Interacciones entre SARS-CoV-2 y el sistema de defensas del aparato respiratorio: consideraciones para la prevención y el manejo de las infecciones

Jose R. Cruz

doi:10.36829/63CTS.v7i3.974

Autores/as

Jose R. Cruz

DOI:

https://doi.org/10.36829/63CTS.v7i3.974

Resumen

Se describe la situación global de las infecciones por SARS-CoV-2 y los cuadros clínicos de COVID-19. Se presentan datos epidemiológicos de Centro América y de Guatemala, para ejemplificar algunos factores de riesgo de infección y morbilidad. Se revisa la función y estructura del sistema respiratorio, sus mecanismos de defensa innata – captura y remoción de agentes extraños, reconocimiento e inactivación de agentes potencialmente nocivos, reparación del daño, y prevención de futuras incursiones por agentes identificados-, los de defensa adaptativa en las vías respiratorias, y el microbioma. Se describen los tejidos linfoides nasal, y bronquio-alveolar, y la contribución de citoquinas, células especializadas, y anticuerpos del tipo IgA secretoria a la protección antiviral, a la respuesta inflamatoria asociada a la infección, y a la reparación del daño tisular. Se discuten las interacciones de SARS-CoV-2 con los mecanismos de defensa. Se presentan consideraciones para las medidas preventivas de infecciones, incluyendo la aplicación de vacunas, y para evitar enfermedad severa.

Descargas

Los datos de descargas todavía no están disponibles.

Citas

Agarwal, A., Chen, A., Ravindran, N., To, C., & Thulivath, P. J. (2020). Gastrointestinal and liver manifestations of COVID-19. Journal of Clinical and Experimental Hepatology, 10(3), 263-265. https://doi.org/10.1016/j.jceh.2020.03.001

Ainai, A., van Riet E., Ito, R., Ikeda, K., Senchi, K., Suzuki, T., … Hasegawa, H. (2020). Human immune responses elicited by an intranasal inactivated H5 influenza vaccine. Microbiology and Immunology, 64(4), 313-325. https://doi.org/10.1111/1348-0421.12775

Amarante-Mendes, G. P., Adjemian, S., Branco L. M., Zanetti, L., Weinlich, R. & Bortoluci, K. R. (2018). Pattern recognition receptors and the host cell death molecular machinery. Frontiers in Immunology, 9, 2379. https://doi.org/10.3389/fimmu.2018.02379

Ammirati, E., & Wang, D. W. (2020). SARS-CoV-2 inflames the heart. The importance of awareness of myocardial injury in COVID-19 patients. International Journal of Cardiology, 311, 122-123. https://doi.org/10.1016/j.ijcard.2020.03.086

Arons, M. M., Hatfield, K. M., Reddy, S. C., Jacobs, J. R., Taylor, J., Spicer, K., … Jernigan, J. A. (2020). Presymptomatic SARS-CoV-2 infection and transmission in a skilled nursing facility. New England Journal of Medicine, 382, 2081-2090. https://doi.org/10.1056/NEJMoa2008457

Berard, R. A., Scuccimari, R., Haddad, E. M., Morin, M.P., Chan, K., … Acute Care Committee. (Jul 6, 2020). Paediatric inflammatory multisystem syndrome temporally associated with COVID-19. Canadian Paediatric Society. https://www.cps.ca/en/documents/position/pims

Berger, A. (2000). Th1 and Th2 responses. What are they? British Medical Journal, 321(7258), 424. https://doi.org/10.1136/bmj.321.7258.424

Brann, D. H., Tsukahara, T., Weinreb, C, Lipovsek, M., Van den Berge, K., Gong, B., … Datta, S. R. (2020). Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory systems suggests mechanisms underlying COVID-19 associated anosmia. bioRxiv. https://doi.org/10.1101/2020/03.25.009084

Breiman, A., Ruven-Clouet, R., & Le Pendu, J. (2020). Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2. PLoS Pathogens, 16, 21008556. https://doi.org/10.1371/journal.ppat.1008556

Byambusaren, O., Cardona M., Bell., K., Clark, J., McLaws M.-L., & Glasziou, P. (2020). Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis. medRxiv. https://doi.org/10.1101/2020.05.10.20097543

Cai, Q., Chen, F., Wang, T., Luo, F., Liu, X., Wu, Q., … Xu, L. (2020). Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. Diabetes Care, 43(7), 1392-1398. https://doi.org/10.2337/dc20-0576

Centers for Disease Control and Prevention. (2020a). Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp

Centers for Disease Control and Prevention. (2020b). Public Health Screening to Begin in 3 US Airports for 2019 Novel Coronavirus (“2019-nCoV”). https://www.cdc.gov/media/releases/2020/p0117-coronavirus-screening.html

Centers for Disease Control and Prevention. (2020c). Testing in High-Density Critical Infrastructure Workplaces. https://www.cdc.gov/coronavirus/2019-ncov/community/worker-safety-support/hd-testing.html

Chan, J. F.-W., Yuan, S., Kok, K-H., Chu, H., Yang, J., Xing, F., … Yuen, K.-Y. (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet, 395(10223), 514-523. https://doi.org/10/1016/S0140-6736(20)30154-9

Cheng, H.-Y., Jian, S.-W., Liu, D.-P., Ng, T.-C., Huang, W.-T., Lin, H.-H., & Taiwan COVID-19 Outbreak Investigation Team. (2020). Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset. JAMA Internal Medicine, 180(9), 1156-1163. https://doi.org/10.1001/jamainternmed.2020.2020

Chou, R., Dana, T., Buckely, D. I., Selph, S., Fu, R., & Totten, A. M. (2020). Epidemiology of and risk factors for Coronavirus infection in health care workers. Annals of Internal Medicine, 173(2), 120-136. https://doi.org/10.7326/M20-1632

Corthésy, B. (2013). Multi-faceted functions of secretory IgA at mucosal surfaces. Frontiers in Immunology, 4, Article 185. https://doi.org/10.3389/fimmu.2013.00185

Cruz, J. R., Pareja, G., de Fernández, A., Peralta, F., Cáceres, P., & Cano, F. (1990). Acute respiratory tract infections among Guatemalan ambulatory preschool children. Reviews on Infectious Diseases, 12(suppl 8), S1029-S1034. https://doi.org/10.1093/clinids/12.supplement_8.s1029

Davies, N. G., Klepac, P., Liu, Y., Prem, K., Jit, M., CMMID COVID-19 Working Group, & Eggo, R. M. (2020). Age-dependent effects in the transmission and control of COVID-19 epidemics. Nature Medicine, 26, 1205-1211 https://doi.org/10.1038/s41591-020-0962-9

Davies, J., & Davies D. (2010). Origins and evolution of antibiotic resistance. Microbiology and Molecular Biology Reviews, 74(3), 417-433. https://doi.org/10.1128/MMBR.00016-10

Debertin, A. S., Tschernig, T., Tonjes, H., Kleemann, W. J., Troger, H. D., & Pabst, R. (2003). Nasal-associated lymphoid tissue (NALT): Frequency and localization in young children. Clinical & Experimental Immunology, 134(3), 503-507. https://doi.org/10.1111/j.1365-2249.2003.02311.x

De Giorgi, V., Recalcati, S., Jia, Z., Chong, W., Ding, R., Deng, Y., … Lotti, T. (2020). Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): A prospective study from China and Italy. Journal of the American Academy of Dermatology, 83(2), 674-675. https://doi.org/10.1016/j.jaad.2020.05.073

Dickson, R. P., Erb-Downward, J. R., Martinez, F. J., & Huffnagle, G. B. (2016). The microbiome and the respiratory tract. Annual Reviews of Physiology, 78, 481-504. https://doi.org/10.1146/annurev-physiol-021115-105238

Divani, A. A., Andalib, S., Di Napoli, M., Lattanzi, S., Hussain, M. S., Biller, J., … Torbey, M. (2020). Coronavirus disease 2019 and stroke: Clinical manifestations and pathophysiological insights. Journal of Stroke and Cerebrovascular Diseases, 29(8), 104941. https://doi.org/10.1016/j.strokecerebrovasdis.2020.104941

Domingo, J. L., Marques, M., & Rovira, J. (2020). Influence of airborne transmission of SARS-CoV-2 on COVID-19 pandemic. A review. Environmental Research, 188, 109861 https://doi.org/10.1016/j.envres.2020.109861

Dyal, J. W., Grant, M. P. Broadwater, K., Bjork, A., Waltenburg M. A., Gibbson, D. D., … Honein, M. A. (2020). COVID-19 among workers in meat and poultry processing facilities – 19 States, April 2020. Morbidity and Mortality Weekly Report, 69(18), 557-561. https://doi.org/10.15585/mmwr.mm6918e3

Dzik, S. (2020). COVID-19 convalescent plasma: Now is the time for better science. Transfusion Medicine Reviews, 34(3), 141-144. https://doi.org/10.1016/j.t,rv.2020.04.002

Ellinghaus, D., Degenhardt, F., Bujanda, L., Buti, M., Albillos, A., Invernizzi, P., … The Severe Covid-19 GWAS Group. (2020a). Genomewide association study of severe Covid-19 with respiratory failure. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2020283

Ellinghaus, D., Degenhardt, F., Bujanda, L., Buti, M., Albillos, A., Invernizzi, P., Karlsen, T. H. (2020b). The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. medRxiv. https://doi.org/10.1101/2020.05.31.20114991

Fahy, J. V., & Dickey, B. F. (2010). Airway mucus function and dysfunction. New England Journal of Medicine, 363(23), 2233-2247.https://doi.org/10.1056/nejmra0910061

Feldstein, L. R., Rose, E. B., Horwitz, S. M., Collins, J. P. Newhams, M. M., Son, M. B., … Randolph, A. G. (2020). Multisystemic inflammatory syndrome in U.S. children and adolescents. New England Journal of Medicine, 383, 334-346. https://doi.org/10.1056/NEJMoa2021680

Felsenstein, S., Herbert, J. A., McNamara, P. S., & Hedrich, C. M. (2020). COVID-19: Immunology and treatment options. Clinical Immunology, 215, 108448 https://doi.org/10.1016/j.clim.2020.1084-48

Garrett, K., Kamdar, A. A., & Stark, J. M. (2019). Lung defenses: Intrinsic, innate, and adaptive. En R. W. Wilmott, R. Deterding, A. Li, F. Ratjen, P, Sly, H. J. Zar & A. Bush (Eds.), Kendig’s disorders of the respiratory tract in children (9th ed., pp. 120-133). Elsevier. https://doi.org/10.1016/c2015-0-1292-8

Global News. (March 3, 2020). Coronavirus: Here’s a timeline of COVID-19 cases in Canada. https://globalnews.ca/news/6627505/coronavirus-covid-canada-timeline/

Gon, Y., & Hashimoto, S. (2018). Role of airway epithelial barrier dysfunction in pathogenesis of asthma. Allergology International, 67, 12-17. https://doi.org/10.1016/j.alit.2017.08.011

Grant, M. C., Geoghegan, L., Arbyn, M., Mohammed, Z., McGuiness, L., Clarke, E. L., & Wade, R. G. (2020). The prevalence of symptoms in 24,410 adults infected with the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS One, 15, e0234765. https://doi.org/10.1371/journal.pone.0234765

Green, W. D., & Beck, M. A, (2017). Obesity altered T cell metabolism and the response to infection. Current Opinion on Immunology, 46, 1-7. https://doi.org/10.1016/j.coi.2017.03.008

Gupta, A., Madhavan, M. V., Sehgal, K., Nair, N., Mahajan, S, Sehrawat, T. V., … Landry, D. W. (2020). Extrapulmonary manifestations of COVID-19. Nature Medicine, 26, 1017-1032. https://doi.org/10.1038/s41591-020-0968-3

Hajifathalian, K., Kristo, T., Mehta, A., Kumar, S., Schwartz, R., Fortune, B., & Sharaiha, R. (2020). Gastrointestinal and hepatic manifestations of 2019 novel coronavirus disease in a large cohort of infected patients from New York: Clinical implications. Gastroenterology. https://doi.org/10.1053/j.gastro.2020.05.010

Hammer, L., Dubbed, P., Capron, I, Ross, A., Jordan, A., Lee, J., … Leibrand, H. (2020). High SARS CoV-2 attack rate following exposure at a choir practice – Skagit County, Washington, March 2020. Morbidity and Mortality Weekly Report, 69(19), 606-610. http://doi.org/10.15585/mmwr.mm6919e6

Hanshew, A. S., Jette, M. E., Rosen, S. P., & Thibeault, S. L. (2017). Integrating the microbiota of the respiratory tract with the unified airway model. Respiratory Medicine, 126, 68-74. https://doi.org/10.1016/j.rmed.2017.03.019

He, X., Lau, E. H., Wu, P., Deng X.; Wang, J., Hao, X., … Leung, G. M. (2020). Temporal dynamics in viral shedding and transmissibility of COVID-19. Nature Medicine, 26, 672-675. https://doi.org/10.1038/s-41591-020-0869-5

Hiemstra, P. S., McGray, P. B., & Bals, R. (2015). The innate immune function of airway epithelial cells in inflammatory lung disease. European Respiratory Journal, 45(4), 1150-1162. https://doi.org/10.1183/09031936.00141514

Hou, Y., Okuda, K., Edwards, C. E., Martinez, D. R., Asakura, T., Dinnon, K. H., ... Baric, R. S. (2020). SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract. Cell, 182(2), 429-446. https://doi.org/10.1016/j.cell.2020.05.042

Huang, C., Wang, Y., Li, X., Ren, L. Zhao, J., Zhang, L., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506. https://doi.org/10.1016/S0140-6736(20)30183-5

Huang, Y., Chen, S., Yang, Z., Guan, W., Liu, D., Lin, Z., … Li, Y. (2020). SARS-CoV-2 viral load in clinical samples from critically ill patients. American Journal of Respiratory and Critical Care Medicine, 201(11), 1435-1438. https://doi.org/10.1164/rccm.202003-0572LE

Hui, K. P. Y., Cheung, M.-C., Perera R. A. P. M., Ng, K.-C., Bui, C. H. T., Ho, J. C. W., … Chan, M. C. W. (2020). Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respiratory Medicine, 8(7), 687-695. https://doi.org/10.1016/S2213-2600(20)30193-4

Huffnagle, G. B., Dickson, R. P., & Lukacs, N. W. (2017). The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunology, 10(2), 299-306. https://doi.org/10.1038/mi.2016.108

Ibarrondo, F. J., Fulcher, J. A., Goodman-Meza, D., Elliott, J., Hoffman, C., Hausner, M. A., … Yang, O. O. (2020). Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19. New England Journal of Medicine, 383, 1085-1087. https://doi.org/10.1056/NEJMc2025179

International Committee for Taxonomy of Viruses. (2020). Naming the 2019 Coronavirus. https://talk.ictvonline.org/information/w/news/1300/page

Invernizzi, R., Lloyd, C. M., & Molyneaux, P. L. (2020). Respiratory microbiome and epithelial interactions shape immunity in the lung. Immunology, 160(2), 171-182. https://doi.org/10.1111/imm.13195

Jang, S., Han, S. H., & Rhee, J.-Y. (2020). Cluster of Coronavirus disease associated with fitness dance classes. Emerging Infectious Diseases Journal, 26(8), 1917-1920. https://doi.org/10.3201/eid2608.200633

Jegaskanda, S., Weinfurter, J. T., Friedrich, T. C., & Kent, S. J. (2013). Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques. Journal of Virology, 87(10), 5512-5522. https://doi.org/10.1128/JVI.03030-12

Johns Hopkins University. (2020). COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Recuperado de https://coronavirus.jhu.edu/map.html

Kato, A., & Scheieimer, R. P. (2007). Beyond inflammation: Airway epithelial cells are at the interface of innate and adaptive immunity. Current Opinion in Immunology, 19(6), 711-720. https://doi.org/10.1016/j.coi.2007.08.004

Kikkert, M. (2020). Innate immune evasion by human respiratory RNA viruses. Journal of Innate Immunity, 12, 4-20. https://doi.org/10.1159/000503030

Khan, N., de Manuel, M., Peyregne, S., Do, R., Prufer, K., Marques-Bonet, T., …Varki, A. (2020). Multiple genomic events altering hominin SIGLEC Biology and innate immunity predated the common ancestor of humans and archaic hominins. Genome Biology and Evolution, 12(7), 1040-1050. https://doi.org/10.1093/gbe/evaa125

Künzli, N., & Tager, I. B. (2005). Air pollution: From lung to heart. Swiss Medical Weekly, 135(47-48), 697-702.

Klompas, M., Baker, M. A., & Rhee, C. (2020). Airborne transmission of SARS-CoV-2. Theoretical considerations and available evidence. Journal of the American Medical Association, 324(5), 441-442. https://doi.org/10.1001/jama.2020.12458

Lai, C.-C., Ko, W.-C., Lee, P.-I., Jean, S.-S., & Hsueh, P.-R. (2020). Extra-respiratory manifestations of COVID-19. International Journal of Antimicrobial Agents, 56(2), 106024. https://doi.org/10.106/j.ijantimicag.2020.106024

Lambrecht, B. N., Neyt, K., & van Helden, M. J. (2015). The mucosal immune response to respiratory viruses. En J. Mestecky, W. Stober, M. Russell, H. Cheroutre, B. N. Lambrecht & B. Kelsall (Eds.), Mucosal immunology (4th ed., pp. 1805-1815). Elsevier.

Lavezzo, E., Franchin, E., Ciavarella, C., Cuomo-Danneburg, G., Barzon, L., Del Vecchio C., … Cristanti, A. (2020). Suppression of COVID-19 outbreak in the municipality of Vo, Italy. medRxiv. https://doi.org/10.1101/2020.04.17.20053157

Li, J.-W., Han, T.-W., Woodward, M., Anderson, C. S., Zhou, H., Chen, Y.-D., & Neal, B. (2020). The impact of 2019 novel coronavirus on heart injury: A systematic review and meta-analysis. Progress in Cardiovascular Diseases. https://doi.org/10.1016/jcad2020.04.008

Lin, L. K., Suzuki, Y., Nakano, H., Ramsburg, E., & Gunn, M. D. (2008). CCR2 monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. Journal of Immunology, 180, 4, 2562-2572. https://doi.org/10.4049/jimmunol.180.4.2562

Liu, L., Poon, R., Chen, L., Frescura, A.-M., Montuschi, P., Ciabattoni, G., … Dales, R. (2009). Acute effects of air pollution on pulmonary function, airway inflammation, and oxidative stress in asthmatic children. Environmental Health Perspectives ,117, 668-674. https://doi.org/10.1289/ehp11813

Luo, L. Liu, D., Liao, X.-I., Wu, X.-B., Jing, Q.-X., Zheng, J.-Z., … Mao, C. (2020). Modes of contact and risk of transmission in COVID-19 among close contacts. medRxiv. https://doi.org/10.1101/2020.03.24.20042606

Lyadova, I. V., & Panteleev, A. V. (2015). Th1 and Th17 cells in tuberculosis: Protection, pathology, and biomarkers. Mediators of Inflammation. https://doi.org/10.1155/2015/854507

Madjid, M., Safavi-Naeini P., Solomon, S. D., & Vardeny, O. (2020) Potential effects of Coronavirus on the cardiovascular system. A review. JAMA Cardiology, 5(7), 831-840. https://doi.org/10.1001/jamacardio.2020.1286

Mantis, N. J., Rol, N., & Corthesy, B. (2011). Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunology,4(6), 603-611.

Menni, C., Sudre, C. H., Steves, C. J., Ourselin, S., & Spector, T. D. (2020). Quantifying additional COVID-19 symptoms will save lives. Lancet, 395(10241), e107-e108. https://doi.org/10.1016/S0140-6736(20)31281-2

Menni, C., Valdes, A. M., Freidin, M. B, Sudre, C. H., Nguyen, L. H, Drew, D. A., Spector, T. D. (2020). Real-time tracking of self-reported symptoms to predict potential COVID-19. Nature Medicine, 26(7), 1037-1040. https://doi.org/10.1038/s41591-020-0916-2

Ministerio de Salud Pública y Asistencia Social de Guatemala. (2020a). Situación de COVID-19 en Guatemala. Casos confirmados por laboratorio. https://tablerocovid.mspas.gob.gt/

Ministerio de Salud Pública y Asistencia Social de Guatemala. (2020b). Expediente UNIP-906-2020. Unidad de Información Pública del Ministerio de Salud y Asistencia Social. Enviado al autor el 15 de junio 2020

Mizumoto, K., Kagaya K., Zarebski, A., & Chowell, G. (2020). Estimating the asymptomatic proportion of coronavirus diseases 2019 (COVID-19) cases on board the Diamond Princess Cruise ship, Yokohama, Japan, 2020. European Surveillance. 25(10), 2000180. https://doi.org/10.2807/1560-7917.ES.2020.25.10.2000180

Muscogniuri, G., Pugliese, G., Barrera, L., Savastano, S., & Colao, A. (2020). Commentary: Obesity: The “Achilles heel” for COVID-19. Metabolism, 108, 154251. https://doi.org/10/1016/j.metabol.2020.154251

Mustafa, N. A., & Selim, L. A. (2020). Characterisation of COVID-19 pandemic in paediatric age group: A systematic review and meta-analysis. Journal of Clinical Virology,128, 104395. https://doi.org/10.1016/j.jcv.2020.104395

Nishiura, H., Linton, N. M., & Akhetzhanov, A. R. (2020). Serial interval of novel coronavirus (COVID-19) infections. International Journal of Infectious Diseases, 93, 284-286. https://doi.org/10.1016/j.ijid.2020.02.060

Pabst, O., Cerovic, V & Honef, M. (2016). Secretory IgA in the coordination of establishment and maintenance of the microbiota. Trends in Immunology, 37(5), 287-296. https://doi.org/10.1016/j.it.2016.03.002

Pan, D., Sze, S., Minhas, J., Bangash, M. N., Pareek, N., Divall, P., … Pareek, M. (2020). The impact of ethnicity on clinical outcomes in COVID-19: A systematic review. EClinicalMedicine, 23, 100404. https://doi.org/10.1016/j.cinm2020.100404

Patwa, A., & Shah, A. (2015). Anatomy and physiology of the respiratory system relevant to anaesthesia. Indian Journal of Anaesthesia, 59(9), 533-541. https://doi.org/10.4103/0019-5049.165849

Petersen, C., & Round, J. L. (2014). Defining dysbiosis and its influence on host immunity. Cellular Microbiology, 16(4), 1024-1033. https://doi.org/10.1111/cmi.12308

Petrakis, D., Margin?, D., Tsarouhas, K., Tekos, F., Stan, M., Nikitovic, D., … Tsatsakis, A. (2020). Obesity – a risk factor for increased COVID-19 prevalence, severity, and lethality (Review). Molecular Medicine Reports, 22, 9-19. https://doi.org/10.3892/mmr.2020.11127

Pizzorno, A., Padey, B., Julien, T., Trouillet-Assant, S., Traversier, A., Rosa-Calatrava, M. (2020). Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia. Cell Reports Medicine, 1(4), 100059. https://doi.org/10.1016/j.xcrm.2020.100059

Randall, T. D. (2015). Structure, organization, and development of the mucosal immune system of the respiratory tract. En J. Mestecky, W. Stober, M. Russell, H. Cheroutre, B. N. Lambrecht & B. Kelsall (Eds.), Mucosal immunology (4th ed., pp. 43-61). Elsevier.

Rezaee, F., Meednu, N., Emo, J. A., Saatian, B., Chapman T. J., … Georas, S. N. (2011). Polyinosinic: polycytidylic acid induces protein kinase D-depended disassembly of apical junctions and barrier dysfunction in airway epithelial cells. Journal of Allergy and Clinical Immunology, 128(6), 1216-1224. https://doi.org/10.1016/j.jaci.2011.08.035

Ricke, D. O., Gherlone, N., Fremont-Smith, P., Tisdall, P., & Fremont-Smith, M. (2020). Kawasaki disease and multisystem inflammatory syndrome in children: Antibody-induced mast cell activation hypothesis. Journal of Pediatrics and Pediatric Medicine, 4(2), 1-7.

Riphagen, S., Gomez, X., Gonzalez-Martinez, C., Wilkinson, N., & Theocharis, P. (2020). Hyperinflammatory shock in children during COVID-19 pandemic. Lancet, 395(10237), 1607-1608. https://doi.org/10.1016/S0140-6736(20)31094-1

Rodríguez-Morales, A. J., Cardona-Ospina, J. A., Gutiérrez-Ocampo, E., Villamizar-Pena, R., Holguín-Rivera, Y., Escalera-Antezana, J. P., … Sah, R. (2020). Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Medicine and Infectious Disease, 34, 101623. https://doi.org/10.1016/j.tmaid.2020.101623

Ronco, C., & Reis, T. (2020). Kidney involvement in COVID-19 and rational for extracorporeal therapies. Nature Reviews, 16(6), 308-310. https://doi.org/10.1038/s41581-020-0284.7

Rubins, J. B. (2013). Alveolar macrophages. Wielding the double-edged sword of inflammation. American Journal of Respiratory and Critical Care Medicine, 167(2), 103-104. https://doi.org/10.1164/rccm.2210007

Sardanelli, F., Cozzi, A., Manfardini, L., Bnà, C., Foà, R. A., Spinazzola, A., Schiaffino, S. (2020). Association of mediastinal lymphadenopathy with COVID-19 prognosis. Lancet Infectious Diseases. https://doi.org/10.1016/S1473-3099(20)30521-1

Sattar, N., McInnes, I. B., & McMurray, J. J. V. (2020). Obesity is a risk factor for severe COVID-19 infection: Multiple potential mechanism. Circulation, 142(1), 4-6. https://doi.org/10.1161/circulationaha.120.047659

Schuster, B. S., Suk, J. S., Woodworth, G. F., & Hanes, J. (2013). Nanoparticle diffusion in respiratory mucus from humans without lung disease. Biomaterials, 34(13), 3439-3446. https://doi.org/10.1016/j.biomaterials.2013.01.064

Segal, L. N., Alekseyenko, A. V., Clemente, J. C., Kulkarni, R., Wu, B., Chen, H., … Weiden, M. D. (2013). Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome, 1(1), 19. https://doi.org/10.1186/2049-2618-1-19

Sharma, G., Volgman, A. S., & Michos, E. D. (2020). Sex differences in mortality from COVID-19 pandemic: Are men vulnerable and women protected? Journal of the American College of Cardiology, 2(9), 1407-1410. https://doi.org/10.1016/j.caccas.2020.04.027

Silva-Sánchez, A., & Randall, T. D. (2020). Anatomical uniqueness of the mucosal immune system (GALT, MALT, iBALT) for the induction and regulation of mucosal immunity and tolerance. En H. Kiyono & D. W. Pascual (Eds.), Mucosal Vaccines (2nd ed., pp. 21-54). Academic Press. https://doi.org/10.1016/B978-0-12-811924-2.00002-X

Siordia, J. A. (2020). Epidemiology and clinical features of COVID-19: A review of current literature. Journal of Clinical Virology, 127, 104357. https://doi.org/10.1016/j.cv.2020.104357

Smith, J. C., Sausville, E. L., Girish, V., Yuan, M. L., Vasudevan, A., John, K. M., & Shetzer, J. M. (2020). Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Developmental Cell, 53(8), 514-529. https://doi.org/10.1016/j.devcel.2020.05.012

Stark, J. M., & Colasurdo, G. M. (2006). Lung defenses: Intrinsic, innate, and adaptative. En V. Chernick, T. F. Boat, R. W. Wilmort & A. Bush (Eds.), Kendig’s disorders of the respiratory tract in children (7th ed., pp. 205-223). Elsevier. https://doi.org/10.1016/B978-0-7216-3695-5-50016-X

Subbarao, K., & Mahanty, S. (2020). Respiratory virus infections: Understanding COVID-19. Immunity, 52(6), 905-909. https://doi.org/10.106/j.immuni.2020.05.004

Sullivan, H. C., & Roback, J. D. (2020). Convalescent plasma: Therapeutic hope or hopeless strategy in the SARS-CoV-2 pandemic. Transfusion Medicine Reviews, 34(3), 145-150. https://doi.org/10.1016/j.tmrv.2020.04.001

Sultan, S., Lim, J. K., Altayar. O., Davitkov, P., Feuerstein, J. D., Siddique, S. M., … El-Serag, H. B. (2020). AGA apid recommendations for gastrointestinal procedures during the COVID-19 pandemic. Gastroenterology, 159(2), 739-758. https://doi.org/10.1053.j.gastro.2020.03.072

Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., … HCA Lung Biological Network (2020). SARS-CoV-2 entry factors are highly expressed in nasal epithelium cells together with innate immune genes. Nature Medicine, 26(5), 681-687. https://doi.org/10.1038/s41591-020-0868-6

Szatmary, P., Arora, A., Raraty, M. G. T., Dunne D. F. J., Baron, R. D., & Halloran, C. M. (2020). Emerging phenotype of SARS-CoV-2 associated pancreatitis. Gastroenterology. https://doi.org/10.1053/j.gastro.2020.05.069

Takeuchi, O., & Akira, S. (2020). Pattern recognition receptors and inflammation. Cell, 140, 805-820. https://doi.org/10.1016/j.cell.2010.01.022

The City, New York. (2020). NYC Subway Crews Hit Hardest by Coronavirus, MTA Numbers Show. 1 June 2020

Toubiana, J., Poirault, C., Corsia, A., Bajolle, F., Fourgeaud, J., Agoulvant, F... & Allali, S. (2020). Kawasaki-lie multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: Prospective observational study. British Medical Journal, 369, m2094. https://doi.org/101136/bmj/m2094

United States Environmental Protection Agency. (2009). Metabolically derived human ventilation rates revised approached based upon oxygen consumption rates (Final Report, 2009). https://cfpub.epa.gov/ncea/risk/recordisplay.cfm?deid=202543

van der Vaart, H., Postma, D., Timens, W., Hylkema, M. N., Willemse, B. W. M., Boezen, H. M., … ten Hacken, N. H. (2005). Acute effects of cigarette smoking on inflammation in healthy intermittent smokers. Respiratory Research, 6(22). https://doi.org/10.1186/1465-9921-6-22

Verdoni, L., Mazza, A., Gervasoni, A., Martelli, L., Ruggeri, M., Ciuffreda, M., … D’Antiga, L. (2020). An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: An observational cohort study. Lancet. 395(10239), 1771-1778. https://doi.org/10.1016/S0140-6736(20)31103-X

Viner, R. M... & Whittaker, E. (2020). Kawasaki-like disease: emerging complication during the COVID-19 pandemic. Lancet, 395, 1741-1743. https://doi.org/10.1016/S0140-6736(20)31129-6

Weber, F. (2020). Antiviral innate immunity. Introduction. Reference Module in Life Sciences. https://doi:10.1016/8978-0-12-809633-8.21290-9

World Healt Organization. (28 February 2020a). Coronavirus disease 2019 (COVID-19). Situation Report-39. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200228-sitrep-39-covid-19.pdf?sfvrsn=5bbf3e7d_4

World Healt Organization. (31 March 2020b). Coronavirus disease 2019 (COVID-19). Situation Report-71. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200331-sitrep-71-covid-19.pdf?sfvrsn=4360e92b_8

World Healt Organization. (21 January 2020c). Novel Coronavirus (2019-nCoV) Situation Report-1. https://apps.who.int/iris/bitstream/handle/10665/330760/nCoVsitrep21Jan2020-eng.pdf?sequence=3&isAllowed=y

World Healt Organization. (23 January 2020d). Novel Coronavirus (2019-nCoV) Situation Report-39. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200123-sitrep-3-2019-ncov.pdf?sfvrsn=d6d23643_8

Wu, X., Nehery, R. C., Sabath, B. M., Braun, D., & Dominici, F. (2020). Exposure to air pollution and COVID-19 mortality in the United States: A nationwide cross-sectional study. medRxiv. https://doi.org/10.1101/2020/04.05/20054502

Wu, Y., Jing, W. Liu, J, Ma, Q., Yuan, J., Wang, Y., … Liu, M. (2020). Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries. Science of the Total Environment, 729, 139051. https://doi.org/10.1016/j.scitotenv.2020.139051

Wiley, J. A., Tighe, M. P., & Harmsen, A. G. (2005). Upper respiratory tract resistance to influenza infection is not prevented by the absence of either nasal-associated lymphoid tissue or cervical lymph nodes. Journal of Immunology. 175(5), 3186-3196.

Yang, L., Liu, J., Zhang, R., Mingwu, L., Li, Z., Zhou, X., … Lei, Y. (2020). Epidemiological and clinical features of 200 hospitalized patients with corona virus disease 2019 outside Wuhan, China. A descriptive study. Journal of Clinical Virology, 129, 104475. https://doi.org/10.1016/j.jcv.2020.104475

Zaidi, A. A., Brooke, C. M., Claes, P., McEcoy, B., Hughes, C., & Shriver, D. (2017). Investigating the case of the human nose shape and climate adaptation. PLoS Genetics, 13(3), 21006916. https://doi.org/10.100.1371/journal.pgen.1006616

Zanin, M., Baviskar, P., Webster, R., & Webby, R. (2016). The interaction between respiratory pathogens and mucus. Cell Host & Microbe, 19(2), 159-168. https://doi.org/10.1016/j.chom.2016.01.001

Zhang, Y., Geng, X., Tan, Y., Li, Q., Xu, Q., Xu, J., … Wang, H. (2020). New understanding of the damage of SARS-CoV-2 infection outside the respiratory system. Biomedicine & Pharmacology, 127, 127, 110195. https://doi.org/10.1016/j.biopha.2020.110.110195

Zhao, J., Yang, Y., Huang, H., Li, D., Gu, D. Lu, X., … Wang, P. G. (2020). Relationship between the ABO blood group and the COVID-19 susceptibility. medRxiv. https://doi.org/10.1101/2020.03.11.20031096

Zhou, R., To, K. K.-W., Wong, Y.-C., Liu, L., Zhou, B., … Chen, Z. (2020). Acute SARS-CoV-2 infection impairs dendritic and T cell responses. Immunity. https://doi.org/10.1016/jimmuni.2020.07.026

Zhu, M. & Fu, Y. (2012). Proinflammatory IL-17 induces iBALT development. Cellular & Molecular Immunology, 9,101-102. https://doi.org/10.1038/cmi.2011.46

Zhu, N., Zhang, D., Wang, W., & Li, X. (2020). A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine, 382(8), 727-733. https://doi.org/10.1056/NEJMoa2001017

Zietz, M. & Tatonetti, N. P. (2020). Testing the association between blood type and COVID-19 infection, intubation, and death. medRxiv. https://doi.org/10.1101/2020.04.08.20058073

Zou, L., Ruan, F., Huang, M., Liang, L., Huanhy, H., Hong, Z., … Wu, J. (2020). SARS-CoV-2 viral load in upper respiratory specimens of infected patients. New England Journal of Medicine, 383(12), 1177-1179. https://doi.org/10.1056/NEJMc2001737

Zubair, A. S., McAlpine, S., Gardin, T., Farhadian, S., Kuruvilla, D. E., & Spudich, S. (2020). Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019. JAMA Neurology, 77(8), 1018-1027.

https://doi.org/10.1001/jamaneurol.2020.2065