Distinct Clinical and Laboratory Features of COVID-19 in Children During the Pre-Delta, Delta and Omicron Wave.

BACKGROUND: The SARS-CoV-2 variants of concern exhibit distinct features in terms of transmissibility and virulence. This study compared the clinical characteristics of COVID-19 in children during pre-Delta, Delta and Omicron waves. METHODS: Medical records of 1163 children <19 years of age with COVID-19 admitted to a designated hospital in Seoul, South Korea, were analyzed. Clinical and laboratory findings during the pre-Delta (March 1, 2020, to June 30, 2021; 330 children), Delta (July 1, 2021, to December 31, 2021; 527 children) and Omicron (January 1, 2022, to May 10, 2022; 306 children) waves were compared. RESULTS: Children during the Delta wave were older and had a higher proportion of fever ≥5 days and pneumonia than children during the pre-Delta and Omicron waves. The Omicron wave was characterized by younger age and a higher proportion of fever ≥39.0 °C, febrile seizure and croup. More children <2 years of age and adolescents aged 10 to <19 years experienced neutropenia and lymphopenia, respectively, during the Delta wave. Children aged 2 to <10 years had a higher incidence of leukopenia and lymphopenia during the Omicron wave. CONCLUSIONS: Distinct features of COVID-19 were observed in children during the Delta and Omicron surges. Continuous scrutiny of the manifestations of variants of concern is needed for appropriate public health response and management.

Application of Minimal Physiologically-Based Pharmacokinetic Model to Simulate Lung and Trachea Exposure of Pyronaridine and Artesunate in Hamsters.

A fixed-dose combination of pyronaridine and artesunate, one of the artemisinin-based combination therapies, has been used as a potent antimalarial treatment regimen. Recently, several studies have reported the antiviral effects of both drugs against severe acute respiratory syndrome coronavirus two (SARS-CoV-2). However, there are limited data on the pharmacokinetics (PKs), lung, and trachea exposures that could be correlated with the antiviral effects of pyronaridine and artesunate. The purpose of this study was to evaluate the pharmacokinetics, lung, and trachea distribution of pyronaridine, artesunate, and dihydroartemisinin (an active metabolite of artesunate) using a minimal physiologically-based pharmacokinetic (PBPK) model. The major target tissues for evaluating dose metrics are blood, lung, and trachea, and the nontarget tissues were lumped together into the rest of the body. The predictive performance of the minimal PBPK model was evaluated using visual inspection between observations and model predictions, (average) fold error, and sensitivity analysis. The developed PBPK models were applied for the multiple-dosing simulation of daily oral pyronaridine and artesunate. A steady state was reached about three to four days after the first dosing of pyronaridine and an accumulation ratio was calculated to be 1.8. However, the accumulation ratio of artesunate and dihydroartemisinin could not be calculated since the steady state of both compounds was not achieved by daily multiple dosing. The elimination half-life of pyronaridine and artesunate was estimated to be 19.8 and 0.4 h, respectively. Pyronaridine was extensively distributed to the lung and trachea with the lung-to-blood and trachea-to-blood concentration ratios (=Cavg,tissue/Cavg,blood) of 25.83 and 12.41 at the steady state, respectively. Also, the lung-to-blood and trachea-to-blood AUC ratios for artesunate (dihydroartemisinin) were calculated to be 3.34 (1.51) and 0.34 (0.15). The results of this study could provide a scientific basis for interpreting the dose-exposure-response relationship of pyronaridine and artesunate for COVID-19 drug repurposing.

Antibody Responses to SARS-CoV-2 in Children With COVID-19.

BACKGROUND: The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19. METHODS: The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020. RESULTS: One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years. CONCLUSIONS: These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic.

Antiviral Activities of High Energy E-Beam Induced Copper Nanoparticles against H1N1 Influenza Virus.

The pandemic outbreak of COVID-19 in the year of 2020 that drastically changed everyone's life has raised the urgent and intense need for the development of more efficacious antiviral material. This study was designed to develop copper nanoparticles (Cu NPs) as an antiviral agent and to validate the antiviral activities of developed copper NP. The Cu NPs were synthesized using a high energy electron beam, and the characteristic morphologies and antiviral activities of Cu NPs were evaluated. We found that Cu NPs are of spherical shape and uniformly distributed, with a diameter of around 100 nm, as opposed to the irregular shape of commercially available copper microparticles (Cu MPs). An X-ray diffraction analysis showed the presence of Cu and no copper oxide II and I in the Cu NPs. A virus inactivation assay revealed no visible viral DNA after 10- and 30-min treatment of H1N1 virus with the Cu NPs. The infectivity of the Cu NPs-treated H1N1 virus significantly decreased compared with that of the Cu MPs-treated H1N1 virus. The viability of A549 bronchial and Madin-Darby Canine Kidney (MDCK) cells infected with Cu NPs-treated H1N1 was significantly higher than those infected with Cu MPs-treated H1N1 virus. We also found cells infected with Cu NPs-treated H1N1 virus exhibited a markedly decreased presence of virus nucleoprotein (NuP), an influenza virus-specific structural protein, compared with cells infected with Cu MPs-treated H1N1 virus. Taken together, our study shows that Cu NPs are a more effective and efficacious antiviral agent compared with Cu MPs and offer promising opportunities for the prevention of devastatingly infectious diseases.

Limited Benefit of Facility Isolation and the Rationale for Home Care in Children with Mild COVID-19.

Considering the mild degree of coronavirus disease 2019 (COVID-19) in children and the enormous stress caused by isolation in unfamiliar places, policies requiring mandatory isolation at medical facilities should be reevaluated especially given the impact of the pandemic on the availability of hospital beds. In this study, we assessed the usefulness of facility isolation and the transmissibility of severe acute respiratory syndrome coronavirus 2 by infected children to uninfected caregivers in isolation units at a hospital and a residential treatment center in Seoul during August-November 2020. Fifty-three children were included and median age was 4 years (range, 0-18). All were mildly ill or asymptomatic and isolated for a median duration of 12 days. Thirty percent stayed home longer than 2 days before entering isolation units from symptom onset. Among 15 uninfected caregivers, none became infected when they used facemasks and practiced hand hygiene. The results suggest children with mild COVID-19 may be cared safely at home by a caregiver in conditions with adherence to the preventive measures of wearing facemasks and practicing hand hygiene.