{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:47:58Z","timestamp":1785775678336,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,21]]},"group-title":"In Review","reference-count":48,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,7]]},"abstract":"<title>Abstract<\/title>\n                <p>Background: Essential agricultural workers in Central America and their households faced a high force of infection during the COVID-19 pandemic. Here, we evaluated if pre-existing seropositivity and vaccination (hybrid immunity) influenced SARS-CoV-2 infection risk and duration of shedding in an agricultural community in rural Guatemala.\nMethods: Individuals from 70 households were enrolled in a community cohort. From September 2021 to December 2022, all participants reported symptoms twice-weekly and provided saliva weekly for SARS-CoV-2 RNA testing by reverse transcriptase polymerase chain reaction (RT-PCR). Upon SARS-CoV-2 detection, participants submitted saliva three times per week for four weeks, which was tested by RT-PCR, to assess duration of shedding. We selected 119 SARS-CoV-2 PCR-positive individuals and 101 month-matched controls to measure nucleocapsid IgG and Omicron neutralizing antibody (NAb) titers. \nResults: Compared to uninfected controls, SARS-CoV-2 cases were more frequently female (60.5% vs 48.5%, p=0.08), had fewer vaccine doses (p=0.07), and were less likely to have hybrid immunity (p=0.08). Compared to controls, SARS-CoV-2 cases had lower median titers of nucleocapsid IgG (cutoff index [COI]=9.6 vs 23.6, p=0.12) and Omicron NAb (28.4 vs 50.4, p=0.15). SARS-CoV-2 cases also had lower NAb than controls among those vaccinated with 1 (16.1 vs 182.7, p=0.01), 2 (11.9 vs 87.0, p=0.04), or 3 doses (13.4 vs 232.5, p=0.004), and those considered up-to-date on vaccination (13.1 vs 155.6, p=0.0001). Nucleocapsid IgG and Omicron NAb were similar between individuals with short (&lt;7 days) vs long (&gt;7 days) viral shedding durations. \nConclusions: In a household cohort of Guatemalan agricultural workers, cumulative vaccine doses associated with lower odds of infection. Among those previously vaccinated, lower titers of nucleocapsid IgG and Omicron NAb were associated with elevated infection risk, highlighting the importance of hybrid immunity in COVID-19 protection in this population.<\/p>","DOI":"10.21203\/rs.3.rs-9348647\/v1","type":"posted-content","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T23:02:12Z","timestamp":1779404532000},"source":"Crossref","is-referenced-by-count":0,"title":["Vaccination and hybrid immunity is associated with SARS-CoV-2 protection but not shedding duration in rural Guatemalan households"],"prefix":"10.21203","author":[{"given":"Bradley S","family":"Barrett","sequence":"first","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly M","family":"Lamb","sequence":"additional","affiliation":[{"name":"Colorado School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejun","family":"Guo","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diva Mirella Calvimontes","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Fundacion para la Salud Integral de los Guatemaltecos"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neudy","family":"Rojop","sequence":"additional","affiliation":[{"name":"Fundacion para la Salud Integral de los Guatemaltecos"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bradley","sequence":"additional","affiliation":[{"name":"Fundacion para la Salud Integral de los Guatemaltecos"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hashem","family":"Anabtawi","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareen","family":"Arias","sequence":"additional","affiliation":[{"name":"Fundacion para la Salud Integral de los Guatemaltecos"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Paiz","sequence":"additional","affiliation":[{"name":"Fundacion para la Salud Integral de los Guatemaltecos"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio del Cid","family":"Villatoro","sequence":"additional","affiliation":[{"name":"Fundacion para la Salud Integral de los Guatemaltecos"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin J","family":"Asturias","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario L","family":"Santiago","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Olson","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s10903-021-01290-9","article-title":"COVID-19 and Agricultural Workers: A Descriptive Study","volume":"24","author":"Chicas R","year":"2022","unstructured":"Chicas R, Xiuhtecutli N, Houser M, Glastra S, Elon L, Sands JM, et al. COVID-19 and Agricultural Workers: A Descriptive Study. J Immigr Minor Health. 2022;24(1):58\u201364.","journal-title":"J Immigr Minor Health"},{"issue":"17","key":"ref2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.15585\/mmwr.mm7017a3","article-title":"COVID-19 Outbreak Among Farmworkers - Okanogan County, Washington, May-August 2020","volume":"70","author":"Miller JS","year":"2021","unstructured":"Miller JS, Holshue M, Dostal TKH, Newman LP, Lindquist S. COVID-19 Outbreak Among Farmworkers - Okanogan County, Washington, May-August 2020. MMWR Morb Mortal Wkly Rep. 2021;70(17):617\u201321.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"32","key":"ref3","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1016\/j.vaccine.2021.05.063","article-title":"Evidence for antibody as a protective correlate for COVID-19 vaccines","volume":"39","author":"Earle KA","year":"2021","unstructured":"Earle KA, Ambrosino DM, Fiore-Gartland A, Goldblatt D, Gilbert PB, Siber GR, et al. Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine. 2021;39(32):4423\u20138.","journal-title":"Vaccine"},{"issue":"11","key":"ref4","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1038\/s41591-021-01540-1","article-title":"Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection","volume":"27","author":"Feng S","year":"2021","unstructured":"Feng S, Phillips DJ, White T, Sayal H, Aley PK, Bibi S, et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat Med. 2021;27(11):2032\u201340.","journal-title":"Nat Med"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.13091","article-title":"Correlates of protection against SARS-CoV-2 infection and COVID-19 disease","volume":"310","author":"Goldblatt D","year":"2022","unstructured":"Goldblatt D, Alter G, Crotty S, Plotkin SA. Correlates of protection against SARS-CoV-2 infection and COVID-19 disease. Immunol Rev. 2022;310(1):6\u201326.","journal-title":"Immunol Rev"},{"issue":"2","key":"ref6","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.vaccine.2021.12.006","article-title":"Towards a population-based threshold of protection for COVID-19 vaccines","volume":"40","author":"Goldblatt D","year":"2022","unstructured":"Goldblatt D, Fiore-Gartland A, Johnson M, Hunt A, Bengt C, Zavadska D, et al. Towards a population-based threshold of protection for COVID-19 vaccines. Vaccine. 2022;40(2):306\u201315.","journal-title":"Vaccine"},{"issue":"7","key":"ref7","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","volume":"27","author":"Khoury DS","year":"2021","unstructured":"Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27(7):1205\u201311.","journal-title":"Nat Med"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/s41591-023-02228-4","article-title":"Predicting the efficacy of variant-modified COVID-19 vaccine boosters","volume":"29","author":"Khoury DS","year":"2023","unstructured":"Khoury DS, Docken SS, Subbarao K, Kent SJ, Davenport MP, Cromer D. Predicting the efficacy of variant-modified COVID-19 vaccine boosters. Nat Med. 2023;29(3):574\u20138.","journal-title":"Nat Med"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3201\/eid2902.221422","article-title":"Correlates of Protection, Thresholds of Protection, and Immunobridging among Persons with SARS-CoV-2 Infection","volume":"29","author":"Khoury DS","year":"2023","unstructured":"Khoury DS, Schlub TE, Cromer D, Steain M, Fong Y, Gilbert PB, et al. Correlates of Protection, Thresholds of Protection, and Immunobridging among Persons with SARS-CoV-2 Infection. Emerg Infect Dis. 2023;29(2):381\u20138.","journal-title":"Emerg Infect Dis"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"e309","DOI":"10.1016\/S2666-5247(23)00012-5","article-title":"Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study","volume":"4","author":"Regev-Yochay G","year":"2023","unstructured":"Regev-Yochay G, Lustig Y, Joseph G, Gilboa M, Barda N, Gens I, et al. Correlates of protection against COVID-19 infection and intensity of symptomatic disease in vaccinated individuals exposed to SARS-CoV-2 in households in Israel (ICoFS): a prospective cohort study. Lancet Microbe. 2023;4(5):e309\u201318.","journal-title":"Lancet Microbe"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1038\/s41467-023-38275-1","article-title":"Protection against SARS-CoV-2 Omicron BA.4\/5 variant following booster vaccination or breakthrough infection in the UK","volume":"14","author":"Wei J","year":"2023","unstructured":"Wei J, Matthews PC, Stoesser N, Newton JN, Diamond I, Studley R, et al. Protection against SARS-CoV-2 Omicron BA.4\/5 variant following booster vaccination or breakthrough infection in the UK. Nat Commun. 2023;14(1):2799.","journal-title":"Nat Commun"},{"issue":"5","key":"ref12","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/s41591-022-01721-6","article-title":"Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines","volume":"28","author":"Wei J","year":"2022","unstructured":"Wei J, Pouwels KB, Stoesser N, Matthews PC, Diamond I, Studley R, et al. Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines. Nat Med. 2022;28(5):1072\u201382.","journal-title":"Nat Med"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"e0252454","DOI":"10.1371\/journal.pone.0252454","article-title":"Excess mortality associated with the COVID-19 pandemic among Californians 18\u201365 years of age, by occupational sector and occupation: March through November 2020","volume":"16","author":"Chen YH","year":"2021","unstructured":"Chen YH, Glymour M, Riley A, Balmes J, Duchowny K, Harrison R, et al. Excess mortality associated with the COVID-19 pandemic among Californians 18\u201365 years of age, by occupational sector and occupation: March through November 2020. PLoS ONE. 2021;16(6):e0252454.","journal-title":"PLoS ONE"},{"issue":"4","key":"ref14","doi-asserted-by":"crossref","first-page":"e0250621","DOI":"10.1371\/journal.pone.0250621","article-title":"Farmer and farm worker illnesses and deaths from COVID-19 and impacts on agricultural output","volume":"16","author":"Lusk JL","year":"2021","unstructured":"Lusk JL, Chandra R. Farmer and farm worker illnesses and deaths from COVID-19 and impacts on agricultural output. PLoS ONE. 2021;16(4):e0250621.","journal-title":"PLoS ONE"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.3201\/eid2705.204949","article-title":"Prevalence and Clinical Profile of Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Farmworkers, California, USA, June-November 2020","volume":"27","author":"Lewnard JA","year":"2021","unstructured":"Lewnard JA, Mora AM, Nkwocha O, Kogut K, Rauch SA, Morga N, et al. Prevalence and Clinical Profile of Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Farmworkers, California, USA, June-November 2020. Emerg Infect Dis. 2021;27(5):1330\u201342.","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1038\/s41467-023-39292-w","article-title":"Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration","volume":"14","author":"Follmann D","year":"2023","unstructured":"Follmann D, O'Brien MP, Fintzi J, Fay MP, Montefiori D, Mateja A, et al. Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration. Nat Commun. 2023;14(1):3605.","journal-title":"Nat Commun"},{"key":"ref17","first-page":"8","article-title":"Clinical and Economic Impact of COVID-19 on Plantation Workers: Preliminary Results from the Guatemala Agricultural Workers and Respiratory Illness Impact (AGRI) Study. medRxiv","author":"Olson D","year":"2022","unstructured":"Olson D, Calvimontes DM, Lamb MM, Guzman G, Barrios E, Chacon A et al. Clinical and Economic Impact of COVID-19 on Plantation Workers: Preliminary Results from the Guatemala Agricultural Workers and Respiratory Illness Impact (AGRI) Study. medRxiv. 2022 Feb 8."},{"issue":"7","key":"ref18","article-title":"High SARS-CoV-2 Seroprevalence and Rapid Neutralizing Antibody Decline among Agricultural Workers in Rural Guatemala, June 2020-March 2021","volume":"10","author":"Iwamoto C","year":"2022","unstructured":"Iwamoto C, Lesteberg KE, Lamb MM, Calvimontes DM, Guo K, Barrett BS et al. High SARS-CoV-2 Seroprevalence and Rapid Neutralizing Antibody Decline among Agricultural Workers in Rural Guatemala, June 2020-March 2021. Vaccines (Basel). 2022;10(7).","journal-title":"Vaccines (Basel)"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"100676","DOI":"10.1016\/j.ijregi.2025.100676","article-title":"SARS-CoV-2 secondary attack rates and risks for transmission among agricultural workers and their households in Guatemala, 2022\u20132023","volume":"16","author":"Carreon JD","year":"2025","unstructured":"Carreon JD, Lamb MM, Chard AN, Calvimontes DM, Iwamoto C, Rojop N, et al. SARS-CoV-2 secondary attack rates and risks for transmission among agricultural workers and their households in Guatemala, 2022\u20132023. IJID Reg. 2025;16:100676.","journal-title":"IJID Reg"},{"issue":"1","key":"ref20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.yapd.2016.04.001","article-title":"The Center for Human Development in Guatemala: An Innovative Model for Global Population Health","volume":"63","author":"Asturias EJ","year":"2016","unstructured":"Asturias EJ, Heinrichs G, Domek G, Brett J, Shick E, Cunningham M, et al. The Center for Human Development in Guatemala: An Innovative Model for Global Population Health. Adv Pediatr. 2016;63(1):357\u201387.","journal-title":"Adv Pediatr"},{"issue":"11","key":"ref21","doi-asserted-by":"crossref","first-page":"e368","DOI":"10.2196\/jmir.8041","article-title":"Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala","volume":"19","author":"Olson D","year":"2017","unstructured":"Olson D, Lamb M, Lopez MR, Colborn K, Paniagua-Avila A, Zacarias A, et al. Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala. J Med Internet Res. 2017;19(11):e368.","journal-title":"J Med Internet Res"},{"key":"ref22","unstructured":"National Center for Immunization and Respiratory Diseases (NCIRD) DoVD. Symptoms of COVID-19. Mar. 15, 2024 [cited 2024 2024]; Available from: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/symptoms-testing\/symptoms.html"},{"issue":"1","key":"ref23","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1186\/s12889-021-11683-y","article-title":"Performance of existing and novel surveillance case definitions for COVID-19 in household contacts of PCR-confirmed COVID-19","volume":"21","author":"Reses HE","year":"2021","unstructured":"Reses HE, Fajans M, Lee SH, Heilig CM, Chu VT, Thornburg NJ, et al. Performance of existing and novel surveillance case definitions for COVID-19 in household contacts of PCR-confirmed COVID-19. 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Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2. Emerg Infect Dis. 2021;27(7):1821\u201330.","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1038\/s41598-023-29858-5","article-title":"A multiplexed, paired-pooled droplet digital PCR assay for detection of SARS-CoV-2 in saliva","volume":"13","author":"Wagner K","year":"2023","unstructured":"Wagner K, Fox P, Gordon E, Hahn W, Olsen K, Markham A, et al. A multiplexed, paired-pooled droplet digital PCR assay for detection of SARS-CoV-2 in saliva. 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[cited 2025 6\/23\/2025]; Available from: https:\/\/view-hub.org\/vaccine\/covid\/neutralization-studies"},{"issue":"10328","key":"ref34","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0140-6736(22)00152-0","article-title":"Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression","volume":"399","author":"Feikin DR","year":"2022","unstructured":"Feikin DR, Higdon MM, Abu-Raddad LJ, Andrews N, Araos R, Goldberg Y, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. 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