Ranjan K. Mohapatra ^1* Ahmed Mahal ² Venkataramana Kandi ³ Abhay Gaidhane ⁴ Zahiruddin Quazi Syed ⁵ Prakasini Satapathy ⁶ Snehasish Mishra ⁷

• ¹ Government College of Engineering, Keonjhar, Keonjhar, India
• ² Cihan University-Erbil, Erbil, Iraq
• ³ Prathima Institute of Medical Sciences, Karimnagar, Andhra Pradesh, India
• ⁴ Jawaharlal Nehru Medical College, Wardha, Wardha, Maharashtra, India
• ⁵ Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra, India
• ⁶ Saveetha University, Chennai, Tamil Nadu, India
• ⁷ KIIT University, Bhubaneswar, Odisha, India

The Chinese surveillance systems recorded rising respiratory illness cases in North China since mid-October 2023 especially among the children [1]. Beyond the northern part of China, the Chinese National Health Commission briefed through a press conference on 13 November 2023 about a nationwide spike in the cases of respiratory diseases that affected the children predominantly there. The Chinese authorities attribute this upsurge of respiratory illness among children to the arrival of cold season in China, and also the lifting of COVID-19 restrictions [1,2]. Alongside the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it could also be associated with known active pathogens like the influenza virus, respiratory syncytial virus (RSV), Mycoplasma pneumoniae [1]. M. pneumonia and RSV are known to be more prevalent in children than in the adults. It was noticed in a recently reported survey of the lower respiratory tract infection (LRTI) incidences among children that occurrences did not significantly vary between the pre-pandemic and pandemic era. However, the study observed a significant rise (28%) in the all-cause mortality during the pandemic era as compared to lower mortality rates in the pre-pandemic times, and a 16% rise in hospitalisation [3].It is argued that the COVID-19 pandemic has irreversibly altered the epidemiology of the circulating microbes that were active in LRTIs. A major factor behind its extensive control during the COVID-19 pandemic was the extensive use of alcohol-based sanitisers and disinfectants [4]. Also, an excessively prevalent novel SARS-CoV-2 and its multiple variants could have played a significant biocontrol role by interfering with and replacing the Influenza virus and RSV and others that were common and prevalent in the pre-pandemic times. A shift in the prevailing Human Parainfluenza Virus (HPIV) serotypes was noticed among the acute respiratory tract infected (aRTI) infants in South Africa [5]. While the pandemic witnessed a rise in the prevalence of aRTIs caused by HPIV 3, a significant decline in the HPIV 1, 2 and 4 incidences was observed. Thus, numerous healthcare intervention measures during the pandemic that allegedly positively benefitted individual immunity could have factored for their reduced prevalence and altered health effects, it was hypothesised [5]. However, the reason behind the prevalence of a specific serotype has not been well-understood.Significant variations in the prevailing RSV before and during the COVID-19 pandemic are suspected to be attributed to dysregulated immunity brought about by SARS-CoV-2 infection and a complex interaction of SARS-CoV-2 with the circulating RSV. It could have resulted in eliminating the RSV from the respiratory tract [6]. Also, a fear of SARS-CoV-2 infection during the pandemic forced the civic population to seek immediate medical assistance which could have prevented the prevalence of common RTI pathogens. A study among the children in the British Columbia, Canada revealed that there was a decrease in RSV-induced infection and hospitalisation during 2020-2021 (the peak SARS-CoV-2 pandemic era). It identified a rise in the RSV-induced infection and hospitalisation during 2022-2023, suspected to be due to the reduced prevalence of RSV during the pandemic and reduced natural immunity [7]. The World Health Organisation (WHO) identified clusters of undiagnosed pneumonia cases in children in several Chinese hospitals [1]. It has officially requested China to provide detailed epidemiological and clinical information about these cases. Whether these 'clusters of undiagnosed pneumonia' cases in various Chinese regions were separate events or part of the known universal rise in respiratory illnesses within the community is yet not clear. The WHO recently engaged in teleconferencing with Chinese health agencies from the Chinese Centre for Disease Control and Prevention and the Pediatric Hospital in Beijing [1]. As per the data shared, a rising outpatient consultations and hospitalisation of children was primarily attributed to Mycoplasma pneumoniae pneumonia since May, and the adenovirus, RSV and influenza virus since October in the reported year. M. pneumoniae, parainfluenza and human rhinovirus predominated in September and October and M. pneumoniae, influenza and RSV predominated in November in 2023, as per a recent surveillance [8]. The factor behind the rising respiratory illness cases in Northern China children is allegedly the known pathogens [9], although the actual cause is uncertain. Other countries also have reported having experienced similar situations after the COVID-19 restrictions were eased there. A schema of the post-pandemic rise of RTIs and the possible associated factors is presented in Fig. 1. It is notable that no unusual or novel pathogens or unusual clinical symptoms were detected [2]. The Chinese health authorities also did not report any altered disease presentation. The rise in respiratory illnesses was due to the circulating multiple known pathogens [9]. It was stated that the rising cases did not overwhelmed the patient load in hospitals. Considering the sudden upsurge of cases, enhanced outpatient and inpatient surveillance and monitoring for respiratory illness within the healthcare facility settings and the community was implemented covering a broad range of respiratory viruses and bacteria, including M. pneumonia [1]. In addition to enhanced disease surveillance, revamping health system capacity and strengthening patient management are also recommended. Systems to capture information on the trends of influenza, influenza-like illness (ILI), pneumonia, RSV, SARS-CoV-2 and other severe acute respiratory infections (SARI) is already in place in China, the report of which it could directly share with the Global Influenza Surveillance and Response System (GISRS).Led by the WHO, GISRS is used for virological and epidemiological surveillance of human influenza internationally. Closely monitoring the situation to discover and report an unusual pattern is also highly recommended. The seasonal cycle of certain respiratory diseases and the prevalence of the responsible viruses were disturbed due to lockdown and restricted movements, it has been observed [10][11][12][13]. It was evident from the negligible occurrence of RSV, influenza virus, parainfluenza virus, adenovirus, rhinovirus infections, which often peaked during the winter. An alarming rise in these infections during off season in contrast was attributable to easing of restrictions and increased public movement. The COVID-19 trend greatly influenced the prevalence of non-SARS-CoV-2 respiratory viruses. Potentially, the COVID-19 virus eliminated the non-SARS-CoV-2 viruses or the cased went unreported, especially during the initial pandemic phases. These viruses supposedly reestablished causing non-seasonal emergency situations and outbreaks as the pandemic receded.The Chinese mainland recorded acute respiratory microbial infection outbreaks by RSV, influenza and M. pneumoniae among children. It was attributed to low immunity among the general population due to strict lockdowns for long implemented by the Chinese government [14]. Easing the restrictions suddenly exposed the public to the infections causing outbreaks and necessitating hospitalisation. A similar trend was also noticed in the USA and the UK despite the COVID-19 restrictions remained milder there. Such scenario of the rising cases in the acute respiratory infections cases among children after the pandemic was attributed to the compromised functioning of the pulmonary system [15]. A study confirmed significant (62±19%; P = 0.006) pulmonary dysfunction among COVID-19 recovered children who developed post-COVID-19 symptoms (60±20%; P = 0.003) as compared to the healthy and uninfected children (81±6.1%). It is speculated that some exposed children did not develop the clinical manifestations and remained asymptomatic.Despite low impact of COVID-19 on children, research compared the pre-pandemic (186; 41%) and post-pandemic (268; 59%) events suggested a significant rise in the occurrence of life-threatening events (ALTEs) or brief resolved unexplained events (BRUEs) [16]. A Chinese study analysed the monthly trends of respiratory infections among children before and during the pandemic and noticed interesting trends in viral, bacterial, rare microbial and viral-bacterial coinfections [17]. It revealed that human rhinovirus (HRV) was consistently responsible for acute respiratory infections before and during the pandemic. M. catarrhalis and other bacterial pathogens like Streptococcus pneumoniae were evident before and during the pandemic. It was also observed that there was a significant rise in HRV, human parainfluenza virus (type 1, and 3), human bocavirus (HboV), human coronavirus OC43 In the current outbreak, the reported symptoms are usual to other respiratory disease. Clinical manifestations as reported by the Chinese surveillance systems hint at known circulating pathogens. Paediatric pneumonia is primarily caused by Mycoplasma pneumoniae which is readily treated with antibiotics. However, full characterisation the overall risk of the reported respiratory illness cases in children is challenging as the available data is limited. Respiratory infections and microbe prevalence that cause RTIs are season-influenced [18]. A highly prevalent RSV, Influenza virus and common coronaviruses is expected during the winter.Temperate is a critical factor in the prevalence of HPIVs, human metapneumovirus, Rhinovirus and other viruses. Climatic conditions in the tropics favour the Influenza viruses to prevail throughout the year. There is a possibility of the prevalence of Influenza like illness (ILI) in the geographic regions where winter sets in, as suggested by reports submitted to the WHO's FluNet [1]. China may potentially see a significant rise in ILI caused by A(H3N2) and B/Victoria lineage viruses this winter, as opined by the National Influenza Centre, China.The rate of detected respiratory pathogen cases was substantially high across all ages during September to November in 2023 including in children, as compared to the number of cases in the same period during the past three years before the COVID-19 pandemic [8]. It may be due to the subsequent decline in the immunity among the susceptible population that occurred due to relatively low infection rates in the period during the epidemic. Theoretically, the implemented COVID-19-appropriate measures during pandemic might have amplified the effect. The mode of transmission is critical, and droplet and direct contact during the present situation is reported, although the airborne transmission was also suspected (file:///C:/Users/USER/Desktop/Children_china_1.pdf). Global M. pneumoniae surveillance suggested a delayed M. pneumoniae epidemic reemergence was attributed to the introduced better hygiene and sanitation practices (non-pharmaceutical intervention measures) against the COVID-19 virus [19]. A rise in M. pneumoniae infection across all age groups was observed in several European countries during this 2023 winter, with increased cases being reported among adolescents and children [20]. The study highlighted that some well-known common pathogens along with the novel respiratory pathogens could significantly strain the healthcare system especially in megacities that are thickly populated [21].A German study assessed the prevalence of the upper respiratory tract infections (URTIs) before, during and after the COVID-19 pandemic [22]. It revealed a 58% increase in the occurrence of URTIs after the pandemic as compared to the rates before the pandemic (732 vs 464, p<0.001). The increase was more evident among 18-30 year old (22%, p<0.001) and the pediatrics less than 5 years (89%). Interestingly, a previous study had noticed a significant reduction in common respiratory tract infections and gastrointestinal infections (GIIs) as compared to the pre-and post-pandemic era (275,033 vs 165,127) [23]. It reported significant reduction in common respiratory infections like influenza (-71%, p<0.001) and an increase in pneumonia caused by rare microbes (229%, p<0.001) after the pandemic. Another German study reported a significant decline in the occurrence of URTIs (683 vs 439, -36%, P<0.001) and GIIs (213 vs 120, -44%, P<0.001) before and after the pandemic [24]. Initial pandemic phase witnessed a decline (54.7% in 2010-19 to 39.1% in 2020) in common RTIs causing virus, like adenovirus, human coronavirus (HCoV), human bocavirus (HBoV), human rhinovirus (HRV), human metapneumovirus (hMPV), human parainfluenza virus (HPIV), influenza virus and respiratory syncytial virus (RSV) in Korea [25]. Korea saw a rising trend in infections by human rhinovirus (HRV) during pandemic [26]. Enveloped viruses like HCoV, HMPV, influenza virus, parainfluenza virus and RSV cases during the pandemic reduced by 100% [27]. The trend remained unaltered in non-enveloped viruses like adenovirus, HRV and HBoV before and during pandemic. It was attributed to the chemical sterilizants and antiseptics sanitisation (predominantly used during pandemic) being effective against enveloped virus as compared to non-enveloped virus. Some physical interventions also were proposed to reduce the incidences of influenza and COVID-19 like illnesses after the pandemic, like social distancing and the use of face masks [28]. It was observed that the available studies do not completely approve such observations in reducing the cases though.A study in New Zealand revealed that hospitalisation due to lower respiratory tract infections (LRTIs) by RSV, influenza A and B viruses, HRV and adenovirus significantly reduced (<200 cases) during the initial phase of the pandemic compared to the figures of 2019 (approximately 1000 cases) or before (2015)(2016)(2017)(2018). It is attributable to strict restrictions (including lockdowns) on public movement [29]. Human metapneumovirus (HMPV) infections increased among the neonates [30]. Improved diagnostic capability, effective vaccines and anti-viral agents could essentially control and prevent the disease and other similar ailments. COVID-19 pandemic saw a rise in the infection rates of S. pneumoniae and group A streptococci in Italy [31], attributed to reduced virus spread due to non-pharma interventions like face masks. With similar hospitalisation rates among infants during (46%) and after (40%) the COVID-19 pandemic, the pathophysiology of RSV remained unaltered [32]. However, the COVID-19 pandemic saw variable trends during the period.A vast majority (80-90%) of respiratory illnesses among children are attributed to viruses. Despite most of these infections are self-limiting and requiring no medication and hospitalization, the cause for concern is the potential for developing secondary bacterial infections like sinusitis, middle ear infections (otitis media), laryngitis, bronchitis, and The supplementation of vitamins, minerals, prebiotics, probiotics, symbiotic, and postbiotics in the management and prevention of recurrent RTIs has been recently suggested.Furthermore, the role of complementary and alternative medicine in preventing RTIs in children is being augmented [34]. Vitamin D and vitamin A supplementation, lactoferrin therapy, adjuvant treatment with yupingfeng granules, and dietary antioxidant supplementation are being explored for their utility in the prevention, treatment and management of recurrent RTIs [35][36][37][38][39].There is a rebound of respiratory viral infections caused by the RSV post COVID-19.Children under five years of age are increasingly predisposed to RSV infection. Expert consensuses recommend effective screening through clinical diagnosis followed by confirmation with laboratory diagnostic methods like nucleic acid amplification methods (PCR), rapid antigen detection methods and viral isolation and identification to ensure physicians take appropriate patient treatment management decisions [40]. The efficacy of long-acting, high-potency monoclonal antibodies like the Nirsevimab (Beyfortus™-AstraZeneca/Sanofi) and Palivizumab (Synagis™-AstraZeneca) in the treatment and prevention of RTIs caused by the RSV among children and pregnant women have recently been explored [41]. Improvement in the indoor air quality to reduce the viral load along with maintenance of temperature and humidity in the living rooms to ensure effective functioning of airways were some non-pharmaceutical preventive measures suggested to minimize RTIs among children [42]. The WHO recommends effective measures to prevent RTIs especially among the children and other susceptible (like the geriatrics) population. Resuming the vaccination drives among such population against influenza, SARS-CoV-2, etc. is also advised. COVID-appropriate preventive measures like social distancing, regular hand-sanitising, face-masking especially in crowded places, appropriate and rapid diagnosis, and seeking timely medical intervention are also suggested to prevent and control the spread of infections. Special advisories like avoiding travel during a reported ILI and seeking medical attention in case of an illness during the travel or immediately after that may be released for the frequent international travellers. Travellers may be encouraged to share their prior illness-related encounters (like inadvertent exposure) with the treating physician that would facilitate appropriate diagnosis, initiate a timely and effective treatment, and adopt fool-proof management strategies.