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BackgroundWe analyzed antibody response patterns according to level of disease severity in patients with novel coronavirus disease 2019 (COVID-19) in Japan. MethodsWe analyzed 611 serum specimens from 231 patients with COVID-19 (mild, 170; severe, 31; critical, 30). IgM and IgG antibodies against nucleocapsid protein (N) and spike 1 protein (S1) were detected by enzyme-linked immunosorbent assays. FindingsThe peaks of fitting curves for the OD values of IgM and IgG antibodies against N appeared simultaneously, while those against S1 were delayed compared with N. The OD values of IgM against N and IgG against both N and S1 were significantly higher in the severe and critical cases than in the mild cases at 11 days after symptom onset. The seroconversion rates of IgG were higher than those of IgM against both N and S1 during the clinical course based on the optimal cut-off values defined in this study. The seroconversion rates of IgG and IgM against N and S1 were higher in the severe and critical cases than in the mild cases. ConclusionOur findings show that a stronger antibody response occurred in COVID-19 patients with greater disease severity and there were low seroconversion rates of antibodies against N and S1 in the mild cases. The antibody response patterns in our population suggest a second infection pattern, leading us to hypothesize that cross-reactivity occurs between SARS-CoV-2 and past infection with other human coronaviruses.
ABSTRACT
BackgroundThe clinical performance of six molecular diagnostic tests and a rapid antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were clinically evaluated for the diagnosis of coronavirus disease 2019 (COVID-19) in self-collected saliva. MethodsSaliva samples from 103 patients with laboratory-confirmed COVID-19 (15 asymptomatic and 88 symptomatic) were collected on the day of hospital admission. SARS-CoV-2 RNA in saliva was detected using a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) laboratory-developed tes (LDT), a cobas SARS-CoV-2 high-throughput system, three direct RT-qPCR kits, and reverse-transcription loop mediated isothermal amplification (RT-LAMP). Viral antigen was detected by a rapid antigen immunochromatographic assay. ResultsOf the 103 samples, viral RNA was detected in 50.5-81.6% of the specimens by molecular diagnostic tests and an antigen was detected in 11.7% of the specimens by the rapid antigen test. Viral RNA was detected at a significantly higher percentage (65.6-93.4%) in specimens collected within 9 d of symptom onset compared to that of specimens collected after at least 10 d of symptom onset (22.2-66.7%) and that of asymptomatic patients (40.0-66.7%). Viral RNA was more frequently detected in saliva from males than females. ConclusionsSelf-collected saliva is an alternative specimen diagnosing COVID-19. LDT RT-qPCR, cobas SARS-CoV-2 high-throughput system, direct RT-qPCR except for one commercial kit, and RT-LAMP showed sufficient sensitivity in clinical use to be selectively used according to clinical settings and facilities. The rapid antigen test alone is not recommended for initial COVID-19 diagnosis because of its low sensitivity. Key pointsSix molecular diagnostic tests showed equivalent and sufficient sensitivity in clinical use in diagnosing COVID-19 in self-collected saliva samples. However, a rapid SARS-CoV-2 antigen test alone is not recommended for use without further study.
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BackgroundWe evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19). MethodsWe examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-CoV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission. FindingsOf the139 COVID-19 serum specimens, IgM was detected in 27.8%, 48.0%, and 95.8% of the specimens collected within 1 week, 1-2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3%, 8.0%, and 62.5%, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4% (26/38) for the asymptomatic patients and 74.3% (55/74) and 82.4% (61/74) for the symptomatic patients, respectively. ConclusionThe IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.
ABSTRACT
BackgroundThe ongoing outbreak of the coronavirus disease 2019 (COVID-19) is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We compared the clinical features on admission among patients who were diagnosed with asymptomatic, mild, and severe COVID-19 at the end of observation. MethodsThis retrospective, single-center study included 104 patients with laboratory-confirmed COVID-19 from the mass infection on the Diamond Princess cruise ship from February 11 to February 25, 2020. Clinical records, laboratory data, and radiological findings were analyzed. Clinical outcomes were followed up until February 26, 2020. Clinical features on admission were compared among those with different disease severity at the end of observation. Univariate analysis identified factors associated with symptom onset and disease progression. FindingsThe median age was 68 years, and 54 patients were male. Briefly, 43, 41, and 20 patients on admission and 33, 43, and 28 patients at the end of observation had asymptomatic, mild, and severe COVID-19, respectively. Serum lactate hydrogenase levels were significantly higher in 10 patients who were asymptomatic on admission but developed symptomatic COVID-19 compared with 33 patients who remained asymptomatic throughout the observation period. Older age, consolidation on chest computed tomography, and lymphopenia on admission were more frequent in patients with severe COVID-19 than those with mild COVID-19 at the end of observation. InterpretationLactate dehydrogenase level is a potential predictor of symptom onset in COVID-19. Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to the clinical management. FundingNot applicable. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched the PubMed database from its inception until March 1, 2020, for articles published in English using the keywords "novel coronavirus," "2019 novel coronavirus," "2019-nCoV," "Severe acute respiratory syndrome coronavirus 2," "SARS-CoV2," "COVID-19," "mass infection," "herd infection," "cruise ship," "Diamond Princess," "asymptomatic," and "subclinical." There were no published clinical studies featuring COVID-19 as a result of mass infection on board a cruise ship. We found published articles entitled "Characteristics of COVID-19 infection in Beijing" and "Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study," which compared patients with asymptomatic, mild, and severe COVID-19. However, none of the studies described potential markers for symptom onset or disease progression in patients with COVID-19. Added value of this studyWe present the differences in clinical characteristics of 104 patients with laboratory-confirmed COVID-19 as a result of mass infection on the Diamond Princess cruise ship who were treated at Self-Defense Forces Central Hospital, Japan from February 11 to February 25, 2020. On admission, 43, 41, and 20 patients had asymptomatic, mild, and severe COVID-19, respectively, whereas 33, 43, and 28 patients were determined to have asymptomatic, mild, and severe COVID-19, respectively, at the end of observation. During the observation period, 10 of the 43 (23.3%) asymptomatic patients on admission developed symptoms of COVID-19. Conversely, eight of the 84 (9.5%) patients with asymptomatic and mild COVID-19 on admission developed severe disease during the observation period. The serum lactate dehydrogenase (LDH) levels were significantly higher in 10 patients who were initially asymptomatic on admission to the hospital and developed symptomatic COVID-19 during the observation period compared with 33 patients who remained asymptomatic throughout the observation period. The prevalence rates of consolidation on chest computed tomography (CT) images and lymphopenia were significantly higher in eight patients who developed severe COVID-19 during the observation period compared with the 76 patients with asymptomatic or mild disease at the end of the observation. Older age, consolidation on chest CT, and lymphopenia on admission were more frequent in patients with severe COVID-19 (n = 28) than those with mild COVID-19 (n = 43) at the end of observation. LDH level might be marker for symptom onset in patients with COVID-19, whereas older age, consolidation on chest CT imaging, and lymphopenia are potential risk factors for disease progression. The current report findings will contribute to the improvement of clinical management in patients with COVID-19. Implications of all the available evidenceSerum LDH level is a potential predictor of symptom onset of COVID-19, whereas older age, consolidation on chest CT imaging, and lymphopenia have potential utility as markers for disease progression.
