Clinical Characteristics, Diagnosis, and Therapeutics of COVID-19: A Review.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that suddenly emerged at the end of December 2019 and caused coronavirus disease 2019 (COVID-19) continues to afflict humanity, not only seriously affecting healthcare systems but also leading to global social and economic imbalances. As of August 2022, there were approximately 580 million confirmed cases of COVID-19 and approximately 6.4 million confirmed deaths due to this disease. The data are sufficient to highlight the seriousness of SARS-CoV-2 infection. Although most patients with COVID-19 present primarily with respiratory symptoms, an increasing number of extrapulmonary systemic symptoms and manifestations have been associated with COVID-19. Since the outbreak of COVID-19, much has been learned about the disease and its causative agent. Therefore, great effort has been aimed at developing treatments and drug interventions to treat and reduce the incidence of COVID-19. In this narrative review, we provide a brief overview of the epidemiology, mechanisms, clinical manifestations, diagnosis, and therapeutics of COVID-19.

Differential diagnosis of lymphoma with 18F-FDG PET/CT in patients with fever of unknown origin accompanied by lymphadenopathy.

PURPOSE: To investigate the value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the differential diagnosis of lymphoma in patients with fever of unknown origin (FUO) accompanied by lymphadenopathy and to develop a simple scoring system to distinguish lymphoma from other etiologies. METHODS: A prospective study was conducted on patients with classic FUO accompanied by lymphadenopathy. After standard diagnostic procedures, including PET/CT scan and lymph-node biopsy, 163 patients were enrolled and divided into lymphoma and benign groups according to the etiology. The diagnostic utility of PET/CT imaging was evaluated, and beneficial parameters that could improve diagnostic effectiveness were identified. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy were 81.0, 47.6, 59.3, and 72.7%, respectively. The lymphoma prediction model combining high SUVmax of the "hottest" lesion, high SUVmax of the retroperitoneal lymph nodes, old age, low platelet count, and low ESR had an area under the curve of 0.93 (0.89-0.97), a sensitivity of 84.8%, a specificity of 92.9%, a PPV of 91.8%, and an NPV of 86.7%. There was a lower probability of lymphoma for patients with a score < 4 points. CONCLUSIONS: PET/CT scans show moderate sensitivity and low specificity in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy. The scoring system based on PET/CT and clinical parameters performs well in differentiating lymphoma and benign causes and can be used as a reliable noninvasive tool. REGISTRATION NUMBER: This study on FUO was registered on http://www. CLINICALTRIALS: gov on January 14, 2014, with registration number NCT02035670.

Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19.

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Combined clinical parameters improve the diagnostic efficacy of 18F-FDG PET/CT in patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO): A prospective study in China.

OBJECTIVES: To improve the diagnostic efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for Chinese patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO), with combined clinical parameters. MATERIALS AND METHODS: FUO/IUO patients who underwent a standard diagnostic work-up and 18F-FDG PET/CT scanning were enrolled and divided into a local uptake lesion subgroup and a non-specific abnormal uptake subgroup. Beneficial clinical parameters for improving the diagnostic efficacy of PET/CT were identified. RESULTS: From January 2014 to January 2019, 253 FUO/IUO patients were studied. In total, 147 patients had local uptake lesions and 106 patients had non-specific abnormal uptake. In the local uptake lesion group, the positioning accuracy of PET/CT was 37.2% in grades 1 and 2, and 66.3% in grades 3 and 4. With the following combination of clinical parameters, the positioning accuracy increased to 75.0% and 90.0%, respectively: time from admission to performing PET/CT scanning <6.5 days and C-reactive protein level >95 mg/l. In the non-specific abnormal uptake group, the combination of sex (male), bicytopenia, and lactic dehydrogenase improved the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignancy from 64.3%, 69%, 60%, and 72.7%, respectively, to 83.3%, 81%, 81.4%, and 82.9%, respectively. With the combination of sex (male), white blood count, serum ferritin level, and hepatosplenomegaly, the infection prediction model had a sensitivity, specificity, PPV, and NPV of 78%, 76.2%, 76.6%, and 77.6%, respectively. CONCLUSIONS: Combined clinical parameters improved the localization diagnostic value of 18F-FDG PET/CT in the local uptake lesion subgroup and the etiological diagnostic value in the non-specific abnormal uptake subgroup.

Exome sequencing revealed novel germline mutations in Chinese Peutz-Jeghers syndrome patients.

BACKGROUND AND AIMS: Peutz-Jeghers Syndrome (PJS) is an autosomal dominant disorder which predisposes to the development of various cancers. Germline mutation in the serine/threonine kinase 11 gene (STK11) is known as one of the major causes of PJS. However, a notable proportion of PJS samples do not carry any mutation in STK11, suggesting possible genetic heterogeneity in the disease and the existence of other causative variants. METHODS AND RESULTS: In order to identify other germline variants in the coding regions of the genome that are associated with PJS, we performed exome sequencing in three Chinese individuals with PJS and identified 16 common germline variants (12 protein-coding including STK11, 4 in pre-microRNAs). We further validated protein-coding variants in six PJS individuals (three with wild-type STK11) and predicted the functional impact. As result, we found that 7 coding variants are likely to have functional impacts. Especially, we identified 2 new germline variants which are represented in all six PJS samples and are independent of STK11 mutation. CONCLUSIONS: Our study provided an exomic view of PJS. The germline variants identified in our analysis may help to resolve the complex genetic background of the disease and thus lead to the discovery of novel causative variants of PJS.