IntroductionIt has been more than one year since the first reported case of the novel coronavirus disease 2019 COVID-19, which has already cost more than 2 million lives Fortunately, vaccines against severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 have been developed with record-breaking speed and vaccine programs are ongoing worldwide to take the pandemic under During this expansion of research focus from treatment to prevention of COVID-19, the immune evasion mechanism and immunopathogenic nature of SARS-CoV-2 adds uncertainty to the efficacy of this global vaccination During natural infection, SARS-CoV-2 could avoid the innate antiviral response mediated by interferons IFNs via an array of possible strategies,4,5 which not only leads to viral replication and spreading but also could delay or impair the adaptive immune response including T cell and antibody The significant prevalence of SARS-CoV-2 RNA re-positive cases among discharged patients further raises the concern about the effectiveness and persistency of immune responses after natural Recent long-term follow-up surveys report significant decrease of SARS-CoV-2 antibody titers 5 to 8 months after infection,10,11,12 but its correlation with reduced capacity of SARS-CoV-2 neutralization and immune memory is still vaccination, equally important is the recovery and rehabilitation of COVID-19 Mild cases usually do not require hospitalization but may share similar long-lasting symptoms or discomforts with severe cases, which may reduce life quality after recovery from Also, cardiac magnet resonance imaging cMRI screening revealed surprisingly high prevalence of subclinical myocardial inflammation and fibrosis in recently recovered Due to the overloading of medical systems and the fear of in-hospital transmission, long-term follow-up studies of the structural and functional recovery of COVID-19-involved organs are still this prospective cohort study of recovered COVID-19 patients from Xiangyang, China, we aimed to assess long-term antibody response at 12 months after infection and comprehensively evaluate the structural and functional recovery of the lung and cardiovascular systems. We also attempted to identify potential risk factors associated with those long-term January 15 through 31 March 2020, a total of 307 patients were diagnosed with COVID-19 at Xiangyang Central Hospital, which represented of 549 cases in the downtown and of 1175 cases city-wide. During hospitalization, 12 patients succumbed to COVID-19-induced respiratory distress or lethal infection, which translated to a mortality rate of in line with the citywide mortality rate of 40/1175. All 295 survivors were invited to participate in this study and the final cohort consisted of 121 survivors including 19 recovered from severe COVID-19 Supplementary Fig. 1. Clinical procedures were performed at Xiangyang Central Hospital between 25 December 2020 and 29 January and clinical features of participantsDemographic-wise, this cohort consisted of middle-aged Chinese population with an overall comorbidity prevalence of including hypertension and diabetes as the most common preexisting conditions, which was typical for the local agricultural and industrial population with a preference of high-salt diets Table 1. The participants of this study were among the earliest confirmed COVID-19 patients with virological confirmation dates as early as January 19, 2020. Standard of care consisted of antivirals, antibiotics, immunomodulants and supplemental oxygen was given to participants following CDC guidelines Supplementary Table 1. Only 1 in this cohort received invasive ventilation Supplementary Table 1, which reflected the dismal mortality rate among critically ill patients relying on respiratory Of note, the basic characteristics of this cohort were comparable with the entire population of COVID-19 survivors treated at this hospital Supplementary Table 2.Table 1 Characteristics of participants by COVID-19 severityFull size tableAfter stratifying the cohort by severity graded according to the guideline,21 severe groups had higher ages, less females, and more comorbidities Table 1. Severe group also presented more symptoms at admission, and received more aggressive immunomodulatory therapies, supplemental oxygen, and ICU care during hospitalization Supplementary Table 1. Both severe and non-severe groups share similar lengths since symptom onset, while the severe group had shorter periods since recovery because of longer hospitalization Table 1.Long-lasting SARS-CoV-2 antibody response 1-year after infectionFirst, blood samples were screened by colloidal gold-based immunochromatographic assays GICA separately detecting IgM and IgG against At a median of 11 months post- infection, only 4% 95% CI, 2–10% participants returned positive IgM results, which included both positive and weakly positive results, while 62% 95% CI, 54–71% were IgG positive Table 1, comparing to prevalence of IgM among pre-discharge samples from the same Severe group showed higher prevalence of IgG, while the prevalence of IgM was equally low in both groups Table 1.Next, the concentration of total antibodies against the receptor-binding domain of SARS-CoV-2 spike protein RBD was quantitatively measured by chemiluminescence microparticle immunoassays CMIA.24 Although signal/cutoff S/CO ratios were lower in non-severe group, all but 1 of the results were above the positive diagnostic threshold of S/CO = when all 100 samples of unexposed individuals, which were randomly chosen from sera of in-hospital patients who had negative results from multiple PCR and serological tests for SARS-CoV-2 before and after the date of serum collection, had S/CO values participants were exposed to SARS-CoV-2 and diagnosed with COVID-19 during January to March 2020. During their COVID-19 disease courses, they have received combinations of therapies including antivirals, immunomodulatory agents, antibiotics, supplemental oxygen, and ICU outcomes of this study were immunity against SARS-CoV-2 and functional recovery of the lung and other involved organs. Immunity against SARS-CoV-2 was assessed by multiple antibody assays. The colloidal gold-based test kit gave positive, weak positive, and negative readout of anti-SARS-CoV-2 IgM and IgG separately. The quantitative chemiluminescence microparticle immunoassay for antibodies against SARS-CoV-2 RBD was performed according to manufacturer’s protocol and previous publication,24 and the results were deemed positive if the signal/cutoff S/CO ratio ≥1. For ELISA tests, results were recorded and analyzed as continuous variables and the limit of sensitivity was calculated as mean + 2 × SD of 20 serum samples negative for SARS-CoV-2 antibodies in chemiluminescence assays. Functional recovery of the lung was assessed based on 1 current CT images comparing to images taken before discharge and during earlier follow-ups, 2 pulmonary function test results, and 3 six-minute walk test results. Recovery of the heart was assessed based on ECG, echocardiogram, and cardiac MRI scans. Recovery of other potentially involved organs were assessed by laboratory tests Roche Diagnostics.Sample sizeAn initial target sample size of 108 was determined based on the assumption of a 15 ratio of severe and non-severe COVID-19 patient enrollment and α = This sample size was calculated to have 90% power to detect a 10% difference of antibody concentrations. The final sample size exceeded the target in both analysisQuantitative data were presented in violin plots with all data points shown. Patient characteristics and clinical data were summarized as incidence with prevalence or median with IQR and were assessed with Fisher’s exact test dichotomous variables or χ2 test variables with more than two categories for categorical variables and Mann–Whitney U test for continuous variables. Antibody concentrations were log-transformed before being analyzed as continuous variables. The difference of antibody concentrations between groups were assessed by the Mann–Whitney U test two groups or Kruskal–Wallis test with post hoc comparisons more than two groups. Special tests were mentioned in figure legends. Correlation was assessed by Spearman’s ρ test. Linearity between two factors was assessed by simple linear regression. Generalized linear models were used to assess factors associated with antibody titers. Analyses were performed using SPSS 26 IBM or Prism 9 GraphPad. Missing data were excluded pairwise from analyses. Significance was evaluated at α = .05 and all tests were 2-sided. *p < **p < ***p < Data availabilityReasonable requests for original dataset and clinical documents would be fulfilled by Dr. Peng Hong P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 2020.Article CAS PubMed PubMed Central Google Scholar Parker, E. P. K., Shrotri, M. & Kampmann, B. Keeping track of the SARS-CoV-2 vaccine pipeline. Nat. Rev. Immunol. 20, 650 2020.Article CAS PubMed Google Scholar Sette, A. & Crotty, S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 184, 861–880 2021.Article CAS PubMed PubMed Central Google Scholar Blanco-Melo, D. et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036– 2020.Article CAS PubMed PubMed Central Google Scholar Lei, X. et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11, 3810 2020.Article CAS PubMed PubMed Central Google Scholar Oved, K. et al. Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation. EClinicalMedicine 29, 100651 2020.Article PubMed Google Scholar Anna, F. et al. High seroprevalence but short-lived immune response to SARS-CoV-2 infection in Paris. Eur. J. Immunol. 51, 180–190 2021.Article CAS PubMed Google Scholar Lu, J. et al. Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR. EBioMedicine 59, 102960 2020.Article PubMed PubMed Central Google Scholar Yang, C. et al. Viral RNA level, serum antibody responses, and transmission risk in recovered COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results a population-based observational cohort study. Emerg. Microbes Infect. 9, 2368–2378 2020.Article CAS PubMed PubMed Central Google Scholar Choe, P. G. et al. Waning antibody responses in asymptomatic and symptomatic SARS-CoV-2 infection. Emerg. Infect. Dis. 27, 327–329 2021.Article CAS PubMed Central Google Scholar Huang, C. et al. 6-month consequences of COVID-19 in patients discharged from hospital a cohort study. Lancet 397, 220–232 2021.Article CAS PubMed PubMed Central Google Scholar Self, W. H. et al. Decline in SARS-CoV-2 antibodies after mild infection among frontline health care personnel in a multistate hospital network - 12 states, April-August 2020. Morb. Mortal. Wkly. Rep. 69, 1762–1766 2020.Article CAS Google Scholar Wajnberg, A. et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science 370, 1227–1230 2020.Article CAS PubMed PubMed Central Google Scholar Dan, J. M. et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science 371, eabf4063 2021.Article CAS PubMed Google Scholar Yelin, D. et al. Long-term consequences of COVID-19 research needs. Lancet Infect. Dis. 20, 1115–1117 2020.Article CAS PubMed PubMed Central Google Scholar Gandhi, R. T., Lynch, J. B. & Del Rio, C. Mild or moderate Covid-19. N. Engl. J. Med. 383, 1757–1766 2020.Article CAS PubMed Google Scholar Carfi, A., Bernabei, R. & Landi, F., Gemelli Against, Persistent symptoms in patients after acute COVID-19. JAMA 324, 603–605 2020.Article CAS PubMed PubMed Central Google Scholar Puntmann, V. O. et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 COVID-19. JAMA Cardiol. 5, 1265–1273 2020.Article PubMed PubMed Central Google Scholar Cortinovis, M., Perico, N. & Remuzzi, G. Long-term follow-up of recovered patients with COVID-19. Lancet 397, 173–175 2021.Article CAS PubMed PubMed Central Google Scholar Dupuis, C. et al. Association between early invasive mechanical ventilation and day-60 mortality in acute hypoxemic respiratory failure related to coronavirus disease-2019 pneumonia. Crit. Care Explor 3, e0329 2021.Article PubMed PubMed Central Google Scholar NHCPRC. National Health Commission of the People’s Republic of China. Chinese management guideline for COVID-19 version 7 [in Chinese]. 2020.Pan, Y. et al. Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients. J. Infect. 81, e28–e32 2020.Article CAS PubMed PubMed Central Google Scholar Shen, L. et al. Delayed specific IgM antibody responses observed among COVID-19 patients with severe progression. Emerg. Microbes Infect. 9, 1096–1101 2020.Article CAS PubMed PubMed Central Google Scholar Liu, W. et al. Clinical application of chemiluminescence microparticle immunoassay for SARS-CoV-2 infection diagnosis. J. Clin. Virol. 130, 104576 2020.Article CAS PubMed PubMed Central Google Scholar Atyeo, C. et al. Distinct early serological signatures track with SARS-CoV-2 survival. Immunity 53, 524– 2020.Article CAS PubMed PubMed Central Google Scholar Long, Q. X. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat. Med. 26, 845–848 2020.Article CAS PubMed Google Scholar Schmidt, F. et al. Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. J. Exp. Med. 217, 11 e20201181 2020.Article PubMed CAS Google Scholar Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205–1211 2021.Article CAS PubMed Google Scholar Wang, P. et al. Antibody resistance of SARS-CoV-2 variants and Nature 593, 130–135 2021.Article CAS PubMed Google Scholar McCrohon, J. A. et al. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation 108, 54–59 2003.Article CAS PubMed Google Scholar Chaowu, Y. & Li, L. Histopathological basis of myocardial late gadolinium enhancement in patients with systemic hypertension. Circulation 130, 2210–2212 2014.Article PubMed Google Scholar Wadhera, R. K. et al. Variation in COVID-19 hospitalizations and deaths across New York City boroughs. JAMA 323, 2192–2195 2020.Article CAS PubMed PubMed Central Google Scholar Paremoer, L., Nandi, S., Serag, H. & Baum, F. Covid-19 pandemic and the social determinants of health. BMJ 372, n129 2021.Article PubMed PubMed Central Google Scholar Wu, Z. & McGoogan, J. M. Characteristics of and important lessons from the coronavirus disease 2019 COVID-19 outbreak in China summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA 323, 1239–1242 2020.Article CAS PubMed Google Scholar Ji, Y., Ma, Z., Peppelenbosch, M. P. & Pan, Q. Potential association between COVID-19 mortality and health-care resource availability. Lancet Glob. Health 8, e480 2020.Article PubMed PubMed Central Google Scholar Li, Q. et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 182, 1284– 2020.Article CAS PubMed PubMed Central Google Scholar Trump, S. et al. Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19. Nat. Biotechnol. 39, 705–716 2021.Article CAS PubMed Google Scholar Hu, F. et al. A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract. Cell Mol. Immunol. 17, 1119–1125 2020.Article CAS PubMed Google Scholar Naidu, S. B. et al. The high mental health burden of "Long COVID" and its association with on-going physical and respiratory symptoms in all adults discharged from hospital. Eur. Respir. J. 57, 2004364 2021.Article CAS PubMed PubMed Central Google Scholar Sudre, C. H. et al. Attributes and predictors of long COVID. Nat. Med. 27, 626–631 2021.Article CAS PubMed PubMed Central Google Scholar Augustin, M. et al. Post-COVID syndrome in non-hospitalised patients with COVID-19 a longitudinal prospective cohort study. Lancet Reg. Health Eur. 6, 100122 2021.Article PubMed PubMed Central Google Scholar Peghin, M. et al. Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients. Clin. Microbiol. Infect. 27, 1507–1513 2021.Article CAS PubMed PubMed Central Google Scholar Rogers, J. P. et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 7, 611–627 2020.Article PubMed PubMed Central Google Scholar Reichard, R. R. et al. Neuropathology of COVID-19 a spectrum of vascular and acute disseminated encephalomyelitis ADEM-like pathology. Acta Neuropathol. 140, 1–6 2020.Article CAS PubMed PubMed Central Google Scholar Varatharaj, A. et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients a UK-wide surveillance study. Lancet Psychiatry 7, 875–882 2020.Article PubMed PubMed Central Google Scholar Francone, M. et al. Chest CT score in COVID-19 patients correlation with disease severity and short-term prognosis. Eur. Radiol. 30, 6808–6817 2020.Article CAS PubMed PubMed Central Google Scholar Holland, A. E. et al. An official European Respiratory Society/American Thoracic Society technical standard field walking tests in chronic respiratory disease. Eur. Respir. J. 44, 1428–1446 2014.Article PubMed Google Scholar Hajiro, T. et al. Analysis of clinical methods used to evaluate dyspnea in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 158, 1185–1189 1998.Article CAS PubMed Google Scholar Graham, B. L. et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am. J. Respir. Crit. Care Med. 200, e70–e88 2019.Article PubMed PubMed Central Google Scholar Milanese, M. et al. Suggestions for lung function testing in the context of COVID-19. Respir. Med. 177, 106292 2020.Article PubMed PubMed Central Google Scholar Download referencesAcknowledgementsWe thank Chun Mao Xiangyang Central Hospital and Juan Xiao Hubei University of Arts and Science for organization and administrative support of patient recruitments and clinical examinations. We also thank Rongjie Zhao, Zhangli Li Thermo Fisher Scientific China, Shanghai, China, and GenScript Nanjing, China for technical support and protocol optimization. This work was supported by Xiangyang Science and Technology Bureau 2020YL10, 2020YL14, 2020YL17, and 2020YL39, National Natural Science Foundation of China 31501116, Shenzhen Science and Technology Innovation Commission JCYJ20190809100005672, Shenzhen Sanming Project of Medicine SZSM201911013, and US Department of Veterans Affairs 5I01BX001353.Author informationAuthor notesThese authors contributed equally Yan Zhan, Yufang Zhu, Shanshan Wang, Shijun Jia, Yunling Gao, Yingying LuAuthors and AffiliationsDepartment of Rehabilitation Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYan Zhan, Shanshan Wang, Peng Du, Hao Yu, Chang Liu & Peijun LiuDepartment of Laboratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYufang Zhu, Caili Zhou & Ran LiangDepartment of Radiology and Medical Imaging, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaShijun Jia & Feng WuDepartment of Research Affairs, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaYunling Gao & Jin ChengDepartment of Nephrology, Center of Nephrology and Urology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, ChinaYingying Lu, Zhihua Zheng & Peng HongDepartment of Biomedical Science, Shenzhen Research Institute, City University of Hong Kong, Kowloon Tong, Hong Kong, ChinaYingying LuDepartment of Rehabilitation Medicine, Xiangzhou District People’s Hospital, Xiangyang, Hubei, 441000, ChinaDingwen SunDepartment of Rehabilitation Medicine, Gucheng People’s Hospital, Affiliated Gucheng Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441700, ChinaXiaobo WangDivision of Quality Control, Xiangyang Central Blood Station, Xiangyang, Hubei, 441000, ChinaZhibing HouDepartment of Respiratory and Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, ChinaQiaoqiao Hu & Yulan ZhengDepartment of Pathology, Mount Sinai St. Luke’s Roosevelt Hospital Center, New York, NY, 10025, USAMiao CuiDepartment of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, ChinaGangling TongDepartment of Dermatology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, ChinaYunsheng Xu & Linyu ZhuDivision of Research and Development, US Department of Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, 11209, USAPeng HongDepartment of Cell Biology, State University of New York Downstate Health Sciences University, Brooklyn, NY, 11203, USAPeng HongAuthorsYan ZhanYou can also search for this author in PubMed Google ScholarYufang ZhuYou can also search for this author in PubMed Google ScholarShanshan WangYou can also search for this author in PubMed Google ScholarShijun JiaYou can also search for this author in PubMed Google ScholarYunling GaoYou can also search for this author in PubMed Google ScholarYingying LuYou can also search for this author in PubMed Google ScholarCaili ZhouYou can also search for this author in PubMed Google ScholarRan LiangYou can also search for this author in PubMed Google ScholarDingwen SunYou can also search for this author in PubMed Google ScholarXiaobo WangYou can also search for this author in PubMed Google ScholarZhibing HouYou can also search for this author in PubMed Google ScholarQiaoqiao HuYou can also search for this author in PubMed Google ScholarPeng DuYou can also search for this author in PubMed Google ScholarHao YuYou can also search for this author in PubMed Google ScholarChang LiuYou can also search for this author in PubMed Google ScholarMiao CuiYou can also search for this author in PubMed Google ScholarGangling TongYou can also search for this author in PubMed Google ScholarZhihua ZhengYou can also search for this author in PubMed Google ScholarYunsheng XuYou can also search for this author in PubMed Google ScholarLinyu ZhuYou can also search for this author in PubMed Google ScholarJin ChengYou can also search for this author in PubMed Google ScholarFeng WuYou can also search for this author in PubMed Google ScholarYulan ZhengYou can also search for this author in PubMed Google ScholarPeijun LiuYou can also search for this author in PubMed Google ScholarPeng HongYou can also search for this author in PubMed Google ScholarContributionsY. Zhan and conceptualized the study; Y. Zhan, and recruited patients, performed physical examinations, and abstracted historic data; Y. Zhu, and performed laboratory tests and interpreted results; and conducted sonographic and radiological examinations and interpreted results; and Y. Zheng conducted PFT and interpreted results; Y. Zhan, and conducted functional tests, assessed rehabilitation status and interpreted data; and interpreted metabolic and immunological findings; Y. Zhan, and conducted data quality checks and performed statistical analyses; Y. Zhan and wrote the manuscript. All authors read and approved the final authorsCorrespondence to Feng Wu, Yulan Zheng, Peijun Liu or Peng declarations Competing interests The authors declare no competing interests. Supplementary informationRights and permissions Open Access This article is licensed under a Creative Commons Attribution International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Reprints and PermissionsAbout this articleCite this articleZhan, Y., Zhu, Y., Wang, S. et al. SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection. Sig Transduct Target Ther 6, 368 2021. citationReceived 06 March 2021Revised 16 September 2021Accepted 20 September 2021Published 13 October 2021DOI

TheAccess SARS -CoV-2 IgG assay is a paramagnetic particle, chemiluminescent immunoassay intended for the virus in the form of anti -SARS-CoV-2

Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status — United States, April 2021–September 2022 Jefferson M. Jones, MD1; Irene Molina Manrique, MS2; Mars S. Stone, PhD3; Eduard Grebe, PhD3; Paula Saa, PhD4; Clara D. Germanio, PhD3; Bryan R. Spencer, PhD4; Edward Notari, MPH4; Marjorie Bravo, MD3; Marion C. Lanteri, PhD5; Valerie Green, MS5; Melissa Briggs-Hagen, MD1; Melissa M. Coughlin, PhD1; Susan L. Stramer, PhD4; Jean Opsomer, PhD2; Michael P. Busch, MD, PhD3 View author affiliations View suggested citationSummary What is already known about this topic? SARS-CoV-2 hybrid immunity immunity derived from both previous infection and vaccination has been reported to provide better protection than that from infection or vaccination alone. What is added by this report? By the third quarter of 2022, an estimated of persons aged ≥16 years in a longitudinal blood donor cohort had SARS-CoV-2 antibodies from previous infection or vaccination, including from infection alone and from vaccination alone; had hybrid immunity. Hybrid immunity prevalence was lowest among adults aged ≥65 years. What are the implications for public health practice? Low prevalence of infection-induced and hybrid immunity among older adults, who are at increased risk for severe disease if infected, reflects the success of public health infection prevention efforts while also highlighting the importance of this group staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose. Altmetric Citations Views Views equals page views plus PDF downloads Changes in testing behaviors and reporting requirements have hampered the ability to estimate the SARS-CoV-2 incidence 1. Hybrid immunity immunity derived from both previous infection and vaccination has been reported to provide better protection than that from infection or vaccination alone 2. To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies or both, data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 April–June, an estimated of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including from vaccination alone, from infection alone, and from both. By the third quarter of 2022 July–September, had SARS-CoV-2 antibodies from previous infection or vaccination, including from infection alone and from vaccination alone; had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years the group with the highest risk for severe disease if infected, and was highest among those aged 16–29 years Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.*,† Since July 2020, SARS-CoV-2 seroprevalence in the United States has been estimated by testing blood donations 3. CDC, in collaboration with Vitalant, American Red Cross, Creative Testing Solutions, and Westat, established a nationwide cohort of 142,758 blood donors in July 2021; the cohort included persons who had donated blood two or more times in the preceding year.§ All blood donations collected during April–June 2021 were tested for antibodies against the spike S and nucleocapsid N proteins. Beginning in 2022, up to one blood donation sample per donor was randomly selected each quarter and tested using the Ortho VITROS SARS-CoV-2 Quantitative S immunoglobulin G¶ and total N antibody** tests. Both SARS-CoV-2 infection and COVID-19 vaccination result in production of anti-S antibodies, whereas anti-N antibodies only result from infection. At each donation, blood donors were asked if they had received a COVID-19 vaccine. Using vaccination history and results of antibody testing, the prevalence of the population aged ≥16 years with vaccine-induced, infection-induced, or hybrid immunity was estimated for four 3-month periods April–June 2021, January–March 2022, April–June 2022, and July–September 2022; in addition, the proportion of persons who transitioned from one immune status to another by quarter was estimated. Analysis was limited to 72,748 donors for whom it was possible to ascertain immune status during each period using their prior classification previously infected or vaccinated, antibody testing results, and their vaccination status at the time of each donation.†† The sample data were weighted to account for selection into the study cohort, for nonresponse during the four analysis periods, and for demographic differences between the blood donor population and the overall population. The weights were obtained through a combination of stratification and raking, an iterative weighting adjustment procedure 4. Rates of infection among those previously uninfected were estimated for each period by determining the percentage of anti-N–negative persons seroconverting to anti-N–positive from one 3-month period included in the study to the next. Estimates were stratified by age group 16–29, 30–49, 50–64, and ≥65 years and race and ethnicity§§ Asian, Black or African American [Black], White, Hispanic or Latino [Hispanic], and other. SAS version SAS Institute was used to compute the final weights, and R version R Foundation was used to calculate all the estimates and create the plots.¶¶ Seroprevalence and infection rates were estimated as weighted means and compared by demographic group and vaccination status using two-sided t-tests with a significance level of α = This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.*** During the first quarter examined April–June 2021, an estimated 95% CI = of persons aged ≥16 years had SARS-CoV-2 antibodies from previous infection or vaccination, including 95% CI = from vaccination alone, 95% CI = from infection alone, and 95% CI = from both Figure 1 Supplementary Figure 1, During January–March 2022, 95% CI = of persons aged ≥16 years had antibodies from previous infection or vaccination, including 95% CI = from vaccination alone, 95% CI = from infection alone, and 95% CI = from both. During July–September 2022, 95% CI = of persons had antibodies from previous infection or vaccination, including 95% CI = with vaccine-induced immunity alone, 95% CI = with infection-induced immunity alone, and 95% CI = with hybrid immunity. During July–September 2022, the prevalence of infection-induced immunity was 95% CI = among unvaccinated persons and 95% CI = among vaccinated persons. During July–September 2022, the lowest prevalence of hybrid immunity, 95% CI = was observed in persons aged ≥65 years, and the highest, 95% CI = in adolescents and young adults aged 16–29 years Figure 2 Supplementary Figure 2, During all periods, higher prevalences of hybrid immunity were observed among Black and Hispanic populations than among White and Asian populations Supplementary Figure 3, Among persons with no previous infection, the incidence of first infections during the study period conversion from anti-N–negative to anti-N–positive was higher among unvaccinated persons Table. From April–June 2021 through January–March 2022, the incidence of first SARS-CoV-2 infections among unvaccinated persons was compared with among vaccinated persons p< From January–March 2022 through April–June 2022, the incidence among unvaccinated persons was and was among vaccinated persons. Between April–June 2022 and July–September 2022, the incidence among unvaccinated persons was compared with among vaccinated persons p< Incidence of first SARS-CoV-2 infections was higher among younger than among older persons and was lower among Asian persons than among other racial and ethnic populations, but the differences among groups narrowed over time. Discussion Both infection-induced and hybrid immunity increased during the study period. By the third quarter of 2022, approximately two thirds of persons aged ≥16 years had been infected with SARS-CoV-2 and one half of all persons had hybrid immunity. Compared with vaccine effectiveness against any infection and against severe disease or hospitalization, the effectiveness of hybrid immunity against these outcomes has been shown to be higher and wane more slowly 2. This increase in seroprevalence, including hybrid immunity, is likely contributing to lower rates of severe disease and death from COVID-19 in 2022–2023 than during the early pandemic.††† The prevalence of hybrid immunity is lowest in adults aged ≥65 years, likely due to higher vaccination coverage and earlier availability of COVID-19 vaccines for this age group, as well as to higher prevalences of behavioral practices to avoid infection 5. However, lower prevalences of infection-induced and hybrid immunity could further increase the risk for severe disease in this group, highlighting the importance for adults aged ≥65 years to stay up to date with COVID-19 vaccination and have easy access to antiviral medications. COVID-19 vaccine efficacy studies have reported reduced effectiveness against SARS-CoV-2 infection during the Omicron-predominant period compared with earlier periods and have shown that protection against infection wanes more rapidly than does protection against severe disease 6,7. In this study, unvaccinated persons had higher rates of infection as evidenced by N antibody seroconversion than did vaccinated persons, indicating that vaccination provides some protection against infection. The differences in incidence could also be due to systematic differences between vaccinated and unvaccinated persons in terms of the prevalence of practicing prevention behaviors such as masking and physical distancing. The relative difference in infection rates narrowed during the most recent months, possibly because of waning of vaccine-induced protection against infection in the setting of increased time after vaccination or immune evasion by the SARS-CoV-2 Omicron variant. The narrowing of difference in infection rates might also be attributable to increasing similarities in behavior among vaccinated and unvaccinated persons during late 2022 8. The findings in this report are subject to at least six limitations. First, although COVID-19 booster vaccine doses and reinfections can strengthen immunity 9,10, this analysis did not account for these effects because blood donor vaccination history did not include the number of doses received, and data on reinfections were not captured. Second, immunity wanes over time, but time since vaccination or infection was not included in the analysis 2. Third, vaccination status was self-reported, potentially leading to misclassification. Fourth, although the results were adjusted based on differences in blood donor and general population demographics, estimates from blood donors might not be representative of the general population; thus, these results might not be generalizable. Fifth, vaccinated and unvaccinated persons might differ in other ways not captured by this analysis 8, nor can causality be inferred from the results on relative infection incidence. Finally, if both vaccination and infection occurred between blood donations included in the study, the order of occurrence could not be determined, and some unvaccinated donors might have been vaccinated before infection and thus misclassified; in 2022, this was uncommon and occurred in < of donors during any 3-month period. This report found that the incidence of first-time SARS-CoV-2 infection was lower among persons who had received COVID-19 vaccine than among unvaccinated persons and that infection-induced and hybrid immunity have increased but remain lowest in adults aged ≥65 years. These adults have consistently had a higher risk for severe disease compared with younger age groups, underscoring the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose. Acknowledgments Brad Biggerstaff, Matthew McCullough, CDC; Roberta Bruhn, Brian Custer, Xu Deng, Zhanna Kaidarova, Kathleen Kelly, Anh Nguyen, Graham Simmons, Hasan Sulaeman, Elaine Yu, Karla Zurita-Gutierrez, Vitalant Research Institute; Akintunde Akinseye, Jewel Bernard-Hunte, Robyn Ferg, Rebecca Fink, Caitlyn Floyd, Isaac Lartey, Sunitha Mathews, David Wright, Westat; Jamel Groves, James Haynes, David Krysztof, American Red Cross; Ralph Vassallo, Vitalant; Sherri Cyrus, Phillip Williamson, Creative Testing Solutions; Paul Contestable, QuidelOrtho; Steve Kleinman, University of British Columbia; CDC, Vitalant Research Institute, Westat, American Red Cross, and Creative Testing Solutions staff members; blood donors whose samples were analyzed and who responded to surveys for this study. Corresponding author Jefferson M. Jones, ioe8 Center for Immunization and Respiratory Diseases, CDC; 2Westat, Rockville, Maryland; 3Vitalant Research Institute, San Francisco, California; 4American Red Cross, Washington, DC; 5Creative Testing Solutions, Tempe, authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed. * † § Blood donors who donated at least twice during the year before July 2021 were included in the cohort, because they might represent persons who were more likely to donate frequently. Among donors who donated more than once during a quarter, one sample was selected at random for testing. ¶ ** †† §§ Persons of Hispanic origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic. ¶¶ Jackknife replication was used to compute replicate weights. Weights were adjusted for nonresponse using adjustment cells created by age category, vaccination and previous infection status, and blood collection organization Vitalant or American Red Cross. Raking was used to further adjust the weights to account for demographic differences between the blood donor population and population. The demographic variables used for raking were sex female and male, age group 16–24, 25–34, 35–44, 45–54, 55–64, and ≥65 years, and race and ethnicity Asian, Black, White, Hispanic, and other. *** 45 part 46, 21 part 56; 42 Sect. 241d; 5 Sect. 552a; 44 Sect. 3501 et seq. ††† Accessed May 25, 2023. References Rader B, Gertz A, Iuliano AD, et al. Use of at-home COVID-19 tests—United States, August 23, 2021–March 12, 2022. MMWR Morb Mortal Wkly Rep 2022;71489–94. PMID35358168 Bobrovitz N, Ware H, Ma X, et al. Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the Omicron variant and severe disease a systematic review and meta-regression. Lancet Infect Dis 2023;23556–67. PMID36681084 Jones JM, Stone M, Sulaeman H, et al. Estimated US infection- and vaccine-induced SARS-CoV-2 seroprevalence based on blood donations, July 2020–May 2021. JAMA 2021;3261400–9. PMID34473201 Deville J-C, Särndal C-E, Sautory O. Generalized raking procedures in survey sampling. J Am Stat Assoc 1993;881013–20. Steele MK, Couture A, Reed C, et al. Estimated number of COVID-19 infections, hospitalizations, and deaths prevented among vaccinated persons in the US, December 2020 to September 2021. JAMA Netw Open 2022;5e2220385. PMID35793085 Higdon MM, Wahl B, Jones CB, et al. A systematic review of coronavirus disease 2019 vaccine efficacy and effectiveness against severe acute respiratory syndrome coronavirus 2 infection and disease. Open Forum Infect Dis 2022;9ofac138. PMID35611346 Feikin DR, Higdon MM, Abu-Raddad LJ, et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease results of a systematic review and meta-regression. Lancet 2022;399924–44. PMID35202601 Thorpe A, Fagerlin A, Drews FA, Shoemaker H, Scherer LD. Self-reported health behaviors and risk perceptions following the COVID-19 vaccination rollout in the USA an online survey study. Public Health 2022;20868–71. PMID35717747 Sette A, Crotty S. Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. Immunol Rev 2022;31027–46. PMID35733376 Atti A, Insalata F, Carr EJ, et al.; SIREN Study Group and the Crick COVID Immunity Pipeline Consortium. Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination a nested case-control within the SIREN study. J Infect 2022;85545–56. PMID36089104 FIGURE 1. Prevalences of vaccine-induced, infection-induced, and hybrid* immunity† against SARS-CoV-2 among blood donors aged ≥16 years — United States, April 2021–September 2022 * Immunity derived from a combination of vaccination and infection. † Ascertained by the presence of anti-spike antibodies present in both COVID-19–vaccinated and SARS-CoV-2–infected persons and anti-nucleocapsid antibodies present only in previously infected persons and self-reported history of vaccination. FIGURE 2. Prevalences of vaccine-induced, infection-induced, and hybrid* immunity† against SARS-CoV-2 among blood donors aged ≥16 years, by age group — United States, April 2021–September 2022 * Immunity derived from a combination of vaccination and infection. † Ascertained by the presence of anti-spike antibodies present in both COVID-19–vaccinated and SARS-CoV-2–infected persons and anti-nucleocapsid antibodies present only in previously infected persons and self-reported history of vaccination. TABLE. Estimated percentage* of persons infected with SARS-CoV-2 for the first time among blood donors, by analysis quarter, sociodemographic characteristics, and vaccination status — United States, April 2021–September 2022 Characteristic Period, % 95% CI Apr–Jun 2021 to Jan–Mar 2022 Jan–Mar 2022 to Apr–Jun 2022 Apr–Jun 2022 to Jul–Sep 2022 Overall Total Unvaccinated Vaccinated Age group, yrs 16–29 Total Unvaccinated Vaccinated 30–49 Total Unvaccinated Vaccinated 50–64 Total Unvaccinated Vaccinated ≥65 Total Unvaccinated Vaccinated Race and ethnicity§ Asian Total Unvaccinated Vaccinated Black or African American Total Unvaccinated Vaccinated White Total Unvaccinated Vaccinated Hispanic or Latino Total Unvaccinated Vaccinated Other and multiple races¶ Total Unvaccinated Vaccinated * Percentage of uninfected persons anti-nucleocapsid–negative in the previous 3-month period seroconverting to anti-nucleocapsid–positive. If both vaccination and infection occurred between donations included in the study, the order could not be determined, and some unvaccinated donors might have been vaccinated before infection and thus misclassified. † If donors who transitioned from no antibodies to hybrid immunity between April–June 2021 and January–March 2022 were excluded, an estimated 95% CI = of unvaccinated donors were infected. For other periods, exclusion did not substantially change results. Between January–March and April–June 2022, of persons shifted from no antibodies to hybrid immunity. Between April–June and July–September 2022, of persons shifted from no antibodies to hybrid immunity. § Persons of Hispanic or Latino Hispanic origin might be of any race but are categorized as Hispanic; all racial groups are non-Hispanic. ¶ Includes American Indian or Alaska Native and non-Hispanic persons of other races. Suggested citation for this article Jones JM, Manrique IM, Stone MS, et al. Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status — United States, April 2021–September 2022. MMWR Morb Mortal Wkly Rep 2023;72601–605. DOI MMWR and Morbidity and Mortality Weekly Report are service marks of the Department of Health and Human Services. Use of trade names and commercial sources is for identification only and does not imply endorsement by the Department of Health and Human Services. References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in MMWR were current as of the date of publication. All HTML versions of MMWR articles are generated from final proofs through an automated process. 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