Exposure to airborne SARS-CoV-2 in four hospital wards and ICUs of Cyprus. A detailed study accounting for day-to-day operations and aerosol generating procedures.

In any infectious disease, understanding the modes of transmission is key to selecting effective public health measures. In the case of COVID-19 spread, the strictness of the imposed measures outlined the lack of understanding on how SARS-CoV-2 transmits, particularly via airborne pathways. With the aim to characterize the transmission dynamics of airborne SARS-CoV-2, 165 and 62 air and environmental samples, respectively, were collected in four COVID-19 wards and ICUs in Cyprus and analyzed by RT-PCR. An alternative method for SARS-CoV-2 detection in air that provides comparable results but is less cumbersome and time demanding, is also proposed. Considering that all clinics employed 14 regenerations per hour of full fresh air inside patient rooms, it was hypothesized that the viral levels and the frequency of positive samples would be minimum outside of the rooms. However, it is shown that leaving the door opened in patient rooms hinders the efficiency of the ventilation system applied, allowing the virus to escape. As a result, the highest observed viral levels (135 copies m-3) were observed in the corridor of a ward and the frequency of positive samples in the same area was comparable to that inside a two-bed cohort. SARS-CoV-2 in that corridor was found primarily to lie in the coarse mode, at sizes between 1.8 and 10 µm. Similar to previous studies, the frequency of positive samples and viral levels were the lowest inside intensive care units. However, if a patient with sufficient viral load (Ct-value 31) underwent aerosol generating procedures, positive samples with viral levels below 45 copies m-3 were acquired within a 2 m distance of the patient. Our results suggest that a robust ventilation system can prevent unnecessary exposure to SARS-CoV-2 but with limitations related to foot traffic or the operations taking place at the time.

Genomic Epidemiology of the SARS-CoV-2 Epidemic in Cyprus from November 2020 to October 2021: The Passage of Waves of Alpha and Delta Variants of Concern.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 resulted in the coronavirus disease 2019 (COVID-19) pandemic, which has had devastating repercussions for public health. Over the course of this pandemic, the virus has continuously been evolving, resulting in new, more infectious variants that have frequently led to surges of new SARS-CoV-2 infections. In the present study, we performed detailed genetic, phylogenetic, phylodynamic and phylogeographic analyses to examine the SARS-CoV-2 epidemic in Cyprus using 2352 SARS-CoV-2 sequences from infected individuals in Cyprus during November 2020 to October 2021. During this period, a total of 61 different lineages and sublineages were identified, with most falling into three groups: B.1.258 & sublineages, Alpha (B.1.1.7 & Q. sublineages), and Delta (B.1.617.2 & AY. sublineages), each encompassing a set of S gene mutations that primarily confer increased transmissibility as well as immune evasion. Specifically, these lineages were coupled with surges of new infections in Cyprus, resulting in the following: the second wave of SARS-CoV-2 infections in Cyprus, comprising B.1.258 & sublineages, during late autumn 2020/beginning of winter 2021; the third wave, comprising Alpha (B.1.1.7 & Q. sublineages), during spring 2021; and the fourth wave, comprising Delta (B.1.617.2 & AY. sublineages) during summer 2021. Additionally, it was identified that these lineages were primarily imported from and exported to the UK, Greece, and Sweden; many other migration links were also identified, including Switzerland, Denmark, Russia, and Germany. Taken together, the results of this study indicate that the SARS-CoV-2 epidemic in Cyprus was characterized by successive introduction of new lineages from a plethora of countries, resulting in the generation of waves of infection. Overall, this study highlights the importance of investigating the spatiotemporal evolution of the SARS-CoV-2 epidemic in the context of Cyprus, as well as the impact of protective measures placed to mitigate transmission of the virus, providing necessary information to safeguard public health.

Introduction, Spread and Impact of the SARS-CoV-2 Omicron Variants BA.1 and BA.2 in Cyprus.

The aim of this study was to investigate and obtain insights into the appearance, spread and impact of the Omicron variants and their sub-lineages in Cyprus by analyzing 611 high-coverage full-genome sequences for the period from November 2021 until April 2022. All viruses sequenced were identified to belong to either Delta (B.1.617.2) or Omicron (lineage BA.1 and BA.2, respectively), with a variety of different sub-lineages. A detailed analysis of the mutational profile is presented and discussed. The Omicron variant BA.1 was shortly followed by BA.2; despite emerging against a background of high vaccination (81% of adult population) and pre-existing natural immunity, they gave rise to the largest waves of infection, with daily numbers rising dramatically, highlighting their increased ability for immune evasion. Within a period of only five months, the percentage of the Cypriot population with a confirmed infection increased from ~15% of the total population to >57%. Despite unprecedented case numbers, a significant reduction in hospital burden and mortality was observed. Our findings highlight the role of the importation of new variants through travel and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures.

Characterization of IgG Antibody Response against SARS-CoV-2 (COVID-19) in the Cypriot Population.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has hit its second year and continues to damage lives and livelihoods across the globe. There continues to be a global effort to present serological data on SARS-CoV-2 antibodies in different individuals. As such, this study aimed to characterize the seroprevalence of SARS-CoV-2 antibodies in the Cypriot population for the first time since the pandemic started. Our results show that a majority of people infected with SARS-CoV-2 developed IgG antibodies against the virus, whether anti-NP, anti-S1RBD, or both, at least 20 days after their infection. Additionally, the percentage of people with at least one antibody against SARS-CoV-2 in the group of volunteers deemed SARS-CoV-2 negative via RT-PCR or who remain untested/undetermined (14.43%) is comparable to other reported percentages worldwide, ranging anywhere from 0.2% to 24%. We postulate that these percentages reflect the underreporting of true infections in the population, and also show the steady increase of herd immunity. Additionally, we showed a significantly marked decrease in anti-NP IgG antibodies in contrast to relatively stable levels of anti-S1RBD IgG antibodies in previously infected individuals across time.

In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches.

BACKGROUND: This study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence. METHODS: We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obtained between March 2020 and January 2021, as well as all data available from GISAID. We combine this with countries' regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of Cyprus-specific mutations are obtained by mutation tracking analysis. This entails calculating specific mutation frequencies within the Cypriot population and comparing these with their prevalence world-wide throughout the course of the pandemic. We further make use of linear regression models to extrapolate additional information that may be missed through standard statistical analysis. RESULTS: We report a single mutation found in the ORF1ab gene (nucleotide position 18,440) that appears to be significantly enriched within the Cypriot population. The amino acid change is denoted as S6059F, which maps to the SARS-CoV-2 NSP14 protein. We further analyse this mutation using regression models to investigate possible associations with increased deaths and cases per million. Moreover, protein structure prediction tools show that the mutation infers a conformational change to the protein that significantly alters its structure when compared to the reference protein. CONCLUSIONS: Investigating Cyprus-specific mutations for SARS-CoV-2 can lead to a better understanding of viral pathogenicity. Researching these mutations can generate potential links between viral-specific mutations and the unique genomics of the Cypriot population. This can not only lead to important findings from which to battle the pandemic on a national level, but also provide insights into viral virulence worldwide.

Molecular epidemiology of SARS-CoV-2 in Cyprus.

Whole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of COVID-19 were identified on March 9, 2020 and since then 33,567 confirmed cases and 230 deaths were documented. In this study, viral whole genome sequencing was performed on 133 SARS-CoV-2 positive samples collected between March 2020 and January 2021. Phylogenetic analysis was conducted to evaluate the genomic diversity of circulating SARS-CoV-2 lineages in Cyprus. 15 different lineages were identified that clustered into three groups associated with the spring, summer and autumn/winter wave of SARS-CoV-2 incidence in Cyprus, respectively. The majority of the Cypriot samples belonged to the B.1.258 lineage first detected in September that spread rapidly and largely dominated the autumn/winter wave with a peak prevalence of 86% during the months of November and December. The B.1.1.7 UK variant (VOC-202012/01) was identified for the first time at the end of December and spread rapidly reaching 37% prevalence within one month. Overall, we describe the changing pattern of circulating SARS-CoV-2 lineages in Cyprus since the beginning of the pandemic until the end of January 2021. These findings highlight the role of importation of new variants through travel towards the emergence of successive waves of incidence in Cyprus and demonstrate the importance of genomic surveillance in determining viral genetic diversity and the timely identification of new variants for guiding public health intervention measures.

Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unprecedented rally to reach a vaccine that can offer widespread immunization, it is equally important to reach effective prevention and treatment regimens for coronavirus disease 2019 (COVID-19). Contributing to this effort, we have curated and analyzed multi-source and multi-omics publicly available data from patients, cell lines and databases in order to fuel a multiplex computational drug repurposing approach. We devised a network-based integration of multi-omic data to prioritize the most important genes related to COVID-19 and subsequently re-rank the identified candidate drugs. Our approach resulted in a highly informed integrated drug shortlist by combining structural diversity filtering along with experts' curation and drug-target mapping on the depicted molecular pathways. In addition to the recently proposed drugs that are already generating promising results such as dexamethasone and remdesivir, our list includes inhibitors of Src tyrosine kinase (bosutinib, dasatinib, cytarabine and saracatinib), which appear to be involved in multiple COVID-19 pathophysiological mechanisms. In addition, we highlight specific immunomodulators and anti-inflammatory drugs like dactolisib and methotrexate and inhibitors of histone deacetylase like hydroquinone and vorinostat with potential beneficial effects in their mechanisms of action. Overall, this multiplex drug repurposing approach, developed and utilized herein specifically for SARS-CoV-2, can offer a rapid mapping and drug prioritization against any pathogen-related disease.