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The AIDS and COVID-19 pandemics demonstrated that nations at similar economic development levels varied widely in their capacity to protect the health of their residents. For AIDS, Britain and Australia brought gay representatives into official counsels and adopted harm reduction far more rapidly than the United States or Spain, and East African countries responded more effectively than South Africa or the Democratic Republic of the Congo. National responses to COVID-19 varied widely, with New Zealand, China, and Vietnam more effective than Italy, Brazil, or the United States. Further, as phylogenetic research has demonstrated, these pandemics spread from one country to another, with those that responded poorly acting as sources for mutations and potentially sources of transmission to countries with more effective responses. Many observers expressed surprise at the poor responses of the United States to COVID-19, but in retrospect the cutbacks in public health funding at state and national levels made it clear that this was a predictable weakness even in addition to the political vacillations that crippled the US and Brazilian responses. In a time of global sociopolitical and climate instability, it is important to measure and conduct research into spatial and time variations in 1. public health and medical funding, 2. social influence networks, social cohesion and trust, and stigmatization, 3. income inequality, 4. social conflict, and 5. other factors that affect responsiveness to pandemics.

Background: HIV DNA mirrors the number of infected cells and the size of the HIV viral reservoir. The aim of this study was to evaluate the effect of pre-cART HIV DNA levels as a predictive marker of immune reconstitution and on the post-cART CD4 counts trends., Methods: HIV DNA was isolated from PBMCs and quantified by real-time PCR. Immune reconstitution was assessed up to four years. Piecewise-linear mixed models were used to describe CD4 count changes., Results: 148 people living with HIV (PLWH) were included. The highest rate of immune reconstitution was observed during the first trimester. There was a trend showing that high HIV RNA level resulted in greater increase in CD4 count, especially during the first trimester of cART (difference above vs. below median 15.1 cells/μL/month; 95% CI -1.4-31.5; p = 0.073). Likewise, higher HIV DNA level would predict greater CD4 increases, especially after the first trimester (difference above vs. below median 1.2 cells/μL/month; 95% CI -0.1-2.6; p = 0.071). Higher DNA and RNA levels combined were significantly associated with greater CD4 increase past the first trimester (difference high/high vs. low/low 2.1 cells/μL/month; 95% CI 0.3-4.0; p = 0.024). In multivariable analysis, lower baseline CD4 counts predicted a greater CD4 rise., Conclusions: In successfully treated PLWH, pre-cART HIV DNA and HIV RNA levels are predictors of immune reconstitution.

Our study aims to describe the global distribution and dispersal patterns of the SARS-CoV-2 Omicron subvariants. Genomic surveillance data were extracted from the CoV-Spectrum platform, searching for BA.1*, BA.2*, BA.3*, BA.4*, and BA.5* variants by geographic region. BA.1* increased in November 2021 in South Africa, with a similar increase across all continents in early December 2021. BA.1* did not reach 100% dominance in all continents. The spread of BA.2*, first described in South Africa, differed greatly by geographic region, in contrast to BA.1*, which followed a similar global expansion, firstly occurring in Asia and subsequently in Africa, Europe, Oceania, and North and South America. BA.4* and BA.5* followed a different pattern, where BA.4* reached high proportions (maximum 60%) only in Africa. BA.5* is currently, by Mid-August 2022, the dominant strain, reaching almost 100% across Europe, which is the first continent aside from Africa to show increasing proportions, and Asia, the Americas, and Oceania are following. The emergence of new variants depends mostly on their selective advantage, translated as enhanced transmissibility and ability to invade people with existing immunity. Describing these patterns is useful for a better understanding of the epidemiology of the VOCs' transmission and for generating hypotheses about the future of emerging variants.

Early identification of COVID-19 cases has been vital for reducing transmission and enabling treatment. In Greece, in autumn 2021 when Delta was the predominant circulating variant, unvaccinated citizens had to be tested before attending activities, and self-testing was required twice a week for students (5−17 years). Here, we describe the time of diagnosis by age group and possible exposure to assess testing strategies (September to November 2021). Information on the presence of symptoms at the time of diagnosis was available for 69,298 cases; 24,855 (36%) were asymptomatic or tested the same day as onset (early diagnosis), 21,310 (31%) reported testing one day after, and 23,133 (33%) did so two or more days after the onset of symptoms. The median lag was 2 days (1−14). Early diagnosis significantly differed among age groups (p-value < 0.001) and was higher among children. For every one-year increase of age, the odds of an early diagnosis were reduced by 1%. Cases exposed during training activities or in settings such as accommodation centers and hospitals were more frequently diagnosed early. The percentage of persons having a positive self-test before a rapid test/PCR diagnosis ranged from 7% in the age group of 60 years and above to 86% in the age group of 5−17 years. The provision of self-tests in schools and increased testing in closed settings led to an earlier diagnosis and probably to a decreased transmission of the virus in the period during which Delta was the predominant variant in Greece. However, more effort is needed for early diagnosis of adults in the community, especially after the onset of symptoms.

Vaccine hesitancy is a major barrier to achieving large-scale COVID-19 vaccination. We report trends in vaccination intention and associated determinants from surveys in the adult general population in Greece. Four cross-sectional phone surveys were conducted in November 2020 and February, April and May 2021 on nationally representative samples of adults in Greece. Multinomial logistic regression was used on the combined data of the surveys to evaluate independent predictors of vaccination unwillingness/uncertainty. Vaccination intention increased from 67.6% in November 2020 to 84.8% in May 2021. Individuals aged 65 years or older were more willing to be vaccinated (May 2021: 92.9% vs. 79.5% in 18−39 years, p < 0.001) but between age-groups differences decreased over time. Vaccination intention increased substantially in both men and women, though earlier among men, and was higher in individuals with prograduate education (May 2021: 91.3% vs. 84.0% up to junior high). From multivariable analysis, unwillingness and/or uncertainty to be vaccinated was associated with younger age, female gender (in particular in the April 2021 survey), lower educational level and living with a child ≤12 years old. Among those with vaccine hesitancy, concerns about vaccine effectiveness declined over time (21.6% in November 2020 vs. 9.6% in May 2021, p = 0.014) and were reported more often by men; safety concerns remained stable over time (66.3% in November 2020 vs. 62.1% in May 2021, p = 0.658) and were reported more often by women. In conclusion, vaccination intention increased substantially over time. Tailored communication is needed to address vaccine hesitancy and concerns regarding vaccine safety.

Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARS-CoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30-250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE.

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It targets human hepatocytes and can lead to chronic HBV infection either after acute infection via horizontal transmission usually during infancy or childhood or via maternal-fetal transmission. HBV has been found in ~85% of HBV-related Hepatocellular Carcinomas (HCC), and it can integrate the whole or part of its genome into the host genomic DNA. The molecular mechanisms involved in the HBV DNA integration is not yet clear; thus, multiple models have been described with respect to either the relaxed-circular DNA (rcDNA) or the double-stranded linear DNA (dslDNA) of HBV. Various genes have been found to be affected by HBV DNA integration, including cell-proliferation-related genes, oncogenes and long non-coding RNA genes (lincRNAs). The present review summarizes the advances in the research of HBV DNA integration, focusing on the evolutionary and molecular side of the integration events along with the arising clinical aspects in the light of WHO's commitment to eliminate HBV and viral hepatitis by 2030.

Some emergent SARS-CoV-2 variants raise concerns due to their altered biological properties. For both B.1.1.7 and B.1351 variants, named as variants of concern (VOC), increased transmissibility was reported, whereas B.1.351 was more resistant to multiple monoclonal antibodies (mAbs), as well as convalescent and vaccination sera. To test this hypothesis, we examined the proportion of VOC over time across different geographic areas where the two VOC, B.1.1.7 and B.1.351, co-circulate. Our comparative analysis was based on the number of SARS-CoV-2 sequences on GISAID database. We report that B.1.1.7 dominates over B.1.351 in geographic areas where both variants co-circulate and the B.1.1.7 was the first variant introduced in the population. The only areas where B.1.351 was detected at higher proportion were South Africa and Mayotte in Africa, where this strain was associated with increased community transmission before the detection of B.1.1.7. The dominance of B.1.1.7 over B.1.351 could be important since B.1.351 was more resistant to certain mAbs, as well as heterologous convalescent and vaccination sera, thus suggesting that it may be transmitted more effectively in people with pre-existing immunity to other VOC. This scenario would lessen the effectiveness of vaccine and urge the need to update them with new strains.

Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS-CoV-2 spread., Methods: We used whole genome SARS-CoV-2 sequences derived from ten European regions belonging to eight countries to perform phylogenetic and phylodynamic analysis. We developed dedicated bioinformatics pipelines to identify regional MTCs and to assess demographic factors potentially associated with their formation., Results: The total number and the scale of MTCs varied from small household clusters identified in all regions, to a super-spreading event found in Uusimaa-FI. Specific age groups were more likely to belong to MTCs in different regions. The clustered sequences referring to the age groups 50-100 years old (y.o.) were increased in all regions two weeks after the establishment of the lockdown, while those referring to the age group 0-19 y.o. decreased only in those regions where schools' closure was combined with a lockdown., Conclusions: The spatiotemporal profiling of the SARS-CoV-2 MTCs can be a useful tool to monitor the effectiveness of the interventions and to reveal cryptic transmissions that have not been identified through contact tracing.

Between June and November 2020, we assessed plasma antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein in 4996 participants (aged 18-82 years, 34.5% men) from the National and Kapodistrian University of Athens. The weighted overall prevalence was 1.6% and monthly prevalence correlated with viral RNA-confirmed SARS-CoV-2 infections in Greece, in the same period. Notably, 49% of seropositive cases reported no history of SARS-CoV-2 infection-related clinical symptoms and 33% were unsuspected of their previous infection. Additionally, levels of anti-SARS-CoV-2 antibodies against the spike-protein receptor-binding domain were similar between symptomatic and asymptomatic individuals, irrespective of age and gender. Using Food and Drug Administration Emergency Use Authorization-approved assays, these results support the need for such studies on pandemic evaluation and highlight the development of robust humoral immune responses even among asymptomatic individuals. The high percentage of unsuspected/asymptomatic active cases, which may contribute to community transmission for more days than that of cases who are aware and self-isolate, underscores the necessity of measures across the population for the efficient control of the pandemic.

Due to early implementation of public health measures, Greece had low number of SARS-CoV-2 infections and COVID-19 severe incidents in hospitalized patients. The National and Kapodistrian University of Athens (ΝΚUA), especially its health-care/medical personnel, has been actively involved in the first line of state responses to COVID-19. To estimate the prevalence of antibodies (Igs) against SARS-CoV-2 among NKUA members, we designed a five consecutive monthly serosurvey among randomly selected NKUA consenting volunteers. Here, we present the results from the first 2500 plasma samples collected during June-July 2020. Twenty-five donors were tested positive for anti-SARS-CoV-2 Igs; thus, the overall seroprevalence was 1.00%. The weighted overall seroprevalence was 0.93% (95% CI: 0.27, 2.09) and varied between males [1.05% (95% CI: 0.18, 2.92)] and females [0.84% (95% CI: 0.13, 2.49)], age-groups and different categories (higher in participants from the School of Health Sciences and in scientific affiliates/faculty members/laboratory assistants), but no statistical differences were detected. Although focused on the specific population of NKUA members, our study shows that the prevalence of anti-SARS-CoV-2 Igs for the period June-July 2020 remained low and provides knowledge of public health importance for the NKUA members. Given that approximately one in three infections was asymptomatic, continuous monitoring of the progression of the pandemic by assessing Ig seroprevalence is needed.

Background: The spread of SARS-CoV-2 generated an unprecedented global public health crisis. Soon after Asia, Europe was seriously affected. Many countries, including Romania, adopted lockdown measures to limit the outbreak., Aim: We performed a molecular epidemiology analysis of SARS-CoV-2 viral strains circulating in Romania during the first two months of the epidemic in order to detect mutation profiles and phylogenetic relatedness., Methods: Respiratory samples were directly used for shotgun sequencing., Results: All Romanian sequences belonged to lineage B, with a different subtype distribution between northern and southern regions (subtype B.1.5 and B.1.1). Phylogenetic analysis suggested that the Romanian epidemic started with multiple introduction events from other European countries followed by local transmission. Phylogenetic links between northern Romania and Spain, Austria, Scotland and Russia were observed, as well as between southern Romania and Switzerland, Italy, France and Turkey. One viral strain presented a previously unreported mutation in the Nsp2 gene, namely K489E. Epidemiologically-defined clusters displayed specific mutations, suggesting molecular signatures for strains coming from areas that were isolated during the lockdown., Conclusions: Romanian epidemic was initiated by multiple introductions from European countries followed by local transmissions. Different subtype distribution between northern and southern Romania was observed after two months of the pandemic.