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Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells

Kumar et al., Cells, doi:10.3390/cells13050369

Feb 2024

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HCQ for COVID-19

1st treatment shown to reduce risk in March 2020

^*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.

Lower risk for mortality, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19hcq.org

In vitro study showing interindividual variability in iPSC-derived alveolar epithelial type 2 cells' susceptibility to SARS-CoV-2 infection and postinfection viral load. Results indicate AT2s mount an antiviral interferon response, though this alone did not control viral replication. Notably, genes involved in cholesterol homeostasis and lipid metabolism were positively correlated with subsequent SARS-CoV-2 infection and viral load, whereas antiviral immunity genes were negatively correlated.

The cholesterol synthesis enzyme SOAT2 and cholesterol transporters MTTP and APOB were among lipid metabolism genes linked to higher infection, suggesting basal cholesterol levels in AT2s may impact SARS-CoV-2 infectivity. Overall, findings indicate AT2s’ pre-infection innate immunity and metabolic state, particularly cholesterol homeostasis pathways, influence COVID-19 severity by affecting cellular susceptibility to infection and viral replication.

Higher cholesterol levels in lung cells may be associated with increased clustering of the ACE2 receptor with lipid rafts, which facilitate more efficient SARS-CoV-2 viral entry.

Yuan et al. showed that HCQ disrupts the association of ACE2 receptors with both lipid rafts (GM1 clusters) and PIP2 clusters, inhibiting viral docking and entry. They demonstrated that HCQ had the strongest effect on disrupting ACE2 receptor clustering in cells with high cholesterol levels.

High cholesterol drives ACE2 association with rafts/endosomes, enabling more efficient SARS-CoV-2 infection. HCQ blocks this by separating ACE2 receptors from lipid rafts and clusters, showing greater efficacy for higher cholesterol levels.

31 preclinical studies support the efficacy of HCQ for COVID-19:

8 In Silico studies Alkafaas, Baildya, González-Paz, Hussein, Navya, Noureddine, Tarek, Yadav

2 In Vivo animal studies Shu-Han Lin, Wen

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1. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

2. Alsmadi et al., The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel, AAPS PharmSciTech, doi:10.1208/s12249-023-02627-3.springer.com, doi.org.

3. Andreani et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228.sciencedirect.com, doi.org.

4. Baildya et al., Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891.sciencedirect.com, doi.org.

5. Clementi et al., Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704.frontiersin.org, doi.org.

6. Dang et al., Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, bioRxiv, doi:10.1101/2021.03.16.435741.biorxiv.org, doi.org.

7. Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, doi:10.3390/ph15040445.mdpi.com, doi.org.

8. Faísca et al., Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, Pharmaceutics, doi:10.3390/pharmaceutics14040877.mdpi.com, doi.org.

9. González-Paz et al., Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data, ACS Omega, doi:10.1021/acsomega.3c06968.acs.org, doi.org.

10. Hussein et al., Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979.sciencedirect.com, doi.org.

11. Kamga Kapchoup et al., In vitro effect of hydroxychloroquine on pluripotent stem cells and their cardiomyocytes derivatives, Frontiers in Pharmacology, doi:10.3389/fphar.2023.1128382.frontiersin.org, doi.org.

12. Liu et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0.nature.com, doi.org.

13. Miao et al., SIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells, Cell Chemical Biology, doi:10.1016/j.chembiol.2023.02.001.sciencedirect.com, doi.org.

14. Milan Bonotto et al., Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection, Antiviral Research, doi:10.1016/j.antiviral.2023.105655.sciencedirect.com, doi.org.

15. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

16. Navya et al., A computational study on hydroxychloroquine binding to target proteins related to SARS-COV-2 infection, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2021.100714.sciencedirect.com, doi.org.

17. Noureddine et al., Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations, Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334.sciencedirect.com, doi.org.

18. Ou et al., Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, PLOS Pathogens, doi:10.1371/journal.ppat.1009212.plos.org, doi.org.

19. Purwati et al., An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia, PLOS One, doi:10.1371/journal.pone.0252302.plos.org, doi.org.

20. Shang et al., Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice, Virology Journal, doi:10.1186/s12985-021-01515-1.biomedcentral.com, doi.org.

21. Sheaff, R., A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, bioRxiv, doi:10.1101/2020.08.02.232892.biorxiv.org, doi.org.

22. Shu-Han Lin et al., Inhalable Chitosan-Based Hydrogel as a Mucosal Adjuvant for Hydroxychloroquine in the Treatment for SARS-CoV-2 Infection in a Hamster Model, Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2023.08.001.sciencedirect.com, doi.org.

23. Tarek et al., Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention, European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6.springer.com, doi.org.

24. Wang et al., Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, Phytomedicine, doi:10.1016/j.phymed.2020.153333.nih.gov, doi.org.

25. Wang (B) et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0.nature.com, doi.org.

26. Wen et al., Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells, Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjad048.oup.com, doi.org.

27. Yadav et al., Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study, Research Square, doi:10.21203/rs.3.rs-628277/v1.researchsquare.com, doi.org.

28. Yao et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237.oup.com, doi.org.

29. Yuan et al., Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, Communications Biology, doi:10.1038/s42003-022-03841-8.nature.com, doi.org.

Kumar et al., 21 Feb 2024, peer-reviewed, 9 authors. Contact: satish.kumar@utrgv.edu (corresponding author), jose.granados04@utrgv.edu, miriam.aceves@utrgv.edu, john.thomas@utrgv.edu, juan.peralta@utrgv.edu, ana.leandro@utrgv.edu, sarah.williams-blangero@utrgv.edu, joanne.curran@utrgv.edu, john.blangero@utrgv.edu.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper HCQ All

Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells

Satish Kumar, Jose Granados, Miriam Aceves, Juan Peralta, Ana C Leandro, John Thomas, Sarah Williams-Blangero, Joanne E Curran, John Blangero

Cells, doi:10.3390/cells13050369

A large portion of the heterogeneity in coronavirus disease 2019 (COVID-19) susceptibility and severity of illness (SOI) remains poorly understood. Recent evidence suggests that SARS-CoV-2 infection-associated damage to alveolar epithelial type 2 cells (AT2s) in the distal lung may directly contribute to disease severity and poor prognosis in COVID-19 patients. Our in vitro modeling of SARS-CoV-2 infection in induced pluripotent stem cell (iPSC)-derived AT2s from 10 different individuals showed interindividual variability in infection susceptibility and the postinfection cellular viral load. To understand the underlying mechanism of the AT2 ′ s capacity to regulate SARS-CoV-2 infection and cellular viral load, a genome-wide differential gene expression analysis between the mock and SARS-CoV-2 infection-challenged AT2s was performed. The 1393 genes, which were significantly (one-way ANOVA FDR-corrected p ≤ 0.05; FC abs ≥ 2.0) differentially expressed (DE), suggest significant upregulation of viral infection-related cellular innate immune response pathways (p-value ≤ 0.05; activation z-score ≥ 3.5), and significant downregulation of the cholesterol-and xenobiotic-related metabolic pathways (p-value ≤ 0.05; activation z-score ≤ -3.5). Whilst the effect of post-SARS-CoV-2 infection response on the infection susceptibility and postinfection viral load in AT2s is not clear, interestingly, pre-infection (mock-challenged) expression of 238 DE genes showed a high correlation with the postinfection SARS-CoV-2 viral load (FDR-corrected p-value ≤ 0.05 and r 2absolute ≥ 0.57). The 85 genes whose expression was negatively correlated with the viral load showed significant enrichment in viral recognition and cytokine-mediated innate immune GO biological processes (p-value range: 4.65 × 10 -10 to 2.24 × 10 -6 ). The 153 genes whose expression was positively correlated with the viral load showed significant enrichment in cholesterol homeostasis, extracellular matrix, and MAPK/ERK pathway-related GO biological processes (p-value range: 5.06 × 10 -5 to 6.53 × 10 -4 ). Overall, our results strongly suggest that AT2s' pre-infection innate immunity and metabolic state affect their susceptibility to SARS-CoV-2 infection and viral load.

Conflicts of Interest: The author declares no conflicts of interest.

References

Abo, Ma, Matte, Huang, Alysandratos et al., Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors, bioRxiv, doi:10.1101/2020.06.03.132639

Aquino, Bisiaux, Li, O'neill, Mendoza-Revilla et al., Dissecting human population variation in single-cell responses to SARS-CoV-2, Nature, doi:10.1038/s41586-023-06422-9

Barkauskas, Cronce, Rackley, Bowie, Keene et al., Type 2 alveolar cells are stem cells in adult lung, J. Clin. Investig, doi:10.1172/JCI68782

Bastard, Michailidis, Hoffmann, Chbihi, Le Voyer et al., Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine, J. Exp. Med, doi:10.1084/jem.20202486

Bastard, Zhang, Zhang, Jouanguy, Casanova, Type I interferons and SARS-CoV-2: From cells to organisms, Curr. Opin. Immunol, doi:10.1016/j.coi.2022.01.003

Bradley, Maioli, Johnston, Chaudhry, Fink et al., Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: A case series, Lancet, doi:10.1016/S0140-6736(20)31305-2

Béliveau, Tarkar, Dion, Désilets, Ghinet et al., Discovery and Development of TMPRSS6 Inhibitors Modulating Hepcidin Levels in Human Hepatocytes, Cell Chem. Biol, doi:10.1016/j.chembiol.2019.09.004

Camaschella, Iron-deficiency anemia, N. Engl. J. Med, doi:10.1056/NEJMra1401038

Cappadona, Rimoldi, Paraboschi, Asselta, Genetic susceptibility to severe COVID-19, Infect. Genet. Evol, doi:10.1016/j.meegid.2023.105426

Carcaterra, Caruso, Alveolar epithelial cell type II as main target of SARS-CoV-2 virus and COVID-19 development via NF-Kb pathway deregulation: A physio-pathological theory, Med. Hypotheses, doi:10.1016/j.mehy.2020.110412

Carethers, Insights into disparities observed with COVID-19, J. Intern. Med, doi:10.1111/joim.13199

Cevik, Tate, Lloyd, Maraolo, Schafers et al., SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: A systematic review and meta-analysis, Lancet Microbe, doi:10.1016/S2666-5247(20)30172-5

Cheemarla, Watkins, Mihaylova, Wang, Zhao et al., Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics, J. Exp. Med, doi:10.1084/jem.20210583

Chen, Tan, Kou, Duan, Wang et al., Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool, BMC Bioinform, doi:10.1186/1471-2105-14-128

Chen, Wu, He, Jiang, He, Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection, Signal Transduct. Target. Ther, doi:10.1038/s41392-023-01510-8

Chen, Zheng, Understand variability of COVID-19 through population and tissue variations in expression of SARS-CoV-2 host genes, Inform. Med. Unlocked, doi:10.1016/j.imu.2020.100443

Costa, Júnior, Nascimento, De Brito, Antonangelo et al., COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS, Respir. Res, doi:10.1186/s12931-023-02555-7

Daamen, Bachali, Owen, Kingsmore, Hubbard et al., Comprehensive transcriptomic analysis of COVID-19 blood, lung, and airway, Sci. Rep, doi:10.1038/s41598-021-86002-x

Dai, Wang, Liao, Tan, Sun et al., Coronavirus Infection and Cholesterol Metabolism, Front. Immunol, doi:10.3389/fimmu.2022.791267

Daniloski, Jordan, Wessels, Hoagland, Kasela et al., Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells, Cell, doi:10.1016/j.cell.2020.10.030

Desai, Brownfield, Krasnow, Alveolar progenitor and stem cells in lung development, renewal and cancer, Nature, doi:10.1038/nature12930

Diamond, Kanneganti, Innate immunity: The first line of defense against SARS-CoV-2, Nat. Immunol, doi:10.1038/s41590-021-01091-0

Dias, Cao, Kwok, Adamalysins in COVID-19-Potential mechanisms behind exacerbating the disease, Biomed. Pharmacother, doi:10.1016/j.biopha.2022.112970

Du, She, Gelbart, Truksa, Lee et al., The serine protease TMPRSS6 is required to sense iron deficiency, Science, doi:10.1126/science.1157121

Ehsani, COVID-19 and iron dysregulation: Distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein, Biol. Direct, doi:10.1186/s13062-020-00275-2

Ellinghaus, Degenhardt, Bujanda, Buti, Albillos et al., Genomewide Association Study of Severe COVID-19 with Respiratory Failure, N. Engl. J. Med, doi:10.1056/NEJMoa2020283

Engler, Albers, Von Maltitz, Groß, Münch et al., ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection, Life Sci. Alliance, doi:10.26508/lsa.202201880

Ganz, Nemeth, Mitchell, Shawki, Mackenzie, Iron imports. IV. Hepcidin and regulation of body iron metabolism, Am. J. Physiol. Gastrointest. Liver Physiol, doi:10.1152/ajpgi.00412.2005

Ge, Jung, Yao, Shinygo, A graphical gene-set enrichment tool for animals and plants, Bioinformatics, doi:10.1093/bioinformatics/btz931

Gong, Wei, Xu, Miller, Thompson et al., Polymorphism in the surfactant protein-B gene, gender, and the risk of direct pulmonary injury and ARDS, Chest, doi:10.1378/chest.125.1.203

Gotoh, Ito, Nagasaki, Yamamoto, Konishi et al., Generation of alveolar epithelial spheroids via isolated progenitor cells from human pluripotent stem cells, Stem Cell Rep, doi:10.1016/j.stemcr.2014.07.005

Han, Yang, Duan, Duan, Nilsson-Payant et al., Identification of Candidate COVID-19 Therapeutics using hPSC-derived Lung Organoids, bioRxiv, doi:10.1101/2020.05.05.079095

Harcourt, Tamin, Lu, Kamili, Sakthivel et al., Isolation and characterization of SARS-CoV-2 from the first US COVID-19 patient, bioRxiv, doi:10.1101/2020.03.02.972935

Hou, Okuda, Edwards, Martinez, Asakura et al., SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract, Cell, doi:10.1016/j.cell.2020.05.042

Huang, Hume, Abo, Werder, Villacorta-Martin et al., SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response, Cell Stem Cell, doi:10.1016/j.stem.2020.09.013

Huang, Wang, Liu, Zhang, Yang et al., Role of the extracellular matrix in COVID-19, World J. Clin. Cases, doi:10.12998/wjcc.v11.i1.73

Hurley, Ding, Villacorta-Martin, Herriges, Jacob et al., Reconstructed Single-Cell Fate Trajectories Define Lineage Plasticity Windows during Differentiation of Human PSC-Derived Distal Lung Progenitors, Cell Stem Cell, doi:10.1016/j.stem.2019.12.009

Jacob, Morley, Hawkins, Mccauley, Jean et al., Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells, Cell Stem Cell, doi:10.1016/j.stem.2017.08.014

Jacob, Vedaie, Roberts, Thomas, Villacorta-Martin et al., Derivation of self-renewing lung alveolar epithelial type II cells from human pluripotent stem cells, Nat. Protoc, doi:10.1038/s41596-019-0220-0

Katsura, Sontake, Tata, Kobayashi, Edwards et al., Human Lung Stem Cell-Based Alveolospheres Provide Insights into SARS-CoV-2-Mediated Interferon Responses and Pneumocyte Dysfunction, Cell Stem Cell, doi:10.1016/j.stem.2020.10.005

Krämer, Green, Pollard, Jr, Tugendreich, Causal analysis approaches in Ingenuity Pathway Analysis, Bioinformatics, doi:10.1093/bioinformatics/btt703

Kulasinghe, Tan, Miggiolaro, Monkman, Sadeghirad et al., Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures, Eur. Respir. J, doi:10.1183/13993003.01881-2021

Kumar, Curran, Espinosa, Glahn, Blangero, Highly efficient induced pluripotent stem cell reprogramming of cryopreserved lymphoblastoid cell lines, J. Biol. Methods, doi:10.14440/jbm.2020.296

Kumar, Curran, Glahn, Blangero, Utility of Lymphoblastoid Cell Lines for Induced Pluripotent Stem Cell Generation, Stem Cells Int, doi:10.1155/2016/2349261

Lee, Kim, Lee, Lee, Kim et al., Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea, JAMA Intern. Med, doi:10.1001/jamainternmed.2020.3862

Loske, Röhmel, Lukassen, Stricker, Magalhães et al., Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children, Nat. Biotechnol, doi:10.1038/s41587-021-01037-9

Lu, Wang, Sakthivel, Whitaker, Murray et al., US CDC Real-Time Reverse Transcription PCR Panel for Detection of Severe Acute Respiratory Syndrome Coronavirus 2, Emerg. Infect. Dis, doi:10.3201/eid2608.201246

Lukassen, Chua, Trefzer, Kahn, Schneider et al., SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells, EMBO J, doi:10.15252/embj.20105114

Nishino, Toyoda, Yamazaki-Inoue, Fukawatase, Chikazawa et al., DNA methylation dynamics in human induced pluripotent stem cells over time, PLoS Genet, doi:10.1371/journal.pgen.1002085

Noguchi-Sasaki, Sasaki, Shimonaka, Mori, Fujimoto-Ouchi, Treatment with anti-IL-6 receptor antibody prevented increase in serum hepcidin levels and improved anemia in mice inoculated with IL-6-producing lung carcinoma cells, BMC Cancer, doi:10.1186/s12885-016-2305-2

Rebendenne, Valadão, Tauziet, Maarifi, Bonaventure et al., SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable to control replication in lung epithelial cells, J. Virol, doi:10.1128/JVI.02415-20

Rendeiro, Ravichandran, Bram, Chandar, Kim et al., The spatial landscape of lung pathology during COVID-19 progression, Nature, doi:10.1038/s41586-021-03475-6

Rouhani, Kumasaka, De Brito, Bradley, Vallier et al., Genetic background drives transcriptional variation in human induced pluripotent stem cells, PLoS Genet, doi:10.1371/journal.pgen.1004432

Schaefer, Padera, Solomon, Kanjilal, Hammer et al., In situ detection of SARS-CoV-2 in lungs and airways of patients with COVID-19, Mod. Pathol, doi:10.1038/s41379-020-0595-z

Sisson, Mendez, Choi, Subbotina, Courey et al., Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis, Am. J. Respir. Crit. Care Med, doi:10.1164/rccm.200810-1615OC

Soares-Schanoski, Sauerwald, Goforth, Periasamy, Weir et al., Asymptomatic SARS-CoV-2 Infection Is Associated with Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19, Front. Immunol, doi:10.3389/fimmu.2022.821730

Strässler, Aalto-Setälä, Kiamehr, Landmesser, Kränkel, Age Is Relative-Impact of Donor Age on Induced Pluripotent Stem Cell-Derived Cell Functionality, Front. Cardiovasc. Med, doi:10.3389/fcvm.2018.00004

Sungnak, Huang, Becavin, Berg, Queen et al., SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes, Nat. Med, doi:10.1038/s41591-020-0868-6

Wang, Simoneau, Kulsuptrakul, Bouhaddou, Travisano et al., Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses, Cell, doi:10.1016/j.cell.2020.12.004

Wang, Zhao, Yan, Wang, Sun et al., Viral and Host Transcriptomes in SARS-CoV-2-Infected Human Lung Cells, J. Virol, doi:10.1128/JVI.00600-21

Wei, Wan, Yan, Wang, Zhang et al., HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry, Nat. Metab, doi:10.1038/s42255-020-00324-0

Williams, Williams, Freidin, Freidin, Mangino et al., Self-Reported Symptoms of COVID-19, Including Symptoms Most Predictive of SARS-CoV-2 Infection, Are Heritable, Twin Res. Hum. Genet, doi:10.1017/thg.2020.85

Wu, Shi, Li, Huang, Li et al., Viral RNA Load in Symptomatic and Asymptomatic COVID-19 Omicron Variant-Positive Patients, Can. Respir. J, doi:10.1155/2022/5460400

Yin, Riva, Pu, Martin-Sancho, Kanamune et al., MDA5 Governs the Innate Immune Response to SARS-CoV-2 in Lung Epithelial Cells, Cell Rep, doi:10.1016/j.celrep.2020.108628

Ziegler, Allon, Nyquist, Mbano, Miao et al., SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues, Cell, doi:10.1016/j.cell.2020.04.035

Zuo, Veldhuizen, Neumann, Petersen, Possmayer, Current perspectives in pulmonary surfactant-Inhibition, enhancement and evaluation, Biochim. Biophys. Acta, doi:10.1016/j.bbamem.2008.03.021

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