Recurrence of Positive SARS-CoV-2 RNA in a COVID-19 Patient: Two Case Reports from Saudi Arabia

Recurrence of Positive SARS-CoV-2 RNA in a COVID-19 Patient: Two Case Reports from Saudi Arabia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Recurrence of Positive SARS-CoV-2 RNA in a COVID-19 Patient: Two Case Reports from Saudi Arabia Sarah Alturaif, Remaaz Alharbi, Waleed Alqurashi, Abdulaziz Alsadoon, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-86920/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The rapid spread of the COVID-19 pandemic which took a place in Wuhan, China and diffused globally required the international public health to take a coordinated international response. As other coronaviruses were described, SARS-CoV-2 was thought to be an immunizing, monophasic disease. Herein, we reported first two COVID-19 cases registered in Saudi Arabia whose nasopharyngeal swabs turned positive for SARS-CoV-2 ribonucleic acid (RNA) after recovery. Case presentation First patient who is symptomatic with recurrence of positive SARS-CoV-2 RNA occurred 115 days after the first symptomatic infection and did not develop protective immune response. Second patient who is asymptomatic during the recurrence of positive SARS-CoV-2 RNA occurred 60 days after the first symptomatic infection in an apparently immunocompetent patient. Conclusion These findings highlight the recurrence of positive SARS-CoV-2 after recovery even if SARS-CoV-2 antibodies were developed. Virology SARS-CoV-2 COVID19 Reinfection Saudi Arabia Background Since the fast expansion of the ongoing global pandemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019, the number of Coronavirus disease (COVID-19) cases have exceeded 27 million worldwide [ 1 ]. Saudi Arabia was among the impacted countries that reported the first case of COVID-19 on March 2, 2020. By September 8, 2020, the Ministry of Health (MOH) reported over 322,000 positive cases, with 4137 deaths and 298,246 recoveries [ 2 ]. COVID-19 is a respiratory illness, person to person contact, and respiratory droplets are the primary route of infection. When the pandemic first started, it was thought to be an immunizing, non-relapsing disease [ 3 ]. However, in some countries, there have been reports of rare suspected cases of COVID-19 reinfection [ 4 ]. Herein, we reported two COVID-19 cases registered in Saudi Arabia with recurrence of positive SARS-CoV-2 ribonucleic acid (RNA). Case Presentation First case Patient 1 is a 23-year old healthy male, with no underlying medical conditions, who had a nasopharyngeal (NP) swab collected on April 13 using a viral transport media (VTM). As recommended by the Saudi Ministry of Health, the diagnostic testing for SARS-CoV-2 was performed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) using at least one confirmatory target, in addition to the screening targets [ 5 ].The RT-PCR test was done as a standard infection control procedure after the patient arrived from a trip abroad. The test result was positive and confirmed by the National Health Laboratory (NHL; Table 1 ). Two days later, the patient started complaining from joints pain, mild headache, and diarrhea. According to the Saudi Ministry of Health guidelines for COVID-19 positive patients, the local health authorities urged him to self-isolate until his symptoms resolve, and the subsequent test is negative [ 6 ]. He received no prescription medications during his quarantine period. To follow up, on April 20 and 25 two NP swabs were collected for RT-PCR assay test at two different laboratories, and both results were negative. As a result, the patient resumed his normal life. Just over three months later (August 6), he developed the following symptoms: moderate headache, fatigue, sore throat, and diarrhea. He suspected reinfection due to close contact with COVID19 patient and performed two SARS-CoV-2 RT-PCR tests at two different laboratories; both were positive. The symptoms were subjectively more intense this time and lasted for three days. A follow-up and confirmatory tests were carried out on August 13 and 16, respectively, and both yielded negative results. For further investigations, a SARS-CoV-2 IgG assay was conducted (August 16) for the detection of SARS-CoV-2 antibodies development, and it came out negative with a titer of 0.16 AU/mL (Reference value < 0.7 AU/mL) indicating a possible non-protective immune response [ 7 ]. Table 1 Timelines and testing results of the SARS-CoV-2 recurrence cases Age (years) Sex Timelines Symptoms NP a Swab Confirmation Serology (SARS-CoV-2 IgG) Patient 1 23 Male April 13 Arthralgia Mild headache Diarrhea Positive b Positive (NHL d ) April 20 No Negative c Negative (DL e ) April 25 No Negative Negative (DL) August 6 Moderate headache Fatigue Sore throat Diarrhea Positive Positive (DL) August 13 No Negative August 16 No Negative Negative Patient 2 59 Male June 16 Fever Arthralgia, Myalgia Fatigue Positive Positive (NHL) July 1 No Negative July 4 No Negative August 15 No Positive August 16 No Positive Positive a NP: Nasopharyngeal b Positive; SARS-CoV-2 detected c Negative; SARS-CoV-2 not detected d NHL: National Health Laboratory e DL: Different Laboratory with new NP swab collection Second Case Patient 2 is a 59-year male with no underlying medical conditions who presented on June 16 for COVID-19 testing after developing flu-like illness symptoms. The test result came out positive and was confirmed by the NHL (Table 1 ). A week later, the patient’s health started to improve, and symptoms began to disappear gradually. On July 1 and 4, two consecutive follow-up tests were done, and both results were negative for SARS-CoV-2, which suggested that the patient was cured. At the beginning of August, some of the patient’s family members were infected with SARS-CoV-2 experienced flu-like symptoms such as fever, fatigue, and headache. Although the patient himself did not experience any symptoms, he decided to do a cautionary SARS-CoV-2 test on mid-August, and it revealed a positive result which was also confirmed on a subsequent NP swab collection. Furthermore, we performed IgG assay at that time, which came back positive (titer of 5.7 AU/mL), confirming the presence of SARS-CoV-2 antibodies. Discussion And Conclusion We report here two cases of healthy adults who had two episodes of possible COVID-19 infection. Interestingly, in one case, the symptomatic patient with recurrence of positive SARS-CoV-2 occurred after three months of the initial infection that did not trigger a protective immune response. In the other case, asymptomatic patient with recurrence of positive SARS-CoV-2 occurred within three months of the initial infection. Recently, Yao et al. demonstrated that SARS-CoV-2 viral particles remain in previously positive patients’ lungs whose NP swabs results were negative three times consecutively; this suggests that SARS-CoV-2 virus may not be eliminated when the symptoms disappear [ 8 ]. Therefore, there is still a reason to be cautious, and we need to be aware of recovered patients and their potential infectivity. Interestingly, there have not been any studies demonstrating that recovered patients are infectious. To our knowledge, our cases are the first to describe positive SARS-CoV-2 viral RNA in recovered COVID-19 patients in the Middle East. According to the Centers for Disease Control and Prevention (CDC), reinfection of SARS-CoV-2 is highly considered in a patient who becomes symptomatic around 90 days after onset of infection and has been in close contact with an infected person, supporting our first case [ 9 ]. A similar case presenting recurrence of SARS-CoV-2 has been reported in Hong Kong, bringing more attention lately. To and his colleagues demonstrated that second episode of asymptomatic infection occurred after the first symptomatic episode in an apparently immunocompetent patient [ 4 ]. In addition, they confirmed SARS-CoV-2 reinfection by performing whole genome sequencing for the first and second episodes indicating different clades [ 4 ]. We assume that the recurrence of COVID-19 is possible due to the presence of nonprotective IgG and recovered patients might be carriers and actively transmitting the virus even after their two negative tests [ 10 , 11 ]. Thus, gatherings of positive cases are not safe, and there should be an emphasis upon such social practices, and for those in convalescence, we suggest that they undergo regular tests for infectivity assessments. The presence of SARS-CoV-2 virus appears to be unstable because of the possibility of false-negative results of the molecular test which might be due to fluctuations in the viral load or pre-analytical errors during the sample collection [ 12 ]. In our case reports, reducing the chance of false-negative and false-positive results was done by confirming each test result in different laboratory with new NP swab collection. For both cases, first positive test results were confirmed by the NHL, and two consecutive negative tests were done before the patients were considered to be cured. Although these are only two case reports and the evidence is not determinant, it gives insight and encourages future cohort studies. In conclusion, the global public health is at risk of the possibility of recurrence of SARS-CoV-2 as we exhibited in our case reports, which could contribute to the spread of the virus. Therefore, additional virologic, immunological, and epidemiological studies should be done to have better understanding of SARS-CoV-2 recurrence mechanism. Abbreviations SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2 COVID-19: Coronavirus disease 2019 RT- PCR: Real-time reverse transcriptase-polymerase chain reaction IgG: Immunoglobin G MOH: Ministry of Health RNA: Ribonucleic acid NP: Nasopharyngeal VTM: viral transport media NHL: National Health Laboratory CDC: Centers for Disease Control and Prevention Declarations Ethics approval and consent to participate Not Applicable. Consent of publication Written consent was obtained from the patient for publication. Availability of data and material Derived data are available on reasonable request. Competing interests The authors have declared that no competing interests exist. Funding The authors received no specific funding for this work. Contributions Sara Alturaif, Remaaz Alharbi, Abdulaziz Alsadoon, and Meshari Alabdullatif conceptualized and refined research idea, and collected and processed the patients’ samples. Sara Alturaif, Remaaz Alharbi, and Waleed Alqurashi created case report design and wrote the manuscript. Waleed Alqurashi and Meshari Alabdullatif edited the manuscript Corresponding author Correspondence to Meshari Alabdullatif Acknowledgements Not applicable. References Coronavirus (COVID-19) Cases - Statistics and Research. Our World in Data. Published 2020. Accessed August 13, 2020. https://ourworldindata.org/covid-cases. COVID 19 Dashboard: Saudi Arabia. Published 2020. Accessed August 13, 2020. https://covid19.moh.gov.sa/. Kiyuka PK, Agoti CN, Munywoki PK, et al. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya. J Infect Dis. 2018;217:1728-1739. To KK-W, Hung IF-N, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis. 2020. doi:10.1093/cid/ciaa1275. MOH Publications - COVID-19 Guidelines. Accessed August 14, 2020. https://www.moh.gov.sa/en/Ministry/MediaCenter/Publications/Pages/covid19.aspx. Saudi MoH Protocol for Patients Suspected of/Confirmed with COVID-19. Accessed August 13, 2020. https://www.moh.gov.sa/Ministry/MediaCenter/Publications/Documents/MOH-therapeutic-protocol-for-COVID-19.pdf. Deeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020. doi:10.1002/14651858.CD013652. Yao X-H, He Z-C, Li T-Y, et al. Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient. Cell Research. 2020;30:541-543. Test for Past Infection | CDC. Published 2020. Accessed September 8, 2020. https://www.cdc.gov/coronavirus/2019-ncov/testing/serology-overview.html. Lan L, Xu D, Ye G, et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. 2020;323:1502-1503. Loconsole D, Passerini F, Palmieri VO, et al. Recurrence of COVID-19 after recovery: a case report from Italy. Infection. 2020. doi:10.1007/s15010-020-01444-1. Xiao AT, Tong YX, Zhang S. False negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence. Journal of Medical Virology. 2020. doi:10.1002/jmv.25855. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-86920","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":3074884,"identity":"5970d980-feb4-4c6f-9b78-42004dd825d2","order_by":0,"name":"Sarah Alturaif","email":"","orcid":"","institution":"SmartLab","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Alturaif","suffix":""},{"id":3074885,"identity":"df79ab42-c89c-4e01-86df-b44987351b8a","order_by":1,"name":"Remaaz Alharbi","email":"","orcid":"","institution":"SmartLab","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Remaaz","middleName":"","lastName":"Alharbi","suffix":""},{"id":3074886,"identity":"1e3064de-d05f-442c-ada3-b531d16c45bc","order_by":2,"name":"Waleed Alqurashi","email":"","orcid":"","institution":"University of Ottawa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Waleed","middleName":"","lastName":"Alqurashi","suffix":""},{"id":3074887,"identity":"b04199f7-9a38-41d6-ba1b-ef6d4a198d3f","order_by":3,"name":"Abdulaziz Alsadoon","email":"","orcid":"","institution":"SmartLab","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Abdulaziz","middleName":"","lastName":"Alsadoon","suffix":""},{"id":3074888,"identity":"09226853-aec4-4b23-8c75-4896ffc17437","order_by":4,"name":"Meshari Alabdullatif","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA60lEQVRIiWNgGAWjYBACgwMMbEBKQo6xvfkAiCFDUIslVIsxc8+xBBCDh6AWe4gWhsT2GTkGIAZhLWbH2589+LnHgrF3Rs7nVzdqLHgY2A8f3YBXy5kz5oY9zySYJXvebrPOOQZ0GE9a2g28Wm7ksEnwHJBgM2zP3WYMYgO9Y4ZXi8H9588k/xyQ4LE/kPPMOOcfMVpuMJhJA22RYOzIYX6c20aMljM5ZtIyByQMGHuOmTHn9knwsBHyi8Hx488k3xyoq29sb378OedbnRw/++FjeLUgAzYJMEmschBg/kCK6lEwCkbBKBg5AAAa4EvAxcTEvgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3354-6221","institution":"SmartLab","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Meshari","middleName":"","lastName":"Alabdullatif","suffix":""}],"badges":[],"createdAt":"2020-10-02 11:25:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-86920/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-86920/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13600814,"identity":"5255c45c-9940-466f-a7e0-7cd05c496807","added_by":"auto","created_at":"2021-09-17 05:45:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":271395,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-86920/v1/b46aa9f6-1a4c-408c-a873-1825396c6b20.pdf"}],"financialInterests":"","formattedTitle":"Recurrence of Positive SARS-CoV-2 RNA in a COVID-19 Patient: Two Case Reports from Saudi Arabia","fulltext":[{"header":"Background","content":"\u003cp\u003eSince the fast expansion of the ongoing global pandemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in December 2019, the number of Coronavirus disease (COVID-19) cases have exceeded 27\u0026nbsp;million worldwide [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. Saudi Arabia was among the impacted countries that reported the first case of COVID-19 on March 2, 2020. By September 8, 2020, the Ministry of Health (MOH) reported over 322,000 positive cases, with 4137 deaths and 298,246 recoveries [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eCOVID-19 is a respiratory illness, person to person contact, and respiratory droplets are the primary route of infection. When the pandemic first started, it was thought to be an immunizing, non-relapsing disease [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, in some countries, there have been reports of rare suspected cases of COVID-19 reinfection [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. Herein, we reported two COVID-19 cases registered in Saudi Arabia with recurrence of positive SARS-CoV-2 ribonucleic acid (RNA).\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eFirst case\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient 1 is a 23-year old healthy male, with no underlying medical conditions, who had a nasopharyngeal (NP) swab collected on April 13 using a viral transport media (VTM). As recommended by the Saudi Ministry of Health, the diagnostic testing for SARS-CoV-2 was performed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) using at least one confirmatory target, in addition to the screening targets [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].The RT-PCR test was done as a standard infection control procedure after the patient arrived from a trip abroad. The test result was positive and confirmed by the National Health Laboratory (NHL; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Two days later, the patient started complaining from joints pain, mild headache, and diarrhea. According to the Saudi Ministry of Health guidelines for COVID-19 positive patients, the local health authorities urged him to self-isolate until his symptoms resolve, and the subsequent test is negative [\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]. He received no prescription medications during his quarantine period. To follow up, on April 20 and 25 two NP swabs were collected for RT-PCR assay test at two different laboratories, and both results were negative. As a result, the patient resumed his normal life. Just over three months later (August 6), he developed the following symptoms: moderate headache, fatigue, sore throat, and diarrhea. He suspected reinfection due to close contact with COVID19 patient and performed two SARS-CoV-2 RT-PCR tests at two different laboratories; both were positive. The symptoms were subjectively more intense this time and lasted for three days. A follow-up and confirmatory tests were carried out on August 13 and 16, respectively, and both yielded negative results. For further investigations, a SARS-CoV-2 IgG assay was conducted (August 16) for the detection of SARS-CoV-2 antibodies development, and it came out negative with a titer of 0.16 AU/mL (Reference value\u0026thinsp;\u0026lt;\u0026thinsp;0.7 AU/mL) indicating a possible non-protective immune response [\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eTimelines and testing results of the SARS-CoV-2 recurrence cases\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003cp\u003e(years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTimelines\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSymptoms\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNP \u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e Swab\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eConfirmation\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSerology (SARS-CoV-2 IgG)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"6\" align=\"left\"\u003e\n\u003cp\u003ePatient 1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"6\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"6\" align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eApril 13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eArthralgia\u003c/p\u003e\n\u003cp\u003eMild headache\u003c/p\u003e\n\u003cp\u003eDiarrhea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive \u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003cp\u003e(NHL \u003csup\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eApril 20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative \u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003cp\u003e(DL \u003csup\u003e\u003cem\u003ee\u003c/em\u003e\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eApril 25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003cp\u003e(DL)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAugust 6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModerate headache\u003c/p\u003e\n\u003cp\u003eFatigue\u003c/p\u003e\n\u003cp\u003eSore throat\u003c/p\u003e\n\u003cp\u003eDiarrhea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003cp\u003e(DL)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAugust 13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAugust 16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003ePatient 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" align=\"char\" char=\".\"\u003e\n\u003cp\u003e59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJune 16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFever Arthralgia, Myalgia\u003c/p\u003e\n\u003cp\u003eFatigue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003cp\u003e(NHL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJuly 1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJuly 4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNegative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAugust 15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAugust 16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePositive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eNP: Nasopharyngeal\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cem\u003eb\u003c/em\u003e\u003c/sup\u003e \u003cem\u003ePositive; SARS-CoV-2 detected\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eNegative; SARS-CoV-2 not detected\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eNHL: National Health Laboratory\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\u003csup\u003e\u003cem\u003ee\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eDL: Different Laboratory with new NP swab collection\u003c/em\u003e\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\u003cp\u003e\u003cstrong\u003eSecond Case\u003c/strong\u003e\u003c/p\u003e\u003cp\u003ePatient 2 is a 59-year male with no underlying medical conditions who presented on June 16 for COVID-19 testing after developing flu-like illness symptoms. The test result came out positive and was confirmed by the NHL (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). A week later, the patient\u0026rsquo;s health started to improve, and symptoms began to disappear gradually. On July 1 and 4, two consecutive follow-up tests were done, and both results were negative for SARS-CoV-2, which suggested that the patient was cured. At the beginning of August, some of the patient\u0026rsquo;s family members were infected with SARS-CoV-2 experienced flu-like symptoms such as fever, fatigue, and headache. Although the patient himself did not experience any symptoms, he decided to do a cautionary SARS-CoV-2 test on mid-August, and it revealed a positive result which was also confirmed on a subsequent NP swab collection. Furthermore, we performed IgG assay at that time, which came back positive (titer of 5.7 AU/mL), confirming the presence of SARS-CoV-2 antibodies.\u003c/p\u003e"},{"header":"Discussion And Conclusion","content":"\u003cp\u003eWe report here two cases of healthy adults who had two episodes of possible COVID-19 infection. Interestingly, in one case, the symptomatic patient with recurrence of positive SARS-CoV-2 occurred after three months of the initial infection that did not trigger a protective immune response. In the other case, asymptomatic patient with recurrence of positive SARS-CoV-2 occurred within three months of the initial infection.\u003c/p\u003e\n\u003cp\u003eRecently, Yao et al. demonstrated that SARS-CoV-2 viral particles remain in previously positive patients\u0026rsquo; lungs whose NP swabs results were negative three times consecutively; this suggests that SARS-CoV-2 virus may not be eliminated when the symptoms disappear [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, there is still a reason to be cautious, and we need to be aware of recovered patients and their potential infectivity. Interestingly, there have not been any studies demonstrating that recovered patients are infectious.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, our cases are the first to describe positive SARS-CoV-2 viral RNA in recovered COVID-19 patients in the Middle East. According to the Centers for Disease Control and Prevention (CDC), reinfection of SARS-CoV-2 is highly considered in a patient who becomes symptomatic around 90 days after onset of infection and has been in close contact with an infected person, supporting our first case [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. A similar case presenting recurrence of SARS-CoV-2 has been reported in Hong Kong, bringing more attention lately. To and his colleagues demonstrated that second episode of asymptomatic infection occurred after the first symptomatic episode in an apparently immunocompetent patient [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. In addition, they confirmed SARS-CoV-2 reinfection by performing whole genome sequencing for the first and second episodes indicating different clades [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. We assume that the recurrence of COVID-19 is possible due to the presence of nonprotective IgG and recovered patients might be carriers and actively transmitting the virus even after their two negative tests [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Thus, gatherings of positive cases are not safe, and there should be an emphasis upon such social practices, and for those in convalescence, we suggest that they undergo regular tests for infectivity assessments.\u003c/p\u003e\n\u003cp\u003eThe presence of SARS-CoV-2 virus appears to be unstable because of the possibility of false-negative results of the molecular test which might be due to fluctuations in the viral load or pre-analytical errors during the sample collection [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. In our case reports, reducing the chance of false-negative and false-positive results was done by confirming each test result in different laboratory with new NP swab collection. For both cases, first positive test results were confirmed by the NHL, and two consecutive negative tests were done before the patients were considered to be cured. Although these are only two case reports and the evidence is not determinant, it gives insight and encourages future cohort studies.\u003c/p\u003e\n\u003cp\u003eIn conclusion, the global public health is at risk of the possibility of recurrence of SARS-CoV-2 as we exhibited in our case reports, which could contribute to the spread of the virus. Therefore, additional virologic, immunological, and epidemiological studies should be done to have better understanding of SARS-CoV-2 recurrence mechanism.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eSARS-CoV-2: \u003c/strong\u003eSevere acute respiratory syndrome coronavirus 2\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOVID-19: \u003c/strong\u003eCoronavirus disease 2019\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRT- PCR:\u003c/strong\u003e Real-time reverse transcriptase-polymerase chain reaction\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIgG:\u003c/strong\u003e Immunoglobin G\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMOH:\u003c/strong\u003e Ministry of Health\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRNA:\u003c/strong\u003e Ribonucleic acid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNP:\u003c/strong\u003e Nasopharyngeal\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVTM:\u003c/strong\u003e viral transport media\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNHL:\u003c/strong\u003e National Health Laboratory\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCDC:\u003c/strong\u003e Centers for Disease Control and Prevention\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent of publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent was obtained from the patient for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDerived data are available on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have declared that no competing interests exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no specific funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSara Alturaif, Remaaz Alharbi, Abdulaziz Alsadoon, and Meshari Alabdullatif conceptualized and refined research idea, and collected and processed the patients\u0026rsquo; samples. Sara Alturaif, Remaaz Alharbi, and Waleed Alqurashi created case report design and wrote the manuscript. Waleed Alqurashi and Meshari Alabdullatif edited the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Meshari Alabdullatif\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCoronavirus (COVID-19) Cases - Statistics and Research. Our World in Data. Published 2020. Accessed August 13, 2020. https://ourworldindata.org/covid-cases.\u003c/li\u003e\n\u003cli\u003eCOVID 19 Dashboard: Saudi Arabia. Published 2020. Accessed August 13, 2020. https://covid19.moh.gov.sa/.\u003c/li\u003e\n\u003cli\u003eKiyuka PK, Agoti CN, Munywoki PK, et al. Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya. J Infect Dis. 2018;217:1728-1739.\u003c/li\u003e\n\u003cli\u003eTo KK-W, Hung IF-N, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis. 2020. doi:10.1093/cid/ciaa1275.\u003c/li\u003e\n\u003cli\u003eMOH Publications - COVID-19 Guidelines. Accessed August 14, 2020. https://www.moh.gov.sa/en/Ministry/MediaCenter/Publications/Pages/covid19.aspx.\u003c/li\u003e\n\u003cli\u003eSaudi MoH Protocol for Patients Suspected of/Confirmed with COVID-19. Accessed August 13, 2020. https://www.moh.gov.sa/Ministry/MediaCenter/Publications/Documents/MOH-therapeutic-protocol-for-COVID-19.pdf.\u003c/li\u003e\n\u003cli\u003eDeeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020. doi:10.1002/14651858.CD013652.\u003c/li\u003e\n\u003cli\u003eYao X-H, He Z-C, Li T-Y, et al. Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient. Cell Research. 2020;30:541-543.\u003c/li\u003e\n\u003cli\u003eTest for Past Infection | CDC. Published 2020. Accessed September 8, 2020. https://www.cdc.gov/coronavirus/2019-ncov/testing/serology-overview.html.\u003c/li\u003e\n\u003cli\u003eLan L, Xu D, Ye G, et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. 2020;323:1502-1503.\u003c/li\u003e\n\u003cli\u003eLoconsole D, Passerini F, Palmieri VO, et al. Recurrence of COVID-19 after recovery: a case report from Italy. Infection. 2020. doi:10.1007/s15010-020-01444-1.\u003c/li\u003e\n\u003cli\u003eXiao AT, Tong YX, Zhang S. False negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence. Journal of Medical Virology. 2020. doi:10.1002/jmv.25855.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"SARS-CoV-2, COVID19, Reinfection, Saudi Arabia","lastPublishedDoi":"10.21203/rs.3.rs-86920/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-86920/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eThe rapid spread of the COVID-19 pandemic which took a place in Wuhan, China and diffused globally required the international public health to take a coordinated international response. As other coronaviruses were described, SARS-CoV-2 was thought to be an immunizing, monophasic disease. Herein, we reported first two COVID-19 cases registered in Saudi Arabia whose nasopharyngeal swabs turned positive for SARS-CoV-2 ribonucleic acid (RNA) after recovery.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase presentation \u003c/strong\u003eFirst patient who is symptomatic with recurrence of positive SARS-CoV-2 RNA occurred 115 days after the first symptomatic infection and did not develop protective immune response. Second patient who is asymptomatic during the recurrence of positive SARS-CoV-2 RNA occurred 60 days after the first symptomatic infection in an apparently immunocompetent patient.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eThese findings highlight\u0026nbsp;the recurrence of positive SARS-CoV-2 after recovery even if\u0026nbsp;SARS-CoV-2\u0026nbsp;antibodies were developed.\u003c/p\u003e","manuscriptTitle":"Recurrence of Positive SARS-CoV-2 RNA in a COVID-19 Patient: Two Case Reports from Saudi Arabia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-10-08 20:17:40","doi":"10.21203/rs.3.rs-86920/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7a19404f-ec08-45d8-bfa4-5cbd5489550b","owner":[],"postedDate":"October 8th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":708226,"name":"Virology"}],"tags":[],"updatedAt":"2021-02-15T11:58:05+00:00","versionOfRecord":[],"versionCreatedAt":"2020-10-08 20:17:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-86920","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-86920","identity":"rs-86920","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}