Abstract
Feasibility of home blood sample collection methods for the presence of SARS-CoV-2 antibodies from VA Million Veteran Program (MVP) participants was tested to determine COVID-19 infection or vaccination status. Participants (n = 312) were randomly assigned to self-collect blood specimens using the Neoteryx Mitra Clamshell (n = 136) or Tasso-SST (n = 176) and asked to rate their experience. Mitra tip blood was eluted and Tasso tubes were centrifuged. All samples were stored at -80 °C until tested with InBios SCoV-2 Detect™ IgG ELISA, BioRad Platelia SARS-CoV-2 Total Ab Assay, Abbott SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Participants rated both devices equally. The Abbott assay had the highest sensitivity (87% Mitra, 98% Tasso-SST) for detecting known COVID infection and/or vaccination. The InBios assay with Tasso-SST had the best sensitivity (97%) and specificity (80%) for detecting known COVID-19 infection and/or vaccination. Veterans successfully collected their own specimens with no strong preference for either device.
Keywords: Capillary blood collection, COVID-19, Antibody, Veterans, Million Veteran Program
1. Introduction
Corona virus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a world-wide pandemic affecting millions of people [1]. The diagnosis of this infection is made primarily by molecular testing of respiratory samples for viral nucleic acid or antigen, or blood samples for detection of antibodies against the nucleocapsid or spike proteins of SARS-CoV-2. Over the course of the pandemic, diagnostic testing has required patients to travel to medical facilities or other testing centers to have samples taken for testing. At home, self-collection of samples may increase the number of people who can be tested to better determine infection status or inform the prevalence of COVID-19 infection or vaccine response. Recently, self-collection and testing respiratory samples for SARS-CoV-2 antigen has become available (i.e., Abbott BinaxNow self-test, Acon Flowflex).
Self-collection of finger stick blood samples has been widely adopted for glucose monitoring. Dried blood collection using dried blood spots (DBS) for detection of HIV, HCV, HBV antibodies, antigen, or nucleic acid has proven effective in the diagnosis of these infections [2]. Recently, DBS or other dried blood collection methods have been evaluated for the detection of SARS-CoV-2 or influenza antibodies [3], [4], [5], [6] Other devices designed for the self-collection and storage of liquid blood potentially allows for different methods for SARS-CoV-2 antibody detection [7].
To examine home blood specimen collection options, The VA Million Veteran Program (MVP) performed a pilot study comparing 2 blood specimen collection devices and evaluated SARS-CoV-2 antibody assays to determine known COVID-19 infection or vaccination status. The goals of this study were to (1) to determine the feasibility of at-home blood specimen collection for scalability purposes; and (2) test the feasibility of low volume capillary blood for SARS-CoV-2 antibody detection.
2. Methods
Recruitment and enrollment for the pilot was conducted from December 2020 through March 2021. Over ten thousand MVP participants met the eligibility criteria for the pilot (currently enrolled, open to contact from MVP, not deceased, valid email address), and of this cohort 599 MVP Participants were randomly selected and emailed an invitation to participate in the pilot. Thirty percent of the eligible participants had a COVID-19 diagnosis, defined as an electronic health record (EHR) documented previously positive SARS-CoV-2 RT-PCR or a self-reported COVID diagnosis from the 2020-2021 MVP COVID-19 survey, prior to being invited. These participants were randomly assigned one of 2 self-collection devices selected for the pilot: Mitra® (Neoteryx, LLC, Torrance, CA) requires a finger prick to collect dried blood on a sampler tip (4 tips × 30 uL, up to 120 uL whole blood in total) and Tasso-SST (Tasso, Inc., Seattle, WA) which collects capillary liquid blood from the upper arm in a mini tube (up to 200 uL). MVP Participants were verbally consented into the pilot and within a week, were sent a collection kit, which included a feedback form to collect date/time of blood collection and feedback questions (using a Likert scale, 1 = worst and 5 = best) to rate their experience using their assigned device. Fig. 1 outlines the pilot data and workflow. The MVP Info Center conducted reminder calls to participants who did not return the kit within 2 weeks and feedback follow-up calls to participants who returned a specimen without including a completed feedback form. MVP is approved through the VA Central Institutional Review Board.
Fig. 1.
Pilot study workflow.
Pilot participants mailed the specimens to the Veterans Health Administration (VHA) Public Health Reference Laboratory (PHRL, Palo Alto, CA) where the specimens were accessioned, processed, and tested across 4 assays for the presence of COVID-19 antibodies (from both natural immunity from COVID-19 infection and post-vaccination). For Mitra devices, previous publications have used different buffers, volumes, and conditions to elute whole blood from Mitra tips [[3], [5], [8]]. Although phosphate buffered saline (PBS), 0.9% normal saline with 0.5% tween were the common elution mixtures, we saw variations in time duration for samples placed on a shaker. We compared elution techniques using PBS, 0.9% normal saline, and 0.5% Tween for 1 vs 24 hours of shaking at 300 rpm at room temperature and found no significant difference in COVID-19 antibody detection (data not shown). Based on this observation, we chose one of these 2 buffers and a time-conservative approach. Therefore, each Mitra tip (up to 4) of dried blood was removed by pulling the tip over the edge of each well of a 2-mL 96-well plate and eluted in 250uL (total 1 mL per participant sample) of 0.9% normal saline with 0.5% Tween for 1 hour at room temperature shaking at 300 rpm. A total of 1 mL of eluent was then transferred to a cryovial. For the Tasso-SST device, the mini tubes of liquid blood were centrifuged according to vendor instructions. Serum was removed and transferred to cryovials. All samples were stored at -80 °C until tested. The following Emergency use authorization (EUA) approved SARS-CoV-2 antibody (Ab) assays were used to test samples: SCoV-2 Detect™ IgG ELISA (InBios, Seattle, WA) Spike IgG, Platelia SARS-CoV-2 Total Ab Assay (BioRad, Hercules, CA) nucleocapsid (NC) total Ab, Alinity i SARS-CoV-2 IgG (NC IgG) and AdviseDx SARS-CoV-2 IgG II (Spike IgG) (Abbott Diagnostics, Abbott Park, IL) according to manufacturer instructions.
3. Results
3.1. Goal 1: determine feasibility of at-home blood specimen collection for scalability purposes
Of those invited, 52% of MVP Participants consented to participate and 90% of pilot participants returned a viable (sufficient quantity and quality) specimen. The consent rate was slightly higher for Mitra compared to Tasso (54% vs 50%). Viable specimens, defined as sufficient volume to conduct at least one SARS-CoV-2 antibody assay, received for Mitra was 98% compared to 74% for Tasso. This is discussed further in the Goal 2 section below. See Fig. 1 for consent and specimen rates per device.
Though there was effectively no difference in age and gender, median income was 4% higher for those who verbally consented to participate compared to those invited to join the pilot. Similarly, the demographics were slightly different between those invited to participate and those who consented, becoming slightly less diverse moving from 83% White to 88% White, and from 4% to 2.6% Hispanic. Some slight shifts in geographic region representation occurred with a West/Pacific 2% increase and South 2% decrease, with those in urban settings decreasing by 2% while those in rural settings stayed steady at an estimated 25% of all recruited and consented participants. The COVID-19 diagnosis rate decreased slightly from 30% to 27% and COVID-19 fully vaccinated rate increased from 16% to 27%, with the unvaccinated rate slightly decreasing from 65% to 61%. See Table 2 for comparison of demographic, COVID-19 diagnosis, and COVID-19 vaccination status, between invited and consented participants.
Table 2.
Pilot invited vs consented participants: age, income, demographics, and COVID-19 diagnosis and COVID-19 vaccination status.
| Emailed for recruitment (N = 599) |
Consented (N = 312) |
|||
|---|---|---|---|---|
| Mean | Std | Mean | Std | |
| Age at pilot consenta | 68.2 | 10.9 | 68.7 | 10.1 |
| Median | IQR | Median | IQR | |
| Income | $32,456 | $13,000 - $51,060 | $33,876 | $13,284 - $52,075 |
| N missing income data | 66 | 31 | ||
| N | % | N | % | |
| Gender | ||||
| Male | 537 | 89.65 | 280 | 89.74 |
| Female | 62 | 10.35 | 32 | 10.26 |
| Unknown | 0 | 0.00 | 0 | 0.00 |
| Race | ||||
| American Indian/Alaska Native | 2 | 0.33 | 2 | 0.64 |
| Asian | 7 | 1.17 | 1 | 0.32 |
| Black/African American | 54 | 9.02 | 18 | 5.77 |
| Native Hawaiian/Other Pacific Islander | 1 | 0.17 | 0 | 0.00 |
| White | 498 | 83.14 | 275 | 88.14 |
| Multiple | 25 | 4.17 | 11 | 3.53 |
| Other | 9 | 1.50 | 2 | 0.64 |
| Unknown | 3 | 0.50 | 3 | 0.96 |
| Ethnicity | ||||
| Hispanic or Latino | 24 | 4.01 | 8 | 2.56 |
| Not Hispanic or Latino | 571 | 95.33 | 302 | 96.79 |
| Unknown | 4 | 0.67 | 2 | 0.64 |
| Region | ||||
| Northeast | 69 | 11.52 | 35 | 11.22 |
| South | 264 | 44.07 | 131 | 41.99 |
| Midwest | 108 | 18.03 | 57 | 18.27 |
| West/Pacific | 157 | 26.21 | 89 | 28.53 |
| Otherb | 1 | 0.17 | 0 | 0.00 |
| Rurality | ||||
| Rural | 148 | 24.71 | 80 | 25.64 |
| Urban | 444 | 74.12 | 227 | 72.76 |
| Highly Urban | 7 | 1.17 | 5 | 1.6 |
| COVID diagnosisc | 182 | 30.38 | 85 | 27.24 |
| COVID vaccination statusd | ||||
| Not vaccinated | 392 | 65.44 | 190 | 60.90 |
| Partially vaccinated (1 dose) | 99 | 16.53 | 30 | 9.62 |
| Fully vaccinated (2 doses) | 98 | 16.36 | 85 | 27.24 |
| Missinge | 10 | 1.67 | 7 | 2.24 |
Defined as age at pilot consent date for consented participants or age as of February 1, 2021 for individuals without a pilot consent date.
The “Other” region contains international bases.
Restricted to positive COVID test from EHR or self-reported COVID diagnosis before pilot consent date or before February 1, 2021 for individuals without a pilot consent date.
Vaccination status as of pilot consent date for consented participants or February 1, 2021 for individuals without a pilot consent date.
Missing vaccination status is a result of the vaccine records being flagged as “Potentially Erroneous.”
Further analysis to compare those who consented to participate to those who provided a viable specimen (by either collection device) showed no major difference in mean age, gender, and race and ethnicity. A larger proportion of Tasso-SST users who returned a viable specimen either had been vaccinated (at least 1 dose) or had evidence of a COVID-19 diagnosis. See Table 3 for demographics, COVID-19 diagnosis, and COVID-19 vaccination status for consented participants and those returning viable specimens.
Table 3.
Consented participants and specimens received with sufficient volume by device type: age, gender, race, and COVID-19 diagnosis and vaccination status.
| Consented (N = 312) | Neoteryx mitra returned, viable specimen (N = 126) | Tasso-SST returned, viable specimen (N = 113) | |
|---|---|---|---|
| Age at pilot consenta | 68.7 (10.1) | 69.7 (10.1) | 66.5 (10.7) |
| Male (Gender)b | 280 (89.7%) | 113 (89.7%) | 100 (88.5%) |
| White (Race)b | 275 (88.1%) | 109 (86.5%) | 100 (88.5%) |
| COVID-19 diagnosisb,c | 85 (27.2%) | 26 (20.6%) | 36 (31.9%) |
| Vaccinated for COVID-19b,d | 115 (36.9%) | 38 (30.2%) | 46 (40.7%) |
Mean (Standard Deviation).
N(%).
Defined as a positive COVID test from electronic health record or self-reported COVID diagnosis from survey, before pilot consent date.
Defined as having received at least 1 COVID-19 vaccine dose, before pilot consent date.
Additionally, participants rated their experience using their assigned self-collection device via a feedback form included in kits. In total, 95% of pilot participants that returned a specimen provided feedback. Generally, participants found both devices easy to use, rating the Mitra and Tasso-SST devices equally on average as 4.4 on a 1-5 scale (Table 1 ).
Table 1.
Participant feedback on devices.
| AT-HOME PILOT - FEEDBACK FORM RESULTS | NEOTERYX AVG RATING | TASSO AVG RATING |
|---|---|---|
| Total Responses | 120 (95%) | 148 (95%) |
| 1. How was your experience receiving and opening the kit? | 4.5 | 4.6 |
| 2. How easy was the at-home collection kit instructions to understand and follow? | 4.2 | 4.5 |
| 3. How easy was the specimen collection device to use? | 4.3 | 4.4 |
| 4. How easy were the mailing return instructions to follow? | 4.6 | 4.4 |
| 5. How was your overall experience receiving the kit, using the collection device, and returning your specimen to MVP? | 4.5 | 4.4 |
| Overall Average Rating | 4.4 | 4.4 |
3.2. Goal 2: test the feasibility of low volume capillary blood for SARS-CoV-2 antibody detection
As shown in Fig. 1, viable samples were received from 98% and 74% of those participants who were sent Mitra or Tasso-SST collection devices, respectively. The average time from self-collection to receipt at the laboratory was 3.6 days (range 1–23 days, N = 235 participants that completed a feedback form with their specimen date of collection). Twenty-five percent of received Tasso-SST samples either had no blood volume or insufficient volume (< 4 uL) to perform 1 or more COVID-19 antibody assays. Since each assay had different volume requirements (see Table 4 ), low volume Tasso-SST samples required prioritization of which assay(s) could be performed. Because of the eluent volume used during Mitra processing, all but 1 Mitra samples had sufficient volume for testing with all assays.
Table 4.
Assay sensitivity and specificity by device type.
| Neoteryx mitra (N = 126)a |
Tasso-SST (N = 113)a |
||||
|---|---|---|---|---|---|
| Antibody positive | Antibody negative | Antibody positive | Antibody negative | ||
| InBios Spike IgG (4 uL)c | COVID-19 Dx and/or vaccinatedd | 35 | 23 | 63 | 2 |
| No COVID-19 Dx/not vaccinated | 8 | 60 | 5 | 20 | |
| Sensitivity | 0.60 | 0.97 | |||
| Specificity | 0.88 | 0.80 | |||
| BioRad (Total NCb Ab) (15 uL) | COVID-19 Dx and/or vaccinated | 19 | 39 | 30 | 37 |
| No COVID-19 Dx/not vaccinated | 4 | 64 | 3 | 42 | |
| Sensitivity | 0.33 | 0.45 | |||
| Specificity | 0.94 | 0.93 | |||
| Abbott NCb IgG (125 uL) | COVID-19 Dx and/or vaccinated | 11 | 47 | 14 | 27 |
| No COVID-19 Dx/not vaccinated | 2 | 66 | 3 | 29 | |
| Sensitivity | 0.19 | 0.34 | |||
| Specificity | 0.97 | 0.91 | |||
| Abbott Spike IgG II (125 uL) | COVID-19 Dx and/or vaccinated | 46 | 7 | 47 | 1 |
| No COVID-19 Dx/not vaccinated | 9 | 4 | 5 | 0 | |
| Sensitivity | 0.87 | 0.98 | |||
| Specificity | 0.31 | 0.00 | |||
Due to volume restrictions, not all samples were tested for all assays.
NC = nucleocapsid.
Sample volume required for assay.
Defined as a positive COVID test from EHR or self-reported COVID diagnosis from survey, or having received at least 1 dose before pilot consent date.
Some subjects may have had COVID-19 infection and were not tested.
The Abbott IgG II assay had the highest sensitivity across both devices (87% Mitra and 98% Tasso-SST) for detecting known COVID infection and/or vaccination. Semiquantitative results ranged from 0 to 5123.5 AU/mL for Mitra samples (N = 65) and 1.8–50,000 AU/mL for Tasso-SST samples (N = 51). InBios IgG assay with the Tasso-SST had the best combination of sensitivity (97%) and specificity (80%) detecting known COVID-19 infection and/or vaccination, see more details in Table 4. Stratification into COVID-19 Infection Only and Vaccinated Only groups display the difference between the spike protein assays and nucleocapsid assays, see Table 5 for more details. The sensitivity remains high in both groups and both devices for the InBios Spike IgG and Abbott Spike IgG II assays. However, the sensitivity in the Vaccinated Only group drops sharply to 3% (Neoteryx Mitra) and 9% (Tasso-SST) for the BioRad NC assay and to 0% (Neoteryx Mitra) and 8% (Tasso-SST) for the Abbot NC IgG assay. Additionally, it should be noted that 1mL of eluent buffer was used to process 120 uL of whole blood from Mitra tips, resulting in an 8-fold reduced starting dilution of all whole blood samples. Since serum represents approximately 55% of whole blood, an additional 1.8-fold dilution is required when considering whole blood as the tested medium. Sample dilution may have contributed to reduced sensitivity results seen with Mitra tip whole blood.
Table 5.
Assay by device type and COVID-19 diagnosis and vaccination
| Tasso-SST (N = 113)a |
Neoteryx mitra (N = 126)a |
||||||
|---|---|---|---|---|---|---|---|
| Antibody positive | Antibody negative | Sensitivity | Antibody positive | Antibody negative | Sensitivity | ||
| InBios Spike IgG (4 uL)c | COVID-19 Dx and vaccinatedd | 5 | 1 | 0.83 | 13 | 0 | 1.00 |
| COVID-19 Dx only | 11 | 9 | 0.55 | 18 | 2 | 0.90 | |
| vaccinated only | 19 | 13 | 0.59 | 32 | 0 | 1.00 | |
| BioRad (Total NCb Ab) (15 uL) | COVID-19 Dx and vaccinated | 4 | 2 | 0.67 | 11 | 3 | 0.79 |
| COVID-19 Dx only | 14 | 6 | 0.70 | 16 | 5 | 0.76 | |
| vaccinated only | 1 | 31 | 0.03 | 3 | 29 | 0.09 | |
| Abbott NCb IgG (30 uL≤ x<125 uL) | COVID-19 Dx and vaccinated | 4 | 2 | 0.67 | 5 | 1 | 0.83 |
| COVID-19 Dx only | 7 | 13 | 0.35 | 7 | 4 | 0.64 | |
| vaccinated only | 0 | 32 | 0.00 | 2 | 22 | 0.08 | |
| Abbot Spike IgG II (30 uL≤ x<125 uL) | COVID-19 Dx and vaccinated | 5 | 0 | 1.00 | 8 | 0 | 1.00 |
| COVID-19 Dx only | 14 | 4 | 0.78 | 12 | 1 | 0.92 | |
| vaccinated only | 27 | 3 | 0.90 | 27 | 0 | 1.00 | |
aDue to volume restrictions, not all samples were tested for all assays.
bNC = nucleocapsid.
cSample volume required for assay.
dDefined as a positive COVID test from EHR or self-reported COVID diagnosis from survey, or having received at least 1 dose before pilot consent date.
Some subjects may have had COVID-19 infection and were not tested.
4. Discussion
MVP Participants are comfortable using either of these devices as evidenced from their consent rate for this additional blood specimen, the rate of returned specimens, and their overall feedback on ease of use. From a Veteran perspective, each group evaluated the ease of use of each device similarly (Table 1). This is particularly interesting, as on average the Veteran population age in this study was 68 (ages ranged from 30 to 89 years old, N = 312), and in general older Veterans tend to face more health challenges than the non-Veteran population within the same age range [9]. This means that despite being an older population, likely with a higher percentage of health issues, participants were able to use either collection device successfully. Blood collected from either device was able to detect SARS-CoV-2 nucleocapsid and spike IgG antibodies using different commercially available assays although with varied sensitivity and specificity. It was determined that 98% Mitra specimens were deemed viable for assay testing compared to 76% Tasso-SST (Fig. 1). However, assays performed on Mitra samples resulted in lower sensitivity due to the dilution factor. Despite having less Tasso-SST samples deemed viable, it was found that the Tasso-SST combined with the InBios Spike IgG assay provided the highest combination of sensitivity and specificity.
Recent studies have shown that DBS can be used to detect SARS-CoV-2 IgG antibodies with laboratory-derived assays or EuroImmun IgG assay and results compared favorably to venous blood serum results after phlebotomy [4,5]. Venous collected blood was compared to capillary collected blood using Microvette 100 capillary tubes and DBS in 39 participants and demonstrated > 94% concordance among the collection methods for SARS-CoV-2 antibodies using the Omega Diagnostics COVID-19 IgG ELISA [10]. Mitra tips were evaluated by Whitcombe et al., in a simulation study where 19 previously collected whole blood samples were compared to serum and found very high correlation among several SARS-CoV-2 antibody assays [11]. Kalish et al, utilized self-collected Mitra tips in a large SARS-CoV-2 antibody seroprevalence study in over 9000 US subjects [6], determining a much larger spread of COVID-19 than originally estimated due to mild/asymptomatic cases that were not diagnosed. One recent study used serum from the Tasso-SST device to determine COVID-19 IgG antibody status among over 2000 college students with the Abbott Architect IgG NC assay and a laboratory developed COVID-19 antibody test [7], demonstrating feasibility of this collection approach for large-scale seroprevalence studies. To our knowledge, no studies have been performed directly comparing the performance of Mitra and Tasso-SST collected samples for SARS-CoV-2 antibodies from the same subjects. But in general, capillary collected blood (either liquid or dried) compares favorably to venous collected blood for SARS-CoV-2 antibody testing.
Our study has several limitations. Only 1 collection device was given to each participant, so no intra-participant testing comparison of devices or assays was possible, and no venous blood was obtained to use as a gold standard. Varied timing of sample collection related to time since COVID-19 infection, receipt of 1 or 2 dose of COVID-19 vaccine, unknown COVID-19 infection or vaccination status among some participants could have affected COVID-19 antibody test results. Other than the BioRad total antibody test, no COVID-19 specific IgM assays were studied. Blood samples were not collected by standard phlebotomy, so assay performance could not be assessed using serum according to the package insert. Finally, variability in Tasso-SST collection volume limited some samples from being tested with all assays, and Mitra whole blood dilution may have affected sensitivity/specificity comparison across assays.
In summary, we have demonstrated the feasibility of self-collected capillary blood samples for SARS-CoV-2 antibody detection. Antibody assay performance varied among assays and collection devices. Additional testing is planned with a new collection device called Tasso+ (Tasso Plus) to address the volume variability associated with Tasso-SST, as well as additional analysis of COVID antibodies at multiple points in time to optimize use of these assays to further our understanding of Veteran's experience with COVID-19 infection and vaccination. The ability for Veterans to self-perform antibody testing may offer valuable insight into how diagnostic testing can occur at-home more broadly in the general population, both in response to the COVID-19 pandemic and beyond.
MVP COVID-19 Science Program Steering Committee
J. Michael Gaziano, M.D., M.P.H. (Co-Chair)
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Philip S. Tsao, Ph.D. (Co-Chair)
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
Sumitra Muralidhar, Ph.D.
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
Jean Beckham, Ph.D.
Durham VA Medical Center, 508 Fulton Street, Durham, NC 27705
Kyong-Mi Chang, M.D.
Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104
Juan P. Casas, M.D., Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Kelly Cho, M.P.H., Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Saiju Pyarajan, Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Jennifer Huffman, Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Jennifer Moser, Ph.D.
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
MVP COVID-19 Science Program Steering Committee Support
Helene Garcon, M.D. (Program Coordinator, Working Group Coordinator)
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Nicole Kosik, M.P.H. (Working Group Coordinator)
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
MVP COVID-19 Science Program Working Groups and Associated Chairs
COVID-19 Related PheWAS
Katherine Liao, M.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Scott Damrauer, M.D.
Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104
Disease Mechanisms
Richard Hauger, M.D.
VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161
Shiuh-Wen Luoh, M.D., Ph.D.
Portland VA Medical Center, 3710 SW U.S. Veterans Hospital Road, Portland, OR 97239
Sudha Iyengar, Ph.D.
VA Northeast Ohio Healthcare System, 10701 East Boulevard, Cleveland, OH 44106
Druggable Genome
Juan P. Casas, M.D., Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Genomics for Risk Prediction, PRS, and MR
Themistocles Assimes, M.D., Ph.D.
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
Panagiotis Roussos, M.D., Ph.D.
James J. Peters VA Medical Center, 130 W Kingsbridge Rd, Bronx, NY 10468
Robert Striker, M.D., Ph.D.
William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705
GWAS & Downstream Analysis
Jennifer Huffman, Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Yan Sun, Ph.D.
Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033
Pharmacogenomics
Adriana Hung, M.D., M.P.H.
VA Tennessee Valley Healthcare System, 1310 24th Avenue, South Nashville, TN 37212
Sony Tuteja, Pharm.D., M.S.
Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104
VA COVID-19 Shared Data Resource – Scott L. DuVall, Ph.D.; Kristine E. Lynch, Ph.D.; Elise Gatsby, M.P.H.
VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, 500 Foothill Drive, Salt Lake City, UT 84148
MVP COVID-19 Data Core – Kelly Cho, M.P.H., Ph.D.; Lauren Costa, M.P.H.; Anne Yuk-Lam Ho, M.P.H.; Rebecca Song, M.P.H.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
MVP Program Office
Program Director - Sumitra Muralidhar, Ph.D.
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
Associate Director, Scientific Programs - Jennifer Moser, Ph.D.
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
Associate Director, Cohort Management & Public Relations - Jennifer E. Deen, B.S.
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
MVP Executive Committee
Co-Chair: J. Michael Gaziano, M.D., M.P.H.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Co-Chair: Sumitra Muralidhar, Ph.D.
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
Jean Beckham, Ph.D.
Durham VA Medical Center, 508 Fulton Street, Durham, NC 27705
Kyong-Mi Chang, M.D.
Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104
Philip S. Tsao, Ph.D.
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
Shiuh-Wen Luoh, M.D., Ph.D.
VA Portland Health Care System, 3710 SW US Veterans Hospital Rd, Portland, OR 97239
US Department of Veterans Affairs, 810 Vermont Avenue NW, Washington, DC 20420
Juan P. Casas, M.D., Ph.D., Ex-Officio
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
MVP Principal Investigators
J. Michael Gaziano, M.D., M.P.H.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Philip S. Tsao, Ph.D.
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
MVP Operations
MVP Executive Director – Juan P. Casas, M.D., Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Director of Regulatory Affairs – Lori Churby, B.S.
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
MVP Cohort Management Director – Stacey B. Whitbourne, Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
MVP Recruitment/Enrollment Director - Jessica V. Brewer, M.P.H.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Director, VA Central Biorepository, Boston – Mary T. Brophy M.D., M.P.H.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Executive Director for MVP Biorepositories - Luis E. Selva, Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
MVP Informatics, Boston – Shahpoor (Alex) Shayan, M.S.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Director, MVP Data Operations/Analytics, Boston – Kelly Cho, M.P.H., Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Director, Center for Computational and Data Science (C-DACS) & Genomics Core – Saiju Pyarajan Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Director, Molecular Data Core – Philip S. Tsao, Ph.D.
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
Director, Phenomics Data Core – Kelly Cho, M.P.H, Ph.D.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
Director, VA Informatics and Computing Infrastructure (VINCI) – Scott L. DuVall, Ph.D.
VA Salt Lake City Health Care System, 500 Foothill Drive, Salt Lake City, UT 84148
MVP Coordinating Centers
Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque – Todd Connor, Pharm.D.; Dean P. Argyres, B.S., M.S.
New Mexico VA Health Care System, 1501 San Pedro Drive SE, Albuquerque, NM 87108
Genomics Coordinating Center, Palo Alto – Philip S. Tsao, Ph.D.
VA Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304
MVP Boston Coordinating Center, Boston - J. Michael Gaziano, M.D., M.P.H.
VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130
MVP Information Center, Canandaigua – Brady Stephens, M.S.
Canandaigua VA Medical Center, 400 Fort Hill Avenue, Canandaigua, NY 14424
Current MVP Local Site Investigators
Atlanta VA Medical Center (Peter Wilson, M.D.)
1670 Clairmont Road, Decatur, GA 30033
Bay Pines VA Healthcare System (Rachel McArdle, Ph.D.)
10,000 Bay Pines Blvd Bay Pines, FL 33744
Birmingham VA Medical Center (Louis Dellitalia, M.D.)
700 S. 19th Street, Birmingham AL 35233
Central Western Massachusetts Healthcare System (Kristin Mattocks, Ph.D., M.P.H.)
421 North Main Street, Leeds, MA 01053
Cincinnati VA Medical Center (John Harley, M.D., Ph.D.)
3200 Vine Street, Cincinnati, OH 45220
Clement J. Zablocki VA Medical Center (Jeffrey Whittle, M.D., M.P.H.)
5000 West National Avenue, Milwaukee, WI 53295
VA Northeast Ohio Healthcare System (Frank Jacono, M.D.)
10701 East Boulevard, Cleveland, OH 44106
Durham VA Medical Center (Jean Beckham, Ph.D.)
508 Fulton Street, Durham, NC 27705
Edith Nourse Rogers Memorial Veterans Hospital (John Wells., Ph.D.)
200 Springs Road, Bedford, MA 01730
Edward Hines, Jr. VA Medical Center (Salvador Gutierrez, M.D.)
5000 South 5th Avenue, Hines, IL 60141
Veterans Health Care System of the Ozarks (Kathrina Alexander, M.D.)
1100 North College Avenue, Fayetteville, AR 72703
Fargo VA Health Care System (Kimberly Hammer, Ph.D.)
2101 N. Elm, Fargo, ND 58102
VA Health Care Upstate New York (James Norton, Ph.D.)
113 Holland Avenue, Albany, NY 12208
New Mexico VA Health Care System (Gerardo Villareal, M.D.)
1501 San Pedro Drive, S.E. Albuquerque, NM 87108
VA Boston Healthcare System (Scott Kinlay, M.B.B.S., Ph.D.)
150 S. Huntington Avenue, Boston, MA 02130
VA Western New York Healthcare System (Junzhe Xu, M.D.)
3495 Bailey Avenue, Buffalo, NY 14215-1199
Ralph H. Johnson VA Medical Center (Mark Hamner, M.D.)
109 Bee Street, Mental Health Research, Charleston, SC 29401
Columbia VA Health Care System (Roy Mathew, M.D.)
6439 Garners Ferry Road, Columbia, SC 29209
VA North Texas Health Care System (Sujata Bhushan, M.D.)
4500 S. Lancaster Road, Dallas, TX 75216
Hampton VA Medical Center (Pran Iruvanti, D.O., Ph.D.)
100 Emancipation Drive, Hampton, VA 23667
Richmond VA Medical Center (Michael Godschalk, M.D.)
1201 Broad Rock Blvd., Richmond, VA 23249
Iowa City VA Health Care System (Zuhair Ballas, M.D.)
601 Highway 6 West, Iowa City, IA 52246-2208
Eastern Oklahoma VA Health Care System (River Smith, Ph.D.)
1011 Honor Heights Drive, Muskogee, OK 74401
James A. Haley Veterans’ Hospital (Stephen Mastorides, M.D.)
13000 Bruce B. Downs Blvd, Tampa, FL 33612
James H. Quillen VA Medical Center (Jonathan Moorman, M.D., Ph.D.)
Corner of Lamont & Veterans Way, Mountain Home, TN 37684
John D. Dingell VA Medical Center (Saib Gappy, M.D.)
4646 John R Street, Detroit, MI 48201
Louisville VA Medical Center (Jon Klein, M.D., Ph.D.)
800 Zorn Avenue, Louisville, KY 40206
Manchester VA Medical Center (Nora Ratcliffe, M.D.)
718 Smyth Road, Manchester, NH 03104
Miami VA Health Care System (Ana Palacio, M.D., M.P.H.)
1201 NW 16th Street, 11 GRC, Miami FL 33125
Michael E. DeBakey VA Medical Center (Olaoluwa Okusaga, M.D.)
2002 Holcombe Blvd, Houston, TX 77030
Minneapolis VA Health Care System (Maureen Murdoch, M.D., M.P.H.)
One Veterans Drive, Minneapolis, MN 55417
N. FL/S. GA Veterans Health System (Peruvemba Sriram, M.D.)
1601 SW Archer Road, Gainesville, FL 32608
Northport VA Medical Center (Shing Yeh, Ph.D., M.D.)
79 Middleville Road, Northport, NY 11768
Overton Brooks VA Medical Center (Neeraj Tandon, M.D.)
510 East Stoner Ave, Shreveport, LA 71101
Philadelphia VA Medical Center (Darshana Jhala, M.D.)
3900 Woodland Avenue, Philadelphia, PA 19104
Phoenix VA Health Care System (Samuel Aguayo, M.D.)
650 E. Indian School Road, Phoenix, AZ 85012
Portland VA Medical Center (David Cohen, M.D.)
3710 SW U.S. Veterans Hospital Road, Portland, OR 97239
Providence VA Medical Center (Satish Sharma, M.D.)
830 Chalkstone Avenue, Providence, RI 02908
Richard Roudebush VA Medical Center (Suthat Liangpunsakul, M.D., M.P.H.)
1481 West 10th Street, Indianapolis, IN 46202
Salem VA Medical Center (Kris Ann Oursler, M.D.)
1970 Roanoke Blvd, Salem, VA 24153
San Francisco VA Health Care System (Mary Whooley, M.D.)
4150 Clement Street, San Francisco, CA 94121
South Texas Veterans Health Care System (Sunil Ahuja, M.D.)
7400 Merton Minter Boulevard, San Antonio, TX 78229
Southeast Louisiana Veterans Health Care System (Joseph Constans, Ph.D.)
2400 Canal Street, New Orleans, LA 70119
Southern Arizona VA Health Care System (Paul Meyer, M.D., Ph.D.)
3601 S 6th Avenue, Tucson, AZ 85723
Sioux Falls VA Health Care System (Jennifer Greco, M.D.)
2501 W 22nd Street, Sioux Falls, SD 57105
St. Louis VA Health Care System (Michael Rauchman, M.D.)
915 North Grand Blvd, St. Louis, MO 63106
Syracuse VA Medical Center (Richard Servatius, Ph.D.)
800 Irving Avenue, Syracuse, NY 13210
VA Eastern Kansas Health Care System (Melinda Gaddy, Ph.D.)
4101 S 4th Street Trafficway, Leavenworth, KS 66048
VA Greater Los Angeles Health Care System (Agnes Wallbom, M.D., M.S.)
11301 Wilshire Blvd, Los Angeles, CA 90073
VA Long Beach Healthcare System (Timothy Morgan, M.D.)
5901 East 7th Street Long Beach, CA 90822
VA Maine Healthcare System (Todd Stapley, D.O.)
1 VA Center, Augusta, ME 04330
VA New York Harbor Healthcare System (Peter Liang, M.D., M.P.H.)
423 East 23rd Street, New York, NY 10010
VA Pacific Islands Health Care System (Daryl Fujii, Ph.D.)
459 Patterson Rd, Honolulu, HI 96819
VA Palo Alto Health Care System (Philip Tsao, Ph.D.)
3801 Miranda Avenue, Palo Alto, CA 94304-1290
VA Pittsburgh Health Care System (Patrick Strollo, Jr., M.D.)
University Drive, Pittsburgh, PA 15240
VA Puget Sound Health Care System (Edward Boyko, M.D.)
1660 S. Columbian Way, Seattle, WA 98108-1597
VA Salt Lake City Health Care System (Jessica Walsh, M.D.)
500 Foothill Drive, Salt Lake City, UT 84148
VA San Diego Healthcare System (Samir Gupta, M.D., M.S.C.S.)
3350 La Jolla Village Drive, San Diego, CA 92161
VA Sierra Nevada Health Care System (Mostaqul Huq, Pharm.D., Ph.D.)
975 Kirman Avenue, Reno, NV 89502
VA Southern Nevada Healthcare System (Joseph Fayad, M.D.)
6900 North Pecos Road, North Las Vegas, NV 89086
VA Tennessee Valley Healthcare System (Adriana Hung, M.D., M.P.H.)
1310 24th Avenue, South Nashville, TN 37212
Washington DC VA Medical Center (Jack Lichy, M.D., Ph.D.)
50 Irving St, Washington, D. C. 20422
W.G. (Bill) Hefner VA Medical Center (Robin Hurley, M.D.)
1601 Brenner Ave, Salisbury, NC 28144
White River Junction VA Medical Center (Brooks Robey, M.D.)
163 Veterans Drive, White River Junction, VT 05009
William S. Middleton Memorial Veterans Hospital (Prakash Balasubramanian, M.D.)
2500 Overlook Terrace, Madison, WI 53705
Data availability
Data will not be made available in order to comply with current VA privacy regulations.
The views expressed in this work are those of the authors and does not represent the views of the Department of Veterans Affairs or the United States Government.
Author contributions
Tseli Mohammed: Conceptualization, Methodology, Resources, Writing – Review & Editing, Visualization, Supervision, Project Administration.
Jessica V.V. Brewer: Conceptualization, Methodology, Resources, Writing – Review & Editing, Supervision.
Mary Pyatt: Software, Formal Analysis, Data Curation.
Stacey B. Whitbourne: Writing – Review & Editing.
J. Michael Gaziano: Writing – Review & Editing, Funding Acquisition.
Connor Edson: Formal Analysis, Investigation, Writing – Original Draft.
Mark Holodniy: Methodology, Formal Analysis, Investigation, Writing – Original Draft, Writing – Review & Editing.
Declaration of competing interests
The authors report no conflicts of interest relevant to this article.
Acknowledgments
Acknowledgments
The authors thank the members of the Million Veteran Program Core, those who have contributed to the Million Veteran Program, and especially the Veteran participants for their generous contributions.
Funding
This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was funded by awards #MVP000 and MVP035. None of the authors have financial conflicts of interest with the work reported in this manuscript.
References
- 1.World Health Organzation. WHO Coronavirus (COVID-19) Dashboard. Available at: https://covid19.who.int. Accessed March 25, 2022.
- 2.Tuaillon E, Kania D, Pisoni A, Bollore K, Taieb F, Ontsira, et al. Dried blood spot tests for the diagnosis and therapeutic monitoring of HIV and Viral Hepatitis B and C. Front. Microbiol. 2020;11:373. doi: 10.3389/fmicb.2020.00373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Wang J, Li D, Wiltse A, Emo J, Hilchey SP, Zand MS. Application of volumetric absorptive microsampling (VAMS) to measure multidimensional anti-influenza IgG antibodies by the mPlex-Flu assay. J Clin Transl Sci. 2019;3(6):332–343. doi: 10.1017/cts.2019.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Toh ZQ, Higgins RA, Anderson J, Mazarakis N, Do LAH, Rautenbacher K, et al. The use of dried blood spots for the serological evaluation of SARS-CoV-2 antibodies. J Public Health (Oxf) 2021 doi: 10.1093/pubmed/fdab011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Turgeon C, Sanders K, Granger D, Nett S, Hilgart H, Matern D, Theel E. Detection of SARS-CoV-2 IgG antibodies in dried blood spots. Diagn Microbiol Infect Dis. 2021;101:1. doi: 10.1016/j.diagmicrobio.2021.115425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kalish H, Klumpp-Thomas C, Hunsberger S, Baus H-A, Fay M, Siripong N, et al. Undiagnosed SARS-CoV-2 seropositivity during the first 6 months of the COVID-19 pandemic in the United States. Sci Transl Med. 2021;13:601. doi: 10.1126/scitranslmed.abh3826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Vusirikala A, Whitaker H, Jones S, et al. Seroprevalence of SARS-CoV-2 antibodies in university students: cross-sectional study, December 2020, England. J Infect. 2021;83(1):104–111. doi: 10.1016/j.jinf.2021.04.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Klumpp-Thomas C., Kalish H., Drew M., et al. Standardization of ELISA protocols for serosurveys of the SARS-CoV-2 pandemic using clinical and at-home blood sampling. Nature Commun. 2021;12:113. doi: 10.1038/s41467-020-20383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.CDC National Center for Health Statistics, Veterans Health Statistics Table. Available at: Veterans Health Statistics - Table (cdc.gov). Accessed on June 30, 2022.
- 10.Brown L., Byrne R.L., Fraser A., et al. Self-sampling of capillary blood for SARS-CoV-2 serology. Sci Rep. 2021;11:7754. doi: 10.1038/s41598-021-86008-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Whitcombe AL, McGregor R, Craigie A, et al. Comprehensive analysis of SARS-CoV-2 antibody dynamics in New Zealand. Clin Transl Immunol. 2021;10(3):e1261. doi: 10.1002/cti2.1261. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data will not be made available in order to comply with current VA privacy regulations.
The views expressed in this work are those of the authors and does not represent the views of the Department of Veterans Affairs or the United States Government.