Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis.

Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.

https://www.thelancet.com/article/S1473309920301985/pdf

Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study.

Importance The current rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection justifies the global effort to identify effective preventive strategies and optimal medical management. While data are available for adult patients with coronavirus disease 2019 (COVID-19), limited reports have analyzed pediatric patients infected with SARS-CoV-2. Objective To evaluate currently reported pediatric cases of SARS-CoV-2 infection. Evidence Review An extensive search strategy was designed to retrieve all articles published from December 1, 2019, to March 3, 2020, by combining the termscoronavirusandcoronavirus infectionin several electronic databases (PubMed, Cochrane Library, and CINAHL), and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Retrospective cross-sectional and case-control studies, case series and case reports, bulletins, and national reports about the pediatric SARS-CoV-2 infection were included. The risk of bias for eligible observational studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline. Findings A total of 815 articles were identified. Eighteen studies with 1065 participants (444 patients were younger than 10 years, and 553 were aged 10 to 19 years) with confirmed SARS-CoV-2 infection were included in the final analysis. All articles reflected research performed in China, except for 1 clinical case in Singapore. Children at any age were mostly reported to have mild respiratory symptoms, namely fever, dry cough, and fatigue, or were asymptomatic. Bronchial thickening and ground-glass opacities were the main radiologic features, and these findings were also reported in asymptomatic patients. Among the included articles, there was only 1 case of severe COVID-19 infection, which occurred in a 13-month-old infant. No deaths were reported in children aged 0 to 9 years. Available data about therapies were limited. Conclusions and Relevance To our knowledge, this is the first systematic review that assesses and summarizes clinical features and management of children with SARS-CoV-2 infection. The rapid spread of COVID-19 across the globe and the lack of European and US data on pediatric patients require further epidemiologic and clinical studies to identify possible preventive and therapeutic strategies.

https://jamanetwork.com/journals/jamapediatrics/articlepdf/2765169/jamapediatrics_castagnoli_2020_rv_200005_1598544887.48635.pdf

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review.

Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children.

Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children.

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS-CoV-2 aim to identify previous SARS-CoV-2 infection, and may help to confirm the presence of current infection. Objectives To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection, and the accuracy of antibody tests for use in seroprevalence surveys. Search methods We undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020. Selection criteria We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS-CoV-2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR) and clinical diagnostic criteria). Data collection and analysis We assessed possible bias and applicability of the studies using the QUADAS-2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random-effects logistic regression where appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs). Main results We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints. We had concerns about risk of bias and applicability. Common issues were use of multi-group designs (n = 29), inclusion of only COVID-19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n = 33) defined COVID-19 cases based on RT-PCR results alone, ignoring the potential for false-negative RT-PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5). We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post-symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands. Authors' conclusions The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.

Antibody tests for identification of current and past infection with SARS‐CoV‐2

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

Analysis of CT features of 15 Children with 2019 novel coronavirus infection

Objective@#To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection.@*Methods@#A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people’s Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed.@*Results@#Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities.@*Conclusions@#The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

Analysis of CT features of 15 Children with 2019 novel coronavirus infection/ 中华儿科杂志/ Analysis of CT features of 15 Children with 2019 novel coronavirus infection/ 中华儿科杂志

Hepatocellular carcinoma (HCC) with symptomatic portal hypertension (SPH) has poor prognosis. A transjugular intrahepatic portosystemic shunt (TIPS) relieves SPH, but its application in HCC remains unclear. We evaluated TIPS efficacy in patients with HCC and SPH.Pre- and post-TIPS Child-pugh(C-P) scores and stages in 123 HCC patients with SPH from three centers were compared. The impact of postoperative C-P stage indicators on overall survival (OS) was explored.Post-TIPS responses to SPH included complete response (CR) (92 [74.8%]), partial response (PR) (23 [18.7%]), and nonresponse (NR) (8 [6.5%]). The control (proportion of CR and PR) for SPH was 93.5%. Median C-P scores pre-TIPS and at one month post-TIPS were 8 (IQR 6-9) and 7 (IQR 6-8), respectively (P < 0.001). Forty-one (33.3%) patients had C-P downstaging; 73 (59.3%) had lowered C-P scores; and 73 (59.3%) received intrahepatic local therapy post-TIPS. The median OS was 10.7 (1.1-55.2) months. Among the five indicators of C-P stage, lower post-TIPS ascites grading [(0/1)/(2/3); P = 0.014, HR = 0.31 (95% CI: 0.12-0.79)] and bilirubin [< 34/ ≥ 34 µmol/L; P = 0.022, HR = 0.47 (95% CI: 0.23-0.82)] and prothrombin time prolongation < 6 s [< 6/ ≥ 6 s; P = 0.001, HR = 0.17 (95% CI: 0.06-0.47)] were independent protective indicators of OS. These three indicators were included in the nomogram model to predict survival probabilities.TIPS is safe and effective for HCC with SPH. This procedure can relieve the symptoms, enable subsequent antitumor therapy, and bring survival benefits, possibly through improved liver function by reducing C-P stage. 

/pdf/tips-improves-outcomes-in-patients-with-hcc-and-symptomatic-3pgolr4h.pdf

TIPS improves outcomes in patients with HCC and symptomatic portal hypertension: a multi-institution experience

OBJECTIVE
To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching.


METHODS
The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up.


RESULTS
The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05).


CONCLUSION
Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.

Kai Feng

Papers

Analysis of CT features of 15 Children with 2019 novel coronavirus infection

Analysis of CT features of 15 Children with 2019 novel coronavirus infection/ 中华儿科杂志/ Analysis of CT features of 15 Children with 2019 novel coronavirus infection/ 中华儿科杂志

TIPS improves outcomes in patients with HCC and symptomatic portal hypertension: a multi-institution experience

[Study on Application of RVD Regimen Sequential Auto-HSCT in the Treatment of Multiple Myeloma Evaluated by Propensity Score Matching].