Children with certain comorbidities and immunocompromising conditions are highly vulnerable to SARS-CoV-2 infection. Vaccination against SARS-CoV-2 is an important strategy to reduce death， critical illness and overall disease burden. With the evolving and increasing transmission of SARS-CoV-2， universal vaccination is essential to achieve this goal. Children with special medical conditions are considered as the priorities for SARS-CoV-2 vaccination. However， vaccine hesitancy towards the implementation of SARS-CoV-2 vaccination currently remains an urgent challenge. In order to promote the sustainable vaccination for those children in Shanghai as well as China， Shanghai municipal center for disease control and prevention， together with the national children’s medical center， children’s hospital of Fudan university and the expert group on immunization planning of the Shanghai preventive medicine association， organized a consensus expert working group to formulate the evidence-based recommendations and implementation suggestions for children with common chronic diseases， allergy history， diseases involving adverse events related to vaccination， and immunocompromising conditions， based on the published evidence of SARS-CoV-2 vaccination for populations and children with special medical conditions.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8⁺ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.

Objective:To investigate the epidemiological characteristics of hospitalized children with respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (ALRTI), and to analyzed the risk factors for severe infection.Methods:The epidemiological and clinical data of hospitalized children with ALRTI and positive RSV test from Children′s Hospital of Fudan University from January 2013 to December 2018 were retrospectively analyzed.The hospitalized children from October 2016 to November 2017 were selected by random singular sequence and divided into severe infection group and non-severe infection group. The clinical data of the two groups were compared. Multivariate logistic regression analysis was used to analyze the risk factors of severe RSV-associated ALRTI.Results:A total of 34 192 hospitalized children were diagnosed with ALRTI, and 8 113(23.73%) children were positive for respiratory tract viruses, including 4 028(11.78%) children with RSV infection, which was higher than other common respiratory tract viruses. Among the 4 028 RSV-positive children, 2 550(63.31%) were under six months of age, 3 623(89.95%) were under two years of age. The detection rates of RSV in spring, summer, autumn and winter were 6.47%(553/8 551), 2.46%(176/7 161), 12.85%(1 042/8 111) and 21.77%(2 257/10 369), respectively. In 347 hospitalized children with RSV-associated ALRTI, 54 cases were severe cases. Multivariate logistic regression analysis showed that RSV-positive patients complicated with respiratory diseases ( Z=3.43), cardiovascular diseases ( Z=4.96), non-exclusive breast-feeding ( Z=-1.97) and premature birth ( Z=-1.98) were independent risk factors for severe RSV-associated ALRTI (all P<0.050). Conclusions:RSV is the most important and common viral pathogen in hospitalized children with ALRTI in Shanghai, and infants under six months of age are the most susceptible to RSV. RSV patients complicated with respiratory diseases, cardiovascular diseases, non-exclusive breast-feeding and premature birth are more likely to develope severe RSV-associated ALRTI.

Objective:To understand the clinical characteristics of children with SARS-CoV-2 Omicron infection imported from Hong Kong Special Administrative Region.Methods:This retrospective study was conducted to collect the data including clinical manifestations, outcomes and vaccination of 107 children with SARS-CoV-2 Omicron infection imported from Hong Kong Special Administrative Region to be admitted to the designated referral hospital in Shanghai from February to March 2022. According to the occurrence of clinical symptoms, the cases were divided into asymptomatic group and symptomatic group. According to the age of diagnosis, the cases were divided into <3 years group, 3-<6 years group and 6-<18 years group, and the clinical manifestations in different age group were analyzed with t-test and Mann-Whitney rank-sum test. Besides, to analyze the effectiveness of vaccination against SARS-CoV-2 Omicron infection in different age group, the cases aged 3-<18 years were also subdivided into unvaccinated group, 1-dose group and 2-dose group, and the relative risk ( RR) was used to demonstrate the effectiveness. Results:Among the 107 cases, 66 were male and 41 were female, with infection age of 10 (5, 14) years. There were 29 cases in the asymptomatic group, and 78 cases in the symptomatic group, and no significant difference in the age of infection was observed between the 2 groups (11 (6, 14) vs. 10 (5, 14) years, Z=0.49, P>0.05). And there were no severe cases in symptomatic group. The length of hospitalization was (18±6) days, and was longer in symptomatic group than that in asymptomatic group ((19±6) vs. (16±7) d, t=0.17, P=0.030). Eight-two cases (76.6%) had a history of epidemiological exposure and, among whom, 81 cases (75.7%) were associated with household transmission. Among symptomatic group, 57 cases (73.1%) had fever and 20 cases (25.6%) had cough. Of the 74 cases undergoing chest CT examination, 17 cases (23.0%) showed mild abnormalities. Of the 83 cases who received the lab tests, 23 cases (27.7%) had white blood cell counts<4×10 9/L, 3 cases (3.6%) had C-reaction protein >8.0 mg/L, and 6 cases (7.2%) had slightly elevated aspartate transaminase and alanine aminotransferase. Among the 92 children aged 3-<18 years, 31 cases were unvaccinated, 34 cases received 1 dose, and 27 cases received 2 doses. The interval between the last vaccination and infection was 2.2 (0.6, 6.0) months; the interval between the last vaccination and infection in the 2-dose group was longer than that in 1-dose group (6.0 (4.5, 7.3) vs. 0.7 (0.3,2.0) months, Z=3.59, P<0.001).The risk of symptomatic infection was reduced by 45% (RR=0.55, 95% CI 0.35-0.87) with two-dose vaccination compared to non-vaccination in cases aged 3-<18 years. All these cases recovered completely. Conclusions:Children infected with SARS-CoV-2 Omicron are usually mild or asymptomatic. Household transmission is the main pattern of infection with SARS-CoV-2 Omicron in children. Two-dose SARS-CoV-2 vaccination in children aged 3-<18 years can provide partial protection against disease caused by SARS-CoV-2 Omicron.

Objective:To investigate the serum measles antibody in children with tumor and to provide the clinical evidence for measles vaccination strategy for this special population.Methods:From January 2016 to December 2018, the blood samples of children who were diagnosed with hematological malignancy or solid tumors and received chemotherapy in the Department of Hematology or Oncology Surgery of Children′s Hospital of Fudan University were collected. Enzyme-linked immunosorbent assay was used to quantitatively detect the level of measles IgG antibody, and dynamically monitor the changes of measles antibody level during chemotherapy. Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:A total of 441 children with tumors were enrolled, with the positive rate of measles antibody of 79.1%(349/441), and only 43.3%(191/441) of children had the protective level of IgG antibody. There was a statistically significant difference of the antibody protection rate in children aged0.05). The protection rate of serum measles antibody in children with hematological malignancy and solid tumor were 45.6%(78/171) and 41.9%(113/270), respectively, and there was no statistically significant ( P>0.05). There were 16.3%(16/98) of children who were observed to lose the pre-existing protective antibody during chemotherapy. There was no statistically significant difference of the protection rate of serum among children who had finished chemotherapy 0.05). Conclusions:Serum measles antibody is below the protective level in more than 50% of children with malignancy after chemotherapy. Chemotherapy can compromise the protective antibody against measles. It is recommended for this special population to re-schedule measles vaccine after individualized evaluation to acquire the immuneprotection against measles.

Objective:To describe the clinical features of liver involvement in children and adolescent with 2019-nCoV infection.Methods:The clinical data of 77 hospitalized cases admitted to the Children’s Hospital of Fudan University were collected from January 19 to November 28, 2020. The characteristics and risk factors of abnormal liver chemistries in children with laboratory-confirmed 2019-nCoV infection were analyzed.Results:Of the 77 cases, 44 were male (57.1%) and 33 were female (42.9%), with a median age of 10 years. 27(35.1%) were asymptomatic, 28(36.4%) had mild illness, 22(28.6%)had non-severe pneumonia. Hydroxychloroquine was used in 7 cases. Of the 75 children without underlying diseases, alanine aminotransferase was elevated in 1 case (1.5%, during hydroxychloroquine therapy), aspartate aminotransferase was elevated in 7 cases (10.3%), alkaline phosphatase was elevated in 7 cases (28%), and total bilirubin, direct bilirubin, albumin, international normalized ratio were in normal range. There was no statistical difference between the pneumonia group and the non-pneumonia group in term of liver chemistries ( P > 0.05), same as between the elevated erythrocyte sedimentation rate group and the normal group. There was no aggravation of liver injury in the child with biliary atresia. The child with epilepsy showed no abnormal liver chemistries after infection. Conclusion:Children with 2019-nCoV infection had mild clinical symptoms with few cases of liver injury. The abnormal liver chemistries in children with COVID-19 infection may be related to the underlying disease and the use of antiviral drugs.

Objective:To monitor the epidemiological characteristics of viral etiology in children with influenza-like illness and to guide the prevention and management of acute respiratory tract infections in childhood.Methods:Nasopharyngeal swabs were collected from the outpatient children seeking medical care in Children′s Hospital of Fudan University, Shanghai for influenza-like illness between January 2015 and December 2018. Multiplex real-time polymerase chain reaction was performed to detect respiratory syncytial virus (RSV), influenza virus (Flu), adenovirus (ADV), parainfluenza virus (PIV, type Ⅰ to type Ⅳ) and enterovirus (EV), and the epidemiological data were analyzed. Chi-square test was used for statistical analysis.Results:A total of 2 271 patients with influenza-like illness were enrolled, age range from two months to 182 months old, 1 280 cases(56.4%) were positive for the target respiratory viruses tested on respiratory samples. The detection rates of FluA, FluB, PIV, EV, ADV, RSV were 15.1%(343/2 271), 12.5%(284/2 271), 8.4%(191/2 271), 7.8%(177/2 271), 5.1%(116/2 271) and 6.7%(152/2 271), respectively.The detection rates of influenza virus were statistically different among the age groups ( χ2=39.33, P<0.05), which showed an increasing trend with the increasing ages. The detection rate of RSV was 9.7%(35/361) in infant group from zero to 12 months old, which was higher than other age groups. Usually, FluA had two epidemic peaks during the winter and summer seasons, the epidemics of FluB and RSV peaked during the winter season, and EV and PIV were more prevalent in the summer season. Conclusions:Influenza virus remains the most common viral pathogen responsible for childhood influenza-like illness in Shanghai.Influenza virus has high incidence in winter.Widely influenza vaccination is highly recommended for the effective prevention the influenza outbreaks.Continuous monitoring the epidemic trend of viral respiratory infections is imperative for the prevention and control of diseases.

Objective To monitor the clinical epidemiology and etiology of acute diarrhea in children in the outpatient setting in Shanghai .Methods An active surveillance study in Children′s Hospital of Fudan University between August 2013 and July 2014 was conducted .Outpatient children with acute diarrhea were enrolled in this study and stool samples were collected .Pathogens including norovirus ,diarrheagenic Escherichia coli (DEC) , nontyphoidal Salmonella spp .(NTS),Campylobacter,Shigella,pathogenic vibrio and Yersinia enterocolitica were identified and typed .The χ2 test was used for statistical analysis .Results Of the 881 stool samples from enrolled children , the pathogens included into the target detection were identified in 246 (27 .92% ) cases . Norovirus ,DEC ,NTS ,Campylobacter and Shigella were detected in 98 (11 .12% ) cases ,74 (8 .40% ) cases , 61 (6 .92% ) cases ,34 (3 .86% ) cases and 2 (0 .23% ) cases ,respectively .Neither pathogenic vibrio nor Yersinia enterocolitica was identified .Children younger than 36 months old (3 .27% ,26/794) had a lower risk (χ2=7 .41 ,P=0 .006) of Campylobacter infection compared with older children (9 .20% ,8/87) .Vomiting (37 .76% ) and watery diarrhea (21 .34% ) were more commonly seen in children with norovirus infection;fever and mucous stool were commonly seen in diarrheal children with NTS infection (40 .98% and 21 .31% ,respectively) and Campylobacter infection (29 .41% and 26 .47% ,respectively) .Conclusion Enteric pathogens play a major role in childhood acute diarrhea in Shanghai .Continuous monitoring of enteric pathogens will be helpful for reasonable treatment and prevention of acute diarrhea in children .