High seroprevalence of anti-SARS-CoV-2 antibodies in the capital of Chad

Background. Since the start of the COVID-19 pandemic, Chad has had 7,417 confirmed cases and 193 deaths, one of the lowest in Africa. Objective. This study assessed SARS-CoV-2 immunity in N'Djamena. Methods. In August-October 2021, eleven N'Djamena hospitals collected outpatient data and samples. IgG antibodies against SARSCoV- 2 nucleocapsid protein were identified using ELISA. "Bambino Gesu" Laboratory, Rome, Italy, performed external quality control with chemiluminescence assay. Results. 25-34-year-old (35.2%) made up the largest age group at 31.9 12.6 years. 56.4% were women, 1.3 women/men. The 7th district had 22.5% and the 1st 22.3%. Housewives and students dominated. Overall seroprevalence was 69.5% (95% CI: 67.7-71.3), females 68.2% (65.8-70.5) and males 71.2% (68.6-73.8). >44-year-old had 73.9% seroprevalence. Under-15s were 57.4% positive. Housewives (70.9%), civil servants (71.5%), and health workers (9.7%) had the highest antibody positivity. N'Djamena's 9th district had 73.1% optimism and the 3rd district had 52.5%. Seroprevalences were highest at Good Samaritan Hospital (75.4%) and National General Referral Hospital (74.7%). Conclusion. Our findings indicate a high circulation of SARS-CoV- 2 in N'Djamena, despite low mortality and morbidity after the first two COVID-19 pandemic waves. This high seroprevalence must be considered in Chad's vaccine policy.

COVID-19-associated lung microvascular endotheliopathy: a "from the bench" perspective

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2;inactivated viral particles;or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

Research progress on the phase separation of SARS - CoV - 2 nucleocapsid protein

COVID-19 pandemic, caused by infection Of severe acute respiratory syndrome Coronavirus 2 (SARS -CoV-2), is an ongoing and severe threat to public health and safety. The Coronavirus nucleoeapsid(N) protein mainly functions as a key structural protein, responsible for binding and packaging viral genome RNA into nucleocapsid and recruiting membrane(M) protein for virion assembly. In addition. the N protein functions as a regulatory protein and plays important roles in suppression of the host innate immune response, and localization with replication transcription complex (RTC) to facilitate Viral transcription and replication. Accumulating evidences have emerged recently that SARS-CoV-2 N protein undergoes liquid-liquid phase separation (LLPS) with RNA or other proteins. Importantly, phase separation of the N protein has been Shown to be essential for its structural and regulatory roles. Here, we summarize recent research progress on the phase separation of SARS-CoV-2 N protein. The potential of the phase separation of the N protein as a therapeutic drug targets is also discussed.

Bioinformatics analysis of mutations in the spike protein of SARS-CoV-2 and their effects

In December 2019, a new type of pneumonia, coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-CoV-2, was detected in hospitals in Wuhan, Hubei Province, China. The World Health Organization announced on 11 March 2020 that COVID-19 can be characterized as a pandemic, and since then COVID-19 has wrought havOc on public-health systems worldwide. The surface "spike" protein CS protein of SARS-CoV-2 mediates host-cell attachment and membrane fusion. The S protein is a key target for urgent development of vaccines, therapeutic antibodies, and diagnostics. To analyze the mutations and their effects on protein structure and function of the S protein, bioinformatics software has been used to analyze its nucleotide and amino-acid sequences, and Wuhan-Hu-1 (GenBank accession number: MN908947.3) was used as standard strain. As of 17 April 2020, there were 1, 002 SARS-CoV-2 strains in the GenBank database, of which 12 strains had mutations in the amino-acid sequence of the S protein. Some of these mutations could affect the physicochemical properties and secondary structures of the S protein. The R4081 mutation was located in the receptor-binding domain (RBD) and displayed on the surface, and could affect the RBD structure. The mutated amino acids 48, 74, 181, 221 and 655 were located in predicted linear epitopes of B cells, and 74, 181 and 655 mutations could greatly affect the structures and properties of linear epitopes of B cells.. The S protein of SARS-CoV-2 isolated from humans, dogs, cats and lions was highly conserved, whereas the D614G mutation was found in the isolated strain from tigers. Furthermore, the unique Flynn protease recognition site was presented in the S protein of SARS-CoV-2 compared with the coronavirus from bats. These results suggest that the S protein of SARS-CoV-2 is relatively conserved within and between species, whereas there are some mutations that can affect the physicochemical properties and structures of the S protein, which may also affect the linear epitopes of B cells. Taken together, these data provide a basis for the research and development of drugs, antibodies and vaccines against SARS-CoV-2.

Genome characterization and potential risk assessment of the novel SARS-CoV-2 variant Omicron (B.1.1.529)

As the novel coronavirus SARS-CoV-2 spread around the world, multiple waves of variants emerged, thus leading to local or global population shifts during the pandemic. A new variant named Omicron (PANGO lineage B.1.1.529), which was first discovered in southern Africa, has recently been proposed by the World Health Organization to be a Variant of Concern. This variant carries an unusually large number of mutations, particularly on the spike protein and receptor binding domain, in contrast to other known major variants. Some mutation sites are associated with enhanced viral transmission, infectivity, and pathogenicity, thus enabling the virus to evade the immune protective barrier. Given that the emergence of the Omicron variant was accompanied by a sharp increase in infection cases in South Africa, the variant has the potential to trigger a new global epidemic peak. Therefore, continual attention and a rapid response are required to decrease the possible risks to public health.

Contemporary zoonoses - a curse of XXI century

This paper presents a review of most important zoonotic diseases that are threatening human World population in the first 20 years of XXI century. Zoonoses diseases naturally transmitted through several modes from vertebrate animal hosts to humans. SARS-CoV-Z - severe acute respiratory syndrome coronavirus 2, was identified as the cause of an outbreak of COVID-2 pandemic in humans in 2019/2020. Coronavirus positive Chinese bats and an unrecognized yet natural reservoir of emerging SARS-Z, are indicated as a primary source of infection. So far, there is no evidence that companion or farm animals can become infected by contact with a sick/infected person, so SARS-2 virus strains isolated from humans are not zoonotic. This review contains a description of SARS-2 virus structure, genetic diversity, structure and function of viral proteins, including class I viral fusion protein S. The review also includes an assessment of epidemiology of SARS-2 infection, criteria and epidemiological interactions, perspectives on emerging zoonoti'c disease research in contact with public health service. More closed cooperation between different services, including Veterinary Services, with WHO and OIE international standards, as eg. One Health partnership, is essential to avoid or minimize risk of new infections in future.

Whole-genome sequence analysis of four human coronavirus NL63 strains regionally prevalent in Shenzhen, 2020

In this study, the genomic RNA of HCoV-NL63 from throat swab samples obtained from cases of respiratory tract infection was sequenced. The cases were collected from clustered or sporadic epidemics in the Nanshan district of Shenzhen City in 2020. Four whole genomes of HCoV-NL63 strains were obtained and analyzed with phylogenetic tree reconstruction and other bioinformatics analyses. The sequence similarity among the four strains was 99.80%~99.98% for nucleotides and 99.64%~99.93% for amino acids. The four strains of HCoV-NL63 belonged to the B genotype, B2 subgenotype, which were on the same branch of the phylogenetic tree and were genetically closest to MK334046.1. Analysis of the amino acid variation sites of the S protein indicated that L196F was present in the strains obtained from sporadic epidemic cases, and A946S was present in the strains acquired from clustered epidemic cases. The prediction of N-glycosylation sites indicated ten N-glycosylation sites in S protein and two N-glycosylation sites in M protein. Through whole genome sequencing and feature analysis, we determined that the HCoV-NL63 obtained in this study probably originated from the Guangzhou virus strain. Our current results provide some clues as to the basis for biological traceability, and might facilitate future epidemic prevention and control.

Is the SARS-cov2 evolved in human being: a prospective genetic analysis

COVID-19 is the deadly respiratory disease of the century caused by new type unknown origin Coronavirus. The recent effort of the word researchers is toward finding the origin of the virus. The current study investigated the extent of molecular similarity and divergence between SARS-CoV2 and other related Coronavirus. An attempt has been made to investigate the epidemiological study of this new contagious virus using molecular biology techniques. The phylogenetic trees for all human coronaviruses with the novel Coronavirus have been built using a several complete amino acid sequences of the four known structural proteins, S (spike), E (envelope), M (membrane), and N (nucleocapsid). The result of the study revealed that the SARS-CoV2 is related to human SARS-CoV isolated from different countries very cloely, especially those strains recovered from China in recent times, 2020. The evolutionary changes observed in the inserted 23 amino acids in the RNA binding domain (RBD) of the coronvirus spike glycoprotein which cannot be detected in any other human coronavirus. Moreover, the 2019-nCoV is not closely related to other alpha, beta and gamma human Coronavirus, including MERS-CoV. The current study concluded that 2019-nCoV is more likely believed to originated from SARS-CoV. The probability is more vital to be originated from the strain isolated in China in 2020, which is coincident with the spraed of COVID-19 in the same country. The phyloepidemiologic analyses suggested that the coronaviruses are circulating in human hosts evolving gradually by times in response to the different environment stimuli facing the virus inside the host in different geographical areas. Furthermore, the analysis showed the flow of transmission, and evolutionary changes of SARS-CoV2 which may be directed from the transmission of SARS-CoV from human to Bat and Pangolin then jumped to human again in the crowded market Wuhan city in China.