Contaminação pelo Covid-19 em profissionais de hospital de referência no Pará / Contamination by Covid-19 in professionals of a reference hospital in Para's state / Contaminación por Covid-19 en profesionales de un hospital de referencia del estado de Pará

A pandemia do novo coronavírus colocou em alerta os sistemas de saúde, estabelecendo sentimentos de instabilidade e de medo. O trabalho é e importante pilar para o traçado de políticas públicas. Objetivo: analisar a contaminação pelo COVID-19 em profissionais de hospital de referência no Pará. Metodologia: Trata-se de estudo retrospectivo, quantitativo, observacional, com aplicação de série temporal no período de março de 2020 a março de 2022. Foram incluídos todos os servidores atuantes durante a pandemia, que apresentaram atestados médicos com diagnóstico de COVID, e/ou testagem positiva, ou atestados por suspeita de contaminação. O perfil de servidores foi analisado, explorando as variáveis sexo, idade, convivência ou não com parceiros, grau de escolaridade, cargo e setor; juntamente com a incidência de casos confirmados e incidência total (suspeitos e confirmados). Resultados: O total de afastamentos do trabalho devido ao diagnóstico de COVID-19 foi de 1.420 casos, mais 839 casos suspeitos; sendo que 173 trabalhadores apresentaram reincidência. A incidência foi maior nos meses de maio de 2020, março de 2021 e janeiro de 2022. Houve predominância do sexo feminino e da categoria de enfermagem. Setores administrativos e financeiros apresentaram maior porcentagem de contaminados durante a pandemia (73,40%), proporcionalmente ao quantitativo de servidores atuantes na lotação. Entretanto, foram servidores da assistência direta ao paciente que apresentaram maior porcentagem de reinfecção. Conclusão: Foi possível visualizar três ondas na distribuição temporal dos casos de COVID-19, com destaque para elevação nos primeiros meses de 2022. O declínio no diagnóstico de casos novos no hospital estudado após dois anos de pandemia pode representar esforços individuais e coletivos em resistir às dificuldades da conjuntura. É importante observar o comportamento da pandemia em distintas regiões do Brasil para atualização de estratégias de enfrentamento como um todo.

The new coronavirus pandemic has put health systems on alert, establishing feelings of instability and fear. Working is an important pillar for the design of public policies. Objective: to analyze the contamination by COVID-19 in professionals of a reference hospital in Para's State. Methodology: This is a retrospective, quantitative, observational study, with the application of a time series from March 2020 to March 2022. All civil servants working during the pandemic, who presented medical certificates with a diagnosis of COVID, and/or or positive test, or attestations for suspected contamination. The servants' profile was analyzed, exploring the variables sex, age, living or not with partners, education level, position and sector; along with the incidence of confirmed cases and total incidence (suspected and confirmed). Results: The total number of absences from work due to the diagnosis of COVID-19 was 1,420 cases, plus 839 suspected cases; 173 workers presented recurrence. The incidence was higher in the months of May 2020, March 2021 and January 2022. There was a predominance of females and the nursing category. Administrative and financial sectors had a higher percentage of people infected during the pandemic (73.40%), proportionally to the number of servers working in the capacity. However, it was direct patient care workers who had the highest percentage of reinfection. Conclusion: It was possible to visualize three waves in the temporal distribution of COVID-19 cases, with emphasis on an increase in the first months of 2022. The decline in the diagnosis of new cases in the hospital studied after two years of the pandemic may represent individual and collective efforts to resist to the difficulties of the situation. It is important to observe the behavior of the pandemic in different regions of Brazil to update coping strategies in a general scenery.

La nueva pandemia de coronavirus ha puesto en alerta a los sistemas de salud, estableciendo sentimientos de inestabilidad y miedo. El trabajo es un pilar importante para el diseño de políticas públicas. Objetivo: analizar la contaminación por COVID-19 en profesionales de un hospital de referencia en el Estado de Pará. Metodología: Se trata de un estudio retrospectivo, cuantitativo, observacional, con la aplicación de una serie de tiempo de marzo de 2020 a marzo de 2022. Todos los funcionarios que trabajaron durante la pandemia, que presentaron certificados médicos con diagnóstico de COVID, y/o o test positivo, o atestados por sospecha de contaminación. Se analizó el perfil de los funcionarios, explorando las variables sexo, edad, convivencia o no con la pareja, nivel de escolaridad, cargo y sector; junto con la incidencia de casos confirmados y la incidencia total (sospechosos y confirmados). Resultados: El número total de bajas laborales por diagnóstico de COVID-19 fue de 1.420 casos, más 839 casos sospechosos; 173 trabajadores presentaron recurrencia. La incidencia fue mayor en los meses de mayo de 2020, marzo de 2021 y enero de 2022. Hubo predominio del sexo femenino y de la categoría de enfermería. Los sectores administrativo y financiero presentaron mayor porcentaje de infectados durante la pandemia (73,40%), proporcionalmente al número de servidores que trabajaban en esa función. Sin embargo, fueron los trabajadores de atención directa al paciente los que presentaron el mayor porcentaje de reinfección. Conclusiones: Fue posible visualizar tres olas en la distribución temporal de los casos de COVID-19, destacándose un aumento en los primeros meses de 2022. La disminución en el diagnóstico de nuevos casos en el hospital estudiado después de dos años de pandemia puede representar esfuerzos individuales y colectivos para resistir a las dificultades de la situación. Es importante observar el comportamiento de la pandemia en diferentes regiones de Brasil para actualizar las estrategias de afrontamiento en un escenario general.

Effects of Severe Acute Respiratory Syndrome Coronavirus Vaccination on Reinfection: A Community-Based Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease that is characterized by frequent reinfection. However, the factors influencing reinfection remain poorly elucidated, particularly regarding the effect of COVID-19 vaccination on preventing reinfection and its effects on symptomatology and the interval until reinfection. METHODS: This retrospective cohort study examined patients with severe acute respiratory syndrome coronavirus reinfection between January 2020 and February 2022. This study included patients aged >17 years who were reinfected at least 90 days between two infections with severe acute respiratory syndrome coronavirus. The main outcome measure was a reduction in symptoms during reinfection, and reinfection interval. RESULTS: Overall, 712 patients (average age: 40.52 ± 16.41 years; 312 males) were included. The reduction rate of symptoms at reinfection than that at first infection was significantly higher in the vaccinated group than in the unvaccinated group (p < 0.001). The average reinfection interval was 265.81 days. The interval between the first and second infection was 63.47 days longer in the vaccinated group than in the unvaccinated group. The interval was also 57.23 days, significantly longer in the asymptomatic group than in the symptomatic group (p < 0.001). CONCLUSIONS: Besides its role in preventing severe acute respiratory syndrome coronavirus infection, vaccination reduces the rate of symptomatic reinfection and increases the reinfection interval; thus, it is necessary to be vaccinated even after a previous infection. The findings may inform the decision to avail COVID-19 vaccination.

Exploring the Impact of COVID-19 on Physical Activity One Month after Infection and Its Potential Determinants: Re-Infections, Pre-Illness Vaccination Profiles/Types, and Beyond.

This study investigated changes in physical activity (PA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while considering age, PA level, underlying medical conditions (UMCs), vaccination profiles/types, re-infections, disease severity, and treatment. Data were collected from 5829 respondents by using a validated web-based questionnaire. The findings showed that there was a significant overall decrease in PA (-16.2%), including in daily occupation (-11.9%), transportation (-13.5%), leisure-time (-16.4%), and sporting (-27.6%) activities. Age, PA level, UMCs, vaccination profiles/types, disease severity, and treatment played a role in determining PA in individuals' post-acute SARS-CoV-2 infections. Re-infections did not impact the decline in PA. Unvaccinated individuals experienced a significant decline in PA (-13.7%). Younger (-22.4%) and older adults (-22.5%), those with higher PA levels (-20.6%), those with 2-5 UMCs (-23.1%), those who were vaccinated (-16.9%) or partially vaccinated (-19.1%), those with mRNA-type vaccines only (-17.1%), those with recurrent (-19.4%)-to-persistent (-54.2%) symptoms, and those that required hospital (-51.8%) or intensive care unit (-67.0%) admission during their infections had more pronounced declines in PA. These findings emphasize the complex relationship between post-acute SARS-CoV-2 infection and PA and highlight the need for targeted interventions, further research, and multidisciplinary care to promote PA resumption and mitigate long-term effects on global public health.

Immunological changes in a cohort of COVID-19 survivors: Mansoura University experience.

Background: COVID-19 is a global pandemic that has affected millions of people all over the world since 2019. Infection with COVID-19 initiates a humoral immune response that produces antibodies against specific viral antigens, which in turn is supposed to provide immunity against reinfection for a period of time. The aim of this research was to study the kinetics of IgM and IgG antibodies against SARS-CoV-2. Methods: One hundred and seventeen post-COVID-19 participants were enrolled in the study.  Qualitative assessment of IgM and IgG antibodies over six months (three visits) post recovery was conducted. Results: The current study revealed a significant reduction in IgM and IgG titers between the first and second visits (p <0.001). After six months, the antibody titer had declined by 78.8% from the first visit for IgM and by 49.2% for IgG antibodies. Regarding younger age and male sex, statistically significant persistence of IgM antibodies was noticed at the six months follow up. Also, statistically significant persistent IgG immunity was found in male patients and diabetics by the end of the six months follow up. Conclusions: We observed a significant waning of IgM and IgG titers over a period of six months follow up.. The persistence of positive IgM and IgG antibodies by the end of six months was variable due to differences in age, gender and presence of diabetes mellitus.

Riding the Wave: Unveiling the Conformational Waves from RBD of SARS-CoV-2 Spike Protein to ACE2.

The binding affinity between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) plays a crucial role in the transmission and reinfection of SARS-CoV2. Here, microsecond molecular dynamics simulations revealed that point mutations in the RBD domain induced conformational transitions that determined the binding affinity between ACE2 and RBD. These structural changes propagated through the RBD domain, altering the orientation of both ACE2 and RBD residues at the binding site. ACE2 receptor shows significant structural heterogeneity, whereas its binding to the RBD domain indicates a much greater degree of structural homogeneity. The receptor was more flexible in its unbound state with the binding of RBD domains inducing structural transitions. The structural heterogeneity observed in the ACE2 unbound form plays a role in the promiscuity of viral entry, as it may allow the receptor to interact with various related and unrelated ligands. Furthermore, rigidity may be important for stabilizing the complex and ensuring the proper orientation of the RBD-binding interface with ACE2. The greater structural homogeneity observed in the ACE2-RBD complex revealed the effectiveness of neutralizing antibodies and vaccines that are primarily directed toward the RBD-binding interface. The binding of the B38 monoclonal antibody revealed restricted conformational transitions in the RBD and ACE2 receptors, attributed to its potent binding interaction.

The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

Molecular epidemiology of SARS-CoV-2 variants in circulation in the state of Maranhão, Brazil.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a coronavirus belonging to the beta CoV genus, responsible for SARS in humans, which became known as COVID-19. The emergence of variants of this virus is related to the presence of cases of reinfection, reduced vaccine effectiveness and greater transmission of the virus. Objective: In this study, we evaluated the molecular epidemiology of SARS-CoV-2 lineages circulating in the state of Maranhão. This is a cross-sectional and retrospective epidemiological study of genomic surveillance of SARS-CoV-2. The study comprised of 338 genomes sequenced by the Next Generation Sequencing technique on Illumina's Miseq equipment, submitted to Global Initiative on Sharing Avian Influenza Data, 190 (56.2%) are from samples of female and 148 (43.8%) from male patients. Sequencing performed covered samples of patients aged between 1 and 108 years, with emphasis on the age groups from 30 to 39 years with 15.0% of sequenced genomes and 20 to 29 years with 12.4%. As for the distribution of sequenced genomes by health macro-regions, 285 (84.3%) are from cities in the northern macro-region. We evidenced the circulation of 29 lineages and sub-lineages, four of which belonging to the Delta variant (AY.43, AY.99.1, AY.99.2 and AY.101 responsible for 4.5% of the genomes) and the others belonging to the Omicron variant, with emphasis on: BA.1 and sub-lineages (42.8%); BA.4, BA.5 and sub-lineages (5.3% and 41.1%); the sub-lineages DL.1 and BQ.1 (5% and 2%). A strong genomic surveillance system allows the study of the natural history of the disease, when there is a resurgence of SARS-CoV-2 cases.

Persistent symptoms and conditions among children and adolescents hospitalised with COVID-19 illness: a qualitative study.

OBJECTIVES: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection. DESIGN, SETTING AND PARTICIPANTS: A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo. RESULTS: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems. CONCLUSIONS: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities.

Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk.

The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections.

Can variants, reinfection, symptoms and test types affect COVID-19 diagnostic performance? A large-scale retrospective study of AG-RDTs during circulation of Delta and Omicron variants, Czechia, December 2021 to February 2022.

BackgroundThe sensitivity and specificity of selected antigen detection rapid diagnostic tests (AG-RDTs) for SARS-CoV-2 were determined in the unvaccinated population when the Delta variant was circulating. Viral loads, dynamics, symptoms and tissue tropism differ between Omicron and Delta.AimWe aimed to compare AG-RDT sensitivity and specificity in selected subgroups during Omicron vs Delta circulation.MethodsWe retrospectively paired AG-RDT results with PCRs registered in Czechia's Information System for Infectious Diseases from 1 to 25 December 2021 (Delta, n = 20,121) and 20 January to 24 February 2022 (Omicron, n = 47,104).ResultsWhen confirmatory PCR was conducted on the same day as AG-RDT as a proxy for antigen testing close to peak viral load, the average sensitivity for Delta was 80.4% and for Omicron 81.4% (p < 0.05). Sensitivity in vaccinated individuals was lower for Omicron (OR = 0.94; 95% confidence interval (CI): 0.87-1.03), particularly in reinfections (OR = 0.83; 95% CI: 0.75-0.92). Saliva AG-RDT sensitivity was below average for both Delta (74.4%) and Omicron (78.4%). Tests on the European Union Category A list had higher sensitivity than tests in Category B. The highest sensitivity for Omicron (88.5%) was recorded for patients with loss of smell or taste, however, these symptoms were almost 10-fold less common than for Delta. The sensitivity of AG-RDTs performed on initially asymptomatic individuals done 1, 2 or 3 days before a positive PCR test was consistently lower for Omicron compared with Delta.ConclusionSensitivity for Omicron was lower in subgroups that may become more common if SARS-CoV-2 becomes an endemic virus.

Effectiveness of various COVID-19 vaccine regimens among 10.4 million patients from the National COVID Cohort Collaborative during Pre-Delta to Omicron periods - United States, 11 December 2020 to 30 June 2022.

OBJECTIVE: This study reports the vaccine effectiveness (VE) of COVID-19 vaccine regimens in the United States, based on the National COVID Cohort Collaborative (N3C) database. METHODS: Data from 10.4 million adults, enrolled in the N3C from 11 December 2020 to 30 June 2022, were analyzed. VE against infection and death outcomes were evaluated across 13 vaccine regimens in recipient cohorts during the Pre-Delta, Delta, and Omicron periods. VE was estimated as (1-odds ratio) × 100% by multivariate logistic regression, using the unvaccinated cohort as reference. RESULTS: Natural immunity showed a highly protective effect (70.33%) against re-infection, but the mortality risk among the unvaccinated population was increased after re-infection; vaccination following infection reduced the risk of re-infection and death. mRNA-1273 full vaccination plus mRNA-1273 booster showed the highest anti-infection effectiveness (47.59%) (95% CI, 46.72-48.45) in the overall cohort. In the type 2 diabetes cohort, VE against infection was highest with BNT162b2 full vaccination plus mRNA-1273 booster (61.19%) (95% CI, 53.73-67.75). VE against death was also highest with BNT162b2 full vaccination plus mRNA-1273 booster (89.56%) (95% CI, 85.75-92.61). During the Pre-Delta period, all vaccination regimens showed an anti-infection effect; during the Delta period, only boosters, mixed vaccines, and Ad26.COV2.S vaccination exhibited an anti-infection effect; during the Omicron period, none of the vaccine regimens demonstrated an anti-infection effect. Irrespective of the variant period, even a single dose of mRNA vaccine offered protection against death, thus demonstrating survival benefit, even in the presence of infection or re-infection. Similar patterns were observed in patients with type 2 diabetes. CONCLUSIONS: Although the anti-infection effect declined as SARS-CoV-2 variants evolved, all COVID-19 mRNA vaccines had sustained effectiveness against death. Vaccination was crucial for preventing re-infection and reducing the risk of death following SARS-CoV-2 infection.

Distinguishing SARS-CoV-2 infection and vaccine responses up to 18 months post-infection using nucleocapsid protein and receptor-binding domain antibodies.

The prediction of the durability of immunity against COVID-19 is relevant, and longitudinal studies are essential for unraveling the details regarding protective SARS-CoV-2 antibody responses. It has become challenging to discriminate between COVID-19 vaccine- and infection-induced immune responses since all approved vaccines in Europe and the USA are based on the viral spike (S) protein, which is also the most commonly used antigen in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a nucleocapsid (N) protein-based sandwich ELISA for detecting pan anti-SARS-CoV-2 Ig with a sensitivity and specificity of 97%. Generalized mixed models were used to determine the degree of long-term humoral immunity against the N protein and the receptor-binding domain (RBD) of the S protein in a cohort of infected individuals to distinguish between COVID-19 vaccine- and infection-induced immunity. N-specific waning could be observed in individuals who did not experience reinfection, while individuals who experienced reinfection had a new significant increase in N-specific Ig levels. In individuals that seroconverted without a reinfection, 70.1% remained anti-N seropositive after 550 days. The anti-RBD Ig dynamics were unaffected by reinfection but exhibited a clear increase in RBD-specific Ig when vaccination was initiated. In conclusion, a clear difference in the dynamics of the antibody response against N protein and RBD was observed over time. Anti-N protein-specific Igs can be detected up to 18 months after SARS-CoV-2 infection allowing long-term discrimination of infectious and vaccine antibody responses.IMPORTANCELongitudinal studies are essential to unravel details regarding the protective antibody responses after COVID-19 infection and vaccination. It has become challenging to distinguish long-term immune responses to SARS-CoV-2 infection and vaccination since most approved vaccines are based on the viral spike (S) protein, which is also mostly used in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a novel nucleocapsid (N) protein-based sandwich ELISA for detecting pan-anti-SARS-CoV-2 Ig, exhibiting high sensitivity and specificity. Generalized mixed models were used to determine long-term humoral immunity in a cohort of infected individuals from the Faroe Islands, distinguishing between COVID-19 vaccine- and infection-induced immunity. A clear difference in the dynamics of the antibody response against N protein and S protein was observed over time, and the anti-N protein-specific Igs could be detected up to 18 months after SARS-CoV-2 infection. This enables long-term discrimination between natural infection and vaccine-dependent antibody responses.

Age and prior vaccination determine the antibody level in children with primary SARS-CoV-2 Omicron infection.

BACKGROUND: Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection relies on immunity generated after primary infection. However, humoral immunity following primary infection with the Omicron variant is not well understood. METHODS: We prospectively recruited children <19 years with virologically-confirmed SARS-CoV-2 infection at National Cheng Kung University Hospital from February 2022 to September 2022 during the first wave of Omicron BA.2 outbreak in Taiwan. Serum samples were collected one month after acute infection to measure anti-spike protein receptor binding domain antibody levels and surrogate virus neutralizing antibody (NAb) levels against wild type disease and variants. RESULTS: Of the 164 patients enrolled, most were under 5 years (65.2%) with a diagnosis of upper respiratory tract infection. Children under 6 months with maternal coronavirus disease 2019 (COVID-19) vaccination had higher levels of both anti-SARS-CoV-2 spike antibody (119.0 vs 27.4 U/ml, p < 0.05) and anti-wild type NAb (56.9% vs 27.6% inhibition, p = 0.001) than those without. Children aged 5-12 years with prior vaccination had higher anti-spike antibody, anti-wild type, and anti-Omicron BA.2 NAb levels than those without (all p < 0.05). In previously naïve children without maternal or self-vaccination, those 6 months to 2 years had the highest antibody levels. Multivariable linear regression analysis showed age was the only independent factor associated with antibody level. CONCLUSIONS: In our study, children aged 6 months to 2 years have the highest antibody responses to SARS-CoV-2 Omicron variant infection. Age and prior vaccination are the main factors influencing the immunogenicity of SARS-CoV-2 infection.

A brief overview of SARS-CoV-2 infection and its management strategies: a recent update.

The COVID-19 pandemic has become a global health crisis, inflicting substantial morbidity and mortality worldwide. A diverse range of symptoms, including fever, cough, dyspnea, and fatigue, characterizes COVID-19. A cytokine surge can exacerbate the disease's severity. This phenomenon involves an increased immune response, marked by the excessive release of inflammatory cytokines like IL-6, IL-8, TNF-α, and IFNγ, leading to tissue damage and organ dysfunction. Efforts to reduce the cytokine surge and its associated complications have garnered significant attention. Standardized management protocols have incorporated treatment strategies, with corticosteroids, chloroquine, and intravenous immunoglobulin taking the forefront. The recent therapeutic intervention has also assisted in novel strategies like repurposing existing medications and the utilization of in vitro drug screening methods to choose effective molecules against viral infections. Beyond acute management, the significance of comprehensive post-COVID-19 management strategies, like remedial measures including nutritional guidance, multidisciplinary care, and follow-up, has become increasingly evident. As the understanding of COVID-19 pathogenesis deepens, it is becoming increasingly evident that a tailored approach to therapy is imperative. This review focuses on effective treatment measures aimed at mitigating COVID-19 severity and highlights the significance of comprehensive COVID-19 management strategies that show promise in the battle against COVID-19.

Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice.

A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.

COVID-19 Infection Rates in Vaccinated and Unvaccinated Inmates: A Retrospective Cohort Study.

Background In 2023, breakthrough COVID-19 infections among vaccinated individuals and reinfections in previously infected people have become common. Additionally, infections are due to Omicron subvariants of the virus that behave differently from those at the onset of the pandemic. Understanding how vaccination and natural immunity influence COVID-19 infection rates is crucial, especially in high-density congregate settings such as prisons, to inform public health strategies. Methods We analyzed COVID-19 surveillance data from January to July 2023 across 33 California state prisons, primarily a male population of 96,201 individuals. We computed the incidence rate of new COVID-19 infections among COVID-bivalent-vaccinated and entirely unvaccinated groups (those not having received either the bivalent or monovalent vaccine). Results Our results indicate that the infection rates in the bivalent-vaccinated and entirely unvaccinated groups are 3.24% (95% confidence interval (CI): 3.06-3.42%) and 2.72% (CI: 2.50-2.94%), respectively, with an absolute risk difference of only 0.52%. When the data were filtered for those aged 50 and above, the infection rates were 4.07% (CI: 3.77-4.37%) and 3.1% (CI: 2.46-3.74%), respectively, revealing a mere 0.97% absolute risk difference. Among those aged 65 and above, the infection rates were 6.45% (CI: 5.74-7.16%) and 4.5% (CI: 2.57-6.43%), respectively, with an absolute risk difference of 1.95%. Conclusion We note low infection rates in both the vaccinated and unvaccinated groups, with a small absolute difference between the two across age groups. A combination of monovalent and bivalent vaccines and natural infections likely contributed to immunity and a lower level of infection rates compared to the height of the pandemic. It is possible that a degree of 'herd immunity' has been achieved. Yet, using p<0.05 as the threshold for statistical significance, the bivalent-vaccinated group had a slightly but statistically significantly higher infection rate than the unvaccinated group in the statewide category and the age ≥50 years category. However, in the older age category (≥65 years), there was no significant difference in infection rates between the two groups. This suggests that while the bivalent vaccine might offer protection against severe outcomes, it may not significantly reduce the risk of infections entirely. Further research is needed to understand the reasons behind these findings and to consider other factors, such as underlying health conditions. This study underscores the importance of developing vaccines that target residual COVID-19 infections, especially in regard to evolving COVID-19 variants.

[Epidemiological characteristics of reinfection of 2019-nCoV and influencing factors in Ningbo].

Objective: To analyze the epidemiological characteristics of reinfection of 2019-nCoV and influencing factors, and provide evidence for effective prevention and control of COVID-19 epidemic. Methods: The incidence data of COVID-19 in Ningbo from January 1, 2020 to November 30, 2022 were collected from the infectious disease surveillance system of Chinese information system for disease control and prevention. The incidence of reinfection of 2019-nCoV was investigated by using questionnaire. logistic regression analysis was used to analyze the influences of gender, age, time interval from the first infection, history of underlying disease, 2019-nCoV vaccination dose and disease severity on the reinfection. Results: A total of 897 previous 2019-nCoV infection cases were investigated, of which 115 experienced the reinfection of 2019-nCoV, the reinfection rate was 12.82%. The interval between the two infections M(Q1, Q3) was 1 052 (504, 1 056) days. Univariate analysis showed that age, 2019-nCoV vaccination dose, history of underlying disease, type of 2019-nCoV variant causing the first infection, time interval from the first infection and severity of the first infection were associated with the reinfection rate (all P<0.05). Multivariate logistic regression analysis showed that the risk for reinfection in age group 30- years was higher than that in age group ≥60 years (OR=2.10, 95%CI: 1.11-3.97). No reinfection occurred in those with time interval from the first infection of <6 months, and the risk for reinfection was higher in those with the time interval of ≥12 months than in those with the time interval of 6- months (OR=6.68, 95%CI: 3.46-12.90). The risk for reinfection was higher in the common or mild cases than in the asymptomatic cases (OR=2.64, 95%CI: 1.18-5.88; OR=2.79, 95%CI: 1.27-6.11). Conclusion: The time interval from the first infection was an important influencing factor for the reinfection of 2019-nCoV, and the probability of the reinfection within 6 months was low.

Early Omicron infection is associated with increased reinfection risk in older adults in long-term care and retirement facilities.

Background: Older adults are at increased risk of SARS-CoV-2 Omicron infection and severe disease, especially those in congregate living settings, despite high SARS-CoV-2 vaccine coverage. It is unclear whether hybrid immunity (combined vaccination and infection) after one Omicron infection provides increased protection against subsequent Omicron reinfection in older adults. Methods: Incidence of SARS-CoV-2 Omicron infection was examined in 750 vaccinated residents of long-term care and retirement homes in the observational cohort COVID in Long-Term Care Study in Ontario, Canada, within a 75-day period (July to September 2022). Risk of infection was assessed by Cox proportional hazards regression. Serum anti-spike and anti-RBD SARS-CoV-2 IgG and IgA antibodies, microneutralization titres, and spike-specific T cell memory responses, were examined in a subset of 318 residents within the preceding three months. Findings: 133 of 750 participants (17.7%) had a PCR-confirmed Omicron infection during the observation period. Increased infection risk was associated with prior Omicron infection (at 9-29 days: 47.67 [23.73-95.76]), and this was not attributed to days since fourth vaccination (1.00 [1.00-1.01]) or residence outbreaks (>6 compared to ≤6: 0.95 [0.37-2.41]). Instead, reinfected participants had lower serum neutralizing antibodies to ancestral and Omicron BA.1 SARS-CoV-2, and lower anti-RBD IgG and IgA antibodies, after their initial Omicron infection. Interpretation: Counterintuitively, SARS-CoV-2 Omicron infection was associated with increased risk of Omicron reinfection in residents of long-term care and retirement homes. Less robust humoral hybrid immune responses in older adults may contribute to risk of Omicron reinfection. Funding: COVID-19 Immunity Task Force of the Public Health Agency of Canada.

Re-Emerging COVID-19: Controversy of Its Zoonotic Origin, Risks of Severity of Reinfection and Management.

The re-emergence of COVID-19 has sparked controversy around its zoonotic origin, management strategies, risks posed by the virus, and the severity of reinfection. While it is widely accepted that the virus originated from animals, the exact source and transmission pathway remain unclear. This has led to debates regarding the regulation of wildlife markets and trade, as well as the need for more robust surveillance and monitoring systems. Hence, the objective of this review is to provide a brief overview of the disease's biology, preventative strategies, risk factors, degree of reinfection, and epidemiological profile. It offers a thorough examination of the disease's root cause, potential zoonotic transmission, and the most recent preventive measures, like vaccines. In terms of management, there is ongoing debate about the most effective strategies to mitigate the spread of the virus. While public health measures such as social distancing and mask-wearing have been widely implemented, there are differing opinions on the effectiveness of lockdowns and restrictions on public movement. The risks posed by COVID-19 are also a topic of debate, with some arguing that the virus is relatively low-risk for the majority of the population while others highlight the potential for severe illness, particularly among vulnerable populations such as the elderly or those with underlying health conditions. Finally, the possibility of reinfection has raised concerns about the longevity of immunity following infection or vaccination. While some studies have suggested that reinfection may be possible and potentially more severe, the overall risk remains uncertain and further research is needed to fully understand the implications of reinfection.

Primary exposure to SARS-CoV-2 via infection or vaccination determines mucosal antibody-dependent ACE2 binding inhibition.

BACKGROUND: Mucosal antibodies play a critical role in preventing SARS-CoV-2 (re)infections by blocking the interaction of receptor binding domain (RBD) with angiotensin converting enzyme 2 receptor (ACE2) on the cell surface. In this study, we investigated the difference between the mucosal antibody response after primary infection or vaccination. METHODS: We assessed longitudinal changes in the quantity and capacity of nasal antibodies to neutralize the interaction of RBD with the ACE2 receptor using Spike protein and RBD from ancestral SARS-CoV-2 (Wuhan-Hu-1), as well as RBD from the Delta and Omicron variant. RESULTS: Significantly higher mucosal IgA concentrations were detected post-infection compared to post-vaccination, while vaccination induced higher IgG concentrations. However, ACE2 inhibiting activity did not differ between the cohorts. When investigating if IgA or IgG drove the ACE2 inhibition, infection-induced binding inhibition was driven by both isotypes, while post-vaccination binding inhibition was mainly driven by IgG. CONCLUSIONS: Our study provides new insights into the relationship between antibody isotypes and neutralization by using a sensitive and high-throughput ACE2 binding inhibition assay. Key differences are highlighted between vaccination and infection at the mucosal level, showing that despite differences in the quantity of the response, post-infection and post-vaccination ACE2 binding inhibition capacity did not differ.