key: cord-0994009-hryhgy77 authors: Zhang, Jin‐jin; Cao, Yi‐yuan; Dong, Xiang; Wang, Bin‐chen; Liao, Mei‐yan; Lin, Jun; Yan, You‐qin; Akdis, Cezmi A.; Gao, Ya‐dong title: Distinct characteristics of COVID‐19 patients with initial rRT‐PCR‐positive and rRT‐PCR‐negative results for SARS‐CoV‐2 date: 2020-04-27 journal: Allergy DOI: 10.1111/all.14316 sha: 741cd6e1645b4579030643494ca5518b38463b45 doc_id: 994009 cord_uid: hryhgy77 Since the coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first emerged in Wuhan, China in December 2019, the outbreak of COVID-19 epidemic has become an increasingly serious global health concern. Currently, over 150 countries have reported COVID-19 cases, and the situation has progressed to a pandemic associated with substantial morbidity and mortality.1. To the Editor, Since the coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first emerged in Wuhan, China, in December 2019, the outbreak of COVID-19 epidemic has become an increasingly serious global health concern. Currently, over 150 countries have reported COVID-19 cases, and the situation has progressed to a pandemic associated with substantial morbidity and mortality. 1 At present, rRT-PCR (real-time reverse transcription-polymerase chain reaction) assay is the most common and only direct method of SARS-CoV-2 detection for the diagnosis of COVID-19. 2 However, false-negative results due to laboratory errors or improper collection of the specimens may inevitably lead to an important percentage of undiagnosed COVID-19 patients. Some patients with suspected COVID-19 have initial negative result of the rRT-PCR test 3, 4 or low viral concentration of SARS-CoV-2 at the sampling site in the early stages of the disease. 5 This study aims to compare the clinical and laboratory characteristics of eventually confirmed COVID-19 patients with initial positive and negative SARS-CoV-2 nucleic acid test results. The present study retrospectively reports 290 laboratory-confirmed COVID-19 patients hospitalized from December 29, 2019, to February 16, 2020. According to initial rRT-PCR results, patients were divided into initial positive and negative groups. Compared to patients with an initial negative rRT-PCR result, patients with an initial positive result were more likely to progress to a severe condition (44.6% vs 24.4%, P = .015) ( (Table S1 ). The laboratory results of patients on admission are shown in Table S2 . (Table S2 ). In general, except for two aspects (surgery history and severity), Previous studies suggested that a false-negative rRT-PCR result may occur in some COVID-19 patients. 3, 4 False-negative results may occur as a result of various factors, such as human errors when following the diagnostic kit protocol, the sensitivity of reagents, the site and method of specimen sampling and collection times. 8 It should be noted that a fraction of initial rRT-PCR negative results may be due to low or no virus expression in the sampled area. In regard to the site of specimen sampling, it has been previously reported that the viral load in the nose is higher than in the pharynx, and the virus detection rate in the lower respiratory tract is higher than in the upper respiratory tract. 9 Currently, most samples are collected from the upper respiratory tract, such as oropharynx swabs, due to ease of sampling or absence of sputum in the patient, which may lead to false-negative rRT-PCR results. Another important point to emphasize here is that the same errors for initial negative results can occur at the time of decision to discharge for clinically healed patients. As can be seen, the patients involved in the study are all hospitalized cases and we had a chance to further confirm the data with clinical diagnosis and repeated rRT-PCR tests. Some of the false-positive results can be because of low virus expression in pharynx samples, which can be even higher percentages in nonhospitalized cases. In this context, the isolation of COVID-19 suspected patients should be more vigorous and the decision should not only depend on rRT-PCR positivity during the time of the pandemics. The findings presented herein suggest that a considerable proportion of COVID-19 patients may have an initial negative rRT-PCR result and that initially positive patients had a higher tendency to progress to severe cases. Therefore, diagnosis of SARS-CoV-2 infection should not be excluded in patients with an initial negative rRT-PCR result, especially when presented with typical clinical manifestations. In view of these results, we recommend repeated rRT-PCR tests to confirm diagnosis and identify potentially infected individuals. We would like to express our gratitude and respect to all healthcare professionals and others who have dedicated themselves to combating COVID-19 and Laura Alberch for critical reading of the manuscript. Jin-jin Zhang https://orcid.org/0000-0002-4414-866X Xiang Dong https://orcid.org/0000-0002-5241-4307 Cezmi A. Akdis https://orcid.org/0000-0001-8020-019X Ya-dong Gao https://orcid.org/0000-0003-1251-7608 Coronavirus disease (COVID-2019) situation reports Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. Interim guidance Use of chest CT in combination with Negative RT-PCR assay for the 2019 novel coronavirus but high clinical suspicion Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR Testing Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study Comparison of the clinical characteristics between RNA positive and negative patients clinically diagnosed with ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China. medRxiv Quantification of mRNA using real-time RT-PCR Detection of SARS-CoV-2 in different types of clinical specimens The authors have no conflict of interest.