Severe acute respiratory syndrome coronavirus 2 and respiratory syncytial virus coinfection in children

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected many people around the world. Children are considered an important target group for SARS-CoV-2, as well as other viral infections such as respiratory syncytial virus infection. Both SARS-CoV-2 and respiratory syncytial virus can affect the respiratory tract. Coinfection of SARS-CoV-2 and respiratory syncytial virus can pose significant challenges in terms of diagnosis and treatment in children. This review compares the symptoms, diagnostic methods, and treatment of COVID-19 and respiratory syncytial virus infection in children.     

成都地区儿童上呼吸道病毒和细菌感染状况及流行病学特征

目的了解成都地区儿童急性上呼吸道病毒和细菌感染状况,并分析其流行病学特征。方法将2018年4月至2020年4月医院收治住院治疗的1324例急性上呼吸道感染患儿纳入研究。对咽拭子标本进行病原体培养、分离与鉴定。结果1324份标本中,检出阳性1012份,阳性率为76.44%,其中单纯病毒感染检出率为50.40%,单纯细菌感染检出率为16.21%,混合感染检出率为33.40%。1324份标本中,细菌和病毒总检出率为76.44%,其中单纯病毒感染检出率为47.13%,单纯细菌感染检出率为16.21%,混合感染检出率为33.40%;细菌类型以流感嗜血杆菌为主,病毒类型以呼吸道合胞病毒A为主;不同年龄儿童上呼吸道病毒感染阳性率差异有统计学意义(P<0.05);不同季节儿童上呼吸道细菌和病毒感染阳性率差异有统计学意义(P<0.05);不同地区儿童上呼吸道病毒感染阳性率差异有统计学意义(P<0.05)。结论成都地区儿童上呼吸道感染以病毒感染为主,流感嗜血杆菌和呼吸道合胞病毒A为儿童上呼吸道感染的主要病原体,0~1岁为上呼吸道细菌感染高发年龄,1~4岁为上呼吸道病毒感染高发年龄,冬季和城区儿童上呼吸道感染阳性率较高。     

Viral agents of acute respiratory infections in young children in Kuala Lumpur

The results of this study indicate that the important viral agents associated with lower respiratory tract infections in young children are respiratory syncytial virus, rhinovirus, and parainfluenza virus, particularly in those under 2 years of age. This is in close agreement with studies done in temperate climates. Influenza A virus is seasonal and plays an important role in upper respiratory tract infections in older children.     

Impact of viral respiratory diseases on infants and young children in a rural and urban area of southern West Virginia

Acute viral respiratory disease occurring in children residing in the community of Huntington, West Virginia (urban children) or in the hollows surrounding Huntington (rural children) was evaluated from September 1978 through March 1980. Cohorts of ambulatory children residing in each area were studied for the occurrence of mild to moderate respiratory disease. All children admitted to hospitals were evaluated for the occurrence of severe viral respiratory disease. Respiratory secretions were obtained from children for isolation of viruses. Epidemics of illnesses occurred simultaneously in the urban and rural groups of children. Among both the urban and rural ambulatory children, adenoviruses were the most common viruses isolated, and respiratory syncytial virus was the second most common viral pathogen isolated. Among the urban and rural hospitalized children, respiratory syncytial virus was the most common virus isolated. The distribution of the diagnoses, pneumonia, bronchiolitis, or croup, was similar among the urban and rural children who required hospitalization. The risk of hospitalization because of respiratory disease was found to be one in every 20 children during the first four years of life, and the estimated risk of hospitalization because of respiratory syncytial virus infection was one in 30. No differences were detected in the incidence of severe viral respiratory disease among children residing in urban or rural areas in southern West Virginia.     

儿童急性呼吸道感染578例病毒检测分析

目的 了解三门峡地区儿童急性呼吸道感染(ARI)的病毒病原学构成,指导临床诊断与治疗。方法 采集578例ARI住院患儿的鼻咽拭子,采用直接免疫荧光法检测7种病毒即呼吸道合胞病毒(RSV)、腺病毒(ADV)、副流感病毒Ⅰ、Ⅱ、Ⅲ(PIVⅠ～Ⅲ)、流感病毒A、B型(IVA、IVB)。结果 儿童ARI的病毒总检出率为61.59%,混合感染占45.22%。病毒总检出率冬季最高(77.35%)、夏季最低(25.00%)。下呼吸道感染的病毒总检出率高于上呼吸道感染。RSV、PIVⅢ、IVA的检出率位居前三位,分别为30.62%、28.89%、21.97%。RSV及PIVⅢ在秋冬季、下呼吸道感染、3岁以下患儿中检出率较高;IVA在冬季、上呼吸道感染患儿中检出率较高。结论 RSV 、PIVⅢ、IVA是三门峡地区儿童急性呼吸道感染的主要病毒病原。RSV 、PIVⅢ是秋冬季节婴幼儿下呼吸道感染的主要病原;IVA是冬季各年龄患儿上呼吸道感染的主要病原。通过检测儿童ARI的病毒病原,对尽早明确病毒病原,避免滥用抗生素具有重要意义。     

A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys

Human metapneumovirus (hMPV) infection causes respiratory tract disease similar to that observed during human respiratory syncytial virus infection (hRSV). hMPV infections have been reported across the entire age spectrum although the most severe disease occurs in young children. No vaccines, chemotherapeutics or antibodies are presently available for preventing or treating hMPV infections. In this study, a bovine/human chimeric parainfluenza virus type 3 (b/h PIV3) expressing the human parainfluenza type 3 (hPIV3) fusion (F) and hemagglutinin-neuraminidase (HN) proteins was engineered to express hMPV fusion (F) protein from the second genome position (b/h PIV3/hMPV F2) with the goal of generating a novel hMPV vaccine. b/h PIV3/hMPV F2 was previously shown to protect hamsters from challenge with wt hMPV (Tang RS, Schickli JH, Macphail M, Fernandes F, Bicha L, Spaete J, et al. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3' proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity. J Virol 2003;77:10819-28) and is here further evaluated for efficacy and immunogenicity in African green monkeys (AGMs). AGMs immunized intranasally and intratracheally with b/h PIV3/hMPV F2 generated hMPV- and hPIV3-specific humoral and cellular immune responses and were protected from wt hMPV infection. In a separate study, the host-range restriction of b/h PIV3/hMPV F2 replication relative to wt hPIV3 was performed in rhesus monkeys to demonstrate attenuation. These studies showed that b/h PIV3/hMPV F2 was immunogenic, protective and attenuated in non-human primates and warrants further evaluation in humans as a vaccine candidate for prevention of hMPV-associated respiratory tract diseases.     

防止常见季节性呼吸道病毒疾病在医院内传播的措施

防止呼吸道病毒疾病在医院内传播是保护医务人员和患者安全的重要环节之一。呼吸道病毒类型各异, 但有相似的传播方式和临床表现。合理实施和运用针对患呼吸道病毒疾病的患者、医务人员及探视者的感控措施可以有效阻止这些病毒在医院内的传播。除新型冠状病毒疫苗外, 对抗流感和呼吸道合胞病毒的疫苗也取得了快速发展。     

儿科重症监护室单一和多重呼吸道病毒感染对比分析

目的 探讨儿科重症监护室(PICU)患儿单一和多重呼吸道病毒感染情况的差异.方法 收集406例入住汕头大学医学院第二附属医院PICU合并有呼吸道感染患儿的咽拭子样本,采用多重PCR及常规PCR对咽拭子行16种呼吸道病毒检测,分析阳性病例的病毒感染情况及与患儿临床特征的关系.结果 406例样本中病毒检测阳性者252例,阳性率62.1％.阳性样本中,以其中鼻病毒(HRV)检出率最高,为105例(41.7％),其次为呼吸道合胞病毒(RSV)[63例(25.0％)]和腺病毒(HADV)[48例(19.0％)];单一病毒感染177例(70.2％),多重病毒感染75例(29.8％),包括66例双重病毒感染,9例三重病毒感染.多重病毒感染最多的病毒组合是HRV+RSV(16例).单一病毒感染和多重病毒感染的患儿中存在基础疾病的病例数分别为46例和6例,两者差异有统计学意义(x2=10.409,P＜0.01);而二者在性别、年龄、住院时间、上下呼吸道感染人数及小儿危重症评分上差异均无统计学意义(x2=3.430,Z=0.315,Z=0.336,x2=0.041,P均＞0.05).结论 呼吸道病毒是PICU中呼吸道感染性疾病的主要病原体之一;存在基础疾病的患儿以单一病毒感染为主,多重病毒与单一病毒感染对于疾病严重程度的影响没有明显差异.     

Resurgence of Respiratory Syncytial Virus Infections during COVID-19 Pandemic,Tokyo, Japan

More than a year into the coronavirus-19 pandemic, intensified infection control measures have controlled most viral respiratory infections in Tokyo, Japan. As of July 2021, however, an unusually high number of respiratory syncytial virus infections were reported in Tokyo. This resurgence may have resulted from restarting social activities for children.     

Respiratory syncytial virus suppression of the antiviral immune response: Implications for evaluation of candidate vaccines

Respiratory syncytial virus infections recur throughout life despite induction of immunity by the first natural infection. Results of an extensive series of studies indicate that the virus adversely affects the human antiviral recall response to challenge, although subsequent infections are less severe than the initial illness. The observations suggest that candidate vaccines for respiratory syncytial virus should not be expected to prevent clinical illness upon subsequent exposure. Candidate vaccines may be considered effective if they render a subsequent natural infection less severe. This is what would be expected from an initial and commonly more severe natural infection and sensitization.     

Formulation of the prefusion RSV F protein with a Th1/Th2-balanced adjuvant provides complete protection without Th2-skewed immunity in RSV-experienced young mice

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections among infants with most infections occurring in the first year of life. Multiple RSV exposures are required for children to mount adult-like immune responses. Although adult RSV immunity is associated with less severe disease, the protection induced through natural infection is short-lived. Therefore, vaccination of RSV-experienced young children may accelerate immunity and provide long-term protection from RSV reinfection. However, the extent to which different Th-biased vaccine regimens influence pre-existing humoral and cellular immunity in RSV-experienced young children is unknown. To address this question, infant BALB/c mice were RSV-infected and subsequently immunized with the prefusion RSV F (PreF) antigen formulated with either a Th2-skewing (Alum) or Th1/Th2-balanced (Advax-SM) adjuvant. These studies show that both adjuvants boosted neutralizing antibody and protected from RSV reinfection, but Advax-SM adjuvant prevented the Th2-skewed immunity observed in RSV-experienced young mice immunized with PreF/Alum.     

Passive immunization for the prevention of otitis media

The safety and protective efficacy of exogenously-administered immunoglobulin for the prevention of otitis media has been demonstrated in the clinical trials of the human-derived polyclonal immune globulin used to prevent Haemophilus influenzae type b disease and respiratory syncytial virus infection in high risk neonates and young children. However, this form of therapy is expensive, difficult to administer due to the requirements of slow intravenous infusion or relatively large volumes given intramuscularly, and associated with side effects related to the volume and nature of the immunoglobulin preparation. In contrast, RSV-specific monoclonal antibody has not been as successful as human-derived immunoglobulin in preventing otitis media in high risk infants. The administration of monoclonal-antibody for the prevention of otitis media will be difficult, potentially due to the need for antibody to multiple epitopes of the viral and bacterial pathogens which could be targets. The use of maternal antibody to provide passive immunity to young infants at a time when they are most vulnerable to severe sequelae of infection can also be considered. We have studied maternal immunization using either a 23-valent pneumococcal polysaccharide vaccine or a conjugate H. influenzae type b (Hib) vaccine. Significant levels of maternally-derived Hib or pneumococcal antibody were transferred from the mother to the infant at the time of birth and persisting, for some antigens, through 2 months of age. The use of maternal immunization to prevent otitis media and other respiratory complications remains to be studied, but results of these small clinical trials indicate further clinical investigation is warranted.     

The sudden infant death syndrome and epidemic viral disease.

A study was done to investigate the relationship between the sudden infant death syndrome (SIDS) and epidemic respiratory viral disease among hospitalized children under 18 months of age. During the 42 month-period of this study, there were 778 sudden infant deaths in Chicago and 3244 hospital admissions of children under 18 months for respiratory disease. Four outbreaks of respiratory syncytial (RS) virus infections, three outbreaks of influenza A virus infections, and several small clusters of parainfluenza virus infections occurred during the course of this study. Influenza A was the only virus infection found to have a statistically significant association with SIDS. Although environmental temperature was also significantly correlated with SIDS, the association with influenza A virus infection was independent of this temperature effect and neither association was strong.     

Ten years of viral and non-bacterial serology in adults with cystic fibrosis

Viral infections are associated with pulmonary exacerbations in children with cystic fibrosis (CF), but few studies have addressed the frequency in adults. This paper investigates the frequency and impact of viral infections in adults with CF receiving intravenous antibiotics. Pre- and post-treatment spirometry, inflammatory markers and antibody titres against influenza A, influenza B, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetti were analysed over a 10-year period. Non-bacterial infections were identified in 5.1% of 3156 courses of treatment. The annual incidence of admissions per patient associated with viral infection was 4.9%. The presence of viral infection in association with a pulmonary exacerbation did not adversely affect lung function or inflammatory markers in the short term. Adults with CF have a lower incidence of respiratory viral infections associated with pulmonary exacerbations requiring intravenous antibiotics compared to children and infants with CF.     

A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits

The military population has a high disease burden of acute viral respiratory infections in China. To assess the efficacy and safety of a low-dose recombinant human interferon α-2b (rIFNα-2b) nasal spray in preventing acute viral respiratory infections in military population, we performed this randomized controlled trial. The results showed that application of the rIFNα-2b nasal spray had the benefits in prevention of infections caused by influenza A virus, influenza B virus parainfluenza viruses 1–3 and adenovirus species B. However, no benefit was seen in preventing respiratory syncytial virus. No severe adverse events were reported. Therefore, the rIFNα-2b nasal spray was effective and well tolerated for preventing common viral respiratory infections in the military recruits.     

Human metapneumovirus infections in hospitalized children

We evaluated the percentage of hospitalizations for acute respiratory tract infections in children < or =3 years of age attributable to human metapneumovirus (HMPV) and other respiratory viruses in a prospective study during winter and spring 2002. We used real-time polymerase chain assays and other conventional diagnostic methods to detect HMPV, human respiratory syncytial virus (HRSV), and influenza viruses in nasopharyngeal aspirates of children. HMPV was detected in 12 (6%) of the 208 children hospitalized for acute respiratory tract infections, HRSV in 118 (57%), and influenza A in 49 (24%). Bronchiolitis was diagnosed in 8 (68%) and pneumonitis in 2 (17%) of HMPV-infected children; of those with HRSV infection, bronchiolitiss was diagnosed in 99 (84%) and pneumonitis in 30 (25%). None of the HMPV-infected children was admitted to an intensive-care unit, whereas 15% of those with HRSV or influenza A infections were admitted. HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV.     

Interferon alpha production in the serum of very young infants after viral infections

IFN-alpha detection is useful in some clinical circumstances, but its use has never been validated in young infants with viral infections. OBJECTIVE: The authors wanted to determine it there was any difference in the assessment of IFN-alpha production between infants under or over six months of age. PATIENTS AND METHOD: A series of 233 children with identified common viral infections who had been assessed for IFN-alpha production was retrospectively analyzed. The viral infections were enteroviral meningitis (n =103), respiratory syncytial virus infections (n =60), and rotavirus gastroenteritis (n =70). Data collected from the group of infants under six months of age (n =105) was compared to that of the older children (n =128). Qualitative and quantitative values of interferon-alpha were determined for each group. RESULTS: Interferon-alpha was detected in very young infants (81.9% of cases) as often as in the older age group (80.3% of cases), for any of the three viral infections (P =0.3-0.63). The mean level of interferon-alpha production detected was not lower in the youngest group, and even higher in the group under six months of age with enteroviral meningitis. CONCLUSION: Interferon-alpha detection in very young infants is efficient and may be useful to differentiate between viral and bacterial infection particularly when the etiological diagnosis appears uncertain.     

The viral etiology of acute respiratory infections in children in Uganda.

The role of viruses in respiratory diseases of young children in Uganda was studied. A viral etiology was established in 36% of the infections investigated. The most important pathogens were found to be respiratory syncytial virus and parainfluenza viruses, which were responsible for 26% of infections investigated. They caused both upper and lower respiratory tract diseases. There was little or no seasonal variation in the etiology of these infections. Adenoviruses were found to be less important and were etiologically related to only 4% of respiratory disease cases. Influenza viruses and enteroviruses were also found to be associated with respiratory infections. However, they were less frequent and their role was insignificant. The role of multiple virus infections was also insignificant.     

The effects of acute respiratory virus infection upon tracheal mucous transport

Tracheal mucous velocity was measured in 13 healthy non-smokers using a radioisotope-labeled aerosol and a multidetector probe during respiratory virus infections. The movement of boluses of tracheal mucous were either absent or reduced in number in five subjects with myxovirus infection (four influenza and one respiratory syncytial virus) within 48 hr of the onset of symptoms and in four subjects 1 wk later. One subject with influenza still had reduced bolus formation 12-16 wk after infection. Frequent coughing was a feature of those subjects with absent tracheal boluses. In contrast, four subjects with rhinovirus infection had normal tracheal mucous velocity at 48 hr after the onset of symptoms (4.1 +/- 1.3 mm/min). Tracheal mucous velocity was also normal (4.6 +/- 1.1 mm/min) in four subjects in whom no specific viral agent could be defined but of respiratory viral infection. During health tracheal mucous velocity was (4.8 +/- 1.6 mm/min) in the eleven subjects who had measurements made. Disturbances in tracheal mucous transport during virus infection appear to depend upon the type of virus and are most severe in influenza A and respiratory syncytial virus infection.