BACKGROUND
A novel coronavirus (now later named SARS-CoV-2, with the resulting illness named COVID-19) identified emerged in Wuhan, China during 2019. WHO declared late 2019, with WHO declaring a global health emergency on 30 January 2020, and the . The epidemic has now since spread to all populated continents, with a global pandemic declared on 11 March 2020.
Public health measures against the COVID-19 pandemic have varied widely in strategy and success around the world. Travel restrictions in particular are presenting major challenges in logistics and transport for donated haemopoietic progenitor cells. Meanwhile there remains no evidence that SARS-CoV-2 is transmissible via blood or haemopoietic progenitor cells HPCs from a healthy donor with no lacking symptoms of COVID-19.AT VERIFICATION TYPING OR WORKUPHistory of
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REFERENCES
WHO:
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Collection should be deferred for at least 28 days after recovery.
If the patient’s need for transplant is urgent, the donor is completely well and there are no suitable alternative donors, earlier collection may be considered if local public health requirements permit*, subject to careful risk assessment.
Risk assessment should be based on:
- The date of full recovery.
- The duration and severity of illness - in particular, the presence of any ongoing sequelae
- The results of post-recovery testing.
*Note that there is evidence that SARS-CoV-2 RNA can remain detectable by PCR in nasopharyngeal samples for an extended period after full recovery. Nasopharyngeal shedding does not equate to viraemia, and other coronaviruses (including SARS and MERS) have not displayed transmissibility via blood or HPC. Nonetheless a donor with detectable nasopharyngeal SARS-CoV-2 RNA could be considered a potential infective risk to staff and other donors at a collection centre.
Contact with COVID-19 – donors who report contact with a confirmed case
Collection should be deferred for 28 days after a donor’s last contact with a person with confirmed COVID-19 infection.
If the patient’s need for transplant is urgent, the donor is completely well and there are no suitable alternative donors, earlier collection may be considered if local public health requirements permit, subject to careful risk assessment.
Risk assessment should be based on:
- The last date of contact.
- The nature of the contact.
- The results of any post-contact testing.
Geographical risk – donors who have travelled internationally
Collection should be deferred for 4 weeks after any international travel. Even in countries where local transmission of COVID-19 is high, people who have travelled internationally are at particular risk of exposure. If the patient’s need for transplant is urgent, the donor is completely well and there are no suitable alternative donors, earlier collection may be considered if local public health requirements permit, subject to careful risk assessment.
Risk assessment should be based on:
- When the donor returned.
- Which countries the donor visited.
- Any contact with a person with known COVID-19 infection.
- The results of any post-travel testing.
Geographical risk – donors residing in a high-risk country
To identify countries where local transmission of COVID-19 is high, registries may refer to national health authorities and/or trans-national sources such as WHO and ECDC. Following the spread of the pandemic to nearly all developed countries, however, it may be more realistic to define geographical risk in terms of whether the donor’s community exposure risk exceeds that of the patient. In the absence of known contact with COVID-19, risk assessment should take into account:
- The level of risk and applicable public health restrictions in the donor’s region.
- Any recent travel to higher-risk regions within the same country.
- Any contact with a person with known COVID-19 infection.
In a healthy donor without symptoms, routine pre-donation testing confers no known benefit to the recipient. However, there is potential value in avoiding G-CSF during the incubation period of COVID-19, as well as potential benefit to staff and others at the collection centre by identifying a pre-symptomatic donor infection.
Collection-day testing
In the absence of symptoms, testing the donor for COVID-19 on the day of collection is not recommended because:
- Unless an instant result is possible, there is no benefit to the donor or to collection staff because collection cannot be prevented.
- A validated blood test is not yet available.
- There is no benefit to the patient because there is no evidence that detectable nasopharyngeal PCR is associated with infectious viraemia in a pre-symptomatic or symptomless COVID-19 infection.
Planned cryopreservation
If there is concern that the donor is at high risk of community-acquired infection between work-up and collection, pre-planned cryopreservation will allow patient conditioning to be withheld until successful donation and delivery are confirmed.
Cryopreservation at the collection site may have additional advantages in relation to transport delays and travel restrictions.
Post-donation cryo-quarantine
Cryopreservation of the product allows patient conditioning to be delayed until after collection, and any donor symptoms that develop in the immediate post-donation period should be reported to the transplant centre.
Applying a formal post-donation “cryo-quarantine” period, however - whereby a donation will only qualify for release if the donor tests negative or remains symptom-free at the end of the cryo-quarantine period - is not recommended because:
- Failed qualification can occur as a result of COVID-19 exposure that occurs after collection.
- In the absence of symptoms, a positive nasopharyngeal swab on Day 14 post-collection or later is not consistent with the presence of pre-symptomatic COVID-19 infection at the time of collection.
- Failed qualification due to the possibility of pre-symptomatic COVID-19 infection at the time of donation is not supported by evidence of transmissibility via blood or HPC during the pre-symptomatic phase.
- Therefore withholding a donation for failed quarantine is detrimental to the patient because they lose their first-choice donor, and detrimental to the donor because their donation and associated community exposure is wasted.
Nonetheless, it is acknowledged that certain jurisdictions may require such “cryo-quarantine” by regulation.
RATIONALES
There is convincing evidence that person-to-person transmission can occur during the pre-symptomatic phase of COVID-19. However, respiratory transmissibility does not necessarily equate to transmissibility via blood or HPC.
Studies of the blood phase of COVID-19 have so far shown limited SARS-CoV-2 RNA detectability in symptomatic infection and very limited RNA detectability in pre-symptomatic and symptomless infection, while any correlation between detectable RNA in the blood and actual infectivity is yet to be established. This is consistent with findings for previous coronaviruses such as SARS and MERS, that have not displayed transmissibility via blood or HPC.
Beyond the possibility of blood or HPC transmission risk, there are also important public health considerations and a variety of community measures around the world that are having major impacts on HPC donors and collection facilities. Considering also the limited evidence base in this rapidly evolving pandemic, every individual case should ideally be assessed in consultation with infectious disease and/or public health experts.
REFERENCES
WHO: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
EBMT: https://www.ebmt.org/covid-19-and-bmt
COVID-19 is presenting major logistical challenges in managing and assessing HPC donors and in collecting and transporting HPC products. WMDA has developed a publicly-available resource page at at https://share.wmda.info/x/Yj6OF.