PMC:7784824 / 1891-7434 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7784824","sourcedb":"PMC","sourceid":"7784824","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7784824","text":"Background\nIn December 2019, several cases of an unidentified pneumonia occurred in the province of Hubei, China. With the use of next-generation sequencing, the Wuhan Institute of Virology identified a new coronavirus as the etiological agent [1,2]. This new virus, which belongs to the genus betacoronavirus, was initially acknowledged as novel coronavirus 2019 (2019-nCOV) [3]. On 11 February 2020, the virus was officially renamed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses [4]. Since then the virus has rapidly spread and on the 18th of July 2020, over 14 million confirmed cases and 600 000 direct casualties have been reported [5]. So far, implementation of strict quarantine measures have contained further exponential spreading of the virus in Europe and have flattened the first epidemic curve.\nConsidering the extent of the pandemic, its socio-economic impact, and the effect on healthcare systems worldwide, there is a high need to extend the diagnostic capacity. So far, the gold standard for the diagnosis of SARS-CoV-2, implemented at the start of the outbreak, is real-time reverse transcriptase polymerase chain reaction (RT-PCR) [6]. In contrast with a high specificity up to 98.8% [7], RT-PCR suffers from a rather long turnaround time when performed in batch testing (2 to 6 hours). Continuous PCR testing has a faster turnaround time (1 u) but a low capacity. False negative results in both the very early as well as the late phase of the disease due to low virus shedding at these stages of infection are reported [8–10]. Studies have shown discrepant results between RT-PCR and chest computed tomography (CT) findings [11,12]. CT imaging findings in 30 patients with suspicion of COVID-19 pneumonia were shown to have a sensitivity of 97.2% compared to 83.3% of initial nasopharyngeal RT-PCR [13].\nEstablishing the diagnosis of COVID-19 is sometimes very challenging and does not only rely on molecular tests. We report on two patients who presented at the emergency department with high suspicion of COVID-19 infection based on clinical findings and/or chest-CT findings. Nevertheless, SARS-CoV-2 RT-PCR testing was repeatedly negative on repetitive nasopharyngeal, throat and anal swabs.\nCase 1 was a 66 year old male experiencing symptoms of shortness of breath, fever and muscle pain since 8 days. Lab findings showed thrombopenia (87,000/µL, ref. 149,000–31,9000/µL), lymphopenia (930/µL, ref. 1,133–3,105/µL), normal neutrophil count (2,980/µL, ref. 1,573–6,100/µL) low eosinophil count (0/µL, ref. 28–273/µL), normal basophil count (10/µL, ref. 6–50/µL), elevated D-dimers (1,480 ng/mL, ref. \u003c500 ng/mL) and elevated C-reactive protein (29 mg/L, ref \u003c5 mg/L). Chest CT on the day of admission showed bilateral ground glass opacities with a crazy paving pattern suspicious for COVID-19 (CT severity score of 10 or CO-RADS classification of 4: COVID-19 likely). Repetitive nasopharyngeal swabs on day 8, 9, 12 and 13 as well as anal swabs on day 9 and 13 after symptom onset were all SARS-CoV-2 RT-PCR negative using the protocol described by Corman and colleagues [6]. Serology on day 13 after symptom onset indicated negative IgM but positive IgG (Prima Professional®, Point-Of-Care antibody Tests). On day 13, the patient was admitted to the intensive care unit (ICU) because of type 1 respiratory insufficiency (pO2 60 mmHg, ref. 83–108 mm Hg; pCO2 31 mmHg, ref. 35–45 mm Hg; pH 7.46, ref. 7.35–7.45). He did not require mechanical ventilation. Based on these findings, he was diagnosed with COVID-19.\nCase 2 was a 14 year old child presenting at the emergency room with 3 days of fever \u003e 39°C, muscle pain, cough, sore throat, headache and fatigue. The girl’s father had suffered from fever and respiratory symptoms after contact with multiple COVID-19 patients 4 weeks earlier. On day 4 after symptom onset, there was a clinical deterioration to refractory shock and multi-organ failure with hypotension and respiratory and cardiac failure. Lab findings showed thrombopenia (89,000/µL, ref. 154,000–452,000/µL), lymphopenia (162/µL, ref. 1,500–6,500/µL), normal neutrophil count (7,564/µL, ref. 2,500–8,000), normal eosinophil count (283/µL, ref. 100–500/µL), low basophil count (0/µL, ref. 10–100/µL), elevated D-dimers (4,420 ng/mL, ref. \u003c500 ng/mL) and high C-reactive protein (308 mg/L, ref. \u003c5 mg/L). Chest CT did not show signs of viral pneumonia. Echocardiography revealed decreased left ventricular function. She responded well to supportive therapy and corticosteroid treatment. Throat swabs on day 3 and 5 after symptom onset were negative for SARS-CoV-2 with RT-PCR [6]. Serology on day 8 after symptom onset was negative for IgM but positive for IgG (Prima Professional®). She was diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS).\nThe case reports mentioned above point out the potential of serological assays to add to the diagnosis of COVID-19. So far, a large number of serological assays have been developed in response to the diagnostic need [14]. Data on the validation and comparison of the performance of these assays are emerging but are still limited [15–18]. Since antibody production by the specific immune system is subject to delay, a lower diagnostic performance of serological assays in the early phase of the disease is expected. So far, studies have revealed that antibodies could be detected as early as 3–6 days after symptom onset 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