Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19.

Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response. Total and virus-specific IgM and IgG ASCs peaked at 3-4 weeks and were still being produced at 3-4 months accompanied by increasing antibody avidity consistent with a slower germinal center B cell response. N-specific ASCs were produced for longer than S-specific ASCs and avidity maturation was greater for antibody to N than S. Patients with more severe disease produced more S-specific IgM and IgG ASCs than those with mild disease and had higher levels of N- and S-specific antibody. Women had more B cells in circulation than men and produced more S-specific IgA and IgG and N-specific IgG ASCs. Flow cytometry analysis of B cell phenotypes showed an increase in circulating B cells at 4-6 weeks with decreased percentages of switched and unswitched memory B cells. These data indicate ongoing antigen-specific stimulation, maturation, and production of ASCs for several months after onset of symptoms in patients hospitalized with COVID-19.

Perceptions towards COVID-19 Vaccines and Willingness to Vaccinate in Nepal.

Vaccination is the most effective preventive measure of COVID-19 available at present, but its success depends on the global accessibility of vaccines and the willingness of people to be vaccinated. As the vaccination rollouts are increasing worldwide, it is important to assess public perception and willingness towards vaccination, so that the aim of mass vaccination will be successful. This study aimed to understand public perception towards COVID-19 vaccines and their willingness to get vaccinated in Nepal. This cross-sectional online survey was conducted among 1196 residents of Nepal in August 2021; most of the participants of this online survey were young adults (18-47 years) with university-level education. A total of 64.5% (771/1196) of the participants perceived COVID-19 vaccines to be safe and risk-free, while 68.6% (820/1196) agreed that vaccination would be efficient in the fight against this pandemic. Most of the participants (841/1196, 70.3%) disagreed that people are getting COVID-19 vaccines easily in Nepal, while they agree with the prioritization of older adults and healthcare workers for vaccination. A total of 61.1% (731/1196) of the participants had received at least one dose of the vaccine. Among the unvaccinated, 93.3% (434/465) were willing to get vaccinated when their turn came. The higher confidence of younger adults in vaccines and the vaccination process is encouraging, as that can help educate others who are hesitant or are not positive towards the idea of receiving vaccines. Dissemination of correct and current information, acquisition of enough doses of vaccines, and equitable distribution of vaccines will be required to achieve successful completion of the COVID-19 vaccination campaign in Nepal.

Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity.

Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils. We investigated whether neutrophil elastase regulates the adjuvanticity of alum, and whether a strategy targeting neutrophil elastase could improve responses to injected vaccines. Mice coadministered a pharmacological inhibitor of elastase, or lacking elastase, developed high-affinity serum IgG and IgA antibodies after immunization with alum-adsorbed protein vaccines, including the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). These mice also developed broader antigen-specific CD4+ T cell responses, including high Th1 and T follicular helper (Tfh) responses. Interestingly, in the absence of elastase activity, mucosal SIgA responses were induced after systemic immunization with alum as adjuvant. Importantly, lack or suppression of elastase activity enhanced the magnitude of anti-SARS-CoV-2 spike subunit 1 (S1) antibodies, and these antibodies reacted with the same epitopes of spike 1 protein as sera from COVID-19 patients. Therefore, suppression of neutrophil elastase could represent an attractive strategy for improving the efficacy of alum-based injected vaccines for the induction of broad immunity, including mucosal immunity.

Coronaviruses in animals and humans, COVID-19 pandemic and one health approach

Coronaviruses can infect several animal species including cattle, pigs, dogs, and cats resulting in diseases related to respiratory and gastrointestinal systems. In humans, coronaviruses generally cause mild to moderate illnesses of the respiratory tract. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which emerged during 2002/03 and 2012/13 respectively, caused severe respiratory illnesses in humans. In December 2019, a novel respiratory coronavirus, SARS coronavirus 2 (SARS-CoV-2) emerged from Wuhan, China and caused coronavirus disease 2019 (COVID-19). Owing to the rapid spread of this virus, World Health Organization (WHO) declared COVID-19 outbreak as a global pandemic, which claimed over 300,000 lives by 16th May 2020. Data available so far indicate that COVID-19-associated severe illnesses, hospitalizations and deaths are more common in elderly above 65 years of age;in men;and in individuals with underlying health conditions such as cardiovascular disease, hypertension and diabetes. SARS-CoV-2 is considered to be emerged from bats and likely involved certain, yet to be identified, intermediate animal host. Prevention and control of ongoing COVID-19 pandemic and possible disease outbreaks in the future by other emerging and reemerging pathogens, requires efficient implementation of one health strategy that utilizes the expertise of human, animal and environmental health sectors.