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      Crucial laboratory parameters in COVID-19 diagnosis and prognosis: An updated meta-analysis Translated title: Parámetros cruciales de laboratorio en diagnóstico y pronóstico de COVID-19: un metaanálisis actualizado

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          Abstract

          Introduction and objectives

          Common laboratory parameters are crucial in aiding coronavirus disease 2019 (COVID-19) case detection. This study aimed to determine the differences between laboratory parameters in (1) COVID-19 versus non-COVID-19 pneumonia, and (2) severe versus non-severe COVID-19 cases.

          Methods

          Studies were collected until March 2020, and retrieved parameters include leukocyte, neutrophil, thrombocyte, and lymphocyte counts in addition to C-reactive protein (CRP), procalcitonin (PCT) and D-dimer levels. In the presence of heterogeneity, the random-effect model (REM) was used instead of the fixed-effect model (FEM).

          Results

          Seven studies in the first analysis showed significantly lower leukocyte, neutrophil and platelet counts in COVID-19 pneumonia (SMD = −0.42, 95%CI −0.60 to −0.25, p < 0.00001, SMD = −0.23, 95%CI −0.41 to −0.06, p = 0.01, SMD = −0.54, 95%CI −0.91 to −0.16, p = 0.0005) compared to non-COVID-19 pneumonia. Twenty-six studies in the second analysis showed significantly lower lymphocyte and thrombocyte counts (SMD = −0.56, 95%CI −0.71 to −0.40, p < 0.0001, SMD = −0.32, 95%CI −0.49 to −0.15, p = 0.0002) and significantly higher leukocyte, neutrophil, D-dimer, and CRP (SMD = 0.31, 95%CI 0.07–0.56, p = 0.01; SMD = 0.44, 95%CI 0.24–0.64, p < 0.0001; SMD = 0.53, 95%CI 0.31–0.75, p < 0.00001; SMD = 0.97, 95%CI 0.70–1.24, p < 0.00001) in severe COVID-19 compared to non-severe COVID-19.

          Conclusions

          In conclusion, thrombocyte count is key in both diagnosis and prognosis. Low leukocyte and neutrophil counts are markers of COVID-19 infection, but contrastingly higher counts indicate progressive COVID-19. And although lymphocyte, D-dimer and CRP levels did not demonstrate diagnostic value, all indicate severity of COVID-19. Confirmation of these findings should be performed in future studies.

          Translated abstract

          Introducción y objetivos

          Los parámetros comunes de laboratorio son cruciales para ayudar a la detección de casos de enfermedad por coronavirus 2019 (COVID-19). Este estudio tuvo como objetivo determinar las diferencias entre los parámetros de laboratorio en: 1) COVID-19 versus neumonía no COVID-19, y 2) Casos severos versus no severos de COVID-19.

          Métodos

          Los estudios se recolectaron hasta marzo de 2020, y los parámetros recuperados incluyen recuentos de leucocitos, neutrófilos, trombocitos y linfocitos además de los niveles de proteína C reactiva (PCR), procalcitonina (PCT) y dímero-D. En presencia de heterogeneidad, se utilizó el modelo de efectos aleatorios en lugar del modelo de efectos fijos.

          Resultados

          Siete estudios en el primer análisis mostraron recuentos de leucocitos, neutrófilos y plaquetas significativamente más bajos en la neumonía por COVID-19 (SMD = −0,42; IC 95%: −0,60 a −0,25; p < 0,00001; SMD = −0,23; IC 95%: −0,41 a −0,06; p = 0,01; SMD = −0,54; IC 95%: −0,91 a −0,16; p = 0,0005) en comparación con la neumonía no COVID-19. Veintiséis estudios en el segundo análisis mostraron recuentos de linfocitos y trombocitos significativamente más bajos (SMD = −0,56; IC 95%: −0,71 a −0,40; p < 0,0001; SMD = −0,32; IC 95%: −0,49 a −0,15; p = 0,0002) y leucocitos, neutrófilos, dímero D y PCR significativamente más altos (SMD = 0,31; IC 95%: 0,07-0,56; p = 0,01; SMD = 0,44; IC 95%: 0,24-0,64; p < 0,0001; SMD = 0,53; IC 95%: 0,31-0,75; p < 0,00001; SMD = 0,97; IC 95%: 0,70-1,24; p < 0,00001) en COVID-19 severo en comparación con COVID-19 no severo.

          Conclusiones

          En conclusión, el recuento de trombocitos es clave tanto en el diagnóstico como en el pronóstico. Los recuentos bajos de leucocitos y neutrófilos son marcadores de infección por COVID-19, pero los recuentos contrastantemente más altos indican COVID-19 progresivo. Y aunque los niveles de linfocitos, dímero D y PCR no mostraron valor diagnóstico, todos indican la gravedad de COVID-19. La confirmación de estos hallazgos debe realizarse en futuros estudios.

          Related collections

          Most cited references 12

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Covert COVID-19 and false-positive dengue serology in Singapore

            Dengue and coronavirus disease 2019 (COVID-19) are difficult to distinguish because they have shared clinical and laboratory features.1, 2 We describe two patients in Singapore with false-positive results from rapid serological testing for dengue, who were later confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative virus of COVID-19. The first case is a 57-year-old man with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 9, 2020, with 3 days of fever and cough. He had thrombocytopenia (platelet count 140 × 109/mL) and a normal chest radiograph. He was discharged after a negative rapid test for dengue NS1, IgM, and IgG (SD Bioline Dengue Duo Kit; Abbott, South Korea). He returned to a public primary health-care clinic with persistent fever, worsening thrombocytopenia (89 × 109/mL), and new onset lymphopenia (0·43 × 109/mL). A repeat dengue rapid test was positive for dengue IgM and IgG (Dengue Combo; Wells Bio, South Korea). He was referred to hospital for dengue with worsening cough and dyspnoea. A chest radiograph led to testing for SARS-CoV-2 by RT-PCR (in-house laboratory-developed test detecting the N and ORF1ab genes) from a nasopharyngeal swab, which returned positive. The original seropositive sample and additional urine and blood samples tested negative for dengue, chikungunya, and Zika viruses by RT-PCR,3, 4, 5 and a repeat dengue rapid test (SD Bioline) was also negative. Thus, the initial dengue seroconversion result was deemed a false positive. The second case is a 57-year-old woman with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 13, 2020, with fever, myalgia, a mild cough of 4 days, and 2 days of diarrhoea. She had thrombocytopenia (92 × 109/mL) and tested positive for dengue IgM (SD Bioline). She was discharged with outpatient follow up for dengue fever. She returned 2 days later with a persistent fever, worsening thrombocytopenia (65 × 109/mL), and new onset lymphopenia (0·94 × 109/mL). Liver function tests were abnormal (aspartate aminotransferase 69 U/L [reference range 10–30 U/L], alanine aminotransferase 67 U/L [reference range <55 U/L], total bilirubin 35·8 μmol/L [reference range 4·7–23·2 μmol/L]). Chest radiography was normal and she was admitted for dengue fever. She remained febrile despite normalisation of her blood counts and developed dyspnoea 3 days after admission. She was found to be positive for SARS-CoV-2 by RT-PCR from a nasopharyngeal swab. A repeat dengue test (SD Bioline) was negative and an earlier blood sample also tested negative for dengue by RT-PCR. 6 The initial dengue IgM result was deemed to be a false positive. Failing to consider COVID-19 because of a positive dengue rapid test result has serious implications not only for the patient but also for public health. Our cases highlight the importance of recognising false-positive dengue serology results (with different commercially available assays) in patients with COVID-19. We emphasise the urgent need for rapid, sensitive, and accessible diagnostic tests for SARS-CoV-2, which need to be highly accurate to protect public health.
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              Thrombocytopenia in patients with severe acute respiratory syndrome (review).

              Severe Acute Respiratory Syndrome (SARS) has been recognized as a new human infectious disease caused by a novel coronavirus (SARS-CoV). Hematological changes in patients with SARS were common, including notably lymphopenia and thrombocytopenia. While the former is the result of decreases in CD4+ or CD8+ T-lymphocytes related to the onset of disease or use of glucocorticoids, the latter may involve a number of potential mechanisms. Although the development of autoimmune antibodies or immune complexes triggered by viral infection may play a significant role in inducing thrombocytopenia, SARS-CoV may also directly infect hematopoietic stem/progenitor cells, megakaryocytes and platelets inducing their growth inhibition and apoptosis. Moreover, the increased consumption of platelets and/or the decreased production of platelets in the damaged lungs are a potential alternative mechanism that can contribute to thrombocytopenia in severe critical pulmonary conditions, which has been rarely revealed and will be discussed.
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                Author and article information

                Contributors
                Journal
                Med Clin (Engl Ed)
                Med Clin (Engl Ed)
                Medicina Clinica (English Ed.)
                Elsevier España, S.L.U.
                2387-0206
                22 August 2020
                28 August 2020
                22 August 2020
                : 155
                : 4
                : 143-151
                Affiliations
                [a ]Department of Biochemistry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, 90245, Indonesia
                [b ]Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University of Malang, Batu, East Java, 65151, Indonesia
                Author notes
                [1]

                Both authors contributed equally to this manuscript.

                Article
                S2387-0206(20)30295-3
                10.1016/j.medcle.2020.05.004
                7442896
                © 2020 Elsevier España, S.L.U. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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