Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicentre, Randomised, Controlled Trial.

RATIONALE: Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in COVID-19-related Acute Respiratory Distress Syndrome (ARDS). OBJECTIVES: We investigated safety and efficacy of ORBCEL-C (CD362-enriched, umbilical cord-derived MSCs) in COVID-related ARDS. METHODS: This multicentre, randomised, double-blind, allocation concealed, placebo-controlled trial (NCT03042143) randomised patients with moderate-to-severe COVID-related ARDS to receive ORBCEL-C (400million cells) or placebo (Plasma-Lyte148). MEASUREMENTS: The primary safety and efficacy outcomes were incidence of serious adverse events and oxygenation index at day 7 respectively. Secondary outcomes included respiratory compliance, driving pressure, PaO2/FiO2 ratio and SOFA score. Clinical outcomes relating to duration of ventilation, length of intensive care unit and hospital stays, and mortality were collected. Long-term follow up included diagnosis of interstitial lung disease at 1 year, and significant medical events and mortality at 2 years. Transcriptomic analysis was performed on whole blood at day 0, 4 and 7. MAIN RESULTS: 60 participants were recruited (final analysis n=30 ORBCEL-C, n=29 placebo: 1 in placebo group withdrew consent). 6 serious adverse events occurred in the ORBCEL-C and 3 in the placebo group, RR 2.9(0.6-13.2)p=0.25. Day 7 mean[SD] oxygenation index did not differ (ORBCEL-C 98.357.2], placebo 96.667.3). There were no differences in secondary surrogate outcomes, nor mortality at day 28, day 90, 1 or 2 years. There was no difference in prevalence of interstitial lung disease at 1year nor significant medical events up to 2 years. ORBCEL-C modulated the peripheral blood transcriptome. CONCLUSION: ORBCEL-C MSCs were safe in moderate-to-severe COVID-related ARDS, but did not improve surrogates of pulmonary organ dysfunction. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03042143. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Designing school reopening in the COVID-19 pre-vaccination period in Bogotá, Colombia: A modeling study

The COVID-19 pandemic has affected millions of people around the world. In Colombia, 1.65 million cases and 43,495 deaths were reported in 2020. Schools were closed in many places around the world to slow down the spread of SARS-CoV-2. In Bogotá, Colombia, most of the public schools were closed from March 2020 until the end of the year. School closures can exacerbate poverty, particularly in low- and middle-income countries. To reconcile these two priorities in health and fighting poverty, we estimated the impact of school reopening for in-person instruction in 2021. We used an agent-based model of SARS-CoV-2 transmission calibrated to the daily number of deaths. The model includes schools that represent private and public schools in terms of age, enrollment, location, and size. We simulated school reopening at different capacities, assuming a high level of face-mask use, and evaluated the impact on the number of deaths in the city. We also evaluated the impact of reopening schools based on grade and multidimensional poverty index. We found that school at 35% capacity, assuming face-mask adherence at 75% in>8 years of age, had a small impact on the number of deaths reported in the city during a third wave. The increase in deaths was smallest when only pre-kinder was opened, and largest when secondary school was opened. At larger capacities, the impact on the number of deaths of opening pre-kinder was below 10%. In contrast, reopening other grades above 50% capacity substantially increased the number of deaths. Reopening schools based on their multidimensional poverty index resulted in a similar impact, irrespective of the level of poverty of the schools that were reopened. The impact of schools reopening was lower for pre-kinder grades and the magnitude of additional deaths associated with school reopening can be minimized by adjusting capacity in older grades.

Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.

MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease. The MDA5/IFN pathway would play a critical role in the response to SARS-CoV-2 infection mediating the extent and severity of COVID-19. Here, we genotyped a cohort of 477 patients with critical ICU COVID-19 (109 death) for three IFIH1 functional variants: rs1990760 (p.Ala946Thr), rs35337543 (splicing variant, intron 8 + 1G > C), and rs35744605 (p.Glu627Stop). The main finding of our study was a significant increased frequency of rs1990760 C-carriers in early-onset patients (< 65 years) (p = 0.01; OR = 1.64, 95%CI = 1.18-2.43). This variant was also increased in critical vs. no-ICU patients and in critical vs. asymptomatic controls. The rs35744605 C variant was associated with increased blood IL6 levels at ICU admission. The rare rs35337543 splicing variant showed a trend toward protection from early-onset critical COVID-19. In conclusion, IFIH1 variants associated with reduced gene expression and lower IFN response might contribute to develop critical COVID-19 with an age-dependent effect.

Transcriptomic clustering of critically ill COVID-19 patients.

Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation has shown a mortality benefit.In a cohort of 56 critically-ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission in an Intensive Care Unit (ICU) and clustered using an unsupervised algorithm. Differences in gene expression, circulating microRNAs (c-miRNA) and clinical data between clusters were assessed, and circulating cell populations estimated from sequencing data. A transcriptomic signature was defined and applied to an external cohort to validate the findings.We identified two transcriptomic clusters characterised by expression of either interferon-related or immune checkpoint genes, respectively. Steroids have cluster-specific effects, decreasing lymphocyte activation in the former but promoting B-cell activation in the latter. These profiles have different ICU outcome, in spite of no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in two external validation cohorts (with 50 and 60 patients), yielding similar results.These results reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19, aimed to ultimately personalise their therapies.

Dolutegravir Plus 3TC in Virologically Suppressed PLWHIV: Immunological Outcomes in a Multicenter Retrospective Cohort in Spain during the COVID-19 Pandemic.

Dolutegravir (DTG) based dual therapies for treating PLWHIV are a standard of care nowadays. Switching to DTG and lamivudine (3TC) safety and efficacy were proven in TANGO randomized clinical trial. This multicenter retrospective study included 1032 HIV virologically suppressed patients switching to DTG+3TC from 13 Spanish hospitals. DTG+3TC provided high rates of undetectable viral load over 96%, corresponding to 96.6% (889/921) at 24 weeks, 97.5% (743/763) at 48 weeks, and 98.3% (417/425) at 96 weeks. No significant differences are evident when comparing the total population according to sex, presence of comorbidity, or presence of AIDS. The analysis for paired data showed an increase in CD4+ cell count. A statistically significant increase in CD4+ lymphocyte count was found in those without comorbidities in the three-time series analyzed [average increase at 24 weeks: 48.7 (SD: 215.3) vs. 25.8 (SD: 215.5), p-value = 0.050; a mean increase at 48 weeks: 75.1 (SD: 232.9) vs. 42.3 (SD: 255.6), p-value = 0.003; a mean increase at 96 weeks: 120.1 (SD: 205.0) vs. 63.8 (SD:275.3), p-value = 0.003]. In conclusion, our cohort demonstrates that DTG+3TC is an effective treatment strategy for virologically-suppressed PLWHIV independent of age, sex, and HIV stage, as well as a safe and durable strategy.

Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients.

The NF-κB signaling pathway is a key regulator of inflammation in the response to SARS-CoV-2 infection. This pathway has been implicated in the hyperinflammatory state that characterizes the severe forms of COVID-19. The genetic variation of the NF-κB components might thus explain the predisposition to critical outcomes of this viral disease. We aimed to study the role of the common NFKB1 rs28362491, NFKBIA rs696 and NFKBIZ rs3217713 variants in the risk of developing severe COVID-19 with ICU admission. A total of 470 Spanish patients requiring respiratory support in the ICU were studied (99 deceased and 371 survivors). Compared to healthy population controls (N = 300), the NFKBIA rs696 GG genotype was increased in the patients (p = 0.045; OR = 1.37). The NFKBIZ rs3217713 insertion homozygosis was associated with a significant risk of death (p = 0.02; OR = 1.76) and was also related to increased D-dimer values (p = 0.0078, OR = 1.96). This gene has been implicated in sepsis in mice and rats. Moreover, we found a trend toward lower expression of the NFKBIZ transcript in total blood from II patients. In conclusion, variants in the NF-κB genes might be associated with the risk of developing severe COVID-19, with a significant effect of the NFKBIZ gene on mortality. Our results were based on a limited number of patients and require validation in larger cohorts from other populations.

Duelo y atención domiciliaria para pacientes al final de la vida durante la pandemia por COVID-19 en Colombia.Análisis desde la perspectiva de familiares Grief and palliative home-care services for patients at the end of life during the COVID-19 pandemic in Colombia. Analysis from the relatives´ perspective

Introducción: El cuidado al final de la vida es una de las experiencias más cruciales tanto para el paciente como para sus seres queridos. Sin embargo, a raíz de los cambios generados por la pandemia de COVID 19, el proceso de final de vida ha sufrido cambios a nivel familiar, social y sanitario. A su vez, esto ha alterado la percepción y desarrollo del duelo de familiares de pacientes que fallecieron durante la pandemia, independiente de la causa de muerte. De forma que el presente estudio tiene el objetivo de analizar las percepciones y algunos aspectos del proceso de duelo de los familiares de pacientes fallecidos durante la pandemia. Métodos: Se aplicó la versión adaptada del cuestionario internacional Care Of the Dying Evaluation (iCODE), a los familiares de personas fallecidas durante la pandemia en dos momentos diferentes tras la muerte de su familiar. Resultados: Se encuestaron 239 familiares, de los cuales 112 realizaron el cuestionario de seguimiento. Los pacientes fallecieron mayoritariamente en su domicilio y su familia estuvo altamente involucrada en su cuidado. La atención médica fue evaluada como adecuada y el síntoma que se percibió con mayor frecuencia fue el dolor. El 87% de los encuestados participaron en ritos fúnebres, y el 42% los calificó como muy sobrios. En cuanto al duelo predomina la subescala de crecimiento personal, sin embargo, en los aspectos negativos predomina la sensación de presión en el pecho y llanto frecuente. Conclusiones: El fin de vida durante la pandemia de pacientes de atención domiciliaria fue percibido como adecuado, permitiendo el acompañamiento por parte de la familia y control de los síntomas. El proceso de duelo no evidencia complicaciones. Es importante la formación de los profesionales de la salud en estos aspectos fundamentales de la atención y el cuidado de los pacientes.

Common mitochondrial haplogroups as modifiers of the onset-age for critical COVID-19.

As a key regulator of innate immunity, mitochondrial function is essential to maintain antiviral activities. Common mitochondrial DNA variants (haplogroups) have been associated with different physiological capacities and the nrisk of developing several diseases. Haplogroup H was associated with increased survival among sepsis patients, and lower risk of progression toward AIDS in HIV infected and lower manifestation of severe manifestation of herpex virus disease. We studied 316 Spanish with critical COVID-19, and found that the 7028C (haplogroup H) was protective among patients with early-onset disease (≤65 vs > 65 years, p = 0.01), while the ancestral 16223T was a risk factor for early-onset critical COVID-19 (OR = 3.36, 95 %CI = 1.49-7.54). Our work suggested that common mitochondrial variants may serve as predictors of COVID-19 severity. Additional studies to confirm this effect from other populations are of special interest.

Designing school reopening in the COVID-19 pre-vaccination period in Bogotá, Colombia: A modeling study.

The COVID-19 pandemic has affected millions of people around the world. In Colombia, 1.65 million cases and 43,495 deaths were reported in 2020. Schools were closed in many places around the world to slow down the spread of SARS-CoV-2. In Bogotá, Colombia, most of the public schools were closed from March 2020 until the end of the year. School closures can exacerbate poverty, particularly in low- and middle-income countries. To reconcile these two priorities in health and fighting poverty, we estimated the impact of school reopening for in-person instruction in 2021. We used an agent-based model of SARS-CoV-2 transmission calibrated to the daily number of deaths. The model includes schools that represent private and public schools in terms of age, enrollment, location, and size. We simulated school reopening at different capacities, assuming a high level of face-mask use, and evaluated the impact on the number of deaths in the city. We also evaluated the impact of reopening schools based on grade and multidimensional poverty index. We found that school at 35% capacity, assuming face-mask adherence at 75% in>8 years of age, had a small impact on the number of deaths reported in the city during a third wave. The increase in deaths was smallest when only pre-kinder was opened, and largest when secondary school was opened. At larger capacities, the impact on the number of deaths of opening pre-kinder was below 10%. In contrast, reopening other grades above 50% capacity substantially increased the number of deaths. Reopening schools based on their multidimensional poverty index resulted in a similar impact, irrespective of the level of poverty of the schools that were reopened. The impact of schools reopening was lower for pre-kinder grades and the magnitude of additional deaths associated with school reopening can be minimized by adjusting capacity in older grades.

IGHG3 hinge length variation was associated with the risk of critical disease and death in a Spanish COVID-19 cohort.

IgG3 would play an important role in the immune adaptive response against SARS-CoV-2, and low plasma levels might increase the risk of COVID-19 severity and mortality. The IgG3 hinge sequence has a variable repeat of a 15 amino acid exon with common 4-repeats (M) and 3-repeats (S). This length IGHG3 polymorphism might affect the IgG3 effector functions. The short hinge length would reduce the IgG3 flexibility and impairs the neutralization and phagocytosis compared to larger length-isoforms. We genotyped the IGHG3 length polymorphism in patients with critical COVID-19 (N = 516; 107 death) and 152 moderate-severe but no-critical cases. Carriers of the S allele had an increased risk of critical ICU and mortality (p < 0.001, OR = 2.79, 95% CI = 1.66-4.65). This adverse effect might be explained by a less flexibility and reduced ability to induce phagocytosis or viral neutralization for the short length allele. We concluded that the IgG3 hinge length polymorphism could be a predictor of critical COVID-19 and the risk of death. This study was based on a limited number of patients from a single population, and requires validation in larger cohorts.

miRNA signatures associated with vulnerability to food addiction in mice and humans.

Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.

FURIN gene variants (rs6224/rs4702) as potential markers of death and cardiovascular traits in severe COVID-19.

Furin is a protease that plays a key role in the infection cycle of SARS-CoV-2 by cleaving the viral proteins during the virus particle assembly. In addition, Furin regulates several physiological processes related to cardio-metabolic traits. DNA variants in the FURIN gene are candidates to regulate the risk of developing these traits as well as the susceptibility to severe COVID-19. We genotyped two functional FURIN variants (rs6224/rs4702) in 428 COVID-19 patients in the intensive care unit. The association with death (N = 106) and hypertension, diabetes, and hyperlipidaemia was statistically evaluated. The risk of death was associated with age, hypertension, and hypercholesterolemia. The two FURIN alleles linked to higher expression (rs6224 T and rs4702 A) were significantly increased in the death cases (odds ratio= 1.40 and 1.43). Homozygosis for the two high expression genotypes (rs6224 TT and rs4702 AA) and for the T-A haplotype was associated with an increased risk of hypercholesterolemia. In the multiple logistic regression both, hypercholesterolemia and the TT + AA genotype were significantly associated with death. In conclusion, besides its association with hypercholesterolemia, FURIN variants might be independent risk factors for the risk of death among COVID-19 patients.

Addressing a critical need for caregiver support in neuro-oncology: development of a caregiver navigation intervention using eSNAP social resource visualization.

Informal caregivers are key to oncology care, but often have unmet needs, leading to poor psychological and physical health outcomes. Comprehensive, proactive caregiver support programs are needed. We describe the development of a support intervention for caregivers of persons with brain tumors. The intervention uses a caregiver navigator to help participants identify and capitalize on existing social support resources captured using a web-based tool (eSNAP) and connects participants to existing formal services. We describe the iterative development process of the manualized intervention with particular focus on the caregiver navigator sessions. The process included review of the literature and published patient navigation programs, expert and stakeholder review, and study team member review. Quantitative and qualitative data were captured from the first 15 participants randomized to receive the intervention, enrolled from February 2020 to December 2020. Four participants dropped from the study, 9 completed at least 7 modules, and 8 participants completed all 8. Quantitative and qualitative data were collected primarily from those who completed the intervention; data suggest caregivers were satisfied with the intervention and found it helpful. Our intervention is one of the first theory-based caregiver support interventions to include caregiver navigation in neuro-oncology. We use best-practice guidelines for design, including extensive stakeholder feedback. COVID-19 may have impacted recruitment and participation, but some preliminary data suggest that those able to engage with the intervention find it helpful. Data collection is ongoing in a larger trial. If effective, caregiver navigation could be a model for future interventions to ensure caregiver support.

The FCGR2A rs1801274 polymorphism was associated with the risk of death among COVID-19 patients.

Polymorphisms of Fcγ receptors have been associated with variable responses to infections. We determined the association of functional polymorphisms rs1801274 in the FCGR2A and rs396991 in the FCGR3A with COVID-19 severity. This study involved 453 patients with severe COVID-19, in which the FCGR2A rs1801274 G-allele (131-Arg) was significantly associated with death (p = 0.02, OR = 1.47). This effect was independent of age and increased IL6 and D-Dimer levels. This study suggests that the FCGR2A gene might be associated with the risk of death among COVID-19 patients. Our study has several limitations, mainly the limited number of patients and the inclusion of a single population. It is thus necessary to confirm this result in larger cohorts from different populations.

A cell-based ELISA as surrogate of virus neutralization assay for RBD SARS-CoV-2 specific antibodies.

SARS-CoV-2, the cause of the COVID-19 pandemic, has provoked a global crisis and death of millions of people. Several serological assays to determine the quality of the immune response against SARS-CoV-2 and the efficacy of vaccines have been developed, among them the gold standard conventional virus neutralization assays. However, these tests are time consuming, require biosafety level 3 (BSL3), and are low throughput and expensive. This has motivated the development of alternative methods, including molecular inhibition assays. Herein, we present a safe cell-based ELISA-virus neutralization test (cbE-VNT) as a surrogate for the conventional viral neutralization assays that detects the inhibition of SARS-CoV-2 RBD binding to ACE2-bearing cells independently of species. Our test shows a very good correlation with the conventional and molecular neutralization assays and achieves 100% specificity and 95% sensitivity. cbE-VNT is cost-effective, fast and enables a large-scale serological evaluation that can be performed in a BSL2 laboratory, allowing its use in pre-clinical and clinical investigations.

Effects of IFIH1 rs1990760 variants on systemic inflammation and outcome in critically ill COVID-19 patients in an observational translational study.

Background: Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. We hypothesized that IFIH1 rs199076 variants would modulate host response and outcome after severe COVID-19. Methods: Patients admitted to an intensive care unit (ICU) with confirmed COVID-19 were prospectively studied and rs1990760 variants determined. Peripheral blood gene expression, cell populations, and immune mediators were measured. Peripheral blood mononuclear cells from healthy volunteers were exposed to an MDA5 agonist and dexamethasone ex-vivo, and changes in gene expression assessed. ICU discharge and hospital death were modeled using rs1990760 variants and dexamethasone as factors in this cohort and in-silico clinical trials. Results: About 227 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a lower expression of inflammation-related pathways, an anti-inflammatory cell profile, and lower concentrations of pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist showed an increase in IL6 expression after dexamethasone treatment. All patients with the TT variant not treated with steroids survived their ICU stay (hazard ratio [HR]: 2.49, 95% confidence interval [CI]: 1.29-4.79). Patients with a TT variant treated with dexamethasone showed an increased hospital mortality (HR: 2.19, 95% CI: 1.01-4.87) and serum IL-6. In-silico clinical trials supported these findings. Conclusions: COVID-19 patients with the IFIH1 rs1990760 TT variant show an attenuated inflammatory response and better outcomes. Dexamethasone may reverse this anti-inflammatory phenotype. Funding: Centro de Investigación Biomédica en Red (CB17/06/00021), Instituto de Salud Carlos III (PI19/00184 and PI20/01360), and Fundació La Marató de TV3 (413/C/2021).

Patients with severe COVID-19 often need mechanical ventilation to help them breathe and other types of intensive care. The outcome for many of these patients depends on how their immune system reacts to the infection. If the inflammatory response triggered by the immune system is too strong, this can cause further harm to the patient. One gene that plays an important role in inflammation is IFIH1 which encodes a protein that helps the body to recognize viruses. There are multiple versions of this gene which each produce a slightly different protein. It is possible that this variation impacts how the immune system responds to the virus that causes COVID-19. To investigate, Amado-Rodríguez, Salgado del Riego et al. analyzed the IFIH1 gene in 227 patients admitted to an intensive care unit in Spain for severe COVID-19 between March and December 2020. They found that patients with a specific version of the gene called TT experienced less inflammation and were more likely to survive the infection. Physicians typically treat patients with moderate to severe COVID-19 with corticosteroid drugs that reduce the inflammatory response. However, Amado-Rodríguez, Salgado del Riego et al. found that patients with the TT version of the IFIH1 gene were at greater risk of dying if they received corticosteroids. The team then applied the distribution of IFIH1 variants among different ethnic ancestries to data from a previous clinical trial, and simulated the effects of corticosteroid treatment. This 'mock' clinical trial supported their findings from the patient-derived data, which were also validated by laboratory experiments on immune cells from individuals with the TT gene. The work by Amado-Rodríguez, Salgado del Riego et al. suggests that while corticosteroids benefit some patients, they may cause harm to others. However, a real-world clinical trial is needed to determine whether patients with the TT version of the IFIH1 gene would do better without steroids.

A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and Neisseria meningitidis outer membrane vesicles.

SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.

Association between the interferon-induced transmembrane protein 3 gene (IFITM3) rs34481144 / rs12252 haplotypes and COVID-19.

The interferon induced transmembrane-protein 3 (IFITM3) plays an important role in the defence against viral infection. IFITM3 gene variants have been linked to differences in expression and associated with the risk of severe influenza by some authors. More recently, these variants have been associated with the risk of COVID-19 after SARS-CoV-2 infection. We determined the effect of two common IFITM3 polymorphisms (rs34481144 â€‹C/T and rs12252 A/G) on the risk of hospitalization due to COVID-19 by comparing 484 patients (152 required support in thr intensive care unit, ICU) and 182 age and sex matched controls (no disease symptoms). We found significantly higher frequencies of rs34481144 â€‹T and rs12252 â€‹G carriers among the patients (OR â€‹= â€‹2.02 and OR â€‹= â€‹1.51, respectively). None of the two variants were associated with ICU-admission or death. We found a significantly higher frequency of rs34481144 CC â€‹+ â€‹rs12252 AA genotype carriers among the controls, suggesting a protective effect (p = 0.001, OR = 0.56, 95%CI = 0.40-0.80). Moreover, haplotype rs34481144 â€‹C - rs12252 A was significantly increased in the controls (p â€‹= â€‹0.008, OR â€‹= â€‹0.71, 95%CI â€‹= â€‹0.55-0.91). Our results showed a significant effect of the IFITM3 variants in the risk for hospitalization after SARS-CoV-2 infection.