Fall College Testing Program


The Clinical Research Sequencing Platform (CRSP) and Broad have a strong interest in helping colleges and universities in New England that wish to reopen their campuses to do so in a safe manner. To serve this public goal, CRSP has established the Safe for School Program, providing colleges and universities a plan for testing their students, faculty, and staff at regular intervals. Because the majority of transmissions occur from people who didn't know they were infected, simply relying on symptoms is not an effective way of detecting infections. It is important to detect infections before there's been much opportunity for transmission in order to keep an academic community safe (in addition to decreasing spread through measures such as masks and physical distancing).

Program Details

Requirements for a school to be included in the program:
  • Minimum commitment of at least 3000 tests for the fall semester
  • Regular testing cadence: either weekly, twice a week, or every other week
Costs of the program will include:
  • Per test cost - discounts dependent on aggregate volume across all schools/universities
  • Transportation coordinated by Broad CRSP
    • For pick ups >300 samples: Free within MA, extra charge outside of MA
    • For batches of fewer than 300 samples: A fixed amount per pick-up based on mileage, average time, and tolls to and from the college
  • Possible additional software services
    • IT integration for usage of non-standard systems
    • Provision of third-party software apps
  • Possible medical and logistical services
    • Ordering physician
    • Supervision of swabbing
    • Site management
Test turnaround time: within 24 hours of receipt

Getting started

  1. Sign a Material Services Agreement (MSA).
    Send the completed MSA to collegetestingprogram@broadinstitute.org.
  2. Choose your desired information flow option.
    At this time, due to the volume of schools and limited time for set up, we cannot offer any customization options. Note: unobserved self collection will require the use of the CoVerified app.

    CareEvolve

    Option 1 CareEvolve portal: NEW!! Updated CareEvolve Instructions
    Basic functionality included
    • standing order creation
    • printing of labels with barcodes

    • participant facing interface to access results
    • school administrator site for global search of results
    Pricing
    This option is already included in the price.

    CoVerified

    Option 2 CoVerified campus management platform NEW!! Onboarding Website
    Detailed information around upcoming webinars, sign up process, timelines, and security documentation can be found at www.coverified.us/broad.
    Features
    • Administrator analytics dashboard
    • Symptom reporting app
    • Contact tracing

    • Test scheduling
    • Direct results integration
    Timeline
    • App and Administrator dashboard available in the coming weeks
    • Onboarding begins within two weeks of signup
    • Full integrations before August 15th (if signed up before July 24th)
    Pricing
    • Requires software services agreement with CoVerified at $1 per user account per month
    • First month due at signing
    • Data transfer services cost of $1 per test paid to the Broad
    For more information about our testing informatics infrastructure and security practices, please see this document. Due to the high volume of institutions we are interacting with for this fall program, we cannot engage in individual security reviews.
  3. Institutional setup and invoicing setup.
    Upon signing the agreement, we will reach out to you and ask for specific information for invoicing and payment (W9, wire information, etc.).
  4. Choose your Operational Point of Contact (OPOC).
    Please choose 1-2 operational / logistics people within your organization to interact directly with the Broad and CoVerified teams. These OPOCs will be asked to join weekly operational tactical calls over the next 6 weeks.
  5. Familiarize yourself with the CRSP provided swab kits and barcode labeling process for your institution's collection method. Swabs, sterile tubes, labels, and label printers are among the provided materials for supervised collection. The rightmost image is an example of a printed Dymo label and labeled tube.
    Swab kits will be shipped in bulk and will include:
    • Individually packaged, sterile anterior nasal swabs
      Fisher Scientific catalog # NC1817884
    • Sterile, capped tubes packed in units of 100 tubes
      BD catalog # BD366703; Fisher Scientific catalog # 02-657-30
      outer diameter: 13mm; length: 75mm
    • Cryoboxes with 64 place fiberboard cell dividers (that will be used to return collected specimens to Broad)
      boxes - VWR catalog # 89128-183; cell dividers - VWR # 82007-152
    • Printer labels (500 labels per roll) - USE ONLY THESE LABELS
      Dymo 30336 Multipurpose Labels 1" X 2-1/8"
    • Dymo Labelwriter 450 printers - DO NOT USE THE LABELS THAT COME WITH THE PRINTER
      Connects to any PC based laptop via USB. We will provide 1 printer for each check-in station (roughly ~200-500 tests per day)
    • Cardboard shipping boxes
  6. Review and resolve any needed courier setup logistics.
    More information can be found in the Sample shipping and courier logistics section.

Sample collection instructions



Supervised collection is currently the only approved method and requires a Medical Professional at the testing site to supervise the process Medical Professionals include MDs, NPs, RNs, LPNs and EMTs.

Observations of self-swabbing can be done by trained staff under the direction of the medical professional. Observers do not have to be healthcare professionals, but must be trained in the self swabbing process, proper use of PPE, and handling of specimens. See CDC website for PPE and training guidance: https://www.cdc.gov/coronavirus/2019-ncov/hcp/broad-based-testing.html

Unsupervised collection is NOT currently approved. Video observation is considered telehealth which is not approved for this process.

How To Properly Apply a Barcode To a Sample Tube from Broad Institute on Vimeo.




Broad Institute CRSP: How to collect an observed nasal swab sample from Broad Institute on Vimeo.


Ready-to-ship tube with properly placed swab and barcode (from CRSP-provided label).



Packing & Shipping

Shipping materials

Materials provided by CRSP:
  • Cardboard shipping box
  • CRSP address labels
    CRSP
    320 Charles Street
    Cambridge, MA 02141
    COVID Testing Lab 130
Other materials:
  • Sender’s address labels
  • Packing tape
  • Packing materials
    i.e. bubble wrap, peanuts, material to prevent Cryoboxes from shifting
  • Category B UN3373 shipping labels
    for FedEx, UPS, air courier only

Specimen storage and shipment storage

Dry specimens are stable long term at room temp. We require tests to arrive at Broad within 56 hours after collection for processing.

Shipment setup

If using your own courier/shipping, please attach the CRSP mailing labels provided in your supplies to your shipment, and ensure your boxes are labeled with a return address, contact name and phone number. Samples can be sent 24 hours a day, 7 days a week to:
CRSP
320 Charles Street
Cambridge, MA 02141
COVID Testing Lab 130
Packages should be dropped off at the front lobby entrance where Security will accept the delivery and contact the lab team to receive/sign for it.


STAT Delivery Services 1-877-522-7828
If you would like to use the Broad contracted courier -- STAT Delivery Services -- please contact STAT directly to make arrangements for regularly scheduled, off-cycle and on-demand pickups.

Packaging specimens

  1. Ensure specimens are consolidated into Cryoboxes.
  2. Consolidate sealed Cryoboxes into as few shipping kits as possible. 45 Cryoboxes can fit in our shipping kits. Do not use any wet ice for packaging.
  3. Place the printed manifest in the shipping box.
  4. Pack the shipping box with packing materials so the contents do not shift around during transport.
  5. Seal the box shut with tape.
  6. Fill out the “Sender’s Address Label” and place it on the shipping box. Ensure that the sender's company name, address, contact name, and contact phone number are included on the label. Examples of shipping labels to include for each specimen shipment
    Examples of sender's address labels. If using FedEx or UPS for shipment, please include UN3373 labels and mark the shipment as "Biological substance, Category B" in addition to the sender's address labels specific to that courier in compliance with UN 3373 Biological Substance, Category B shipping regulations.
  7. Affix a CRSP shipping label to shipping boxes.
  8. If shipping with FedEx or UPS, follow shipping regulations for UN 3373 Biological Substance, Category B. Refer to Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 (COVID19). The IATA Regulations require that:
    • Shipments containing Biological substance, Category B materials are triple packaged according to Packing Instruction 650. The triple packaging consists of the following:
      • A leak proof primary receptacle (collection tube)
      • A leak proof secondary packaging (3” 8x8 Cryobox)
      • An outer rigid packaging of adequate strength for its capacity, mass and intended use (shipping box)
    • Packages containing UN3373 materials must be clearly marked with the proper shipping name of "Biological substance, Category B" with the characters being at least 6mm high.
    • Packages have the mark illustrated in Packing Instruction 650 clearly and legibly displayed on the external surface of the outer packaging adjacent to the proper shipping name. The UN3373 mark must be in a square on point configuration (diamond shaped) with each side being a minimum of 50mm (or 2 inches) in length with the UN3373 characters being at least 6mm in height.

Shipping packaged specimens

  1. Bring the shipping box(es) to the pick up location for courier service at your designated time.
  2. Shipments are accepted at any time and any day at 320 Charles St.
    • FedEx, UPS and larger shipments should use the loading dock located on Bent St.
      • Loading dock hours are 8am to 4pm M-F.
      • If delivering via truck, the maximum trailer length is 43’. The loading dock height is 4’6” from the ground. Note: There is only one loading bay at this location, so only one vehicle can be accommodated at a time.
    • All other shipments (and off hour Fedex and UPS) shipments should be delivered to the front lobby on the Charles St side of the building.
      • Face masks are required to enter the building.
      • Security will call the lab for direct hand off and signing from the courier.
Image of 320 Charles St loading dock.
320 Charles St loading dock (located on Bent St) for FedEx, UPS, and larger shipments between 8am to 4pm M-F.
Image of 320 Charles St front lobby.
320 Charles St front lobby (located on Charles St) for all other shipments. Shipments are accepted at the lobby 24/7.

Results

Test turnaround time: within 24 hours of receipt at Broad

Students can login and register for results at: https://docs.google.com/presentation/d/1izY-518Esba1tcTcwtR05SZNvNrURvqDhXN-x86Qedk/edit#slide=id.g8bd924a234_2_0

If you have any questions regarding your test results, please contact your COVID test site administrator.

Specimen rejection criteria

Regardless of option chosen above, samples may be rejected or significantly delayed if they arrive with any of the following nonconformances:

  • Non-scannable barcodes
  • Unlabeled, mislabeled or incomplete labeled specimen tubes
  • Tubes with insufficient media
  • Improperly capped tubes
  • Tubes with media that has congealed
  • Missing electronic manifest file
  • Incomplete electronic manifest file
  • Paper manifest not included in the box with samples
  • Specimens(s) deemed unacceptable due to the requirements of test; i.e. unvalidated specimen type, wrong swab type or placement in specimen tube
  • Suspected specimen contamination
  • Pre-analytic handling and transport requirements not met

Unsatisfactory/TNP (test not performed) result code information*

*updated July 28, 2020

Unsatisfactory reason codes that only apply to samples submitted in media are NOT italicized.

Possible Unsatisfactory/“Test Not Performed (TNP)” Reason Codes for samples submitted using dry, anterior nasal swab collection (aka NO media) OR in media are italicized.

TNP reasons found in CareEvolve are shown in bold/italics.

When the laboratory issues an unsatisfactory or TNP result in a report, the individual must be tested again and a NEW sample must be submitted to the laboratory in order to receive a confirmed test result.

Result Definition ("reason" or column J in the results file) Description
NEGATIVE 2019-novel Coronavirus (2019-nCoV) not detected by the qRT-PCR assay. Consider testing for other respiratory viruses or re-collecting for 2019-nCoV testing. Note: Optimum timing for peak viral levels during infections caused by 2019-nCoV have not been determined. Collection of multiple specimens from the same patient may be necessary to detect the virus. Applies to both assays with and without media.
POSITIVE Positive for detection of 2019-novel Coronavirus (2019-nCoV) by qRT-PCR. Applies to both assays with and without media.
INVALID This specimen failed to produce a valid result. An invalid result means no nucleic acids (viral or human) were detected by qRT-PCR. Consider re-collection of specimen. Applies to both assays with and without media.
CANCELED Testing canceled per submitter. Canceled by ordering provider.
UNSATISFACTORY_1 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: improper specimen transport medium. Applies to samples submitted in media. The media cannot be pipetted (too viscous).
UNSATISFACTORY_2 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: inappropriate timing of collection relative to specimen receipt. Specimens must be received within 72 hrs of collection unless frozen. Samples are received more than 72 hours after collection date
UNSATISFACTORY_3 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: sample tube unlabeled. Sample tube is unlabeled and cannot be matched to an order.
UNSATISFACTORY_4 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: insufficient volume. Applies to samples submitted in media. The tube is either empty or does not contain enough media volume to perform the test.
UNSATISFACTORY_5 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: tube sample data does not match the submission form. This is used when the order and tube label do not match.
UNSATISFACTORY_6 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: laboratory accident. This is used when a test can not be performed due to a laboratory error and the sample must be resubmitted.
UNSATISFACTORY_7 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: leaking/broken tube. This is used for broken or leaking tubes. Very similar to reason #10, but this is used for samples submitted in media.
UNSATISFACTORY_8 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: sample not received. This is used when we have an electronic or physical order in hand but do not receive a physical specimen.
UNSATISFACTORY_9 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: incomplete requisition. This is used when required elements of the requisition are missing and we are unable to obtain the information before the sample expires, or if there is not enough information to know who to reach out to for the missing information.
UNSATISFACTORY_10 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: Specimen tube received uncapped or broken. This is used in cases where the sample arrives in an uncapped or broken tube.
UNSATISFACTORY_11 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: Sample unsuitable for automated processing. The first step in processing is to add media to the swab. After adding media, some samples are too viscous to process. This most often happens when the patient does not blow their nose before collecting the sample, resulting in excessive mucus. This reason may also be used if we cannot read the barcode on the tube.
UNSATISFACTORY_12 Unsatisfactory for 2019-novel Coronavirus (2019-nCoV) testing by PCR: Swab collection not to submission standards. This is used when the swab is upside down in the tube, there are multiple swabs in the tube, or when there is no swab in the tube.

How does COVID-19 testing work?

Assay overview

The Broad CRSP SARS-CoV-2 RT-PCR Diagnostic Assay is used for in vitro qualitative detection of SARS-CoV-2 in respiratory specimens. This means the test is designed to detect the presence of the genomic material of the SARS-CoV2 novel coronavirus, the pathogen responsible for the disease known as COVID-19.

The test is performed at the Clinical Research Sequencing Platform (CRSP) which is the clinical testing laboratory at the Broad Institute of MIT and Harvard. This laboratory operates under a set of government regulations known as CLIA that allow us to run high complexity molecular tests, such as the one used to detect coronavirus. The test that is run by CRSP is a modified version of a test developed by the CDC. Our laboratory has tested approximately 250,000 people for the presence of coronavirus so far.

The test we have developed for the Safe For School program incorporates many improvements to the process that we have made in response to our experience and observations in running a quarter of a million tests so far. In place of the narrow swabs that are placed deeply into the upper nasal cavity (nasopharyngeal swabs) we now use a swab that is much shorter and can collect sample from the lower nasal cavity (anterior nares swabs). This is a much more pleasant experience for the person being tested. The swab is also placed into a tube without liquid (dry swabbing) as this allows the laboratory more flexibility in getting the most material off the swab for testing as possible. Our laboratory has performed validation studies to confirm that this swab type and collection method perform similarly (and in fact are better) than the wet swab collection method.

After the swab arrives at our laboratory, the collected material (human cells and virus particles, if present) are reconstituted off the swab using our automated liquid handling robots. The material is treated to inactivate any virus present (making it safer) and the cells are broken up to release the genetic material within. The genetic material is then amplified with probes that target either the virus genome or a human gene. We test for the presence of a human gene to confirm that the swab was successfully taken and that the testing process is working. If viral particles are present they are amplified in a way that produces a signal that can be detected on a specialized piece of equipment known as a real-time PCR machine. The data from this instrument is sent to our pipeline which interprets the signal as the presence or absence of the virus and checks the validity of the test. A test report is then created and returned.

Assay performance

Limit of detection - analytical sensitivity

The limit of detection (LoD) is defined as the lowest concentration at which 19/20 replicates (or approximately 95% of all true positive replicates) are positively detected. Initial LoD estimates were made based on a dilution series of a synthetic SAR-CoV2 construct brought all the way through the process. The preliminary LoD established by the dilution series was confirmed by testing a total of 20 replicates of the Synthetic SARS-CoV-2 RNA Control at the varying copy levels (Table 1).

Table 1. LoD replicate dilutions of COVID construct
Concentration # positive replicates/total # replicates % True Positives Detected
100 copies (2.67 copies/µL) 19/20 95%
60 copies (1.6 copies/µL) 19/20 95%
40 copies (1.1 copies/µL) 18/20 90%
20 copies (0.5 copies/µL) 14/20 70%
10 copies (0.3 copies/µL) 13/20 65%
5 copies (0.15 copies/µL) 4/20 20%

The LoD for this assay was determined to be 60 viral copies into RNA extraction (1.6 copies/µL). 19/20 extraction replicates of RNA construct spiked into human cell controls tested at this concentration (19/20) were positive.

Clinical evaluation

30 positive specimens and 28 negative specimens, from upper respiratory swabs with positive SARS-CoV-2 results or negative test results previously tested using the CRSP v1 assay. Additionally, 20 replicates at ~2X of the LoD were also run through the process from extraction to detection. In order to be considered passing, there had to be 95% agreement at 1x-2x LoD, and 100% agreement at all other concentrations and for negative specimens (Table 2). Both evaluations passed.

Table 2. Summary of clinical evaluation sample runs
Samples Mean Ct (SD) % Agreement (# Pos or Neg)/Total
SARS-CoV-2 Positive Clinical Samples 20.48 (SD:4.43) 100% (30/30)
SARS-CoV-2 Positive Clinical Samples at 2X LoD 32.39 (SD: 0.87) 95% (19/20)
Negative Clinical Samples N/A 100% (28/28)
Dry swab LoD bridging study

Spun polyester swabs were coated in a negative clinical matrix and allowed to dry. A high viral load positive clinical specimen was diluted to create a range of copies/mL at between 1-3X the LoD of the assay and spiked on to each swab. Swabs were processed through the dry swab reconstitution, extraction, and detection protocols. LoD was determined as the level at which 19/20 replicates were successfully called positive (Table 3). The LoD was confirmed at 60 copies/µL.

Concentration # positive replicates/# total replicates Avg N Ct Std Dev Ct
15 copies/µL 12/20 33.6 1.4
30 copies/µL 17/20 33.6 1.4
60 copies/µL 20/20 32.5 0.9
Conclusion

The Broad CRSP v2 assay (high throughput) with dry swabs as an input is validated with an LoD of 1.6 copies/µL (or 1600 copies/mL). For context, a study published in The Lancet1 found median viral load in COVID positive patients at presentation to be 158,489 copies/mL.

Limit of detection chart showing median viral load in COVID positive patients at presentation to be 158,489 copies/mL.
1 Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Kai-Wang To et al. The Lancet Vol 20 May 2020.

Clinical sensitivity

The ability to detect the virus is impacted not just by the performance of the test, but also by the timecourse of the infection in an individual. Researchers have shown2 that the longer in time after the onset of symptoms a person is tested, the lower the chance of detecting the virus in that person (as they have largely cleared the virus out of their system).

Infographic showing sensitivity of the COVID-19 RT-PCR.
2 Estimating false-negative detection rate of SARS-CoV-2 by RT-PCR. Paul Wikramaratna, Robert S Paton, Mahan Ghafari, Jose Lourenco. University of Oxford, UK. doi: https://doi.org/10.1101/2020.04.05.20053355

Assay sensitivity and specificity

The absolute sensitivity and specificity of the type of testing we and others are doing for COVID-19 diagnostics are difficult to calculate, as there is no gold standard assay against which we can compare results. In the absence of this, the FDA and clinical best practice guidance is to compare the test on clinical specimens with positive and negative results that have been established using another FDA-approved test. To this end, we initially validated our assay with samples that had been run at another laboratory using their FDA-approved test. This validation cohort included 103 positives and 40 negative samples. Further, 20 of the positive samples were diluted to the established limit of detection of the assay (the lowest concentration of virus at which we see 95% accuracy in test results). In all cases, we saw 100% concordance with the established result. Subsequently, we ran 543 cases through our assay and a collaborating clinical labs FDA-approved assay and again saw 100% concordance of results. In additional studies where we have run a range of clinical samples several times internally, we have seen sensitivity and specificity >95% when we are at or above our limit of detection. Studies have now shown that the infectivity of an individual relates to their viral load and that the viral load and infectivity are both highest in the few days immediately preceding and following the onset of symptoms. When we see a low viral load we believe it is most often a person who has been infected but has largely cleared the virus and may therefore be less infectious.

When there are large numbers of positive individuals in a tested population, the main mode of test failure that we are concerned with is False Negatives (a negative test result for a person who does in fact have the virus). When the tested population has a low viral prevalence then we become more concerned with False Positives (a positive result in a person who does not have the virus). Since our validation cohorts did not show evidence of any false positives we have a high degree of confidence that false positives are not a significant source of error in our assay. Based on data from recent weeks in large cohorts where the prevalence is expected to be very low, we validate this observance. In one institution with >5000 tests run between mid-May and mid-June, we find only 3 positives. In each of the individuals who tested positive we have reason to believe that they were in fact exposed to the viral material being tested for (therefore in testing terms, we consider them True Positives). This empirical data would suggest that the assay False Positive Rate can be no higher than 1/5000 (or 0.02%) and may in fact be lower. Given the significant implications of False Positives, especially within a campus setting, we plan to routinely repeat testing of some proportion of positive results to further ensure the very high specificity of our test.

Assay fact sheets

Frequently asked questions

Please see FAQs here.

Contact/Support

Safe for school program testing workflow