Amir Emami

Farrokh Habibzadeh

Mahboobeh Yadollahie

Maryam Kucheki

Mohammad Hossein Karimi

Mohammad M. Sajadi

Parham Habibzadeh

Sahar Akbarpoor

English

HRČAK - Portal of Croatian Scientific and Professional Journals

https://doi.org/10.11613/BM.2020.030401 Biochem Med (Zagreb) 2020;30(3):030401   1Keywords: COVID-19; RT-PCR; laboratory testSubmitted: June 20, 2020 Accepted: June 23, 2020Rate of re-positive RT-PCR test among patients recovered from COVID-19Parham Habibzadeh1, Mohammad M. Sajadi2, Amir Emami3, Mohammad Hossein Karimi4, Mahboobeh Yadollahie5, Maryam Kucheki5, Sahar Akbarpoor6, Farrokh Habibzadeh*51Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran2Institute of Human Virology, University of Maryland School of Medicine, Baltimore, United States of America3Burn and Wound Healing Research Center, Microbiology Department, Shiraz University of Medical Sciences, Shiraz, Iran4Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran5R&D Headquarters, Petroleum Industry Health Organization, Shiraz, Iran6Department of Nursing, Larestan University of Medical Sciences, Larestan, Iran*Corresponding author: Farrokh.Habibzadeh@theijoem.comLetter to the editorReverse transcription polymerase chain reaction (RT-PCR) test is the most important laboratory test we currently rely on for the diagnosis of Coronavi-rus disease 2019 (COVID-19). There is no effective treatment or vaccine for COVID-19 (1). One option proposed to save lives is to use convalescent plas-ma obtained from recovered patients (2). There are reports that recovered patients may carry the whole virus and/or viral ribonucleic acid (RNA) (RT-PCR-positive) for long periods (3,4).Recently, health care officials in Larestan (Iran) de-cided to use the convalescent plasma to treat new-ly infected patients. They asked 35 patients with confirmed COVID-19 who had been hospitalized in Larestan Hospital during March 22 to March 26, 2020, to donate plasma. The diagnosis was made by RT-PCR according to a method described earlier (5). The RNA was extracted from nasopharyngeal swabs (Invitrogen ChargeSwitch Total RNA Cell Kit, Invitrogen Co, USA). The assay tested the E and RdRP genes (5). Both internal and negative con-trols were performed for tests. Thirteen of the 35 invited patients did agree to donate. They were thus re-tested with RT-PCR (using the same meth-od) to determine if they were RT-PCR-negative. The study protocol was approved by the Petrole-um Industry Health Organization Institutional Re-view Board. Reverse transcription polymerase chain reaction test was positive in 9 (5 male, 4 female) of 13 recov-ered patients. They had a median age of 52 (inter-quartile range (IQR) 30 to 56) years. They present-ed mostly with cough, fever, malaise, and dysp-noea. On admission, 6 had abnormal findings in their chest and mediastinal unenhanced spiral computed tomography, including ground-glass opacities with or without consolidation; 4 had a positive C-reactive protein test; and 5 had 1 or 2 underlying medical conditions, most commonly hypertension (4 of 5). The disease severity was mild to moderate. The patients were hospitalized for a median of 5 (IQR 3 to 10) days. During hospi-talization, they received osteltamivir (75 mg taken orally every 12 hours) and/or lopinavir/ritonavir (400/100 mg taken orally every 12 hours). They were discharged home when their symptoms re-solved completely. Other laboratory parameters measured at the time of admission were within normal limits (Table 1). The second RT-PCR test was found positive in these patients after a medi-Biochem Med (Zagreb) 2020;30(3):030401  https://doi.org/10.11613/BM.2020.030401 2Habibzadeh P. et al. Re-positive RT-PCR Rate after recovery from COVID-19an of 29 (range 22 to 54) days after initiation of their symptoms/illness and 18 (range 15 to 48) days after complete resolution of their symptoms.Observing 9 positive RT-PCR tests in 13 recovered patients after a median of 18 days of complete res-olution of their symptoms – a positive rate of al-most 70% – is very high. Even if we assume that all the remaining invited (but unattended) 22 recov-ered patients would have tested negative, the rate was still high – 26% (95% confidence interval (CI): 11% to 41%). Considering the low sensitivity (high false-negative rate) of RT-PCR test for the diagno-sis of COVID-19 in nasopharyngeal samples, this rate would clearly be an underestimation (6). On account of the low sample size studied, the results might be considered trivial, at the first glance; however, even the lower limit of the 95% CI of the rate, 11%, is unacceptably high and potentially dangerous. This high RT-PCR re-positive rate would have seri-ous health implications in the world and might even change our strategies to tackle with the cur-rent pandemic. These patients, although asympto-matic, can potentially spread the virus after more than 2 weeks (even 48 days) of complete resolu-tion of their symptoms. It is, however, worth to note that RT-PCR does not discriminate between intact whole virus and viral RNA. Therefore, a posi-tive test does not necessarily imply an active infec-tion or ability to transmit infection. This underlines the importance of developing tests to detect ac-tive viral replication and employing an active sur-veillance for identifying those infected with the vi-rus, even asymptomatic people.Potential conflict of interestNone declared.Parameter Median (IQR)Body mass index (kg/m2) 26.5 (22.8–29.0)Haemoglobin (g/L) 141 (129–168)White blood cell count (x109/L) 4.4 (3.9–5.3)Absolute lymphocyte count (x109/L) 1.77 (1.38–2.17)Platelet (x109/L) 172 (129–201)Serum creatinine (μmol/L) 88 (88–115)Serum sodium (mmol/L) 143 (139–145)Serum potassium (mmol/L) 3.5 (3.3–4.0)Serum bicarbonate (mmol/L) 23.8 (22.7–25.4)Arterial pH 7.39 (7.34–7.42)Arterial pCO2 (kPa) 5.5 (5.1–5.9)IQR – interquartile range.Table 1. Baseline characteristics at hospital admission in 9 stud-ied patientsReferences1. Habibzadeh P, Stoneman EK. The Novel Coronavirus: A Bird’s Eye View. Int J Occup Environ Med. 2020 Apr;11:65-71. https://doi.org/10.15171/ijoem.2020.19212. Rubin R. Testing an Old Therapy Against a New Disease: Convalescent Plasma for COVID-19. JAMA. 2020;323:2114-7. https://doi.org/10.1001/jama.2020.74563. Lan L, Xu D, Ye G, Xia C, Wang S, Li Y, Xu H. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. 2020;323:1502-3. https://doi.org/10.1001/jama.2020.27834. Korea Centers for Disease Control and Prevention. Fin-dings from investigation and analysis of re-positive cases 2020. Available at: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030. Accessed June 9th 2020. 5. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25: pii=2000045. https://doi.org/10.2807/1560-7917.ES.2020.25.3.20000456. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcripta-se Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med. 2020:M20-1495. https://doi.org/10.7326/M20-1495

Rate of re-positive RT-PCR test among patients recovered from COVID-19

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Rate of re-positive RT-PCR test among patients recovered from COVID-19

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