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1.
Frontiers in Pediatrics ; 10, 2022.
Article in English | Scopus | ID: covidwho-2199088

ABSTRACT

Objectives: Paediatric Multisystem Inflammatory Syndrome (PIMS-TS) is a rare life-threatening complication that typically occurs several weeks after SARS-CoV-2 infection in children and young people (CYP). We used national and regional-level data from the COVID-19 pandemic waves in England to develop a model to predict PIMS-TS cases. Methods: SARS-CoV-2 infections in CYP aged 0–15 years in England were estimated using the PHE-Cambridge real-time model. PIMS-TS cases were identified through the British Paediatric Surveillance Unit during (March-June 2020) and through Secondary Uses Services (SUS) from November 2020. A predictive model was developed to estimate PIMS-TS risk and lag times after SARS-CoV-2 infections. Results: During the Alpha wave, the model accurately predicted PIMS-TS cases (506 vs. 502 observed cases), with a median estimated risk of 0.038% (IQR, 0.037–0.041%) of paediatric SARS-CoV-2 infections. For the Delta wave, the median risk of PIMS-TS was significantly lower at 0.026% (IQR, 0.025–0.029%), with 212 observed PIMS-TS cases compared to 450 predicted by the model. Conclusions: The model accurately predicted national and regional PIMS-TS cases in CYP during the Alpha wave. PIMS-TS cases were 53% lower than predicted during the Delta wave. Further studies are needed to understand the mechanisms of the observed lower risk with the Delta variant. 2022 Shingleton, Burton, Williams, Finnie, Bennett, Birrell, Kenny, Watson- Koszel, Viner, Arditi, DeAngelis, Gent and Ladhani.

2.
Open Forum Infectious Diseases ; 9(Supplement 2):S746, 2022.
Article in English | EMBASE | ID: covidwho-2189906

ABSTRACT

Background. One of Singapore's national strategies for the COVID-19 pandemic was containment. Efforts included a fourteen-day quarantine of close contacts, were subjected to an entry and exit SARS-CoV-2 PCR test, the latter being done between 11-14 days post exposure. Additionally, symptomatic contacts were tested for SARS-CoV-2. We aim to determine the trend in COVID-19 incubation periods during three distinct pandemic waves corresponding to different SARS-CoV-2 variants. Incubation Period Incubation period of the prevalent SARS-CoV-2 variant in circulation Methods. This is an ecological study and information collected from the SingHealth COVID-19 Registry, a database of all inpatients admitted to any of the SingHealth hospitals. For patients under quarantine, the start date of the quarantine period was assumed to be the last date of exposure to the index case. Incubation period was determined by the duration between date of exposure and date of the first positive SARS-CoV-2 PCR test. The prevalent strain in circulation was identified from the Singapore database in the GISAID collection. Only variants of concern, as categorized by WHO, Alpha (23rd Jan 2020 - 1st Mar 2021), Delta (5th May 2021 - 31st Oct 2021) and Omicron (1st Jan 2022 - Present) were considered. For the Omicron variant, quarantine was discontinued, hence the last date of arrival from international travel was assumed to be the date of exposure. Results. From January 2020 to March 2022, there were 19,905 patients in the COVID-19 registry, of whom 11,235 were under quarantine and 8,612 had preceding international travel. Of the 11,235 patients under quarantine, 8,189 patients were infected when SARS-CoV-2 Alpha variant and 3,046 patients were infected when SARS-CoV-2 Delta variant were in circulation. Of the 8,612 patients with preceding travel, 6,503 patients were infected when SARS-CoV-2 Omicron variant was in circulation. The median incubation period for the Alpha variant was 11 days (IQR: 7-14 days) versus 3 days (IQR: 2-4 days) for the Delta variant versus 3 days (IQR: 0-5 days) for the Omicron variant. Pairwise comparisons between the variants were (p-value = < .001) Conclusion. The significant differences between incubation periods of the SARS-CoV-2 variants in circulation poses a challenge to containment efforts and has emphasize the importance of dynamic national strategies.

3.
Heliyon ; 9(1):e12704, 2023.
Article in English | ScienceDirect | ID: covidwho-2165332

ABSTRACT

Critically ill patients infected with SARS-CoV-2 display adaptive immunity, but it is unknown if they develop cross-reactivity to variants of concern (VOCs). We profiled cross-immunity against SARS-CoV-2 VOCs in naturally infected, non-vaccinated, critically ill COVID-19 patients. Wave-1 patients (wild-type infection) were similar in demographics to Wave-3 patients (wild-type/alpha infection), but Wave-3 patients had higher illness severity. Wave-1 patients developed increasing neutralizing antibodies to all variants, as did patients during Wave-3. Wave-3 patients, when compared to Wave-1, developed more robust antibody responses, particularly for wild-type, alpha, beta and delta variants. Within Wave-3, neutralizing antibodies were significantly less to beta and gamma VOCs, as compared to wild-type, alpha and delta. Patients previously diagnosed with cancer or chronic obstructive pulmonary disease had significantly fewer neutralizing antibodies. Naturally infected ICU patients developed adaptive responses to all VOCs, with greater responses in those patients more likely to be infected with the alpha variant, versus wild-type.

4.
New Zealand Medical Journal ; 135(1563):105-107, 2022.
Article in English | EMBASE | ID: covidwho-2111930

ABSTRACT

COVID-19 is a global pandemic with over 600 million cases worldwide and over 1.7 million cases in New Zealand to date. The most recent spread of Omicron variant saw widespread infection across the country that was unable to be controlled like the initial Alpha or Delta variants. There is limited information on ocular complications of COVID 19. In our case, there was a close relationship between time of COVID-19 infection and acute visual changes including ongoing scotomas (blind spots). This report explores a case of a young female with positive visual phenomena following COVID-19 infection, with the diagnosis of acute macula neuroretinopathy. Copyright © 2022 New Zealand Medical Association. All rights reserved.

5.
Swiss Medical Weekly ; 152:10S, 2022.
Article in English | EMBASE | ID: covidwho-2040808

ABSTRACT

Progress in the fight against COVID-19 is jeopardized by the emergence of SARS-CoV-2 variants that diminish or abolish the efficacy of vaccines and antiviral monoclonal antibodies. Novel immune therapies are therefore needed, that are broadly effective against present and future coronavirus threats. In principle, this could be achieved by focusing on portions of the virus that are both functionally relevant and averse to change. The Subdomain 1 (SD1) of SARS-CoV-2 Spike protein is adjacent to the RBD and its sequence is conserved across SARS-CoV-2 variants, except for substitutions A570D in Alpha (B.1.1.7) and T547K in Omicron BA.1 (B.1.1.529). In order to specifically identify and study human antibodies targeting SD1, we designed a flow cytometry-based strategy that combines negative selection of B cells binding to the Receptor Binding Domain (RBD) with positive selection of those binding to SD1-RBD fusion protein. Among the 15 produced human monoclonal antibodies, 6 are SD1-specific. 3 of them cross-react with SD1-RBDs corresponding to all six variants of concern and 2 are neutralizing SARS-CoV-2 pseudovirus. Antibody sd1.040 also neutralizes Delta, Omicron BA.1 and Omicron BA.2 pseudovirus, synergizes with an antibody to the RBD for neutralization, and protects mice when present in a bispecific antibody. Thus, naturally occurring antibodies can neutralize SARS-CoV-2 variants by binding to SD1 and can act synergistically against SARS-CoV-2 in preclinical models.

6.
Microorganisms ; 10(9)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2033059

ABSTRACT

Background: Despite a vaccination rate of 82.0% (n = 123/150), a SARS-CoV-2 (Alpha) outbreak with 64.7% (n = 97/150) confirmed infections occurred in a nursing home in Bavaria, Germany. Objective: the aim of this retrospective cohort study was to examine the effects of the Corminaty vaccine in a real-life outbreak situation and to obtain insights into the antibody response to both vaccination and breakthrough infection. Methods: the antibody status of 106 fully vaccinated individuals (54/106 breakthrough infections) and epidemiological data on all 150 residents and facility staff were evaluated. Results: SARS-CoV-2 infections (positive RT-qPCR) were detected in 56.9% (n = 70/123) of fully vaccinated, compared to 100% (n = 27/27) of incompletely or non-vaccinated individuals. The proportion of hospitalized and deceased was 4.1% (n = 5/123) among fully vaccinated and therewith lower compared to 18.5% (n = 5/27) hospitalized and 11.1% (n = 3/27) deceased among incompletely or non-vaccinated. Ct values were significantly lower in incompletely or non-vaccinated (p = 0.02). Neutralizing antibodies were detected in 99.1% (n = 105/106) of serum samples with significantly higher values (p < 0.001) being measured post-breakthrough infection. α-N-antibodies were detected in 37.7% of PCR positive but not in PCR negative individuals. Conclusion: Altogether, our data indicate that SARS-CoV-2 vaccination does provide protection against infection, severe disease progression and death with regards to the Alpha variant. Nonetheless, it also shows that infection and transmission are possible despite full vaccination. It further indicates that breakthrough infections can significantly enhance α-S- and neutralizing antibody responses, indicating a possible benefit from booster vaccinations.

7.
Journal of Public Health in Africa ; 13:28-29, 2022.
Article in English | EMBASE | ID: covidwho-2006909

ABSTRACT

Introduction/ Background: By July 202, the SARS-CoV-2 B.1.617.2 variant became the predominant circulating strain, isolated in more than 80%. This study compared indicators of morbidity, mortality and related hospitalization of COVID -19 in two periods: April to June 2021, (predominance of B.1.1.7 variant) and July to September 2021 (predominance of B.1.617.2 variant). Methods: National surveillance COVID-19 data concerning morbidity, mortality and related hospitalisation collected by the National Observatory of New and Emerging Diseases from April to September 2021 was analyzed. The following indicators were calculated: incidence rate (Crude mortality rate per 100,000 inhabitants was calculated), mortality rate (Crude mortality rate per 100,000 inhabitants was calculated), total hospitalisation rate and intesive care unit hospitalisation rate (hospitalizations per 100,000 persons). These indicators were compared during the period of of B.1.1.7 variant predominance and the period of B.1.617.2 variant predominance. Results: Based on 488054 confirmed cases of COVID-19 during April 1-September 30, 2021, incidence rate increased significantly during the delta predominance period from 1670,5 per 100000 persons to 2515,8 per 100000 persons (p<10-4). We noted a mortality rate of 18,2 per 100000 persons during period before delta variant predominance and 27,3 per 100000 persons during period of Delta variant predominance (p<10-4) whereas we did not find significantly higher rate of related hospitalizations and proportion of Intensive care unit admissions during this period. Impact: The results of this study highlighted the impact of the delta variant in the resurgence of COVID -19 in Tunisia during the second phase of the epidemic and the importance of rigorous prevention and control measures to reduce transmission, particularly ongoing vaccination program, and preparedness plans for hospital capacity. Conclusion: The results of this study that took place during the predominance period of B.1.617.2 variant in Tunisia showed significant increase in the incidence and mortality rate . This was probably related to low COVID-19 vaccination coverage, proved effective in reducing the incidence of infection and severe disease.

8.
Journal of Public Health in Africa ; 13:18-19, 2022.
Article in English | EMBASE | ID: covidwho-2006884

ABSTRACT

Introduction/ Background: There are 249,851,155 cases of COVID-19 globally as of 6th November 2021. SARS-CoV-2, accounts for 5,053,813 deaths worldwide. In Nigeria 212,511 cases and 2,902 deaths were recorded at the same time point. his report describes the first 596 SARS-CoV-2 genomes sequenced at the National Reference Laboratory (NRL) of NCDC. Methods: Samples sequenced include positive samples from baseline surveillance and in-bound travellers from several states in-country. Isolates were obtained from nasopharyngeal and oropharyngeal swabs and Library preparation was done using ARTIC NEB SARSCoV- 2 or the NEBNext FS Library preparation kits and sequencing on Oxford Nanopore MinION or Illumina MiSeq. Sequence analysis was done using ARTIC bioinformatics pipeline for MinION and Illumina Basespace DRAGEN COVID Lineage app for MiSeq sequence data respectively Results: Of the 596 sequences, 51.8% were Delta variants, 17.4% Eta variants, and 1.0% Alpha variants. The sequences represented mostly the second and third waves of the COVID-19 pandemic in Nigeria, mostly driven by the Eta and Delta variants respectively. The first wave was driven by D614G, L452R and Y1155F spike mutations, while the second wave was characterized by the Eta variant and the Third wave was driven by Delta variants. Impact: Genomic surveillance has been recognised as a major element for pandemic response and has become a necessity for public health. To monitor local transmission and importation of SARS-CoV-2 variants in Nigeria, whole genome sequencing of SARS-CoV-2 was carried out as part of the response to the ongoing COVID-19 pandemic. Conclusion: There were multiple introductions of SARS-CoV-2 variants into Nigeria despite all the measures in place at various points of entry. The importance of timely detection of circulating variants of SARS-CoV-2 for effective preparedness and response activities cannot be overemphasised. Sequencing helped inform rational public health advisory and response.

9.
Journal of Public Health in Africa ; 13:74-75, 2022.
Article in English | EMBASE | ID: covidwho-2006874

ABSTRACT

Introduction/ Background: May 2021, Kisumu County was affected by a COVID- 19 Delta variant outbreak. For non-resilient health systems with data channels based on paper, such outbreaks are a major challenge. A public-private partnership was initiated in Kisumu, Kenya. This partnership emphasizes digital mobile solutions that have a high potential for scalability. Methods: The partnership was between Kisumu County, KEMRI, PharmAccess, and healthcare facilities to roll out the implementation research. All those accessing tests as per the case definition of the MoH case definition were eligible for inclusion. We digitalized the Ministry of Health COVID-19 Case Identification Form, gathered data in healthcare facilities on digital tools, and shared aggregated results via a co-created (semi-) live dashboard to all relevant stakeholders. We performed descriptive analyses on the data. Additionally, semi-structured interviews with key stakeholders on the experiences of the project will provide qualitative insights. Results: As of November 2021, 32 healthcare facilities are connected to the dashboard, over 23,000 COVID-19 tests have been done with more than 2,800 positive cases: 52% Delta variant, 45% Alpha variant, and 4% Beta variant. All key staff are connected to the digital tools and actively use them for decision-making. Geomapping of cases has shown to be useful for disease surveillance, especially case-tracking. Proper training and technical support for the digital tools and dashboard, co-creation with all users, and having a strong roll-out plan are key for success. Impact: Public-private partnerships offer the possibility of scaling up diagnostic capacity and using technology to track the epidemic in real-time guiding efficient allocation of limited resources in an evidence-based manner, a good step towards epidemic preparedness. Better decision making and targeted action can be taken because of this digitalized systems approach. Conclusion: Digital platforms have a key role to play in epidemics tracking and preparedness. From these outcomes, the digital platform we developed during this study is being scaled up to 14 more counties of Kenya to be used to track the epidemic in a population of over 15 million people.

10.
Journal of Public Health in Africa ; 13:31, 2022.
Article in English | EMBASE | ID: covidwho-2006865

ABSTRACT

Introduction/ Background: Genomic surveillance of SARS-CoV-2 is crucial for monitoring the spread of the disease and guiding public health decisions but the capacity for SARSCoV- 2 sequencing in Africa remains low. This research aims to increase the genomic contribution from the Africa and gain insights of the SARS-CoV-2 infections in Ghana and Africa. Methods: We utilised samples from two sources;firstly, community surveillance undertaken using the Ghana Influenza Surveillance Network and secondly imported cases of SARS-CoV-2 detected in travellers. A total of 457 patients from Ghana, collected from 1st April 2020 to 31st August 2021, were sequenced using Oxford Nanopore Technology sequencing and the ARTIC tiled amplicon method. The sequence lineages were typed using Pangolin and the phylogenetic analysis was carried out using IQtree and TreeTime. Results: We detected three waves of SARS-CoV-2 infections in Ghana. The first wave of infection was mainly contained in the Greater Accra, later spreading to other regions in the second and third wave. B.1 and B.1.1. were the most prevalent lineages in wave one, while the B.1.1.7/alpha variant is responsible for the second wave. An investigation into the lineages detected in Ghana led us to discover that B.1.1.318 (which contains the E484K mutation shown to impact antibody recognition) has a high cumulative prevalence rate in a number of neighbouring West African countries, suggesting that there might be a regional circulation. Impact: The high-quality sequences produced from this study were submitted to the largest open-access SARSCoV- 2 sequence database, increasing the genomic contribution from Africa. By sequencing both community samples and imported cases in Ghana, the study revealed an insight into the SARS-CoV-2 epidemiology in Ghana and West Africa. Conclusion: This study not only informed us of the epidemiological characteristics of the SARS-CoV-2 outbreaks in Ghana, but also shed light on the epidemiological trends of neighbouring countries that may have less sequencing capacity, highlighting the important role of pathogen genomic sequencing in cross-border and regional disease surveillance.

11.
Journal of Public Health in Africa ; 13:16-17, 2022.
Article in English | EMBASE | ID: covidwho-2006863

ABSTRACT

Introduction/ Background: The COVID-19 pandemic has caused significant mortality and multiple variants of SARS-CoV-2 have been documented. Delta is the predominant variant around the world. Genomic surveillance can help country to overcome the pandemic by informing/prevention strategies. We aim to determine the dynamic of SARS-CoV-2 in Brazzaville, ROC, between December 2020-July 2021. Methods: Between December 2020 and July 2021, oropharyngeal swabs from symptomatic individuals (n=600) were screened for COVID-19 from different districts of Brazzaville, ROC. RNA was extracted from swabs using the QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany) and subjected to RealStar® SARS-CoV-2 real-time PCR targeting the S gene of SARS-CoV-2 (Altona Diagnostics, Hamburg, Germany) was performed in LightCycler® 480 Instrument II (Roche diagnostics, Mannheim, Germany). Found 317 individuals tested positive for COVID-19 and 182 samples that were having Ct <30 were subjected to Next- Generation Sequencing (NGS). Results: The characteristics of the study population from 171 genomes sequenced are as following, the median age of the subjects was 34 years (IQR: 25 to 47) and 67% (115/171) were males. The genomes were assigned to different pangolin lineages. A total of 15 variants were found circulating during the study period. For phylogenetic analysis, variants B.1.544 and B.1 were clustered into a single, and four sister lineages, B.1.214, B.1.214.1, B.214.2 and B.1.214.3, were clustered into a single clade. The B.1.214.2 was the predominant lineage. The VOC lineages B.1.1.7 and B.1.627.2 now have been finding in circulation in the ROC. Impact: The results from the present study indicate that many SARS-COV-2 variants are circulating in the ROC, and the detection of B.1.1.7 and B.1.617.2 variants for the first time in the country is the raised alarm to the health authorities. Conclusion: Many SARS-COV-2 variants are circulating in the ROC, and the detection of B.1.1.7 and B.1.617.2 variants for the first time in the country is the raised alarm to the health authorities. Thus, the spatiotemporal genomic surveillance of SARS-CoV-2 variants contributes to our understanding of viral dynamics.

12.
Pediatria Polska ; 97(2):71-80, 2022.
Article in English | EMBASE | ID: covidwho-1969655

ABSTRACT

Since late 2021, we have observed a significant increase in the proportion of children infected with SARS-CoV-2. The course of the disease in children is usually sparsely symptomatic or asymptomatic. However, the predominance of new virus variants makes children more likely to become symptomatically ill and require hospitalisation. This paper aims to update recommendations for managing a child with COVID-19 in out- and inpatient settings. Current options for prevention and antiviral treatment are discussed, noting the limited availability of therapy for children. In most children with COVID-19, the basis for treatment remains symptomatic and supportive therapy and measures to reduce SARS-CoV-2 infection spread.

13.
Asian Journal of Pharmaceutical and Clinical Research ; 15(7):6-16, 2022.
Article in English | EMBASE | ID: covidwho-1957630

ABSTRACT

The novel coronavirus and its emerging variants have continued to affect 50.4 million people worldwide, increasing the need for safe and effective vaccines. According to the World Health Organization guidelines, the efficacy of a vaccine should be at least 30% in all age groups and protect for a longer duration without any life-threatening adverse effects. At present, there are 319 vaccines in various stages of development, of which 16 are authorized for emergency use. Of these 16 vaccines, five vaccines are based on adenoviral vectors. This review is focused on understanding the safety and efficacy of the approved adenoviral vector vaccines for COVID-19, particularly highlighting the interim analysis of phase 3 clinical trials of AZD1222, Gam-Covid-Vac, Ad26.COV2.S, and AD5-nCOV vaccine. The efficacy of AZD1222, Gam-Covid-Vac, Ad26.COV2.S, and AD5-nCOV vaccine were found to be 70.4%, 95%, 66%, and 65.7%, respectively. Some serious adverse events such as deep vein thrombosis and thrombosis with thrombocytopenia syndrome were observed among AZD1222 and Ad26.COV2.S vaccinated individuals. Meanwhile, Gam-Covid-Vac and AD5-nCOV vaccines did not report any significant adverse events. In addition, we have also focused on the efficacy of these vaccines against SARS-CoV-2 variants such as B.1.1.7, B.1.351, and P.1. Although the efficacy of these approved vaccines against novel SARS-CoV-2 variants, pediatric and geriatric population and long-term efficacy remains uncertain, they are reasonably efficient in preventing mortality due to COVID-19.

14.
Journal of Pediatric Infectious Diseases ; 2022.
Article in English | EMBASE | ID: covidwho-1956444

ABSTRACT

Objective The research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly consists of adult patients, leaving its impact on children understudied. This study aims to investigate the correlations between viral load, clinical course, age, and Alpha variant (B.1.1.7) in children. Methods The study was conducted on children under the age of 18 years, who were admitted to Amasya University Sabuncuoglu Serefeddin Research and Training Hospital in Turkey between February and April 2021. ΔCt values, which were obtained by real-time polymerase chain reaction (PCR), were analyzed to estimate the viral loads of the patients. Alpha variant (B.1.1.7) positivity was determined by real-time PCR. Results There was no difference between estimated viral loads of different clinical courses (p > 0.05), or between asymptomatic and symptomatic patients (p > 0.05). Viral loads were found to decrease with increasing age (p = 0.002). Also, a higher rate of symptomatic disease was found in children under the age of 4 years (p < 0.05). Alpha variant (B.1.1.7) was not found to be associated with severe disease in children (p > 0.05). Conclusion Our results demonstrate higher viral loads and symptomatic disease in children under the age of 4 years. Alpha variant (B.1.1.7) was not found to be related to disease severity. There has not been a consensus on the vaccination of the pediatric population worldwide. More studies are needed to understand the viral kinetics of SARS-CoV-2 and its severity on children to build effective vaccination strategies in children as public health restrictions are eased.

15.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927906

ABSTRACT

Introduction: The rapid emergence of the SARS-CoV-2 Omicron variant that evades many monoclonal antibody therapies illustrates the need for anti-viral treatments with low susceptibility to evolutionary escape. The small molecule PAV-104, identified through a moderate-throughput screen involving cell-free protein synthesis, was recently shown to target a subset of host protein assembly machinery in a manner specific to viral assembly. This compound has minimal host toxicity, including once daily oral dosing in rats that achieves >200-fold of the 90% effective concentration (EC90) in blood. The chemotype shows broad activity against respiratory viral pathogens, including Orthomyxoviridae, Paramyxoviridae, Adenoviridae, Herpesviridae, and Picornaviridae, with low suceptability to evolutionary escape. We hypothesized that PAV-104 would be active against SARSCoV- 2 variants in human airway epithelial cells. Methods: Airway epithelial cells were differentiated from lung transplant tissue at air-liquid interface (ALI) for four weeks prior to challenge with Alpha (Pango lineage designation B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) SARS-CoV-2 variants. Viral replication was determined by quantitative PCR measurement of the SARS-CoV-2 nucleocapsid (N) gene. Dose-dependent virus inhibition and cytotoxicity of PAV-104 in the Calu-3 airway epithelial cell line was determined by PCR and MTT assay. Student's t-tests were used to evaluate statistical significance. Results: Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 showed comparable infectivity in human primary airway epithelial cells at ALI (N=3 donors), 47- to 550-fold higher than the parent (USA-WA1/2020) strain. PAV-104 reached 50% cytotoxicity in Calu-3 cells at 240 nM (Fig. 1A). Dose-response studies in Calu-3 cells demonstrated PAV-104 has a 6 nM 50% inhibitory concentration (IC50) for blocking replication of SARS-CoV-2 (USA-WA1/2020) (Fig.1B). In primary cells at ALI from 3 donors tested, there was >99% inhibition of infection by SARS-CoV-2 Gamma variant (N=3, MOI 0.1, P <0.01) with 100 nM PAV-104 (Fig. 1C). Addition of 100 nM PAV-104 2-hours post-infection, but not pre-infection, resulted in >99% suppression of viral replication, indicating a post-entry drug mechanism. PAV-104 bound a small subset of the known allosteric modulator 14-3-3, itself implicated in the interactome of SARS-CoV-2. Conclusion: PAV-104 is a host-targeted, orally bioavailable, pan-viral small molecule inhibitor with promising activity against SARS-CoV-2 variants in human primary airway epithelial cells. (Figure Presented).

16.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927889

ABSTRACT

SARS-CoV-2 is detectable in gastrointestinal secretions and has been associated with changes to the gut microbiome during severe infection. However, the majority of individuals with COVID-19 will develop mild infection and remain outpatient for the duration of infection, with a relative paucity of information on the gut microbiome of this group. Furthermore, symptoms can persist for 6 months or longer in some patients, which has presented additional health care burdens given incomplete understanding of the long term impact of SARS-CoV-2 infection. To fill these knowledge gaps, we longitudinally sampled the gut microbial community of subjects infected with SARS-CoV-2 and their household contacts living in San Francisco at varying lengths of time after infection. We report an association between COVID-19 and the gut microbiome. COVID-19 positive subjects exhibited greater variability in the gut microbiome over time. In concordance with this finding, COVID-19 positive gut microbial communities were more self-distinct when compared to COVID-19 negative individuals across sample collections. Population level social distancing practices varied during the time of sample collection in our cohort, and we found an association between population level movement and gut microbial community variation. To better define the impacts of SARS-Cov-2 independent of genetic and environmental variables, are utilizing five SARS-CoV-2 variants (Alpha, Beta, Washington, Delta, and Omicron) in separate mouse models to test the impact of SARSCoV- 2 on the gut microbiome in severe and mild infections to define the impacts of SARS-CoV-2 on gut microbial ecology independent of genetic and environmental variables. We conclude that even mild cases of COVID-19 result in months-long disruption in the gut microbial community, with additional perturbations linked to massive shifts in population level social distancing practices.

17.
Virologie ; 26(2):181-182, 2022.
Article in English | EMBASE | ID: covidwho-1913255

ABSTRACT

The binding of the SARS-CoV-2 spike to angiotensin-converting enzyme 2 (ACE2) promotes virus entry into the cell. Targeting this interaction represents a promising strategy to generate antivirals. By screening a phage-display library of biosynthetic protein sequences build on a rigid alpha-helicoidal HEAT-like scaffold (named αReps), we selected candidates recognizing the spike receptor binding domain (RBD). Two of them (F9 and C2) bind the RBD with affinities in the nM range, displaying neutralisation activity in vitro and recognizing distinct sites, F9 overlapping the ACE2 binding motif. The F9-C2 fusion protein and a trivalent -Rep form (C2-foldon) display 0.1 nM affinities and EC50 of 8- 18 nM for neutralization of SARS-CoV-2. In hamsters, F9-C2 instillation in the nasal cavity before or during infections effectively reduced the replication of a SARS-CoV-2 strain harbouring the D614G mutation in the nasal epithelium and pathogenicity. Furthermore, F9-C2 and/or C2- foldon effectively neutralized SARS-CoV-2 variants (including delta and omicron variants) with EC50 values ranging from 13 to 32 nM. With their high stability and their high potency against SARS-CoV-2 variants, αReps provide a promising tool for SARS-CoV-2 therapeutics to target the nasal cavity and mitigate virus dissemination in the proximal environment.

18.
Virologie ; 26(2):183, 2022.
Article in English | EMBASE | ID: covidwho-1913015

ABSTRACT

The SARS-CoV-2 genetic variants emergence doesn't spare the West African continent which has to face vaccination implementation delay. Beside classical qRT-PCR diagnostic testing, strengthening of sequencing capacity is the cornerstone for tracking and fighting the emergence of SARS-CoV-2 variants in real time. From March 12th, 2020 to July 16th, 2021, a panel of 136 full length genomes of SARS-CoV-2 mutants/variants present in human nasopharyngeal swab samples conserved in the Biobank of the Institut Pasteur De Guinée were sequenced using Illumina methodology. The Guinean sequences, originating from the general population, expatriates, and travelers, were distributed into 7 clades. During March- August 2020, the sequences were exclusively distributed into 2 clades, 20A and 20B, most originating from Europe. The 20D and 20C clades were furtively observed in October 2020 and February 2021 respectively. The SARS-CoV-2 variant of concern (VOC) 20I/B.1.1.7/Alpha was first identified in January 2021, increased in incidence up to March 2021, and then decreased from April to June 2021, corresponding to the dynamic described in Africa. The variant of interest (VOI) 21D/B.1.525/Eta originating from Nigeria circulated in February-May 2021. The 21A/B.1.617.2/Delta VOC was detected from May 2021 in Guinea, became dominant in July and persisted behind the present sampling over August and September 2021. A similar dynamic was globally observed in Africa resulting in a clear increase of lethality in the population. In contrast, other variants previously found in Africa, such as the 20H/B.1.351/Beta VOC and variants from the sublineage A (A.23.1 lineage from East Africa and the A.27 lineage), were not detected in this study. This overview of SARS-CoV-2 over 1.5 years in Guinea demonstrates that virus clades, VOC and VOI were progressively introduced, mostly by travelers through the Conakry Airport, before spreading through the country. The tracking of viral evolution by sequencing is a continuous task. Since November 2021, a new wave is related to the emergence of the VOC Omicron. Making countries autonomous in sequencing is a challenge in Africa, not only to fight Covid-19, but also to face the numerous other emerging zoonoses which circulate across the continent.

19.
Topics in Antiviral Medicine ; 30(1 SUPPL):302, 2022.
Article in English | EMBASE | ID: covidwho-1880962

ABSTRACT

Background: Spain has been one of the main epicenters for Covid-19 in Europe. The country is divided into 17 Autonomous Communities (AC) and two Autonomous Cities (ACi). This study aims to describe the epidemiology of SARS-CoV-2 in Spain across 3 study periods established from the beginning of the pandemic to the third epidemiologic wave, after analyzing genomes from all AC/ACi from February 2020 to March 2021. Methods: All 14,256 available partial and complete Spanish SARS-CoV-2 human genomic sequences deposited in the GISAID repository (https://www. gisaid.org/) until 21 March 2021 were downloaded in nucleotides and classified according to the AC/ACi and to the epidemiological week by collection date. The sequences were assigned to the genetic lineages according to Pangolin COVID-19 Lineage Assigner (https://pangolin.cog-uk.io/). Epiweeks were grouped into three main periods adjusted to the Spanish epidemic curve, as informed in the National Epidemiological Surveillance Network (RENAVE, https://cnecovid.isciii. es). The first period comprised from the beginning of the pandemic to the end of the first state of emergency (June 2020). The second period included the second epidemic wave (June-December 2020), and the third period covered the third wave (December 2020-March 2021). Only AC with at least 10 sequences for each period were described in the results. The two ACi were considered together. Results: Before the national lockdown (14 March 2020), 11 SARS-CoV-2 lineages were circulating in Spain with A.2 lineage predominance. During the lockdown the SARS-CoV-2 variant diversity increased, decreasing during the confinement. During this period, B.1 was the main circulating variant. During summer 2020, B.1.177 became the main circulating variant. The third wave was characterized by the introduction and fast spread of the B.1.1.7 or Alpha Variant of Concern. Conclusion: The reduction of diversity during the lockdown suggests this measure was effective in reducing the import of SARS-CoV-2 lineages. After the opening of borders within Europe during summer 2020, the variant diversity increased again and B.1.177 became the predominant variant, suggesting that despite the efforts to avoid SARS-CoV-2 spread between countries, travel restrictions during summer 2020 were not sufficient to control viral spreading. The variant distribution was heterogeneous among the AC and periods, reflecting different incidence and sequencing capacities across AC.

20.
Topics in Antiviral Medicine ; 30(1 SUPPL):8, 2022.
Article in English | EMBASE | ID: covidwho-1880637

ABSTRACT

Background: We recently showed that genuine SARS-CoV-2 hijacks endogenously expressed interferon-induced transmembrane proteins, especially IFITM2, as entry cofactors for efficient infection (Prelli Bozzo, Nchioua et al., Nat. Com., 2021). This came as a surprise, since IFITMs have been reported to inhibit entry of numerous enveloped viruses, including SARS-CoV-2. However, most data were obtained using IFITM overexpression and pseudoparticle infection assays. In our initial study, we used a SARS-CoV-2 strain isolated in the Netherlands in February 2020 (NL-02-2020). Since then several "variants of concern" (VOCs) have emerged that show increased transmission fitness and evasion of vaccine-induced immunity. These VOCs contain various alterations in their Spike (S) proteins that may alter their dependency on entry cofactors. Here, we examined whether SARS-CoV-2 VOCs, including the currently dominating Delta variant, still depend on IFITMs for efficient infection and replication. Methods: To determine the role of IFITMs in infection of SARS-CoV-2 VOCs, we silenced IFITM1, 2, or 3 expression in Calu-3 cells using siRNAs and infected them with NL-02-2020 as well VOCs B.1.1.7, B.1.351, P.1 and B.1.617.2, also referred to as Alpha, Beta, Gamma and Delta variants, respectively. Viral entry and replication were quantified by qRT-PCR as well as TCID50 analysis. In addition, we determined the inhibitory effect of an α-IFITM2 antibody on VOC infection in iPSC-derived human alveolar epithelial type 2 (iAT2) cells. Results: Depletion of IFITM2 reduced viral RNA production from 31-(B.1.1.7) to 754-fold (P.1). In comparison, KD of IFITM1 generally had little effect, while silencing of IFITM3 resulted in 2-to 20-fold reduction of viral RNA yields by the four VOCs. An antibody directed against the N-terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iAT2 cells. Conclusion: Endogenously expressed IFITM proteins (especially IFITM2) are important cofactors for entry and replication of SARS-CoV-2 VOCs, including the Delta variant that currently dominates the COVID-19 pandemic.

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