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1.
Transfusion ; 63(7): 1354-1365, 2023 07.
Article in English | MEDLINE | ID: covidwho-20233322

ABSTRACT

BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.


Subject(s)
Blood Donors , COVID-19 , Humans , Uganda/epidemiology , SARS-CoV-2 , COVID-19 Vaccines , Seroepidemiologic Studies , COVID-19/epidemiology , Antibodies, Viral
2.
PLoS One ; 17(6): e0264298, 2022.
Article in English | MEDLINE | ID: covidwho-2021610

ABSTRACT

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR] = 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR = 4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR = 0.25; CI 0.08, 0.80 and aOR = 0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR = 0.16; CI 0.03, 0.97 and aOR = 0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.


Subject(s)
COVID-19 , Pharyngitis , Antibodies, Viral , Antibody Formation , COVID-19/therapy , Cough , Humans , Immunization, Passive , Immunoglobulin G , RNA, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , COVID-19 Serotherapy
3.
Open Forum Infect Dis ; 9(5): ofac130, 2022 May.
Article in English | MEDLINE | ID: covidwho-1784386

ABSTRACT

Background: We sought to determine the prevalence and sociodemographic and clinical correlates of acute and convalescent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections among emergency department (ED) patients in Baltimore. Methods: Remnant blood samples from 7450 unique patients were collected over 4 months in 2020 for SARS-CoV-2 antibody (Ab), HCV Ab, and HIV-1/2 antigen and Ab. Among them, 5012 patients were tested by polymerase chain reaction for SARS-CoV-2 based on clinical suspicion. Sociodemographics, ED clinical presentations, and outcomes associated with coinfections were assessed. Results: Overall, 729 (9.8%) patients had SARS-CoV-2 (acute or convalescent), 934 (12.5%) HCV, 372 (5.0%) HIV infection, and 211 patients (2.8%) had evidence of any coinfection (HCV/HIV, 1.5%; SARS-CoV-2/HCV, 0.7%; SARS-CoV-2/HIV, 0.3%; SARS-CoV-2/HCV/HIV, 0.3%). The prevalence of SARS-CoV-2 (acute or convalescent) was significantly higher in those with HCV or HIV vs those without (13.6% vs 9.1%, P < .001). Key sociodemographic disparities (race, ethnicity, and poverty) and specific ED clinical characteristics were significantly correlated with having any coinfections vs no infection or individual monoinfection. Among those with HCV or HIV, aged 18-34 years, Black race, Hispanic ethnicity, and a cardiovascular-related chief complaint had a significantly higher odds of having SARS-CoV-2 (prevalence ratios: 2.02, 2.37, 5.81, and 2.07, respectively). Conclusions: The burden of SARS-CoV-2, HCV, and HIV co-pandemics and their associations with specific sociodemographic disparities, clinical presentations, and outcomes suggest that urban EDs should consider implementing integrated screening and linkage-to-care programs for these 3 infections.

4.
J Clin Microbiol ; 60(3): e0239021, 2022 03 16.
Article in English | MEDLINE | ID: covidwho-1765077

ABSTRACT

Emergency departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to monitor the prevalence of vaccination against coronavirus disease 2019 (COVID-19) among patients attending an urban ED in Baltimore City. Using 1,914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4,360 samples from ED patients obtained in the spring of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. For the algorithm, sensitivity and specificity for identifying vaccinated individuals were 100% and 99%, respectively, and 84% and 100% for previously infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vaccination prevalence rose to 11% by mid-March 2021. Marked differences in burden of disease and vaccination coverage were seen by sex, race, and ethnicity. Hispanic patients, though accounting for 7% of the study population, had the highest relative burden of disease (17% of total infections) but with similar vaccination rates. Women and white individuals were more likely to be vaccinated than men or Black individuals. Individuals previously infected with SARS-CoV-2 can often be differentiated from vaccinated individuals using a serologic testing algorithm. The utility of this algorithm can aid in monitoring SARS-CoV-2 exposure and vaccination uptake frequencies and can potentially reflect gender, race, and ethnic health disparities.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Emergency Service, Hospital , Female , Humans , Male , Seroepidemiologic Studies , White People
5.
J Clin Microbiol ; 59(7): e0083721, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1486488

ABSTRACT

We assessed the performance of the CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Plasma samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive individuals (Uganda, 78 samples from 78 individuals, and Baltimore, 266 samples from 38 individuals) and from prepandemic individuals (Uganda, 1,077, and Baltimore, 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. After the first positive PCR in Ugandan samples, the sensitivity was 45% (95% confidence interval [CI], 24,68) at 0 to 7 days, 79% (95% CI, 64 to 91) at 8 to 14 days, and 76% (95% CI, 50 to 93) at >15 days. In samples from Baltimore, sensitivity was 39% (95% CI, 30 to 49) at 0 to 7 days, 86% (95% CI, 79 to 92) at 8 to 14 days, and 100% (95% CI, 89 to 100) at 15 days after positive PCR. The specificity of 96.5% (95% CI, 97.5 to 95.2) in Ugandan samples was significantly lower than that in samples from Baltimore, 99.3% (95% CI, 98.1 to 99.8; P < 0.01). In Ugandan samples, individuals with a false-positive result were more likely to be male (PR, 2.04; 95% CI, 1.03,3.69) or individuals who had had a fever more than a month prior to sample acquisition (PR, 2.87; 95% CI, 1.12 to 7.35). Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False-positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Female , Humans , Male , Sensitivity and Specificity , Uganda
6.
Am J Emerg Med ; 48: 261-268, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1213001

ABSTRACT

BACKGROUND: Emergency Departments (EDs) have served as critical surveillance sites for infectious diseases. We sought to determine the prevalence and temporal trends of acute (by PCR) and convalescent (by antibody [Ab]) SARS-CoV-2 infection during the earliest phase of the pandemic among patients in an urban ED in Baltimore City. METHODS: We tested remnant blood samples from 3255 unique ED patients, collected between March 16th and May 31st 2020 for SARS-CoV-2 Ab. PCR for acute SARS-CoV-2 infection from nasopharyngeal swabs was obtained on any patients based on clinical suspicion. Hospital records were abstracted and factors associated with SARS-CoV-2 infection were assessed. RESULTS: Of 3255 ED patients, 8.2% (95%CI: 7.3%, 9.2%) individuals had evidence of SARS-CoV-2 infection; 155 PCR+, 78 Ab+, and 35 who were both PCR+ and Ab+. Prevalence of disease increased throughout the study period, ranging from 3.2% (95%CI: 1.8%, 5.2%) PCR+ and 0.6% (95%CI: 0.1%, 1.8%) Ab+ in March, to 6.2% (95%CI: 5.1%, 7.4%) PCR+ and 4.2% (95%CI: 3.3%, 5.3%) Ab+ in May. The highest SARS-CoV-2 prevalence was found in Hispanic individuals who made up 8.4% (95%CI: 7.4%, 9.4%) of individuals screened, but 35% (95%CI: 29%, 41%) of infections (PCR and/or Ab+). Demographic and clinical factors independently associated with acute infection included Hispanic ethnicity, loss of smell or taste, subjective fever, cough, muscle ache and fever. Factors independently associated with convalescent infection were Hispanic ethnicity and low oxygen saturation. CONCLUSIONS: The burden of COVID-19 in Baltimore City increased dramatically over the 11-week study period and was disproportionately higher among Hispanic individuals. ED-based surveillance methods are important for identifying both acute and convalescent SARS-CoV-2 infections and provides important information regarding demographic and clinical correlates of disease in the local community.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/epidemiology , Emergency Service, Hospital , Hypoxia/physiopathology , Acute Disease , Adolescent , Adult , Black or African American , Aged , COVID-19/ethnology , COVID-19/physiopathology , Convalescence , Female , Hispanic or Latino/statistics & numerical data , Humans , Male , Middle Aged , Prevalence , SARS-CoV-2 , Seroepidemiologic Studies , United States/epidemiology , White People , Young Adult
7.
J Infect Dis ; 222(12): 1974-1984, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-1059701

ABSTRACT

BACKGROUND: Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19-susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood. METHODS: SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression. RESULTS: Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19-2.12]), independent of age, sex, and hospitalization. CONCLUSIONS: SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.


Subject(s)
Antibodies, Neutralizing/administration & dosage , Antibodies, Viral/administration & dosage , Antibody Affinity , COVID-19/therapy , Immunoglobulin G/administration & dosage , SARS-CoV-2 , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Blood Donors , Cohort Studies , Cross-Sectional Studies , Female , Humans , Immunization, Passive , Immunoglobulin G/blood , Linear Models , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Young Adult , COVID-19 Serotherapy
8.
J Clin Microbiol ; 59(2)2021 01 21.
Article in English | MEDLINE | ID: covidwho-1045660

ABSTRACT

Accurate serological assays to detect antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) donation. This study compared the performances of commercial enzyme immunoassays (EIAs) with respect to detection of IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAbs). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) for detection of IgG or total antibodies to SARS-CoV-2 was evaluated using cross-sectional samples from potential CCP donors who had prior molecular confirmation of SARS-CoV-2 infection (n = 214) and samples from prepandemic emergency department patients without SARS-CoV-2 infection (n = 1,099). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority (n = 16 [7.5%]) had been hospitalized due to COVID-19; 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. Performed according to the protocols of the manufacturers to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff value of ≥160 as the reference representing a positive test result (n = 140 CCP donors), the empirical area under the receiver operating curve for each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAb titers. Some but not all commercial EIAs may be useful in the identification of individuals with high nAb titers among convalescent individuals.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , COVID-19/blood , Cross-Sectional Studies , Humans , Immune Sera/immunology , Immunoenzyme Techniques , Immunoglobulin G/blood , Neutralization Tests , SARS-CoV-2/immunology , Sensitivity and Specificity
9.
J Clin Microbiol ; 59(2)2021 01 21.
Article in English | MEDLINE | ID: covidwho-934065

ABSTRACT

Rapid point-of-care tests (POCTs) for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies vary in performance. A critical need exists to perform head-to-head comparisons of these assays. The performances of 15 different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies were compared on a well-characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (collected an average of 45 days after symptom onset) were used to assess sensitivity. Sixty samples from the prepandemic era (negative control) that were known to represent infections with other respiratory viruses (rhinoviruses A, B, and C and/or coronavirus 229E, HKU1, and NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed using five lateral flow assays (LFAs) and a panel of 272 longitudinal samples from 47 patients for whom the time since symptom onset was known. Among the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55% to 97% and from 78% to 100%, respectively. Assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0% to 88% and 80% to 100% for IgM and from 25% to 95% and 90% to 100% for IgG, respectively. Longitudinal testing revealed that the median times after symptom onset to a positive result were 7 days (interquartile range [IQR], 5.4 to 9.8) for IgM and 8.2 days (IQR, 6.3 to 11.3) for IgG. The testing performances differed widely among LFAs, with greatest amount of variation related to the sensitivity of the assays. The IgM band was the band most likely to misclassify prepandemic samples. The appearances of IgM and IgG bands occurred almost simultaneously.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , Point-of-Care Testing , SARS-CoV-2/isolation & purification , Antibodies, Viral/blood , COVID-19/blood , Cross Reactions , Humans , Immunoassay , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Sensitivity and Specificity , Seroconversion
10.
medRxiv ; 2020 Aug 04.
Article in English | MEDLINE | ID: covidwho-721059

ABSTRACT

BACKGROUND: Rapid point-of-care tests (POCTs) for SARS-CoV-2-specific antibodies vary in performance. A critical need exists to perform head-to-head comparison of these assays. METHODS: Performance of fifteen different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies was performed on a well characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (average of 45 days post symptom onset) were used to assess sensitivity. Sixty samples from the pre-pandemic era (negative control), that were known to have been infected with other respiratory viruses (rhinoviruses A, B, C and/or coronavirus 229E, HKU1, NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed on five POCTs on a panel of 272 longitudinal samples from 47 patients of known time since symptom onset. RESULTS: For the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55%-97% and 78%-100%, respectively. When assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0%-88% and 80%-100% for IgM and 25%-95% and 90%-100% for IgG. Longitudinal testing revealed that median time post symptom onset to a positive result was 7 days (IQR 5.4, 9.8) for IgM and 8.2 days (IQR 6.3 to 11.3). CONCLUSION: The testing performance varied widely among POCTs with most variation related to the sensitivity of the assays. The IgM band was most likely to misclassify pre-pandemic samples. The appearance of IgM and IgG bands occurred almost simultaneously.

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