Khani, E., Entezari-Maleki, T. Fluvoxamine and long COVID-19; a new role for sigma-1 receptor (S1R) agonists. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01545-3
https://www.nature.com/articles/s41380-022-01545-3

Posted in Uncategorized | Comments Off on Fluvoxamine and long COVID-19; a new role for sigma-1 receptor (S1R) agonists

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.

Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martínez A, Yang R, Haljasmägi L, Migaud M, Särekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garçon P, Rivière JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Mégarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Solé-Violán J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs CM, Moncada-Vélez M, Arias AA, Lorenzo L, Boucherit S, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarström Q, Hammarström L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari FS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Erikstrup C, Condino-Neto A, Prando C, Bondarenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S; HGID Lab; COVID Clinicians; COVID-STORM Clinicians; NIAID Immune Response to COVID Group; NH-COVAIR Study Group; Danish CHGE; Danish Blood Donor Study; St. James’s Hospital, SARS CoV2 Interest Group; French COVID Cohort Study Group; Imagine COVID-Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank Investigators; COVID Human Genetic Effort; CP-COVID-19 Group; CONSTANCES cohort; 3C-Dijon Study; Cerba Health-Care; Etablissement Français du Sang Study group, Anderson MS, Boisson B, Béziat V, Zhang SY, Andreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Burdet C, Bouadma L, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodríguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Casanova JL, Abel L, Cobat A. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proc Natl Acad Sci U S A. 2022 May 24;119(21):e2200413119. doi: 10.1073/pnas.2200413119. Epub 2022 May 16. PMID: 35576468; PMCID: PMC9173764.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173764/pdf/pnas.202200413.pdf

Posted in Uncategorized | Comments Off on The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D’Angio’ M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech, Tandjaoui-Lambiotte Y, Duval X, Laouénan C; COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; NIAID-USUHS/TAGC COVID Immunity Group, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science.  Oct 23;370(6515):eabd4570. doi: 10.1126/science.abd4570. Epub 2020 Sep 24. PMID: 32972995; PMCID: PMC7857407.

https://pubmed.ncbi.nlm.nih.gov/32972995/

Posted in Uncategorized | Comments Off on Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Guo K, Barrett BS, Morrison JH, Mickens KL, Vladar EK, Hasenkrug KJ, Poeschla EM, Santiago ML. Interferon resistance of emerging SARS-CoV-2 variants. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2203760119. doi: 10.1073/pnas.2203760119. Epub 2022 Jul 22. PMID: 35867811; PMCID: PMC9371743.

https://pubmed.ncbi.nlm.nih.gov/35867811/

 

Posted in Uncategorized | Comments Off on Interferon resistance of emerging SARS-CoV-2 variants

https://www.cell.com/cell-reports/pdf/S2211-1247(22)01434-6.pdf

Posted in Uncategorized | Comments Off on SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19

Abstract: First infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risk of acute and postacute death and sequelae in various organ systems. Whether reinfection adds to risks incurred after first infection is unclear. Here we used the US Department of Veterans Affairs’ national healthcare database to build a cohort of individuals with one SARS-CoV-2 infection (n = 443,588), reinfection (two or more infections, n = 40,947) and a noninfected control (n = 5,334,729). We used inverse probability-weighted survival models to estimate risks and 6-month burdens of death, hospitalization and incident sequelae. Compared to no reinfection, reinfection contributed Abstract: additional risks of death (hazard ratio (HR) = 2.17, 95% confidence intervals (CI) 1.93–2.45), hospitalization (HR = 3.32, 95% CI 3.13–3.51) and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders. The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the postacute phase at 6 months. Compared to noninfected controls, cumulative risks and burdens of repeat infection increased according to the number of infections. Limitations included a cohort of mostly white males. The evidence shows that reinfection further increases risks of death, hospitalization and sequelae in multiple organ systems in the acute and postacute phase. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

Bowe, B., Xie, Y. & Al-Aly, Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nature Medicine (2022). https://doi.org/10.1038/s41591-022-02051-3

https://www.nature.com/articles/s41591-022-02051-3

Posted in Uncategorized | Comments Off on Acute and postacute sequelae associated with SARS-CoV-2 reinfection

Nguyen, L.S., Cooper, L.T., Kerneis, M. et al. Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database. Nat Commun 13, 25 (2022). https://doi.org/10.1038/s41467-021-27631-8

https://www.nature.com/articles/s41467-021-27631-8

 

Posted in Uncategorized | Comments Off on Systematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database

Background:  Postmarketing evaluations have linked myocarditis to COVID-19 mRNA vaccines. However few population-based analyses have directly compared the safety of the 2 mRNA COVID-19 vaccines.

Posted in Uncategorized | Comments Off on Myocarditis Higher With Moderna COVID Vaccine, but Overall Risk is Low

Abstract: “Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane (MFGM) inhibit SARS-CoV-2 related coronavirus GX_P2V and SARS-CoV-2 trVLP in vitro and block viral entry into cells. We confirmed that bovine lactoferrin (bLf) blocked the binding between human angiotensin-converting enzyme 2 (hACE2) and SARS-CoV-2 spike protein by combining receptor binding domain (RBD). Importantly, bLf inhibited RNA-dependent RNA polymerase (RdRp) activity of both SARS-CoV-2 and SARS-CoV in vitro in the nanomolar range. So far, no biological macromolecules have been reported to inhibit coronavirus RdRp. Our result indicated that bLf plays a major role in inhibiting viral replication rather than viral entry, which has been widely explored. bLf treatment reduced viral load in lungs and tracheae and alleviated pathological damage. Our study provides evidence that bLf prevents SARS-CoV-2 infection by combining SARS-CoV-2 spike protein RBD and inhibiting coronaviruses’ RdRp activity, and may be a promising candidate for the treatment of COVID-19.”

He ST, Qin H, Guan L, Liu K, Hong B, Zhang X, Lou F, Li M, Lin W, Chen Y, He C, Liu F, Lu S, Luo S, Zhu S, An X, Song L, Fan H, Tong Y. Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model. J Med Virol. 2022 Nov 3. doi: 10.1002/jmv.28281. Epub ahead of print. PMID: 36329614.

https://pubmed.ncbi.nlm.nih.gov/36329614/

Posted in Uncategorized | Comments Off on Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model

Abstract: The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by KD to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1-4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed.

Sokolov AV, Isakova-Sivak IN, Mezhenskaya DA, Kostevich VA, Gorbunov NP, Elizarova AY, Matyushenko VA, Berson YM, Grudinina NA, Kolmakov NN, Zabrodskaya YA, Komlev AS, Semak IV, Budevich AI, Rudenko LG, Vasilyev VB. Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin. Biometals. 2022 Nov 5. doi: 10.1007/s10534-022-00458-6. Epub ahead of print. PMID: 36334191.

https://pubmed.ncbi.nlm.nih.gov/36334191/

Posted in Uncategorized | Comments Off on Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin