We confirmed the re-detection of SARS-CoV-2 after discharge from hospital in 12.16% of these COVID-19 patients. Xiaomin Wu, Zengmiao Wang, Zhenyu He, Yapin Li and Huaiyu Tian contributed equally to this work. doi:10.1001/jama.2020.2783. COVID-19 diagnosis and illness severity was defined in accordance with the Chinese management guidelines for COVID-19 published by the National Health Commission of the Peoples Republic of China. https://doi.org/10.1007/s10096-020-04024-1. Accessibility Statement, Our website uses cookies to enhance your experience. Recover your password. The patient was tested again on the 3rd5th day after transfer and on the 11th13th day. Usually, you can expect to test positive on an antigen or rapid test for up to 10 days. A positive test means you likely have COVID-19. Taken together, we believe that the re-positive tests resulted from viral shedding of non-viable viral fragments, and not re-infection. A previous study of 87 re-positive cases showed that no infectious virus could be obtained by culturing, and no full-length viral genomes could be sequenced [12]. Symptoms of the original infection for recovered COVID-19 patients with a re-positive PCR test were 0.24% asymptomatic, 49.67% mild, 35.59% moderate, 12.05% severe, and 2.40% critical. A. The first is that the COVID-19 test is detecting remains and traces of the virus, but not the live, infectious virus itself. So what else do you need to know about testing for COVID? collected the statistical data. However, we cannot fully exclude the possibility of reinfection owing to the lack of whole-genome sequencing data and immune assessment tests even though there was a 28-day isolation period and 84.07% (2058/2448) of the re-positive cases occurred during this isolation. DaweiWang,MD; BoHu,MD; ChangHu,MD; FangfangZhu,MD; XingLiu,MD; JingZhang,MD; BinbinWang,MD; HuiXiang,MD; ZhenshunCheng,MD; YongXiong,MD; YanZhao,MD; YirongLi,MD; XinghuanWang,MD; ZhiyongPeng,MD, Clinical Characteristics of Patients With Novel Coronavirus (2019-nCoV) Infection Hospitalized in Beijing, China. Positive RT-PCR Test Results in Patients Recovered From COVID-19 JAMA. In this Viewpoint Anthony Fauci and colleagues review the emergence of pathogenic human coronaviruses (SARS-Cov and MERS-CoV) as background for discussing a rapidly spreading novel coronavirus (2019-nCoV) identified in 2019 in China and the public health strategies necessary to contain the threat. PCR positivity is a necessary but not a sufficient condition for the diagnosis of reinfection due to evidence of prolonged detection that can last weeks or in some cases months after symptom resolution. Definitely, ideally, you'd be seeking out that test at five and I would do it again, you know, at the seven, potentially at that 10.". Drs H. Xu and Li contributed equally as senior authors. You can end isolation after five days if you are fever-free for 24 hours without using fever-reducing . 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Re-positive cases of nucleic acid tests in discharged patients with COVID-19: a follow-up study. But even if it's rare, there are more than 140 million people who have been infected already, right?. Y, Fu ZJ. A negative test means you probably did not have COVID-19 at the time of the test. Here's What We Know So Far, Exclusive: Trinity Fatu, Formerly WWE's Naomi, Talks Making Surprise Return with IMPACT Wrestling in Chicago, This 28-Year-Old Pays $62 a Month to Live in a Dumpster He Built for $5,000Take a Look Inside, 25-Year-Old Makes $200/Hour Without a Bachelor's Degree: I Work Less Than 6 Hours a Day'. The estimated number of false-positive cases in these 1265 patients is 89.5 (174.4/2466*1265). In Chinese. The primers and probes used targeted the ORF1ab and N gene regions of SARS-CoV-2. CAS Correspondence to Note that a re-positive test could result from virus fragments coming from the original infectionthe PCR test only detects fragments of the SARS-CoV-2 genome, not viable virus. This study was approved by the Institutional Review Boards from Wuhan Center for Disease Control and Prevention. Drs Lan and D. Xu contributed equally to the study. New research from Whitehead Institute Founding Member Rudolf Jaenischs lab adds evidence to their finding that SARS-CoV-2 can integrate into the human genome, but finds that a model of the mRNA vaccine does not integrate. https://doi.org/10.1001/jama.2020.2783. RT-PCR was performed again 5 to 13 days later and repeated three times over the next 4 or 5 daysand all tests were positive. Third, limited patient factors were collected in this study. T, Sun Get tested at least 5 days post exposure . With ones mouth wide open, making a sound ah to expose the lateral pharyngeal tonsils, the sampler inserts the swabs, wipes it across the tongue roots, and wipes both sides of the pharyngeal tonsils with pressure at least three times. It is then slowly removed, and the swab tip is dipped into a tube containing 23ml of virus preservation solution (isotonic saline solution, tissue culture solution, or phosphate buffer). If the culture is negative for viable virus, then the viral RNA detected by PCR is likely a result of non-viable viral RNA shedding rather than an ongoing infection. In this retrospective analysis, culturing results were obtained for more than 300 recovered COVID-19 patients with a re-positive PCR test and no viable virus was obtained. All Rights Reserved. This case series describes reverse transcriptase-polymerase chain reaction (RT-PCR) test results in 4 health professionals discharged from hospitalization or quarantine after 2 negative RT-PCR test results and resolution of clinical COVID-19 infection. Wei DH, Nian CJ, Bin PX, Ling CX, Yixian-Zhang, Fang FS, et al. If the transcripts were the product of random viral integration into the genome, however, there would be a near 50-50 split half the transcripts would have been read forwards, the other half backwards, relative to the host genes. volume19, Articlenumber:77 (2021) This may warrant extending the duration of isolation and precautions for up to 20 days after symptom onset (with day 0 being the day symptoms appeared) and after resolution of fever for at least 24 hours (without the taking fever-reducing medications) and improvement of other symptoms. There are some limitations to our study. After meeting the criteria for hospital release or lifting of quarantine, the patients were asked to remain at home for another 5 days. Because many potential confounding factors were not analyzed, these results need to be verified using a more complete dataset. 2020;30:12. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused more than 108 million cases of coronavirus disease 2019 (COVID-19) illness, and over 2.4 million people globally have died from this disease as of February 2021 [1]. People who've recovered from COVID-19 can have " detectable SARS-CoV-2 RNA " in their body for up to three months after the initial . Critical revision of the manuscript for important intellectual content: Xia, Wang, Li. Although the patients had contacts with the staff at the rehabilitation center, the contact was limited, and the staff wore personal protective equipment (including medical protective clothing, medical protective masks, protective goggles, medical latex gloves, shoes protectors, and work caps). When a commercial kit was used, the instructions provided by the manufacturer prevailed. Among the re-positive cases, the hospital stay for the re-positive test was shorter than that of the original infection (P<0.001 from Students t-test). If you test too early, you may be more likely to get an inaccurate result. The demographic and epidemiological characteristics of these patients were similar to those who did not have a re-positive test (Table 1). According to the Centers for Disease Control and Prevention, some people who contract COVID-19 can have detectable virus for up to three months, but that doesn't mean they are contagious. But one thing we do think we can explain is why some patients are long-term PCR positive.. For those isolating due to a COVID infection, there is no testing requirement to end isolation, however, the CDC recommends using a rapid antigen test for those who choose to take one. We identified 2466 re-positive cases. In the present paper, the researchers were able to eliminate these artefacts that could have been obscuring the results. This finding is consistent with previous studies [12, 19]. "If you did want to get a test on please don't get a PCR. The sampler then wipes on the upper and lower walls of the pharynxes for at least three times and dips the swab in a tube containing 23ml of storage solution (isotonic saline solution, tissue culture solution, or phosphate buffer solution). C, Wang Terms and Conditions, Part of With the help of Jaenisch lab postdoc Alexsia Richards, the researchers infected human cells with coronavirus in the lab and then sequenced the DNA from infected cells two days later to see whether it contained traces of the virus genetic material. All 4 patients had 2 consecutive negative RT-PCR test results. Blue represents DNA, green shows the SARS-CoV-2 nucleocapsid protein, and red represents double-stranded RNA, which occurs when the virus replicates its genome. In total, 20,280 patients were included in the retrospective analysis. The data supporting the findings of this study are available within the article. In our study, the duration between hospital discharge and a re-positive test was 11.00 (IQR, 9.00 to 17.00). 2020 Apr . In our follow study, the recovered COVID-19 patients experienced two 14-days isolation periods, and the chance of viral exposure was quite low. 2020;59:102960. https://doi.org/10.1016/j.ebiom.2020.102960. Also called a molecular test, this COVID-19 test detects genetic material of the virus using a lab technique called reverse transcription polymerase chain reaction (PCR). No patients had these three symptoms at the same time, and 11 of the 2466 patients passed away (not due to COVID-19). It's been seen before that the remnants of the virus are detected but not the live, infectious virus . For SARS-CoV-2, the frequency of integration in humans is still unknown. In this Viewpoint, Gostin and colleagues review the emerging novel coronavirus (2019-nCoV) outbreak, discuss the public health benefits and risks of the Chinese governments large city quarantines, and call for WHO leadership to coordinate a global coordinated response that could contain this and prevent similar future outbreaks. A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious. It is possible that only a very few human cells experience any kind of viral integration at all. YanBai,MD; LingshengYao,MD; TaoWei,MD; FeiTian,MD; Dong-YanJin,PhD; LijuanChen,PhD; MeiyunWang,MD, PhD, COVID-19New Insights on a Rapidly Changing Epidemic. N Microbes N Infect. A logistic regression model was used to elucidate the factors related to the risk of a re-positive test. Ann Transl Med. Introduce exercise into your weekly plans slowly and carefully. Alexandra L.Phelan,SJD, LLM; RebeccaKatz,PhD, MPH; Lawrence O.Gostin,JD, Discussing the ABCs of Health SecurityAntibiotic Resistance, Biothreats, and Coronavirus. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Learn how the field of RNA biology has been working to meet the challenges of the virus, and what Whitehead Institute RNA researchers have been working on throughout the pandemic. The patients were tested again 1month after hospital discharge, with retests every month thereafter. These findings may explain why there was no subsequent infection in the majority of those with a re-positive test. Phone: 617-452-4630 2020;323:15023. The COVID-19 outbreak was first reported in Wuhan [6] and lasted for more than 3months; after May 18, 2020, there were no further locally acquired infections. Note that our conclusion is consistent with the three studies. Although false-negative RT-PCR test results could have occurred as suggested by a previous study,6 2 consecutively negative RT-PCR test results plus evidence from clinical characteristics and chest CT findings suggested that the 4 patients qualified for hospital discharge or discontinuation of quarantine. Some people who recover from COVID may test positive for weeks or even months after they were sick. The swab is then discarded the tube cap is tightened. With this in mind, Zhang and Jaenisch began to design experiments to test whether this viral integration could be happening with the novel coronavirus. ZunyouWu,MD, PhD; Jennifer M.McGoogan,PhD, Editorial ConcernPossible Reporting of the Same Patients With COVID-19 in Different Reports, HowardBauchner,MD; Robert M.Golub,MD; JodyZylke,MD, Presumed Asymptomatic Carrier Transmission of COVID-19. This study investigates the timeframe that optimizes saliva sensitivity for SARS-CoV-2 detection using reverse transcriptasepolymerase chain reaction (RT-PCR) testing. When the tip of the swab reaches the posterior wall of the nasopharyngeal cavity, it is gently rotated once (pause for a moment in case of reflex cough). The median hospital stay for recovered COVID-19 patients without a re-positive PCR test was 15.71days (IQR, 9.83 to 23.21), and the median hospital stay for the original infection in the re-positive cases was 18.54days (IQR, 11.96 to 27.04). PubMed PubMed Central After recovery, patients and their families were contacted directly, and patients were asked to visit the hospital to collect throat swabs for the RT-PCR tests. Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test. The false-positive cases had a small effect on the re-positivity rate. Clinical features of COVID-19 convalescent patients with re-positive nucleic acid detection. Zengmiao Wang or Zhenyu He. EBioMedicine. A new study from the Jaenisch lab suggests that some virus RNA can be reverse transcribed and inserted into the human genome, which may explain why some patients continue to test positive for COVID-19 even after recovery. Positive RT-PCR test results in patients recovered from COVID-19. X, Zhang In this Medical News article, Tom Inglesby, MD, director of the Center for Health Security at the Johns Hopkins Bloomberg School of Public Health, speaks about natural and deliberate biological threats to US national security. JAMA. Threat Assessment Brief: reinfection with SARS-CoV-2: considerations for public health response. Homepage tests and antibody tests are not accepted. Article The Foundation for Innovative New Diagnostics (FIND) [23] conducted independent evaluations of the 22 nucleic acid test kits for SARS-CoV-2 and reported their clinical sensitivity and clinical specificity. Cao S, Gan Y, Wang C, Bachmann M, Wei S, Gong J, et al. Second, some false positives and false negatives in our study were included. Zhu H, Fu L, Jin Y, Shao J, Zhang S, Zheng N, et al. The patients were followed up via regular hospital visits every 2weeks. "Why? On the basis of the study by Jing Lu et al [12], the prevalence of re-positive cases in the discharged patients is 14%. PubMed Central Habibzadeh P, Sajadi MM, Emami A, Karimi MH, Yadollahie M, Kucheki M, et al. The researchers identified these features in nearly 70 percent of the DNAs that contained viral sequences, but not all, suggesting that the viral RNA may be integrating into cellular DNA via multiple mechanisms. National major science and technology project (2018ZX10713003-001-015). A total of 1265 patients tested positive after they returned home, and 4079 individuals had close contact with them. This Viewpoint reviews options legally available to state Medicaid programs to respond to the COVID-19 pandemic, including increasing coverage of the uninsured, expanding telehealth capabilities, removing financial barriers to testing and treatment, and easing limits on drug prescriptions. et al. The RT-PCR test results for 4079 individuals who had close contact with the re-positive cases were also obtained. https://doi.org/10.11613/BM.2020.030401. Blue represents DNA, green shows the . PEM can affect your energy levels, concentration, sleep and memory. Most people who contract COVID-19 likely won't experience symptoms for more than two weeks at most, but could test positive months following infection. "If you're taking multiple at home tests, you know, the recommendation is five days later take a test. If the viral reads were the result of live viruses or existing viral RNAs in the cell, the researchers would expect that most of the viral transcripts would have been read in the correct orientation for the sequences in question; in acutely infected cells in culture, more than 99 percent are in the correct orientation. Antiviral treatment (75 mg of oseltamivir taken orally every 12 hours) was provided for the 4 patients. At this point, we can only speculate, says Jaenisch. (1) Results from investigations of possible exposure. had positive RT-PCR test results 5 to 13 days later. F, Liu Springer Nature. These sections of the genome can then be read into RNAs, which could potentially be picked up by a PCR test. Get tested if you have symptoms of COVID-19 or have been exposed to someone who tested positive for COVID-19. With a PCR, you can continue to test positive for weeks or even months after an antigen test delivers a negative result. J Med Virol. The Centers for Disease Control would later make it known that PCR tests could continue to detect the presence of COVID for up to three months after infection, while the infectious period lasts. Overall, 56.12% of the re-positive cases were women. Due to privacy concerns, data cannot be made openly available. Google Scholar. Previous studies on coronavirus disease 2019 (COVID-19) mainly focused on epidemiological, clinical, and radiological features of patients with confirmed infection.1-4 Little attention has been paid to the follow-up of recovered patients. D, Hu Customize your JAMA Network experience by selecting one or more topics from the list below. Theres a very clear footprint for LINE1 integration, Jaenisch says. https://doi.org/10.1016/j.cmi.2020.04.023. K-H, Students t-test was used to compare the continuous variables of two groups. We thank the many thousands of CDC staff and local health workers in China who collected the data. The nose swab PCR test for COVID-19 is an accurate and reliable test for diagnosing COVID-19. From Containment to Mitigation of COVID-19 in the US. Now, new research published by the Korea Centers for Disease Control and Prevention has found that recovered COVID-19 patients who test positive again aren't infectious. Acquisition, analysis, or interpretation of data: Lan, Ye, Wang, Li. Nat Commun. The hospital stay for the original infection in the re-positive cases was significantly longer than that in patients without a re-positive PCR test (P<0.001, Students t-test). Positive RT-PCR Test Results in Patients Recovered From COVID-19. Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing. , Coronavirus Outbreakan Evolving Global Health Emergency, FDA Warns Coronavirus Outbreak May Disrupt Supply of Critical Medical Products, Coronavirus InfectionsMore Than Just the Common Cold. Yuan B, Liu HQ, Yang ZR, Chen YX, Liu ZY, Zhang K, et al. In this study, categorical variables are presented as numbers and percentages, and continuous variables are presented as the median (interquartile range, IQR). Individuals who had close contact with the patient were quarantined in the isolation center and were tested on the 1st2nd day after entering quarantine and again on the 10th14th day. They are often activated to jump in conditions of high stress or during cancer or aging, and are powerful agents of genetic change. Cevik M, Bamford CGG, Ho A. COVID-19 pandemica focused review for clinicians. This Viewpoint discusses challenges to managing a COVID-19 outbreak in low- and middle-income countries (LMICs), reviewing how absence of testing, critical care capacity, climate, war, distrust, and large refugee populations could complicate implementation of proven infection prevention and control measures. In total, 2466 (12.16%) of the 20,280 patients had a re-positive SARS-CoV-2 PCR test after they were discharged from the hospital, and 4079 individuals had close contact with members of this patient group. The RT-PCR tests were repeated 5 to 13 days later and all were positive. If this duration is short, re-detection of the initial infection is a more likely than a true reinfection, because a longer time-lapse would relate to waning immunity and lower antibody levels. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. https://doi.org/10.1080/22221751.2020.1837018. Privacy Policy| After persistent negative RT-PCR test results for SARS-CoV-2 over four times, some patients re-tested positive for the virus nucleic acid," the researcher noted. The median age of the patients was 56.00years (IQR, 42.25 to 65.00), and more than half of the patients (50.9%, n=1256) were aged between 50 and 70years (accounting for 28.21%of the total population in Wuhan according to Wuhan Statistical Yearbook (2020) (http://tjj.wuhan.gov.cn/tjfw/tjnj/202102/t20210202_1624450.shtml)). California Privacy Statement, Thus, the number of false-negative cases would be 20,280*14%*1%, which is 28.4. This retrospective study in Wuhan clarifies the basic characteristics of recovered COVID-19 patients with a re-positive PCR test. Specifically, 158 (6.41%) patients had a fever, 59 (2.39%) patients had a cough, and 18 (0.73%) patients had shortness of breath, 32 (1.30%) patients had fever and cough, 1 (0.04%) patient had cough and shortness of breath, and 9 (0.36%) patients had fever and shortness of breath. Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia. This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei. Additional testing beyond PCR: To ensure that their results could be confirmed with different methodology, they used three different DNA sequencing techniques. The kits used are listed in Supplementary Table2. Lu J, Peng J, Xiong Q, Liu Z, Lin H, Tan X, et al. This retrospective study in Wuhan analyzed the basic characteristics of recovered COVID-19 patients with re-positive PCR test and found that these cases may not be infectious. "If you want to be extra careful, you can do it at 10, but just with what we're seeing, I would consider you really in the clear. T, Yu https://doi.org/10.1126/science.abb6105. BMC Med 19, 77 (2021). C. JasonWang,MD, PhD; Chun Y.Ng,MBA, MPH; Robert H.Brook,MD, ScD, Priorities for the US Health Community Responding to COVID-19. This Viewpoint discusses the policy and legal ramifications of the national public health emergency declared by the US government in response the coronavirus disease 2019 (COVID-19) outbreak, and examines the lawfulness of quarantine and other compulsory measures. If they do, and trigger immune responses, it may provide continuous protection against the virus, Zhang says. PubMedGoogle Scholar. So these are not false positive results - the test is detecting residual virus - your body hasn't completely eliminated it yet. When it comes to testing, the PCR tests are more likely to continue picking up the virus following infection. An image of lung cancer cells infected with the SARS-CoV-2 virus. Now, a PCR test, remember, can pick up up sort of traces of the virus for a long time, even if that virus is bad and even if it's not potentially transmitting.". Cevik M, Tate M, Lloyd O, Maraolo AE, Schafers J, Ho A. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Gray zone: Ct value between 37 and 40; in these cases, a repeat test was recommended. Further studies should follow up patients who are not health care professionals and who have more severe infection after hospital discharge or discontinuation of quarantine. The multivariable and univariable logistic regression model was used to determine the associated factors. "They keep picking up dead virus in your nose for sometimes for weeks, but you can't grow that virus in the lab. Z, Zhao , Pan Antibody get and COVID home tests (self-tests) unable be used as proof regarding optimistic COVID test unless PROCTORED. This Viewpoint discusses the importance of protecting health care workers caring for patients with coronavirus disease 2019 (COVID-19) and measures that can be taken in and out of the hospital to prevent their and their families exposure to SARS-CoV-2. Accessed 15 Feb 2021. Negative: no Ct value or Ct value 40. During the outbreak in Wuhan, there were 50,340 confirmed COVID-19 cases, with 3869 deaths, and 46,471 patients were clinically cured and discharged in accordance with the WHO guidelines [7]. Recovery normally takes 24 hours or longer. Use a rapid antigen test," she said. Among 3 of the patients, fever, cough, or both occurred at onset. "PCR test can stay positive for a long time," Chicago Department of Public Health Commissioner Dr. Allison Arwady said in March. "If you had an exposure, you're vaccinated and boosted, I don't think that there is any need to be testing, frankly, past about seven days," she said. Unlike our own genomes, the genetic material of the novel coronavirus is RNA and RNA also makes up some of the vaccines. The patients continued to be asymptomatic by clinician examination and chest CT findings showed no change from previous images. In our study, 20,280 COVID-19 patients and 4079 close contacts were collected from December 31, 2019, and August 4, 2020, in Wuhan. W, Zheng Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirusinfected pneumonia in Wuhan, China. If you're not vaccinated or boosted, I certainly have a much higher concern that you could get infected. Novel coronavirus infection in hospitalized infants under 1 year of age in China. Then wear a well-fitting mask at all times around others for an additional 5 days. An J, Liao X, Xiao T, Qian S, Yuan J, Ye H, et al. GiacomoGrasselli,MD; AntonioPesenti,MD; MaurizioCecconi,MD, Managing COVID-19 in Low- and Middle-Income Countries. We used the average clinical sensitivity and clinical specificity of these 22 kits as the final sensitivity (99%) and specificity (99%). Google Scholar. This result shows that the false-negative cases had small effect on the re-positivity rate. However, recent research revealed that at least some of the viral-cellular reads could be the product of misleading artefacts of the RNA sequencing method. The sampler then immerses the swabs in sterile saline (virus preservation solution is not allowed so as to avoid antibiotic allergies) and holds the persons head up slightly. M, Yuan PubMed Some viruses, called retroviruses, rely on integration into human DNA in order to replicate themselves.
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