key: cord-0729693-9950e2hh
authors: Ayittey, Foster Kofi; Chiwero, Nyasha Bennita; Dhar, Bablu Kumar; Tettey, Ebenezer Larteh; Saptoro, Agus
title: Epidemiology, clinical characteristics and treatment of SARS‐CoV‐2 infection in children: A narrative review
date: 2021-11-29
journal: Int J Clin Pract
DOI: 10.1111/ijcp.15012
sha: 04800ffdc7c0e42b6eceedfb80bcd41ee3736d84
doc_id: 729693
cord_uid: 9950e2hh

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has infected millions of people around the world, with most cases recorded among adults. The cases reported among children have been acknowledged to be minimal in comparison to adults. Nevertheless, coronavirus disease 2019 (COVID‐19) has been reported to affect children of all ages, including newborns. The symptoms among children have also been identified to be similar to those observed among adults, although paediatric patients have been noted to display a spectrum of clinical features ranging from asymptomatic to moderate symptoms. Despite ample publications on the ongoing pandemic, the literature is only replete with guidelines on treating SARS‐CoV‐2 infection among older people. In this narrative review, comprehensive updates on the infection in children have been discussed. The latest information on the spread of the disease among children around the world, the clinical features observed among the paediatric population, as well as recommended pharmaceutical treatments of COVID‐19 among this special group of patients have been covered. Further, expert consensus statements regarding the management of this highly contagious disease among pregnant women and neonates have been discussed. It is believed that this comprehensive review will provide updated information on the epidemiology and clinical features of the ongoing pandemic among paediatric patients. Additionally, the guidelines for handling SARS‐CoV‐2 among pregnant women and children, as reviewed in this article, are anticipated to be useful to frontline clinicians battling this fatal disease around the globe.

and subsequently detected as a novel beta-coronavirus, using deep genome sequencing analyses. [7] [8] [9] The World Health Organization [10] [11] [12] Owing to the fast transmission nature of COVID-19, and its widespread across the whole world, the WHO declared the outbreak as a public health emergency of international concern (PHEIC) and later announced that the infection has attained a pandemic status in early March, 2020. 12, 13 Presently, the outbreak has spread to over 200 nations and territories in 6 continents across the world, in exception of Antarctica. Table 1 shows the number of confirmed patients, deaths and case-fatality rates in the top-ranked 23 nations across the world, all of which have over 10,000 patients as of 16 April 2020. Globally, the total number of confirmed patients has surpassed 2 million patients, with ~135,000 deaths. 14, 15 The high fatality rates in some countries have resulted in more deaths than in countries where the number of patients is much higher. This could be seen in the case of Belgium. Even though the number of confirmed patients in this country is less than the patients in Germany, China, and Turkey, the fatalities recorded in Belgium is higher than in these nations.

Considering the increasing trends of new patients and deaths globally, as represented in Figure 1 , health experts opined that the fatal COVID-19 could persist for another 12 months; following the typical nature of similar past pandemics which have all lasted between 12 and 36 months. 16, 17 During the early days of the outbreak, COVID-19 was predominantly reported among adults of age 15 years and above, with the proportion of patients recorded among paediatric patients being comparatively trivial. 10 Nevertheless, as noted by Wei et al., 18 the number of cases began to increase among children, especially in infants, in late January. This observation was made by PRC and was believed to be spurred by the fact that younger children were unable to observe the control and preventive measures instituted, such as wearing face masks. This discovery prompted the health officials and authorities in PRC to issue a notice in early February regarding the control and prevention of SARS-CoV-2 infections in infants and pregnant women. The new notice clearly indicated that children are vulnerable to the novel coronavirus contagion because of the immaturity of their immune systems. Also included in the latest procedures is the fact that all populations, regardless of age, were vulnerable to the novel disease. Additionally, as children were recognised to have difficulties with recounting their health status and trace their contact history, it was obvious that the challenges in protecting, diagnosing, and treating this age group could be critical. 10 More recently, the widespread outbreak has been reported to infect children not only in PRC, but globally. Although many of the cases have been reported as mild, there are equally severe cases recorded, and deaths as well. As updated information on the characteristics of the ongoing pandemic in this special population is scarce in the literature, this article conducts comprehensive reviews of the latest information on the clinical and epidemiological features of SARS-CoV-2 infections in paediatric patients around the world. This article also covers the expert consensus for managing and treating the infection in pregnant women, neonates, and children in general. Articles were searched from 1 April 2020, through 21 April 2020. A total of 58 studies were retrieved. Articles were thoroughly screened for similarities in information, common clinical presentations, and dates of data compilation to select the most up-to-date and relevant literature. The state-of-the-art information compiled from these studies has been discussed comprehensively below.

The results of several analyses on the genomic characteristics of SARS-CoV-2 have shown that the new virus is over 85% homologous to two bat-derived SARS-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern

China, but were more distant from SARS-CoV and MERS-CoV. 8, 19 Detailed phylogenetic analyses revealed that the novel virus belongs to the Beta (β)-coronavirus genus, in the subgenus Sarbecovirus. The analyses also disclosed that the 2019-nCoV has a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Despite amino acid variations at some key residues, homology modelling showed that the 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV. Based on these findings, scientists have concluded that, although the 2019-nCoV is similar to SARS-CoV, it is sufficiently different to be considered a new human-infecting β- In a more recent research conducted by the Wuhan Institute of Virology (WIV), the virologists have reported that they have obtained sufficient evidence to conclude that SARS-CoV-2 has originated from bats. They also concluded that SARS-CoV-2 enters cells by binding to the angiotensin-converting enzyme 2 (ACE-2) cell receptor, similar to SARS-CoV. 10 Later publications also indicate that TA B L E 1 Number of confirmed patients and deaths in 23 topranked nations 14 [22] [23] [24] Another study which analysed the genomic evolution of over 100 2019-nCoVs discovered that the pathogen has evolved into two subtypes, namely L and S. The authors also found that the virus strain has roughly 149 mutation points, which raises fears that SARS-CoV-2 could be more infectious and spread wider than SARS-CoV. 25 These fears have become realities around the world as scientists continue to unveil more strains of the novel coronavirus every day. One recent findings believe that there could be up to 49 new strains of the virus, with one of the strains referred to as the ZJ01 having a preference of binding to the Furin cleavage site, rather than ACE-2. Other latest findings also observe that SARS-CoV-2 has at least four modes of binding to human host cells. 26 

Coronavirus disease 2019 (COVID-19) has been declared by the That notwithstanding, the primary transmission route of COVID-19

has been identified to be direct contact with infected persons in a cluster scenario.

In a letter published by Bhopal, 34 emeritus professor of public health, the expert expressed concerns over the need to precisely stratify infected SARS-CoV-2 patients by age group and sex nationwide. He noted that such data are required in handling the ongoing pandemic as the disease is highly variable by age and sex, requiring the need to examine age and sex-specific mortality rates. 34 The letter accentuates the necessity to review the epidemiology and demographic data on 2019-nCoV-infected patients, including children.

Even though the tally of infections among age groups less than Figure 2 .

Nonetheless, CDC-US noted that the rates of hospitalisation for February 2020. Children from 10 to 19 years of age accounted for 1.2% of the same group. This same publication found that the fatality rate rises gradually with increasing age. Among children of age 9 years and less, no fatalities were recorded, whilst the rate among children from 10 to 19 years was 0.2%. [43] [44] [45] As one of the most important laboratory findings observed in SARS-CoV-2 infected paediatric patients, Xia et al. 46 noted that procalcitonin (PCT) elevation was common among children, although it was rare in adults.

Depending on exposure history and symptomatology, Dong et al. 47 Based on these results, the authors concluded that, although young children, especially infants are more susceptible to contagion, children at all ages are vulnerable to SARS-CoV-2 infection, without any significant gender biases. They also noted that the clinical features of this fatal disease in children appeared to be generally less severe than those observed in adults. 47, 48 Another study completed by Lu et al. 49 thrombocytopenia with abnormal liver function (n = 2), fever (n = 2), rapid heart rate (n = 1), pneumothorax (n = 1) and vomiting (n = 1).

One of the neonates was reported dead. The pharyngeal swab specimens collected from the remaining 9 within 1 to 9 days after birth were analysed for COVID- 19 

In a letter to the editor of Acta Paediatricia by Dayal, 53 a paediatrician from the Postgraduate Institute of Medical Education and Research (PIMER), Chandigarh, India, the scientist noted that children have been suggested to have relative protection from the ongoing pandemic because of their less-mature ACE-2, which the SARS-CoV-2 protein binds to for pathogenic effects. That notwithstanding, the author raised the concern over an increased risk of critical disease and fatality rate in infants and young children, which could partly be associated with their less efficient immune system response to infections. As a result of this concern, Dr. Dayal expressed the urgent need for guidelines to manage the highly-infectious COVID-19

in children, especially in those with comorbidities. 53 In another article, commentary published in Clinical Paediatrics, the authors reviewed the epidemiology, clinical features, diagnosis, treatment and mortality rates among 2019-nCoV infected paediatric patients. 48 It was recognised that paediatric patients were spared from symptoms such as headache, lethargy, altered mental status and myalgia, which are common in COVID-19 infected adults.

Fatality in children was also described as an extremely rare occurrence. Diagnosis in paediatric patients was also noticed to be mainly 

Oseltamivir doses for at least 5 days • Can also be used as a single dose in high-risk patients Pregnant women who have a suspected or confirmed COVID-19 infection should be encouraged to report symptoms immediately. They should be screened promptly by qualified medical personnel and directed to present to the appropriate hospital if clinically required. Hospitals with isolation rooms or negative pressure wards should preferentially admit these patients into those units rather than have the patient triaged and transferred between multiple clinics and facilities Quality: High Importance: Critical 5

For pregnant women with confirmed COVID-19 infection, routine antenatal examination delivery should be carried out in a negative pressure isolation ward whenever possible, and the medical staff who take care of these women should wear protective clothing, N95 masks, goggles and gloves before contact with the patients Quality: Low Importance: Critical 6 The timing of childbirth should be individualised. Timing should be based on maternal and foetal well-being, gestational age and other concomitant conditions, not solely because the pregnant patient is infected. The mode of delivery should be based on routine obstetrical indications, allowing vaginal delivery when possible and reserving caesarean delivery for when obstetrically necessary. Quality: Low Importance: Important 7

In pregnant women with COVID-19 infection who need a caesarean delivery, it is reasonable to consider regional analgesia. If the maternal respiratory condition appears to be rapidly deteriorating, general endotracheal anaesthesia may be safer; multidisciplinary planning with the anaesthesiology team is recommended Quality: Very low Importance: Important 57 The recommended dosages of the four different antiviral drugs for varying age groups, as listed by these Iranian medical experts, are shown in Table 4 . 

The authors have declared no conflicts of interest.

All data underlying this article are incorporated into the article. 

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