonia of initially unknown aetiology was reported&#44; to present&#44; when there are more than 11 million confirmed cases of coronavirus disease 2019 &#40;COVID-19&#41;&#44; our knowledge about severe acute respiratory syndrome coronavirus 2 &#40;SARS-CoV-2&#41; has been increasing&#46; In Spain&#44; the Asociaci&#243;n Espa&#241;ola de Pediatr&#237;a &#40;Spanish Association of Pediatrics&#41; created a specific working group<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and we have at our disposal the entire international scientific output of the past months&#46; However&#44; several aspects of this disease remain unknown&#46; The duration of the period of infectiousness and viral shedding is still under investigation&#46; Based on the most recent evidence&#44; the period during which polymerase chain reaction &#40;PCR&#41; tests for SARS-CoV-2 are positive is longer than the period of infectiousness&#46; Some studies have evinced absence of viral culture viability despite positive PCR tests in samples with viral loads of less than 10<span class="elsevierStyleSup">5</span> copies RNA&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Other studies have reported positive PCR tests following negative tests and clinical recovery&#44; but this new detection has not been associated with clinical worsening or transmission to contacts in any case&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Although this is known&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> there are cases in which uncertainty arises in clinical practice and we need to rely on different aspects to discern between prolonged viral shedding&#44; detection of nonviable microorganisms&#44; reinfection or reactivation&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">What differentiates the case presented here from others is the positive detection of SARS-CoV-2 by PCR more than 50 days after the first positive test in association with respiratory symptoms&#46; The patient was a girl aged 4 years that received a diagnosis of SARS-CoV-2 infection on March 31&#44; 2020 based on a positive PCR test after presenting with isolated fever of 5 days&#8217; duration&#46; The fever was managed at home&#44; with a good outcome and full resolution after 6 days of illness&#46; A follow-up PCR was not performed at the time to confirm clearance of the virus&#46; On May 20&#44; 2020 the patient presented in our hospital with a new episode of fever with onset 3 days prior&#44; this time associated with cough and moderate respiratory distress&#46; The physical examination revealed mild chest retractions and disseminated subcrepitant rales predominantly on the right side&#44; and the haemoglobin concentration remained at 95&#37;&#46; The chest radiograph revealed peribronchial cuffing with a mild infiltrate in the right lower lobe&#46; The salient findings of the initial blood workup were a white blood cell count of 15&#46;7&#8239;&#215;&#8239;10<span class="elsevierStyleSup">9</span>&#47;L&#44; with 84&#37; neutrophils&#44; and a level of C-reactive protein of 159&#8239;mg&#47;L and a procalcitonin &#40;PCT&#41; level of 0&#46;38&#8239;ng&#47;mL&#46; The patient received a diagnosis of superinfection in the context of bronchitis and was admitted to hospital to receive inhaled bronchodilators and intravenous antibiotherapy&#59; she did not require oxygen therapy during the stay&#46; Per the current protocol&#44; we performed SARS-CoV-2 and respiratory pathogen panel PCR tests at the time of admission&#46; The PCR test for detection of SARS-CoV-2 was positive again&#46; The results of the blood tests were not positive for any other indicators typically found in this infection or markers of severity &#40;total lymphocytes&#44; 1&#46;4&#8239;&#215;&#8239;10<span class="elsevierStyleSup">9</span>&#47;L&#59; D-dimer&#44; 488&#8239;ng&#47;mL&#59; lactate dehydrogenase&#44; 270&#8239;U&#47;L&#59; interleukin-6&#44; 17&#46;85&#8239;pg&#47;mL&#59; ferritin&#44; 78&#8239;ng&#47;mL&#41;&#46; The PCR panel was negative for viruses&#46; This panel also included automatic testing for 7 bacterial species and was positive for <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#46; Antibiotherapy proceeded&#46; Given the positive result of the PCR test for SARS-CoV-2 e 50 days after the initial positive PCR result and the associated respiratory manifestations&#44; additional tests were performed for detection of antibodies against SARS-CoV-2 by means of immunochromatography &#40;IC&#41; and ELISA&#44; which yielded positive results for IgG &#40;IC &#43;&#47;ELISA&#44; 8&#46;49&#41; and negative results for IgM &#40;IC &#8211;&#47;ELISA&#44; 0&#46;26&#41;&#46; After nearly 72&#8239;h of intravenous antibiotherapy&#44; the patient showed clinical improvement with resolution of fever and decreasing levels of inflammatory markers&#46; In light of these results&#44; the clinical outcome and microbiological tests&#44; we approached the illness as a case of respiratory superinfection in the context of bronchitis&#44; with shedding of SARS-CoV-2 that was not replication-competent&#46; The day of discharge&#44; another viral PCR test was performed&#44; yielding the first negative result 55 days after the initial test&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The high frequency of respiratory illnesses in childhood may be a source of confusion in the efforts to control the SARS-CoV-2 pandemic&#46; To prepare for periods when SARS-CoV-2 will coexist with other respiratory viruses&#44; we believe it necessary to develop scores combining clinical&#44; laboratory and microbiological parameters to guide the initial differentiation between an acute SARS-CoV-2 infection or a different type of infection in the context of a past episode of COVID-19 with prolonged viral shedding&#46;</p></span>"
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Journal Information
Vol. 93. Issue 4.
Pages 264-265 (1 October 2020)
Vol. 93. Issue 4.
Pages 264-265 (1 October 2020)
Scientific letter
Open Access
PCR test for SARS-CoV-2 persistently positive. Virus detection is not always COVID-19
Test de PCR a SARS-CoV-2 persistentemente positivo. No siempre la detección del virus es COVID-19
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Carlos Herrero Hernando
Corresponding author
carlosherrero7@hotmail.com

Corresponding author.
, Javier Amadeo Álvarez Serra, María José Elizari Saco, Silvia Martínez-Nadal, Clara Vila Cerén
Hospital de Barcelona, Barcelona, Spain
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To the Editor:

From December 31, 2019, when the detection of 27 cases of pneumonia of initially unknown aetiology was reported, to present, when there are more than 11 million confirmed cases of coronavirus disease 2019 (COVID-19), our knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing. In Spain, the Asociación Española de Pediatría (Spanish Association of Pediatrics) created a specific working group1 and we have at our disposal the entire international scientific output of the past months. However, several aspects of this disease remain unknown. The duration of the period of infectiousness and viral shedding is still under investigation. Based on the most recent evidence, the period during which polymerase chain reaction (PCR) tests for SARS-CoV-2 are positive is longer than the period of infectiousness. Some studies have evinced absence of viral culture viability despite positive PCR tests in samples with viral loads of less than 105 copies RNA/mL.2 Other studies have reported positive PCR tests following negative tests and clinical recovery, but this new detection has not been associated with clinical worsening or transmission to contacts in any case.3 Although this is known,4 there are cases in which uncertainty arises in clinical practice and we need to rely on different aspects to discern between prolonged viral shedding, detection of nonviable microorganisms, reinfection or reactivation.

What differentiates the case presented here from others is the positive detection of SARS-CoV-2 by PCR more than 50 days after the first positive test in association with respiratory symptoms. The patient was a girl aged 4 years that received a diagnosis of SARS-CoV-2 infection on March 31, 2020 based on a positive PCR test after presenting with isolated fever of 5 days’ duration. The fever was managed at home, with a good outcome and full resolution after 6 days of illness. A follow-up PCR was not performed at the time to confirm clearance of the virus. On May 20, 2020 the patient presented in our hospital with a new episode of fever with onset 3 days prior, this time associated with cough and moderate respiratory distress. The physical examination revealed mild chest retractions and disseminated subcrepitant rales predominantly on the right side, and the haemoglobin concentration remained at 95%. The chest radiograph revealed peribronchial cuffing with a mild infiltrate in the right lower lobe. The salient findings of the initial blood workup were a white blood cell count of 15.7 × 109/L, with 84% neutrophils, and a level of C-reactive protein of 159 mg/L and a procalcitonin (PCT) level of 0.38 ng/mL. The patient received a diagnosis of superinfection in the context of bronchitis and was admitted to hospital to receive inhaled bronchodilators and intravenous antibiotherapy; she did not require oxygen therapy during the stay. Per the current protocol, we performed SARS-CoV-2 and respiratory pathogen panel PCR tests at the time of admission. The PCR test for detection of SARS-CoV-2 was positive again. The results of the blood tests were not positive for any other indicators typically found in this infection or markers of severity (total lymphocytes, 1.4 × 109/L; D-dimer, 488 ng/mL; lactate dehydrogenase, 270 U/L; interleukin-6, 17.85 pg/mL; ferritin, 78 ng/mL). The PCR panel was negative for viruses. This panel also included automatic testing for 7 bacterial species and was positive for Haemophilus influenzae. Antibiotherapy proceeded. Given the positive result of the PCR test for SARS-CoV-2 e 50 days after the initial positive PCR result and the associated respiratory manifestations, additional tests were performed for detection of antibodies against SARS-CoV-2 by means of immunochromatography (IC) and ELISA, which yielded positive results for IgG (IC +/ELISA, 8.49) and negative results for IgM (IC –/ELISA, 0.26). After nearly 72 h of intravenous antibiotherapy, the patient showed clinical improvement with resolution of fever and decreasing levels of inflammatory markers. In light of these results, the clinical outcome and microbiological tests, we approached the illness as a case of respiratory superinfection in the context of bronchitis, with shedding of SARS-CoV-2 that was not replication-competent. The day of discharge, another viral PCR test was performed, yielding the first negative result 55 days after the initial test.

The high frequency of respiratory illnesses in childhood may be a source of confusion in the efforts to control the SARS-CoV-2 pandemic. To prepare for periods when SARS-CoV-2 will coexist with other respiratory viruses, we believe it necessary to develop scores combining clinical, laboratory and microbiological parameters to guide the initial differentiation between an acute SARS-CoV-2 infection or a different type of infection in the context of a past episode of COVID-19 with prolonged viral shedding.

References
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C. Calvo, M.G. López-Hortelano, J.C. De Carlos Vicente, J.L. Vázquez Martínez.
Recomendaciones sobre el manejo clínico de la infección por el < <nuevo coronavirus=""> > SARS-CoV2. Grupo de trabajo de la Asocicción Española de Pediatría (AEP) </nuevo>.
An Pediatr (Barc)., 92 (2020), pp. 241
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R. Wölfel, V.M. Corman, W. Guggemos, M. Seilmaier, S. Zange, M.A. Müller, et al.
Virological assessment of hospitalized patients with cCOVI19.
Nature., 581 (2020), pp. 465-469
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L. Lan, D. Xu, G. Ye, C. Xia, S. Wang, Y. Li, et al.
Positive RT-PCR test results in patients recovered from COVID19.
JAMA., 323 (2020), pp. 1502-1503
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Y. Xing, P. Mo, Y. Xiao, O. Zhao, Y. Zhang, F. Wang.
Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020.

Please cite this article as: Herrero Hernando C, Álvarez Serra JA, Elizari Saco MJ, Martínez-Nadal S, Vila Cerén C. Test de PCR a SARS-CoV-2 persistentemente positivo. No siempre la detección del virus es COVID-19. An Pediatr (Barc). 2020;93:264–265.

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