CORD-19-Sentences  

CORD-19:12f1cc78e99a0b82f3225d10abe9a5649f1b33fc JSONTXT 8 Projects

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TextSentencer_T1 0-113 Sentence denotes Prevalence of Antibodies to Four Human Coronaviruses Is Lower in Nasal Secretions than in Serum ᰔ Downloaded from
TextSentencer_T2 115-123 Sentence denotes Abstract
TextSentencer_T3 124-320 Sentence denotes Little is known about the prevalence of mucosal antibodies induced by infection with human coronaviruses (HCoV), including HCoV-229E and -OC43 and recently described strains (HCoV-NL63 and -HKU1).
TextSentencer_T4 321-586 Sentence denotes By enzyme-linked immunosorbent assay, we measured anti-HCoV IgG antibodies in serum and IgA antibodies in nasal wash specimens collected at seven U.S. sites from 105 adults aged 50 years and older (mean age, 67 ؎ 9 years) with chronic obstructive pulmonary disease.
TextSentencer_T5 587-650 Sentence denotes Most patients (95 [90%]) had at least one more chronic disease.
TextSentencer_T6 651-1038 Sentence denotes More patients had serum antibody to each HCoV strain (104 [99%] had antibody to HCoV-229E, 105 [100%] had antibody to HCoV-OC43, 103 [98%] had antibody to HCoV-NL63, and 96 [91%] had antibody to HCoV-HKU1) than had antibody to each HCoV strain in nasal wash specimens (12 [11%] had antibody to HCoV-229E, 22 [22%] had antibody to HCoV-OC43, 8 [8%] had antibody to HCoV-NL63, and 31 [31%]
TextSentencer_T7 1039-1093 Sentence denotes had antibody to HCoV-HKU1), respectively (P < 0.0001).
TextSentencer_T8 1094-1288 Sentence denotes The proportions of subjects with IgA antibodies in nasal wash specimens and the geometric mean IgA antibody titers were statistically higher for HCoV-OC43 and -HKU1 than for HCoV-229E and -NL63.
TextSentencer_T9 1289-1418 Sentence denotes A higher proportion of patients with heart disease than not had IgA antibodies to HCoV-NL63 (6 [16%] versus 2 [3%]; P ‫؍‬ 0.014).
TextSentencer_T10 1419-1714 Sentence denotes Correlations were highest for serum antibody titers between group I strains (HCoV-229E and -NL63 [r ‫؍‬ 0.443; P < 0.0001]) and between group II strains (HCoV-OC43 and -HKU1 [r ‫؍‬ 0.603; P < 0.0001]) and not statistically significant between HCoV-NL63 and -OC43 and between HCoV-NL63 and -HKU1.
TextSentencer_T11 1715-1938 Sentence denotes Patients likely had experienced infections with more than one HCoV strain, and IgG antibodies to these HCoV strains in serum were more likely to be detected than IgA antibodies to these HCoV strains in nasal wash specimens.
TextSentencer_T12 1940-2068 Sentence denotes Coronaviruses comprise a genus of the family Coronaviridae and are enveloped, single-stranded, positive-sense RNA viruses (30) .
TextSentencer_T13 2069-2393 Sentence denotes Four human coronavirus (HCoV) strains have been described, which are associated with a spectrum of disease, from mild, febrile upper respiratory tract illnesses to severe illnesses, including croup, bronchiolitis, and pneumonia, and have a wide geographic distribution (1, 2, 6, 7, 9-14, 16, 20, 25, 26, 31, 32, 35, 39-46) .
TextSentencer_T14 2394-2569 Sentence denotes HCoV infection has been a contributor to severe illnesses requiring emergency care and hospitalization of patients with chronic medical conditions (7, 9, 12, 15, 16, 21, 22) .
TextSentencer_T15 2570-2988 Sentence denotes The earliest-described HCoV strains, HCoV-229E and HCoV-OC43, which are group I and group II coronaviruses, respectively, have now been joined by the more recently described group I and II strains HCoV-NL63 and HCoV-HKU1 (13, 30, 42, 45, 46) , which were discovered in the search for other pathogenic coronaviruses after the identification of the coronavirus that causes severe acute respiratory syndrome (SARS) (29) .
TextSentencer_T16 2989-3183 Sentence denotes HCoV-NL63 may have infected human populations for a long time, since it diverged phylogenetically from HCoV-229E about 1,000 years ago (33) , and seroprevalence would likely be high as a result.
TextSentencer_T17 3184-3506 Sentence denotes Cross-sectional and longitudinal seroepidemiological studies have found large proportions of children and healthy adults to have detectable serum antibodies to the four HCoV strains, and seroconversion occurs often in childhood; seroprevalence increases with age, and reinfections may occur (5, 8, 23, 28, (36) (37) (38) .
TextSentencer_T18 3507-3697 Sentence denotes More information is needed about the seroprevalence of these viruses, the durability of the humoral immune response, correlates of immunity, and mucosal antibody responses to HCoV infection.
TextSentencer_T19 3698-4006 Sentence denotes The present study questioned whether the prevalence of antibodies to the four HCoV strains would be different in nasal secretions than in serum of older adult veterans with underlying chronic obstructive pulmonary disease (COPD) who participated in Department of Veterans Affairs Cooperative Study 448 (18) .
TextSentencer_T20 4007-4388 Sentence denotes A convenience sample of 105 patients who met spirometric criteria for COPD and were enrolled in a larger influenza virus vaccine efficacy trial of patients Ն50 years of age (18) were chosen for analysis in this substudy of the prevalence of antibodies to HCoV, because residual serum and nasal wash specimens collected at the same time for each subject were available for analysis.
TextSentencer_T21 4389-4518 Sentence denotes The 105 subjects were enrolled at seven geographically diverse study sites in the United States, located in the following states:
TextSentencer_T22 4519-4592 Sentence denotes Alabama, Florida, Illinois, Massachusetts, Michigan, Missouri, and Texas.
TextSentencer_T23 4593-4830 Sentence denotes The paired serum and nasal wash specimens were collected at about 3 to 4 weeks following influenza virus vaccination between October 1998 and February 1999 and were not associated with acute respiratory illness at the time of collection.
TextSentencer_T24 4831-4949 Sentence denotes All patients gave written informed consent, and responsible committees on human experimentation approved of the study.
TextSentencer_T25 4950-4980 Sentence denotes Antigen preparation and ELISA.
TextSentencer_T26 4981-5107 Sentence denotes The HCoV antigens used for the antibody enzyme-linked immunosorbent assay (ELISA) were produced as described previously (16) .
TextSentencer_T27 5108-5280 Sentence denotes HCoV-229E and HCoV-OC43 were obtained from the American Type Culture Collection (ATCC, Manassas, VA) and were grown in MRC-5 and HCT-8 cell monolayers (ATCC), respectively.
TextSentencer_T28 5281-5408 Sentence denotes HCoV-NL63 was grown in LLC-MK2 cell monolayers (a gift from Lia van der Hoek, University of Amsterdam, Amsterdam, Netherlands).
TextSentencer_T29 5409-5662 Sentence denotes Virus-infected cells were frozen and thawed three times, the supernatant fluid was cleared of cell debris by centrifugation, the virus was concentrated by overnight centrifugation, and the virus pellet was resuspended in phosphate-buffered saline (PBS).
TextSentencer_T30 5663-5832 Sentence denotes The concentrated virus was inactivated by a psoralen compound (Sigma, St. Louis, MO), followed by irradiation by long-wavelength UV light, as described previously (34) .
TextSentencer_T31 5833-5899 Sentence denotes Mock antigen was prepared, in the same way, from uninfected cells.
TextSentencer_T32 5900-6021 Sentence denotes The His 6 -tagged recombinant N protein of HCoV-HKU1 was used as an antigen in the ELISA to detect antibody to HCoV-HKU1.
TextSentencer_T33 6022-6275 Sentence denotes Expression vector pET-28b(ϩ) (Novagen, Inc., New Canaan, CT), encoding the N protein of HCoV-HKU1 cloned into the EcoRI and NotI sites in frame and downstream from a series of six-histidine residues, as described previously (45, 46) , was a gift from K.
TextSentencer_T34 6276-6278 Sentence denotes Y.
TextSentencer_T35 6279-6321 Sentence denotes Yuen (University of Hong Kong, Hong Kong).
TextSentencer_T36 6322-6638 Sentence denotes The recombinant N protein was expressed by the transformation of BL21(DE3) single competent cells (Novagen, Inc.) by the plasmid and was purified by use of the Ni 2ϩ -loaded HiTrap chelating system (Amersham Biosciences, Piscataway, NJ) according to the manufacturer's instructions and as described previously (16) .
TextSentencer_T37 6639-6783 Sentence denotes In brief, transformed cells were disrupted, and the protein sample was prepared by the isolation of inclusion bodies via sonication and washing.
TextSentencer_T38 6784-6908 Sentence denotes The protein sample was loaded onto the HiTrap chelating HP column prepacked with precharged highperformance Ni 2ϩ Sepharose.
TextSentencer_T39 6909-7178 Sentence denotes The protein was then purified and refolded by serial buffer washes of the column and by liquid chromatography in a fast protein liquid chromatography (FPLC) system (Pharmacia LBK Biotechnology, Piscataway, NJ), with elution of protein, which was collected in fractions.
TextSentencer_T40 7179-7258 Sentence denotes The fractions were analyzed for the presence of the 53-kDa protein by SDS-PAGE.
TextSentencer_T41 7259-7407 Sentence denotes The protein concentration was determined by the Bio-Rad protein assay (Bio-Rad Laboratories, Hercules, CA) and was adjusted to 3 g/ml for the ELISA.
TextSentencer_T42 7408-7531 Sentence denotes Mock antigen was produced from the same plasmid DNA vector, but without the N protein gene sequence, by the same procedure.
TextSentencer_T43 7532-7680 Sentence denotes Each viral antigen and its respective control were used to coat flat-bottom 96-well Maxisorp Immunoplates (Nalge-Nunc International, Rochester, NY).
TextSentencer_T44 7681-8049 Sentence denotes To measure serum IgG antibodies, the sequence of reagents consisted of serum in a series of eight 2-fold dilutions starting at a 100-fold dilution to generate a broad dose-response curve, mouse anti-human IgG (Fc specific) conjugated with horseradish peroxidase (Accurate Chemical and Scientific, Westbury, NY), and ophenylenediamine substrate (KPL, Gaithersburg, MD).
TextSentencer_T45 8050-8170 Sentence denotes The optical density (OD) was measured at 405 nm by use of a Tecan (Research Triangle Park, NC) SLT400 spectrophotometer.
TextSentencer_T46 8171-8275 Sentence denotes The anti-HCoV antibody titer in the ELISA was calculated by the reference-line least-squares-fit method.
TextSentencer_T47 8276-8490 Sentence denotes The cutoff OD was set at 0.3 for all viral antigens, a level that was at least twice the background OD for the respective mock antigens, and corresponded to the linear range of OD versus reciprocal-dilution curves.
TextSentencer_T48 8491-8730 Sentence denotes To measure IgA antibodies in nasal wash specimens, the nasal wash specimens were first sonicated and then concentrated by using centrifugal filter devices (Centriprep; Millipore Corp., Ireland) according to the manufacturer's instructions.
TextSentencer_T49 8731-9073 Sentence denotes The concentrated nasal wash specimens were tested in an ELISA, which was the same as that used for sera, except that the nasal wash specimens were diluted in a series of six 2-fold dilutions starting at a 5-fold dilution and goat anti-human IgA (␣-chain) conjugated with horseradish peroxidase (MP Biomedicals-Cappel, Solon, OH) was employed.
TextSentencer_T50 9074-9311 Sentence denotes An endpoint anti-HCoV antibody titer was the final dilution of the nasal wash specimen with an OD in the antigen-coated well of 0.3 or greater and that was at least twice that of the respective control, as described previously (17, 19) .
TextSentencer_T51 9312-9418 Sentence denotes The total IgA antibody concentration in the nasal wash specimens was determined previously by ELISA (17) .
TextSentencer_T52 9419-9693 Sentence denotes Briefly, the sequence of reagents beginning with the solid phase was goat anti-human IgA (ICN/Cappel Pharmaceuticals, Inc., Aurora, OH), the nasal wash specimen, goat anti-human IgA (␣-chain specific) conjugated with horseradish peroxidase, and o-phenylenediamine substrate.
TextSentencer_T53 9694-9899 Sentence denotes The standard curve of known secretory IgA concentrations was determined by using serial dilutions of human secretory IgA (ICN Biomedical, Inc., Costa Mesa, CA) instead of nasal wash specimens in the ELISA.
TextSentencer_T54 9900-10128 Sentence denotes We repeated the measurement of total IgA concentrations in this study, finding that there was no decay in the total IgA concentration in these specimens that were stored at Ϫ70°C for about 9 years after their initial collection.
TextSentencer_T55 10129-10349 Sentence denotes The anti-HCoV IgA antibody titer in nasal wash specimens was mathematically adjusted to an arbitrary total IgA antibody concentration of 100 mg/liter using the measured total IgA antibody concentration for each specimen.
TextSentencer_T56 10350-10370 Sentence denotes Statistical methods.
TextSentencer_T57 10371-10447 Sentence denotes Demographic and antibody data were analyzed by using descriptive statistics.
TextSentencer_T58 10448-10594 Sentence denotes Reciprocal antibody titers were logarithmically transformed, and geometric mean titers (GMTs) were compared by using the Wilcoxon signedrank test.
TextSentencer_T59 10595-10700 Sentence denotes McNemar's test was used to compare pairwise proportions of subjects with detectable anti-HCoV antibodies.
TextSentencer_T60 10701-10804 Sentence denotes Nonpaired data were compared by using the 2 test or Fisher's exact test and the Wilcoxon rank sum test.
TextSentencer_T61 10805-10956 Sentence denotes Logarithmically transformed serum IgG antibody titers against HCoV strains were assessed by linear regression, and Pearson correlations were performed.
TextSentencer_T62 10957-11042 Sentence denotes Of the 105 patients studied, 101 (96%) were male and 97 (92%) were white ( Table 1 ).
TextSentencer_T63 11043-11220 Sentence denotes All had spirometrically confirmed obstructive pulmonary disease, 95 (90%) had one or more additional underlying illnesses, and 68 (65%) were 65 years of age or older (Table 1) .
TextSentencer_T64 11221-11374 Sentence denotes At least 98% of the 105 patients had serum IgG antibodies to HCoV-229E, -NL63, and -OC43, while 96 (91%) had serum IgG antibody to HCoV-HKU1 ( Table 2 ).
TextSentencer_T65 11375-11586 Sentence denotes The proportions of patients with detectable IgG antibodies to HCoV-229E, -NL63, and -OC43 were all greater than the proportion with IgG antibody to HCoV-HKU1 (P ϭ 0.011, P ϭ 0.035, and P ϭ 0.0004, respectively).
TextSentencer_T66 11587-11884 Sentence denotes Compared to serum IgG antibody, smaller proportions of patients had IgA antibody to each of the HCoV strains in nasal wash specimens (12 [11%] were HCoV-229E positive, 8 [8%] were HCoV-NL63 positive, 22 [22%] were HCoV-OC43 positive, and 31 [31%] were HCoV-HKU1 positive) (P Ͻ 0.0001) ( Table 2 ).
TextSentencer_T67 11885-12145 Sentence denotes The proportions of patients with IgA antibodies against HCoV-OC43 and -HKU1 were significantly greater than those with IgA antibodies against HCoV-229E (P ϭ 0.03 and P ϭ 0.0013, respectively) and HCoV-NL63 (P ϭ 0.001 and P Ͻ 0.0001, respectively) ( Table 2) .
TextSentencer_T68 12146-12314 Sentence denotes Anti-HCoV IgA antibody GMTs for nasal wash specimens with detectable antibody were within a 2-fold dilution range when the four viral strains were compared ( Table 2 ).
TextSentencer_T69 12315-12516 Sentence denotes The GMTs were higher and the ranges of individual IgA antibody titers included higher values for HCoV-OC43 and -HKU1 than HCoV-229E (P ϭ 0.003 and P ϭ 0.0006, respectively) and -NL63 (both P Ͻ 0.0001).
TextSentencer_T70 12517-12717 Sentence denotes The serum IgG antibody GMT for HCoV-229E was less than that for HCoV-OC43 (P ϭ 0.003), and the serum IgG GMTs for HCoV-229E and -OC43 were each greater than those for HCoV-NL63 and -HKU1 (P Ͻ 0.0001).
TextSentencer_T71 12718-12830 Sentence denotes The serum IgG antibody GMTs for HCoV-229E and -OC43 were about 2-fold higher than those for HCoV-NL63 and -HKU1.
TextSentencer_T72 12831-13493 Sentence denotes The ranges of individual IgG antibody titers extended more than 7-fold higher for HCoV-229E over HCoV-NL63 and 5-fold higher for HCoV-OC43 over HCoV-HKU1 (Table 2 ), but only 11 sera had an IgG antibody titer against HCoV-229E (16) a Spirometric criteria for COPD were an FEV 1 that was 80% or less of the predicted value and an FEV 1 /FVC ratio of less than 0.70, as described previously (18) , where FEV 1 is the forced expiratory volume in 1 s and FVC is the forced vital capacity. that was greater than the highest titer against HCoV-NL63, and only 2 sera had an IgG antibody titer against HCoV-OC43 that was greater than the highest titer against HCoV-HKU1.
TextSentencer_T73 13494-13623 Sentence denotes Between 13% and 75% of nasal wash specimens with IgA antibody to one HCoV strain had antibody to another viral strain (Table 3) .
TextSentencer_T74 13624-13827 Sentence denotes Five nasal wash specimens had titers of IgA antibody to HCoV-OC43 that exceeded the highest titer against HCoV-229E in any specimen, and none of these five specimens had detectable antibody to HCoV-229E.
TextSentencer_T75 13828-14039 Sentence denotes Similarly, seven nasal wash specimens had IgA antibody titers against HCoV-HKU1 that exceeded the highest titer against HCoV-NL63 in any specimen, and only one of these seven specimens had antibody to HCoV-NL63.
TextSentencer_T76 14040-14219 Sentence denotes Hence, the cross-reactive IgA antibodies to more than one viral strain that might be expected for high-titer specimens were often not present for a strain in the other HCoV group.
TextSentencer_T77 14220-14466 Sentence denotes Since most sera had IgG antibodies to all four HCoV strains, we assessed correlations between serum IgG antibody titers against HCoV strains to characterize possible antigenic relationships between HCoV strains and groups based on seroreactivity.
TextSentencer_T78 14467-14584 Sentence denotes The highest levels of correlation were between strains within each of HCoV group I (Fig. 1A) and group II (Fig. 1B) .
TextSentencer_T79 14585-14864 Sentence denotes Comparisons of serum IgG antibody titers against HCoV strains between groups had lower correlation coefficients that were either not statistically significant or at weaker significance levels ( Fig. 1C to F) than those observed for the within-group comparisons ( Fig. 1A and B) .
TextSentencer_T80 14865-15002 Sentence denotes Thus, these data are also consistent with patients having experienced infections with both group I and group II HCoV strains in the past.
TextSentencer_T81 15003-15287 Sentence denotes Serum IgG and nasal wash specimen IgA antibody GMTs against each HCoV strain were not significantly different when current smokers were compared to nonsmokers and when patients with a history of heart disease were compared to those without a history of heart disease (data not shown).
TextSentencer_T82 15288-15470 Sentence denotes The proportions of patients with nasal wash specimen IgA antibodies to the HCoV strains who were current smokers compared to nonsmokers did not differ significantly (data not shown).
TextSentencer_T83 15471-15857 Sentence denotes The proportion with IgA antibodies to HCoV-NL63 in nasal wash specimens of patients with a history of heart disease was higher than that of patients without heart disease (6 [16%] versus 2 [3%]; P ϭ 0.014), but the proportions with IgA antibodies to the other three HCoV strains in nasal wash specimens from patients with and those without heart disease did not differ (data not shown).
TextSentencer_T84 15858-16114 Sentence denotes Serum IgG antibodies to all four HCoV strains were present in most study subjects, but IgA antibodies to the four HCoV strains were detected less frequently in nasal wash specimens, a GMT, geometric mean titer, calculated by the inclusion of all specimens.
TextSentencer_T85 16115-16328 Sentence denotes Sera without detectable antibody titers against HCoV were arbitrarily assigned a titer of 50, and nasal wash (NW) specimens without detectable antibody titers against HCoV were arbitrarily assigned a titer of 2.5.
TextSentencer_T86 16329-16655 Sentence denotes b Four specimens were depleted prior to the finishing of testing against all viral antigens. c There was significant nonagreement between antibody pairs against HCoV-229E and HCoV-HKU1, between HCoV-NL63 and HCoV-HKU1, and between HCoV-0C43 and HCoV-HKU1 (P ϭ 0.011, P ϭ 0.035, and P ϭ 0.004, respectively, by McNemar's test).
TextSentencer_T87 16656-16819 Sentence denotes The proportion with serum IgG antibody was different than the proportion with IgA antibody in nasal wash specimens for each HCoV strain, respectively (P Ͻ 0.0001).
TextSentencer_T88 16820-16947 Sentence denotes d The GMT against HCoV-229E was greater than the GMT against HCoV-NL63 and HCoV-HKU1 (P Ͻ 0.0001 by Wilcoxon signed-rank test).
TextSentencer_T89 16948-17055 Sentence denotes The GMT against HCoV-229E was less than the GMT against HCoV-OC43 (P ϭ 0.003 by Wilcoxon signed-rank test).
TextSentencer_T90 17056-17395 Sentence denotes e The GMT against HCoV-OC43 was greater than the GMTs against HCoV-NL63 and HCoV-KHU1 (P Ͻ 0.0001 by Wilcoxon signed-rank test). f There was significant nonagreement between antibody pairs against HCoV-229E and HCoV-OC43 and between antibody pairs against HCoV-229E and HCoV-HKU1 (P ϭ 0.03 and P ϭ 0.0013, respectively, by McNemar's test).
TextSentencer_T91 17396-17607 Sentence denotes g There was significant nonagreement between antibody pairs against HCoV-NL63 and HCoV-OC43 and between antibody pairs against HCoV-NL63 and HCoV-HKU1 (P ϭ 0.001 and P Ͻ 0.0001, respectively, by McNemar's test).
TextSentencer_T92 17608-17761 Sentence denotes h The GMT against HCoV-229E was less than the GMT against HCoV-OC43 and HCoV-HKU1 (P ϭ 0.003 and P ϭ 0.0006, respectively, by Wilcoxon signed-rank test).
TextSentencer_T93 17762-17919 Sentence denotes i The GMT against HCoV-NL63 was less than the GMTs against HCoV-OC43 and HCoV-HKU1 (P Ͻ 0.0001 by Wilcoxon signed-rank test). for only 8% to 31% of subjects.
TextSentencer_T94 17920-18051 Sentence denotes Patients represented a broad geographic distribution, from the Midwestern, Southern, and Northeastern regions of the United States.
TextSentencer_T95 18052-18122 Sentence denotes A wide range of IgG and IgA antibody titers against HCoV was observed.
TextSentencer_T96 18123-18260 Sentence denotes The levels of mean IgG antibody to HCoV-229E and -OC43 were higher than levels of mean IgG antibody to HCoV-NL63 and -HKU1, respectively.
TextSentencer_T97 18261-18482 Sentence denotes Nasal wash specimen IgA antibodies to the two group II HCoV strains were more frequently detected than were antibodies to the two group I strains, and the mean antibody titers were higher for the group II strains as well.
TextSentencer_T98 18483-18700 Sentence denotes Since the mean antibody titers against the HCoV strains in serum and also in nasal wash specimens were within about a 2-fold range, it is unclear if the statistical differences in mean titers are important clinically.
TextSentencer_T99 18701-18874 Sentence denotes The concomitant presence of IgA antibody to more than one HCoV strain was observed for some nasal wash specimens but was universal in the case of serum IgG antibody to HCoV.
TextSentencer_T100 18875-19403 Sentence denotes The findings may reflect previous infections of patients with more than one viral strain, antibody cross-reactivity between strains due to HCoV group-specific rather than strain-specific antigens, better induction of mucosal IgA antibodies by certain HCoV strains and a shorter period of detectability after infection in secretions than in serum, and a better preservation of antibodies in the nasal wash specimens with antibody to HCoV than in those that had no detectable anti-HCoV antibody despite similar storage conditions.
TextSentencer_T101 19404-19561 Sentence denotes However, the amount of total IgA in the specimens did not decline during storage, so strainspecific IgA antibodies should not have decayed in storage either.
TextSentencer_T102 19562-19756 Sentence denotes Correlation of serum IgG antibody titers within and across HCoV groups showed a more striking association between the levels of antibody to the HCoV strains within each group than across groups.
TextSentencer_T103 19757-19846 Sentence denotes This may reflect antigenic crossreactivity within HCoV groups but less so between groups.
TextSentencer_T104 19847-19982 Sentence denotes Also, cross-reactive IgA antibodies to HCoV strains between HCoV groups were generally not observed in high-titer nasal wash specimens.
TextSentencer_T105 19983-20305 Sentence denotes Levels of serum antibody to HCoV-229E and -OC43 in our study in terms of GMT and the frequency of detection were similar to data reported previously by Schmidt et al. (36) , who described repeated significant increases in antibody longitudinally over time, suggesting that reinfections occurred with the same virus strain.
TextSentencer_T106 20306-20705 Sentence denotes The prevalence of serum antibodies to HCoV-229E and -OC43 in our study was higher than those reported previously by Hruskova et al. (23) in Czechoslovakia and was higher than the prevalence of serum antibodies to HCoV-229E in children and adolescents in the United States reported previously by Shao et al. (38) but was similar to those reported for HCoV-OC43 in health care workers in France (28) .
TextSentencer_T107 20706-20882 Sentence denotes Children in the Netherlands aged 2.5 to 3.5 years had serum antibodies to HCoV-NL63 and HCoV-229E in 75% and 65% of serum samples collected cross-sectionally, respectively (8).
TextSentencer_T108 20883-21144 Sentence denotes Severance et al. (37) previously reported seroprevalence rates of about 90% for HCoV-229E, -NL63, and -OC43 among a largely adult population in Maryland but a seroprevalence rate of only 59% for HCoV-HKU1, which is lower than that reported in the present study.
TextSentencer_T109 21145-21387 Sentence denotes In seroepidemiological studies of families including children and young adults in one community, a high prevalence of antibodies to HCoV-229E and -OC43 was reported, and frequent reinfections occurred despite preexisting serum antibody (27) .
TextSentencer_T110 21388-21559 Sentence denotes Thus, there is evidence for infections with these viruses being common in children and adults and occurring over a wide geographical distribution and frequently over time.
TextSentencer_T111 21560-21744 Sentence denotes We did not identify a difference in antibody titers when current smokers were compared to nonsmokers, unlike what was reported by Severance et al. (37) for IgG antibodies to HCoV-OC43.
TextSentencer_T112 21745-21897 Sentence denotes For unclear reasons, patients with a history of heart disease were more likely to have IgA antibodies to HCoV-NL63 in nasal wash specimens in our study.
TextSentencer_T113 21898-22052 Sentence denotes The receptor that HCoV-NL63 uses to find and enter target cells is unique among group I and II coronaviruses but is the same as that for SARS coronavirus.
TextSentencer_T114 22053-22263 Sentence denotes This receptor is angiotensin-converting enzyme 2 (ACE2), which is present on arterial and venous endothelial cells, arterial smooth-muscle cells, and small intestine and tracheobronchial airway epithelia (32) .
TextSentencer_T115 22264-22474 Sentence denotes ACE2 helps regulate the renin-angiotensin-aldosterone system, which is activated in heart failure, by inactivating angiotensin II, and ACE2 plays a role in protection from severe acute lung injury (3, 24, 32) .
TextSentencer_T116 22475-22575 Sentence denotes Among the human coronaviruses, HCoV-NL63 in particular has been associated with croup (31, 35, 43) .
TextSentencer_T117 22576-22667 Sentence denotes Two reports of IgA antibodies to HCoV in nasal secretions could be found in the literature.
TextSentencer_T118 22668-22952 Sentence denotes Callow et al. (5) reported previously that IgA antibodies to HCoV-229E were detectable in nasal wash specimens after experimental infection of adults with the virus and that the IgA antibody levels declined during follow-up but remained higher than preinfection levels 52 weeks later.
TextSentencer_T119 22953-23292 Sentence denotes Another previous report by Callow (4) suggested that HCoV-229E-specific antibodies in serum and nasal wash specimens were correlated with protection from experimental infection with HCoV-229E and disease, and IgA antibodies to HCoV-229E in nasal wash specimens were associated with a reduced duration of viral shedding in nasal secretions.
TextSentencer_T120 23293-23575 Sentence denotes Hence, despite the near-universal presence of serum antibodies to the HCoV strains in our study, the lower rates of detectable IgA antibodies to HCoV suggest a possible reason for susceptibility to reinfections with HCoV, if IgA antibodies in nasal secretions are indeed protective.
TextSentencer_T121 23576-23675 Sentence denotes In summary, serum IgG antibodies to all four HCoV strains were detectable in most patients studied.
TextSentencer_T122 23676-23768 Sentence denotes It appears likely that patients may experience infections with more than one strain of HCoV.
TextSentencer_T123 23769-23981 Sentence denotes We did not measure IgA antibody to HCoV in serum in this study, since we were more interested in its presence in respiratory secretions, the compartment in which IgA is an important mediator of specific immunity.
TextSentencer_T124 23982-24457 Sentence denotes Based on the much lower frequency of patients with HCoV-specific IgA antibody in nasal wash specimens than of those with IgG in serum in our older adult population, one might hypothesize that antibodies to HCoV in nasal secretions decline in titer more rapidly after infection than do serum antibodies or that infection does not induce IgA antibody to HCoV in nasal secretions to high titers or at all in a significant proportion of older, chronically ill patients with COPD.
TextSentencer_T125 24458-24680 Sentence denotes Whether the induction of virus-specific, mucosal IgA antibodies by HCoV infection and their durability are different in older, chronically ill adults than in younger, healthy adults and children will require further study.
TextSentencer_T126 24681-25074 Sentence denotes Delineation of the relative importance of IgA antibodies in nasal secretions and serum IgG antibodies as immune correlates of protection against infection with HCoV and the role that antibodies that cross-react among HCoV strains may play in protection from or pathogenesis of HCoV infection would assist in devising approaches to the development of vaccines that could prevent HCoV infection.