Evaluation of Clinical and Immune Responses in Recovered Children with Mild COVID-19.

The coronavirus disease 2019 (COVID-19) has spread globally and variants continue to emerge, with children are accounting for a growing share of COVID-19 cases. However, the establishment of immune memory and the long-term health consequences in asymptomatic or mildly symptomatic children after severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We collected clinical data and whole blood samples from discharged children for 6-8 months after symptom onset among 0-to-14-year-old children. Representative inflammation signs returned to normal in all age ranges. The infants and young children (0-4 years old) had lung lesions that persisted for 6-8 months and were less responsive for antigen-specific IgG secretion. In the 5-to-14-year-old group, lung imaging abnormalities gradually recovered, and the IgG-specific antibody response was strongest. In addition, we found a robust IgM+ memory B cell response in all age. Memory T cells specific for the spike or nucleocapsid protein were generated, with no significant difference in IFN-γ response among all ages. Our study highlights that although lung lesions caused by COVID-19 can last for at least 6-8 months in infants and young children, most children have detectable residual neutralizing antibodies and specific cellular immune responses at this stage.

The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice.

As COVID-19 continues to spread rapidly worldwide and variants continue to emerge, the development and deployment of safe and effective vaccines are urgently needed. Here, we developed an mRNA vaccine based on the trimeric receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein fused to ferritin-formed nanoparticles (TF-RBD). Compared to the trimeric form of the RBD mRNA vaccine (T-RBD), TF-RBD delivered intramuscularly elicited robust and durable humoral immunity as well as a Th1-biased cellular response. After further challenge with live SARS-CoV-2, immunization with a two-shot low-dose regimen of TF-RBD provided adequate protection in hACE2-transduced mice. In addition, the mRNA template of TF-RBD was easily and quickly engineered into a variant vaccine to address SARS-CoV-2 mutations. The TF-RBD multivalent vaccine produced broad-spectrum neutralizing antibodies against Alpha (B.1.1.7) and Beta (B.1.351) variants. This mRNA vaccine based on the encoded self-assembled nanoparticle-based trimer RBD provides a reference for the design of mRNA vaccines targeting SARS-CoV-2.

The SARS-CoV-2 Nucleocapsid Protein and Its Role in Viral Structure, Biological Functions, and a Potential Target for Drug or Vaccine Mitigation.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the world is still expanding. Thus, there is an urgent need to better understand this novel virus and find a way to control its spread. Like other coronaviruses, the nucleocapsid (N) protein is one of the most crucial structural components of SARS-CoV-2. This protein shares 90% homology with the severe acute respiratory syndrome coronavirus N protein, implying functional significance. Based on the evolutionary conservation of the N protein in coronavirus, we reviewed the currently available knowledge regarding the SARS-CoV-2 N protein in terms of structure, biological functions, and clinical application as a drug target or vaccine candidate.

Analysis of ACE2 Gene-Encoded Proteins Across Mammalian Species.

Human beings are currently experiencing a serious public health event. Novel coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has infected about 3 million people worldwide and killed more than 200,000, most being the elderly or people with potential chronic diseases or in immunosuppressive states. According to big data analysis, there are many proteins homologous to or interacting with the angiotensin-converting enzyme 2 (ACE2), which, therefore, may not be the only receptor for the novel coronavirus; other receptors may also exist in host cells of different species. These potential receptors may also play an important role in the infection process of the novel coronavirus. The current study aimed to discover such key proteins or receptors and analyze the susceptibility of different animals to the novel coronavirus, in order to reveal the transmission process of the virus in cross-species infection. We analyzed the proteins coded by the ACE2 gene in different mammalian species and predicted their correlation and homology with the human ACE2 receptor. The major finding of our predictive analysis suggested ACE2 gene-encoded proteins to be highly homologous across mammals. Based on their high homology, their possibility of binding the spike-protein of SARS-CoV-2 is quite high and species such as Felis catus, Bos taurus, Rattus norvegicus etc. may be potential susceptible hosts; special monitoring is particularly required for livestock that are in close contact with humans. Our results might provide ideas for the prevention and control of the novel coronavirus pneumonia.

The Rapid Assessment and Early Warning Models for COVID-19.

Human beings have experienced a serious public health event as the new pneumonia (COVID-19), caused by the severe acute respiratory syndrome coronavirus has killed more than 3000 people in China, most of them elderly or people with underlying chronic diseases or immunosuppressed states. Rapid assessment and early warning are essential for outbreak analysis in response to serious public health events. This paper reviews the current model analysis methods and conclusions from both micro and macro perspectives. The establishment of a comprehensive assessment model, and the use of model analysis prediction, is very efficient for the early warning of infectious diseases. This would significantly improve global surveillance capacity, particularly in developing regions, and improve basic training in infectious diseases and molecular epidemiology.