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Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study – The Lancet

Summary

Background

Many patients receiving dialysis in the USA share the socioeconomic characteristics of underserved communities, and undergo routine monthly laboratory testing, facilitating a practical, unbiased, and repeatable assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence.

Methods

For this cross-sectional study, in partnership with a central laboratory that receives samples from approximately 1300 dialysis facilities across the USA, we tested the remainder plasma of 28 503 randomly selected adult patients receiving dialysis in July, 2020, using a spike protein receptor binding domain total antibody chemiluminescence assay (100% sensitivity, 99·8% specificity). We extracted data on age, sex, race and ethnicity, and residence and facility ZIP codes from the anonymised electronic health records, linking patient-level residence data with cumulative and daily cases and deaths per 100 000 population and with nasal swab test positivity rates. We standardised prevalence estimates according to the overall US dialysis and adult population, and present estimates for four prespecified strata (age, sex, region, and race and ethnicity).

Findings

The sampled population had similar age, sex, and race and ethnicity distribution to the US dialysis population, with a higher proportion of older people, men, and people living in majority Black and Hispanic neighbourhoods than in the US adult population. Seroprevalence of SARS-CoV-2 was 8·0% (95% CI 7·7–8·4) in the sample, 8·3% (8·0–8·6) when standardised to the US dialysis population, and 9·3% (8·8–9·9) when standardised to the US adult population. When standardised to the US dialysis population, seroprevalence ranged from 3·5% (3·1–3·9) in the west to 27·2% (25·9–28·5) in the northeast. Comparing seroprevalent and case counts per 100 000 population, we found that 9·2% (8·7–9·8) of seropositive patients were diagnosed. When compared with other measures of SARS-CoV-2 spread, seroprevalence correlated best with deaths per 100 000 population (Spearman’s ρ=0·77). Residents of non-Hispanic Black and Hispanic neighbourhoods experienced higher odds of seropositivity (odds ratio 3·9 [95% CI 3·4–4·6] and 2·3 [1·9–2·6], respectively) compared with residents of predominantly non-Hispanic white neighbourhoods. Residents of neighbourhoods in the highest population density quintile experienced increased odds of seropositivity (10·3 [8·7–12·2]) compared with residents of the lowest density quintile. County mobility restrictions that reduced workplace visits by at least 5% in early March, 2020, were associated with lower odds of seropositivity in July, 2020 (0·4 [0·3–0·5]) when compared with a reduction of less than 5%.

Interpretation

During the first wave of the COVID-19 pandemic, fewer than 10% of the US adult population formed antibodies against SARS-CoV-2, and fewer than 10% of those with antibodies were diagnosed. Public health efforts to limit SARS-CoV-2 spread need to especially target racial and ethnic minority and densely populated communities.

Funding

Ascend Clinical Laboratories.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus stimulates a rapid antibody response in people with symptomatic

  • Pollán M
  • Pérez-Gómez B
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  • et al.

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study.

  • Hung IF
  • Cheng VC
  • Li X
  • et al.

SARS-CoV-2 shedding and seroconversion among passengers quarantined after disembarking a cruise ship: a case series.

  • Long QX
  • Liu BZ
  • Deng HJ
  • et al.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

  • Caturegli G
  • Materi J
  • Howard BM
  • Caturegli P

Clinical validity of serum antibodies to SARS-CoV-2: a case-control study.

US Food and Drug Administration

EUA authorized serology test performance.

and asymptomatic

  • Hung IF
  • Cheng VC
  • Li X
  • et al.

SARS-CoV-2 shedding and seroconversion among passengers quarantined after disembarking a cruise ship: a case series.

  • Sakurai A
  • Sasaki T
  • Kato S
  • et al.

Natural history of asymptomatic SARS-CoV-2 infection.

  • Payne DC
  • Smith-Jeffcoat SE
  • Nowak G
  • et al.

SARS-CoV-2 infections and serologic responses from a sample of US navy service members—USS Theodore Roosevelt, April 2020.

infection. Seroprevalence of SARS-CoV-2 antibodies in a population thus serves as a reasonable measure of exposure and spread. Seroprevalence surveys in the USA, however, have been restricted to single hotspots

  • Sood N
  • Simon P
  • Ebner P
  • et al.

Seroprevalence of SARS-CoV-2-specific antibodies among adults in Los Angeles County, California, on April 10–11, 2020.

  • Bendavid E
  • Mulaney B
  • Sood N
  • et al.

COVID-19 antibody seroprevalence in Santa Clara County, California.

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

or under-represented high-risk or vulnerable populations.

  • Bendavid E
  • Mulaney B
  • Sood N
  • et al.

COVID-19 antibody seroprevalence in Santa Clara County, California.

  • Havers F
  • Reed C
  • Lim T
  • et al.

Seroprevalence of antibodies to SARS-CoV-2 in six sites in the United States, March 23-May 3, 2020.

Moreover, these studies face challenges to timely repetition and longitudinal follow-up, limiting their utility for surveillance.

  • Sood N
  • Simon P
  • Ebner P
  • et al.

Seroprevalence of SARS-CoV-2-specific antibodies among adults in Los Angeles County, California, on April 10–11, 2020.

  • Bendavid E
  • Mulaney B
  • Sood N
  • et al.

COVID-19 antibody seroprevalence in Santa Clara County, California.

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

Patients receiving dialysis might be considered an ideal sentinel population in which to study the evolution of the COVID-19 public health crisis. Patients receiving dialysis in the USA undergo routine monthly laboratory studies to gauge the effectiveness of therapy and to screen for associated complications. In haemodialysis, regular access to the bloodstream abrogates the need for phlebotomy to acquire blood samples. Risk factors for acquisition of SARS-CoV-2 and for severe COVID-19, including advanced age, non-white race, poverty, and diabetes, are the rule rather than the exception in the US dialysis population.

United States Renal Data System

2018 annual data report: epidemiology of kidney disease in the United States.

Research in context

Evidence before this study

Measuring the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies provides a comprehensive assessment of its community spread. Community seroprevalence surveys require considerable infrastructure and expense, and face implementation challenges during the COVID-19 pandemic due to restricted outreach in the worst-affected communities. Of the two largest seroprevalence surveys in the USA, one was limited only to New York state (n=15 101) and used convenience sampling at grocery stores. A second survey used remainder plasma from people visiting commercial laboratories in six cities (n=11 933), but lacked details on race and ethnicity and other community-level risk factors.

Added value of this study

We tested the remainder plasma of 28 503 patients receiving dialysis throughout the USA, using a chemiluminescence assay with high sensitivity and specificity. To our knowledge, we provide the first nationally representative estimate of SARS-CoV-2 seroprevalence in the US dialysis and US adult population, and estimates for differences in seroprevalence by neighbourhood race and ethnicity, poverty, population density, and mobility restriction. We also evaluate which of the existing measures of COVID-19 incidence most closely correlate with seroprevalence. Most importantly, we show that as patients receiving dialysis have monthly blood draws, without fail and without bias, and are a population with increased representation of racial and ethnic minorities, repeated cross-sectional analyses of seroprevalence within this sentinel population can be implemented as a practical and unbiased surveillance strategy in the USA.

Implications of all the available evidence

Similar to data from other highly affected countries and regions (eg, Spain and Wuhan, China), despite the intense strain on resources and unprecedented excess mortality being experienced in the USA during the COVID-19 pandemic, fewer than 10% of US adults had formed antibodies to SARS-CoV-2 as of July, 2020. There was significant regional variation from less than 5% prevalence in the west to more than 25% in the northeast. Public health efforts to curb the spread of the virus need to continue, with focus on some of the highest-risk communities that we identified, such as majority Black and Hispanic neighbourhoods, poorer neighbourhoods, and densely populated metropolitan areas. A surveillance strategy relying on monthly testing of remainder plasma of patients receiving dialysis can produce unbiased estimates of SARS-CoV-2 spread inclusive of hard-to-reach, disadvantaged populations in the USA. Such surveillance can inform disease trends, resource allocation, and effectiveness of community interventions during the COVID-19 pandemic.

Testing remainder plasma from monthly samples obtained for routine care of patients on dialysis for SARS-CoV-2 antibodies therefore represents a practical approach to a population-representative surveillance strategy,

  • Peeling RW
  • Wedderburn CJ
  • Garcia PJ
  • et al.

Serology testing in the COVID-19 pandemic response.

informing risks faced by a susceptible population while ensuring representation from racial and ethnic minorities. In addition, seroprevalence surveys in patients receiving dialysis can be linked to patient-level and community-level data to enable evaluation and quantification of differences in SARS-CoV-2 prevalence by demographic and neighbourhood strata, and thus facilitate effective mitigation strategies targeting the highest-risk individuals and communities.

In partnership with a commercial clinical laboratory, we tested seroprevalence of SARS-CoV-2 antibodies in a randomly selected representative sample of patients. Our goal was to provide a nationwide estimate of exposure to SARS-CoV-2 during the first wave of COVID-19 in the USA, up to July, 2020, with stratification by region, age, sex, and race and ethnicity. We also harnessed population data on SARS-CoV-2 cases and deaths and percentage testing positive using nasal swab testing to assess how seroprevalence estimates correlated with other epidemiological measures of COVID-19 incidence. Finally, to inform preventive strategies for the high-risk dialysis population as well as the general population, we investigated community-level correlates for seropositivity.

Methods

 Study design and participants

We did a cross-sectional analysis of adult (≥18 years) patients undergoing monthly laboratory testing at Ascend Clinical using samples obtained for routine clinical care that otherwise would have been discarded. Ascend Clinical is a commercial clinical laboratory based in Redwood City, California, that receives samples from a nationwide network of around 1300 dialysis facilities, serving approximately 65 000 patients. We randomly selected patients from the patient list on June 15, 2020, for seroprevalence testing to be done in July, 2020, using implicit stratification by region, age, sex, and race and ethnicity followed by systematic sampling with fractional polynomials.

After sample selection and processing, Ascend Clinical sent anonymised data on patient age, sex, race and ethnicity, and residence and facility ZIP codes to Stanford University investigators for analyses. Stanford University investigators further linked patient geographical information (ZIP code) to census data and publicly available COVID-19 burden and community mobility data. The study received expedited approval from the Stanford University of Medicine Institutional Review Board; informed consent was waived.

 Procedures

We used the US Food and Drug Administration-approved Siemens Healthineers SARS-CoV-2 spike protein receptor binding domain (S1RBD) total antibody (immunoglobulin) chemiluminescence assay, which has 100% sensitivity (≥14 days after a positive PCR test) and 99·8% specificity.

US Food and Drug Administration

EUA authorized serology test performance.

We chose this assay on the basis of its Emergency Use Authorization in June, 2020, in the context that S1RBD is also the target of vaccine development efforts.

US Food & Drug Administration

Study of antibody response to SARS-CoV-2 spike proteins could help inform vaccine design.

Sample processing is detailed in the appendix (p 3)).

We linked patient-level residence data with cumulative and daily cases and deaths per 100 000 population as compiled on a county level by the Center for Systems Science and Engineering at Johns Hopkins University

  • Dong E
  • Du H
  • Gardner L

An interactive web-based dashboard to track COVID-19 in real time.

and with nasal swab test positivity rates, as compiled on a state level by the Covid Tracking Project.

The COVID Tracking Project

Data API.

For Utah, we followed the Utah Department of Health groupings of several smaller counties and extracted data directly.

Utah Department of Health

Overview of COVID-19 surveillance.

New York City data are not available by county within the Johns Hopkins University dataset; therefore, we directly extracted data from the New York City Dashboard.

NYC Health

COVID-19: data, by borough.

For county-level mobility restrictions, we used Google Mobility Data that report an average percentage change in the number of workplace visits over the period March 1–15, 2020, before the implementation of shelter-in-place restrictions in the majority of the country. Percentage changes in the Google Mobility data are indexed to a corresponding weekday (eg, Tuesdays are matched to Tuesdays) from Jan 3 to Feb 6, 2020.

Google

Google COVID-19 community mobility reports.

We also linked patient-level residence data with ZIP code tabulation area (ZCTA) data from the 2018 American Community Survey (ACS) 5-year estimates

US Census Bureau American Community Survey

2018 American Community Survey 5 year estimates, tables B03002, S1701, and B01003.

to ascertain patient neighbourhood proportion living below the poverty level and race and ethnicity mix, and with American Census Bureau 2010 estimates

US Census Bureau

Zip code tabulation areas (ZCTA).

to ascertain population density. We defined ZCTA majority race and ethnicity as Hispanic, non-Hispanic Black, or non-Hispanic white if the population in the ZCTA was at least 60% Hispanic, non-Hispanic Black, or non-Hispanic white, respectively; where this was not the case, if the Hispanic and Black population combined was at least 60% of the population, the ZCTA majority was defined as Hispanic and Black, otherwise as other. For urban versus rural ZCTA status, we used the 2010 Rural Urban Commuting Area codes by census tract, categorising a ZCTA as dense urban, metropolitan, micropolitan, or small town or rural area if more than 50% of the population in the ZCTA was living in one of these area codes.

United States Department of Agriculture

2010 rural-urban commuting area (RUCA) codes.

 Statistical analysis

We assumed a nationwide prevalence of SARS-CoV-2 antibody of 5%.

  • Sood N
  • Simon P
  • Ebner P
  • et al.

Seroprevalence of SARS-CoV-2-specific antibodies among adults in Los Angeles County, California, on April 10–11, 2020.

  • Benatia D
  • Godefroy R
  • Lewis J

Estimating COVID-19 prevalence in the United States: a sample selection model approach.

To generate prevalence estimates for patients on dialysis using preselected regional strata with precision within 0·5%, a sample of 27 364 was required (appendix p 2). Based on previous trends, we expected 15% of selected samples to be unavailable in July, 2020, due to death, move to other facilities, or other reasons for missing laboratory data (eg, hospitalisation or non-adherence). Accounting for this potential dropout, we randomly selected 31 509 patients.

We present prevalence estimates with 95% CIs in our sample, standardised to the US adult dialysis population and to the US adult population. For the US adult dialysis population, we used the distribution of all adults receiving maintenance dialysis, excluding those living in the territories, on Jan 1, 2017, identified through the United States Renal Data System database. For the US adult population, we used 2018 ACS 1-year estimates.

US Census Bureau American Community Survey

2018 American Community Survey 5 year estimates, tables B03002, S1701, and B01003.

Based on the test sensitivity range obtained by Schnurra and colleagues in their external validation,

  • Schnurra C
  • Reiners N
  • Biemann R
  • Kaiser T
  • Trawinski H
  • Jassoy C

Comparison of the diagnostic sensitivity of SARS-CoV-2 nucleoprotein and glycoprotein-based antibody tests.

we also provide test characteristic-adjusted sample population estimates, ranging sensitivity from 85% to 98%.

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

To compute the percentage of estimated seroprevalent cases that were likely to be diagnosed cases,

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

  • Stringhini S
  • Wisniak A
  • Piumatti G
  • et al.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.

we compared the estimated seroprevalent cases per 100 000 adult population with Johns Hopkins University estimates of cumulative diagnosed cases per 100 000 US adult population as of June 15, 2020.

To standardise estimates, we assigned weights to each person based on their membership to each of 32 strata of census regions (northeast, south, midwest, and west), age (18–44, 45–64, 65–79, and ≥80 years), and sex. We defined post-stratification weights as the proportion of each stratum represented in the US dialysis population or US adult population divided by the analogous proportion in the sample.

  • Kolenikov S

Post-stratification or non-response adjustment?.

  • Korn EL
  • Graubard BI

Analysis of health surveys.

We then computed weighted frequencies and 95% CIs according to four prespecified strata (region, age, sex, and race and ethnicity) with differences evaluated using Rao-Scott χ2 tests.

  • Rao JNK
  • Scott AJ

The analysis of categorical data from complex surveys: chi-squared tests for goodness of fit and independence in two-way tables.

  • Rao JNK
  • Scott AJ

On chi-squared tests for multiway contingency tables with cell properties estimated from survey data.

Due to the missingness of race and ethnicity data in the electronic health records, we used the additional measure of ZCTA race and ethnicity distribution with categories adapted from Moore and colleages.

  • Moore LV
  • Diez Roux AV
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  • McGinn AP
  • Brines SJ

Availability of recreational resources in minority and low socioeconomic status areas.

  • Bower KM
  • Thorpe Jr, RJ
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The intersection of neighborhood racial segregation, poverty, and urbanicity and its impact on food store availability in the United States.

Next, we correlated five measures of COVID-19 incidence—cumulative cases on June 15, 2020 (or first available date between June 15 and June 30, 2020); cumulative deaths on June 30, 2020 (or last available date between June 15 and June 30, 2020); 15-day averages of daily cases and daily deaths; and percentage testing positive on nasal swab tests between June 15 and June 30, 2020—with SARS-CoV-2 seroprevalence in patients on dialysis in July, 2020. To do this, we first collapsed all measures to a state level and then assessed the Spearman’s correlation coefficient ρ for the association of each measure with seroprevalence. Because of the high density of Ascend Clinical facilities in New York, Texas, and California, we also chose those states to present county-level correlations.

Finally, using logistic regression, we determined the age-adjusted and sex-adjusted correlates of seropositivity for patient ZCTA race and ethnicity distribution, percentage living below poverty level, rural or urban classification, population density, and county mobility restriction.

We assumed statistical significance at α<0·05. All statistical analyses were done with SAS Enterprise Guide (version 7.1) and Stata (version 15.1).

 Role of the funding source

Ascend Clinical Laboratories supported the remainder plasma testing for SARS-CoV-2 antibodies. SA, MM-R, and JH had complete access to all data in the study and SA, MM-R, JH, JP, and GMC were responsible for the decision to submit for publication.

Results

Of the 31 509 people selected for testing on June 15, 2020, 28 503 were tested in July, 2020 (figure 1), with 25 217 (88·5%) tested in the first 2 weeks (appendix p 4). The sampling was representative of the US dialysis patient distribution by age, sex, race and ethnicity (when excluding patients without race and ethnicity data), and region, except sampled patients were less likely to be non-Hispanic Black (table 1). Compared with the US adult population, our sampled patient population was older, had more men, and was more likely to be non-Hispanic Black and living in non-white neighbourhoods (table 1). A greater proportion of our sampled population and the US dialysis population lived in the west, and a lower proportion lived in the midwest, compared with the US adult population. Patients in our sample lived in 46 states and in 1013 (32%) of 3141 US counties (appendix p 6).

Figure thumbnail gr1

Table 1Comparison of sampled population, US adult dialysis population, and US adult population

US adult population given is for 2018 and US adult patients dialysis population as of Jan 1, 2017. ZCTA=ZIP code tabulation area.

Overall, sample seroprevalence was 8·0% (95% CI 7·7–8·4). Accounting for the externally validated test sensitivity,

  • Schnurra C
  • Reiners N
  • Biemann R
  • Kaiser T
  • Trawinski H
  • Jassoy C

Comparison of the diagnostic sensitivity of SARS-CoV-2 nucleoprotein and glycoprotein-based antibody tests.

seroprevalence ranged from 8·2% (7·9–8·5) to 9·4% (9·1–9·8) in our sampled population (appendix p 7). When standardised to the US dialysis population, seroprevalence was 8·3% (8·0–8·6), with high regional variation in seroprevalence (ranging from 3·5% [3·1–3·9] in the west to 27·2% [25·9–28·5] in the northeast; table 2). Seroprevalence was similar by sex and modestly lower in people aged 80 years or older compared with those aged 45–64 years (table 2). Differences in seroprevalence by race and ethnicity were similar using both our patient-level (electronic health record) and neighbourhood-level (ZCTA majority race and ethnicity) measures, with non-Hispanic Black patients having the highest seropositivity, followed by Hispanic patients, and non-Hispanic white patients having the lowest.

Table 2Seroprevalence of SARS-CoV-2 antibodies in patients receiving dialysis in the USA

SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. ZCTA=ZIP code tabulation area.

We estimated the SARS-CoV-2 standardised seroprevalence in the US population to be 9·3% (95% CI 8·8–9·9; table 3). Based on the Johns Hopkins University cumulative case data as of June 15, 2020, the prevalence of (nasal swab) diagnosed cases was 826 per 100 000 US adult population, compared with our estimate of 8989 seropositive people per 100 000 population, meaning that 9·2% (8·7–9·8) of seropositive people were diagnosed.

Using data from our sampled population, variation by state was high, ranging from 0·0% in seven states to 33·6% (31·7–35·6) in New York, with the highest regional variation occurring in the northeast (figure 2; appendix pp 8–9). When comparing state seroprevalence against cumulative cases and deaths per 100 000 population, deaths correlated best (ρ=0·66 for cases vs 0·77 for deaths; figure 3). The percentage of people testing positive by nasal swab test and 15-day average of daily deaths in the latter half of June, 2020, showed a weaker correlation (ρ=0·58 and 0·66, respectively), whereas 15-day average of daily cases did not correlate with seroprevalence (ρ=−0·14). On a county level in California, New York, and Texas, there was even more heterogeneity in the correlation between seroprevalence and other disease measures (ρ≤0·51 for all correlations for all three states’ county-level data; appendix p 10).

Figure thumbnail gr3

Figure 3Cumulative cases (A) and cumulative deaths (B) per 100 000 population, by state

Data are in the US population as of June 15 (A) and June 30 (B), 2020.

  • Dong E
  • Du H
  • Gardner L

An interactive web-based dashboard to track COVID-19 in real time.

Utah Department of Health

Overview of COVID-19 surveillance.

NYC Health

COVID-19: data, by borough.

US Census Bureau American Community Survey

2018 American Community Survey 5 year estimates, tables B03002, S1701, and B01003.

States in white were not included in the sample.

Likelihood of SARS-CoV-2 seropositivity was lower among older people (odds ratio 0·8 [95% CI 0·7–0·9] for people aged 80 years or older vs people aged 45–64 years), but did not differ by sex (1·0 [0·9–1·1] for women vs men). In age-adjusted and sex-adjusted models, neighbourhood racial and ethnic distribution, poverty level, dense urbanisation, population density, and percentage change in workplace visits in early March, 2020, were all strongly associated with seropositivity (figure 4).

Figure thumbnail gr4

Figure 4Forest plot for odds of SARS-CoV-2 seropositivity

All variables are at a neighbourhood (ie, ZCTA) level, except for reduction in workplace visits, which is at a county level, and are modelled separately, accounting for age and sex. Poverty level is defined as percentage of people living below the federal poverty level in the ZCTA. Population density quintiles are derived from the ZCTA (median 2884 people per square mile [IQR 603–6800]). Reductions in workplace visits were measured during the first 2 weeks of March, 2020, compared with a baseline in January–February, 2020. OR=odds ratio. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. ZCTA=ZIP code tabulation area.

Discussion

In our analysis of seroprevalence of SARS-CoV-2 spike protein receptor binding antibodies from a nationwide representative sample of patients receiving dialysis, we find that despite the USA contemporaneously leading the world in the numbers of diagnosed cases, overall, fewer than 10% of US adults had evidence of seroconversion in July, 2020. A vast majority of US adults, including people receiving dialysis who are among the highest risk for mortality upon contracting SARS-CoV-2,

  • Alberici F
  • Delbarba E
  • Manenti C
  • et al.

A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection.

do not have evidence of exposure or immune response. Furthermore, we find increased likelihood of SARS-CoV-2 seropositivity in residents of predominantly Black and Hispanic neighbourhoods (two to three times higher), poorer areas (two times higher), and the most densely populated areas (ten times higher). Early reduction in community mobility in March, 2020, was associated with 60% lower likelihood of individual-level seroconversion by July that year.

Unlike most published estimates of SARS-CoV-2 seroprevalence from the USA,

  • Sood N
  • Simon P
  • Ebner P
  • et al.

Seroprevalence of SARS-CoV-2-specific antibodies among adults in Los Angeles County, California, on April 10–11, 2020.

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

  • Havers F
  • Reed C
  • Lim T
  • et al.

Seroprevalence of antibodies to SARS-CoV-2 in six sites in the United States, March 23-May 3, 2020.

patients included in our study sample had antibodies measured from blood collected as part of routine medical care. Thus, our prevalence estimates should not be subject to selection bias due to presence versus absence of symptoms, availability of testing materials, local or regional testing strategies, geography, income, educational attainment, language proficiency, immigration status, mobility, anxiety, fear, or other factors. Moreover, since end-stage kidney disease qualifies affected patients for Medicare insurance, and since end-stage kidney disease disproportionately affects Black, Hispanic, and other disadvantaged populations,

United States Renal Data System

2018 annual data report: epidemiology of kidney disease in the United States.

  • Volkova N
  • McClellan W
  • Klein M
  • et al.

Neighborhood poverty and racial differences in ESRD incidence.

  • Crews DC
  • Gutiérrez OM
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  • et al.

Low income, community poverty and risk of end stage renal disease.

we are able to determine—with a high level of precision—differences in seroprevalence among patient groups within and across regions of the USA. Of the two larger seroprevalence surveys published from the USA thus far, one was confined to New York state (n=15 101), employed a convenience sampling technique at grocery stores, and relied on a microsphere immunoassay with lower sensitivity.

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

The second, the Centers for Disease Control and Prevention (CDC) Six Sites study (n=11 933), used remainder plasma from people getting testing for undefined clinical indications, and did not have detailed sociodemographic information about the tested people.

  • Havers F
  • Reed C
  • Lim T
  • et al.

Seroprevalence of antibodies to SARS-CoV-2 in six sites in the United States, March 23-May 3, 2020.

Uncertainty exists as to whether seroprevalence estimates in the dialysis population can be extrapolated to the US population more broadly. A recent analysis of SARS-CoV-2 IgG antibodies in two dialysis units in London, UK, reported seroprevalence of 36%, higher than in healthy blood donors (15%) but lower than in health-care workers (45%) sampled within a similar time frame.

  • Clarke C
  • Prendecki M
  • Dhutia A
  • et al.

High prevalence of asymptomatic COVID-19 infection in hemodialysis patients detected using serologic screening.

Our data might overestimate overall seroprevalence in the general population since patients on dialysis are disproportionately from racial and ethnic minorities;

  • Choi AI
  • Rodriguez RA
  • Bacchetti P
  • Bertenthal D
  • Hernandez GT
  • O’Hare AM

White/black racial differences in risk of end-stage renal disease and death.

  • Hsu CY
  • Lin F
  • Vittinghoff E
  • Shlipak MG

Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States.

for example, Black Americans have a nearly four-times higher risk of end-stage kidney disease than white Americans.

United States Renal Data System

2018 annual data report: epidemiology of kidney disease in the United States.

Moreover, the process of undergoing in-centre haemodialysis might include the use of public or non-public shared transportation to and from the facility, and 10–12 h of care delivered in indoor facilities.

Conversely, these data might underestimate overall seroprevalence in the general population. Patients receiving dialysis are less likely to be employed

  • Erickson KF
  • Zhao B
  • Ho V
  • Winkelmayer WC

Employment among patients starting dialysis in the United States.

and more likely to restrict their mobility and social activity due to advanced age and frailty;

  • Bao Y
  • Dalrymple L
  • Chertow GM
  • Kaysen GA
  • Johansen KL

Frailty, dialysis initiation, and mortality in end-stage renal disease.

therefore, they might have fewer opportunities to acquire the infection, particularly from asymptomatic individuals. Extrapolating from multiple prospective hepatitis B immunisation studies—in which 50–75% of vaccinated patients receiving dialysis mounted a response compared with 95% or more people from the general population—patients receiving dialysis might mount a weaker immune response and thus be less likely to seroconvert.

  • Edey M
  • Barraclough K
  • Johnson DW

Review article: hepatitis B and dialysis.

Finally, patients receiving dialysis might have been more likely to die or have been hospitalised due to complications of SARS-CoV-2 infection. If so, these patients would not have been present for testing in the dialysis facilities, creating a survival bias and yielding lower estimates of exposure.

Nonetheless, the ten-times difference we observed between diagnosed cases per 100 000 population and our estimates of seropositive people per 100 000 has been similarly reported in studies from New York,

  • Rosenberg ES
  • Tesoriero JM
  • Rosenthal EM
  • et al.

Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

the CDC Six Sites study,

  • Havers F
  • Reed C
  • Lim T
  • et al.

Seroprevalence of antibodies to SARS-CoV-2 in six sites in the United States, March 23-May 3, 2020.

and in a population-representative analysis from Geneva.

  • Stringhini S
  • Wisniak A
  • Piumatti G
  • et al.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.

Thus, our findings comport with other seroprevalence estimates. We confirm that as in other studies from COVID-19 hotspots,

  • Pollán M
  • Pérez-Gómez B
  • Pastor-Barriuso R
  • et al.

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study.

  • Stringhini S
  • Wisniak A
  • Piumatti G
  • et al.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.

  • Xu X
  • Sun J
  • Nie S
  • et al.

Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.

a minority of the population has evidence of exposure and immune response, and a vast majority, including people at high risk for mortality (ie, the population on dialysis), remain vulnerable. In fact, even if the seroprevalence estimates derived from the US dialysis population overestimated true seroprevalence in the overall US adult population, our data nonetheless support that fewer than 10% of the US population has seroconverted as of July, 2020, and herd immunity remains out of reach, as has been the conclusion from large international surveys from the UK

  • Ward HAC
  • Whitaker M
  • et al.

Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults.

and Spain,

  • Pollán M
  • Pérez-Gómez B
  • Pastor-Barriuso R
  • et al.

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study.

where intense outbreaks of COVID-19 occurred during the spring and summer of 2020.

Furthermore, the seroprevalence differences captured by region, age, sex, and community-level risk factors (ie, internal comparisons) are expected to be similar in the US dialysis and US general adult population. Our study provides convincing evidence that the COVID-19 pandemic has dramatically amplified existing health disparities. Data from the CDC highlighting SARS-CoV-2 health disparities evaluate hospitalisations and deaths by race and ethnicity,

Centers for Disease Control and Prevention

COVIDView: a weekly surveillance summary of US Covid-19 activity.

  • Cowger TL
  • Davis BA
  • Etkins OS
  • et al.

Comparison of weighted and unweighted population data to assess inequities in coronavirus disease 2019 deaths by race/ethnicity reported by the US Centers for Disease Control and Prevention.

calling into question whether Black and Hispanic populations are experiencing more severe illness versus facing higher likelihoods of exposure. Some US state dashboards also report higher cumulative cases among Black and Hispanic people compared with non-Hispanic white people,

  • Yancy CW

COVID-19 and African Americans.

but none have as precisely quantified differences on a national level.

Neighbourhood poverty and population density were also highly correlated with seroprevalence, with a possible threshold effect for population density, such that there was a ten-times higher risk in the highest density ZCTAs (>8607 people per square mile). Population density is recognised as a crucial factor, driving the spread in metropolitan areas, in confined spaces (eg, the Diamond Princess cruise ship), large gatherings (eg, the New Orleans’ Mardi Gras),

  • Bialek S
  • Bowen V
  • Chow N
  • et al.

Geographic differences in COVID-19 cases, deaths, and incidence—United States, February 12-April 7, 2020.

  • Sy KTL
  • White LF
  • Nichols BE

Population density and basic reproductive number of COVID-19 across United States counties.

and in populous regions across the world.

  • Baqui P
  • Bica I
  • Marra V
  • Ercole A
  • van der Schaar M

Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study.

Rocklöv and Sjödin suggest that the basic reproduction number (R0) of SARS-CoV-2 increases linearly with population density.

  • Rocklöv J
  • Sjödin H

High population densities catalyse the spread of COVID-19.

Our data also show slightly lower likelihood of seropositivity among older people, as was seen in a recent report from Geneva

  • Stringhini S
  • Wisniak A
  • Piumatti G
  • et al.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.

and attributed to better adherence to physical distancing measures by the authors. A higher competing risk from hospitalisations or mortality after SARS-CoV-2 exposure might be a larger contributing factor in the observed lower seroprevalence in older compared with younger age groups.

In addition to providing an overall estimate of SARS-CoV-2 seroprevalence and quantifying differences by patient and community characteristics, our study puts forth a viable surveillance strategy for SARS-CoV-2 spread in the USA. WHO and other experts

  • Peeling RW
  • Wedderburn CJ
  • Garcia PJ
  • et al.

Serology testing in the COVID-19 pandemic response.

  • Koopmans M
  • Haagmans B

Assessing the extent of SARS-CoV-2 circulation through serological studies.

advocate for repeated cross-sectional analyses of seroprevalence as a disease tracking system able to most completely measure the true incidence of SARS-CoV-2, since these can more likely capture incidence of exposure in both symptomatic and asymptomatic individuals. In fact, we observed substantial heterogeneity in the correlation between seroprevalence and other measures of SARS-CoV-2 that are currently being used—with the exception of deaths per 100 000, which are a late outcome

  • Grasselli G
  • Greco M
  • Zanella A
  • et al.

Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy.

—supporting the use of rapidly instituted seroprevalence surveys as a complementary surveillance tool. Additional pu

































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