Lessons Learned From SARS-CoV-2 Pandemic in Donation and Tissue Banking Activities: Key Takeaways

Abstract

INTRODUCTION

Spain had one of the highest burdens of coronavirus disease 2019 (COVID-19) worldwide,^1,2 with one of the highest rates of infections and deaths per million inhabitants,³ particularly during the first months of the outbreak in Europe. The formal declaration of a national health emergency (NHE) was issued by the Spanish Government on March 14,⁴ when 6391 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were registered in the international registries,⁵ and >39 000 cases were thereafter confirmed.⁶

Despite no documented cases of transmission of similar viruses through transplantation or transfusion, since the beginning of the outbreak, the National and European Competent Authorities issued a set of recommendations and urged tissue establishments (TE) and donation centers (DC) to adopt alternative procedures, with the aim of ensuring the safe and sustainable supply of substances of human origin (SoHO).^7,8

The Barcelona Tissue Bank (BTB; is the TE of the Banc de Sang i Teixits [BST]), a public agency of the Catalan Health Department whose mission is to guarantee the supply and proper use of human tissues to the 7.652 million inhabitants⁹ of Catalonia. Our organizational structure includes a DC, which is responsible for the evaluation of donors and the procurement of tissues and cells.¹⁰

MATERIALS AND METHODS

This study used anonymous data and data that are publicly available; therefore, it was exempt from approval from an ethics’ board.

The exceptional procedures and safety measures implemented by the DC and BTB were defined and constantly updated, based on (1) risk assessment exercises¹¹ of all DC and TE activities (Table 1); (2) the constant monitoring of the material resources available; and (3) the reviewed recommendations periodically issued by the national⁸ and European authorities.⁷

TABLE 1. - Examples of risk assessment exercises performed before and during COVID-19 outbreak

Process	Potential failure mode	Potential effect(s) of failure	Potential cause(s) of failure	Current process controls (prevention and detection)	Severity (S) classification 1–4	Probability (P) classification 1–5	Detectability (D) classification 1–5	Risk priority number (=S × P × D)	Recommended action(s); risk reduction strategy	Introduction of new risks	Priority	Severity (S) classification 1–4	Probability (P) classification 1–5	Detectability (D) classification 1–5	Risk priority number (=S × P × D)
Donor selection	Acceptance of donor infected with SARS-CoV-2	Infection transmission—infection of recipients, DC and TE personnel with SARS-CoV-2	Airborne transmission or, infection transmission through blood, mucous, or tissues	Donor selection criteria defined, based on European Tissue and Cells Directives,12–14 and EDQM good Practices Guide15	4	3	5	60	(1) Exclusion of all donors: with confirmed SARS-CoV-2;	No	High	4	2	2	16
					High severity to individuals with preexisting medical conditions	Possible	No specific test	Not accepted	(2) Exclusion of donor that have had contact with patients with confirmed SARS-CoV-2 infection; (3) Acceptance of donors without respiratory symptoms related to SARS-CoV-2 infection, when measures 4, 5, and 6 are in place; (4) Nasopharyngeal swab and SARS-CoV-2 rRT-PCR testing of all donors; (5) Cover oral and nasal cavities of the donors during procurement; (6) Halting the recovery of tissues from the thorax whenever the rRT-PCR testing results are not known			High severity for individuals with preexisting medical conditions	Unlikely, but not impossible due to the number of asymptomatic cases, and test sensitivity	Moderately high detectability due to additional rRT-PCR test implemented	Accepted
							The potential failure will be detected only after the infection of the recipient, or DC/TE staff
Procurement	SARS-CoV-2 transmission during procurement procedures	Infection transmission—infection of DC personnel with SARS-CoV-2	Airborne transmission or, infection transmission through blood or mucous	Use of surgical FFP masks and standard operating room PPE	4	2	5	40 Not accepted	(1) Use of specific PPE FFP3/FFP2, 2 pairs of gloves, impermeable garments and protective goggles; (2) Exclusion of personnel with preexisting medical conditions; (3) Cover oral and nasal cavities of the donors during procurement; (4) Halting recovery of tissues from the thorax whenever the rRT-PCR testing results are not known; (5) Periodic screening (rRT-PCR) of all DC staff	No	High	2	1	2	4 Accepted
					High severity due to f individuals with preexisting medical conditions	Not expected to happen but may occur occasionally	There is no control of infection for DC personnel					Lower severity for individuals without preexisting medical conditions	Unlikely due to the additional safety measures and PPE used by the personnel	Periodic rRT-PCR of all DC staff. Active follow-up of any COVID-19 symptoms in DC personnel (fever, cough, diarrhea, and asthenia)
Processing	SARS-CoV-2 transmission during processing procedures which generate high levels of droplets and particles	Infection transmission—infection of DC personnel with SARS-CoV-2	Airborne transmission or, infection transmission through blood or mucous	Use of standard PPE for clean rooms class B16: 2 pairs of sterile gloves, impermeable garments, and surgical FPP	4	3	5	60	(1) Exclusion of personnel with preexisting medical conditions; (2) Use of protective goggles, face shields, and FFP2; (3) Periodic screening (rRT-PCR) of all TE staff	No	High	2	1	2	4
					High severity due to for individuals with preexisting medical conditions	Likely to happen considering that several solutions and tissues generate droplets and particles during processing	There is no active control of SARS-CoV-2 infection of TE personnel	Not accepted				Lower severity for individuals without preexisting medical conditions	Unlikely due to the additional safety measures and PPE used by the personnel	Periodic rRT-PCR of all TE staff	Accepted
														Active follow-up of any COVID-19 symptoms in TE personnel (fever, cough, diarrhea, and asthenia)

COVID-19, coronavirus disease 2019; DC, donor center; FFP, filtering face piece masks; PPE, personal protective equipment, rRT-PCR, reverse transcriptase-polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TE, tissue establishment.

A quantitative evaluation of the impact on donation, processing, and distribution was performed by assessing the volume of BTBs activities during the same period—January to August—in the previous year (2019).

RESULTS

As a result of the risk assessment exercises performed before and during the outbreak, donation procedures were reviewed, and extraordinary donor selection criteria were implemented. Before the NHE declaration,⁴ the internal risk assessment determined the exclusion of all donors with confirmed SARS-CoV-2, with observable COVID-19 symptoms, and/or that had been in contact with any confirmed cases, and/or donors with prior travel history to regions with reported active transmission—defined and periodically updated by the European Centre for Disease Prevention and Control (ECDC)—during the previous 21 days. After March 14,⁴ in addition to these criteria, the acceptance of potential deceased donors was conditioned to the results of mandatory SARS-CoV-2 screening, performed with real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) from nasopharyngeal swabs. Donors with positive or inconclusive results were also to be excluded. For convalescent COVID-19 cases, according to the established criteria, a minimum of 21 d after recovery was recommended with an individual risk assessment and a negative result in the rRT-PCR test.⁸ These safety measures were sustained by a new risk assessment, the recommendations published,⁸ and the valuable technical inputs received from national and European peers.

After the declaration of the NHE, tissue donation activities completely ceased during 4 wks, decreasing by 94.7% in April 2020, when comparing with the same period of 2019. The absence of autopsies and the shortage of test kits during the outbreak’s peak discontinued donation, both in the hospitals and other donation sites such as Legal and Forensic Institute (Institut de Medicina Legal i Ciències Forenses de Catalunya).

Routine recovery procedures were also reviewed to include (1) the use of additional personal protective equipment, specifically filtering face piece (FFP) masks FFP3/FFP2; (2) covering the oral and nasal cavities of the donors; and (3) halting the recovery of tissues from the thorax whenever the rRT-PCR testing results were not known in advance (Table 1). These measures prevent the exposure to possible droplets produced when handling the retrieval in deceased donors, as recommended by ECDC.

Similarly, the processing procedures were updated to include the use of FFP2 and face shields to handle tissues, which release high levels of particles into the environment, namely musculoskeletal tissues during shaping with oscillating saws (Table 1). In the absence of newly donated tissues during the outbreak’s peak, smaller teams ensured the continuity of processing of musculoskeletal tissues recovered and stored (before processing) before the declaration of the NHE. These procedures were adopted as part of the strategy employed to ensure tissue stocks, to be distributed once planned surgeries resumed their routine.

Because of the cancelation of all elective surgeries at national level, the distribution of tissues decreased significantly (78%) in April 2020, compared with the same period of the previous year. In fact, in 6 wks after the NHE declaration, tissue distribution was limited only to urgent procedures. BTBs organizational model and its definition of minimal stocks of tissues for situations of normal activity were able to ensure the self-sufficiency of tissues, except corneas, even during the pandemic outbreak.

Last, risk assessment exercises have raised concerns related to the management of tissues stocked by the TE before the outbreak, which could have been eventually donated by SARS-CoV-2–infected donors, in the absence of a correct diagnosis. This assessment led to a retrospective look at all tissues and donors processed between December 15, 2019, and March 14, 2020, and the consequent quarantine of 17.9% of donors (85/476) with a clinical history compatible with COVID-19, who had been previously validated (Supplemental Visual Abstract, SDC, https://links.lww.com/TP/C165).

DISCUSSION

The Spanish donation model is mostly performed by intensive care unit (ICU) professionals, intensivists, and anesthesiologists who work part-time as in-hospital transplant coordinators.¹⁷ During the NHE, ICU services were the most impacted, and tissue donation became unfeasible due to the limited access to the human and material resources mobilized to treat COVID-19 and other critical patients. Because ICU professionals were not available to detect, assess, and select potential donors, and also due to the inability to isolate potential donors in “COVID-19 free areas,” the viability of donation in accordance with the extraordinary exclusion criteria defined by the BTB and the National Competent Authority^7,8 was limited. Furthermore, the unpredictable nature of the outbreak situation led to a scarce availability of personal protective equipment, test kits, and an inability to test all patients and potential donors in a timely manner. This translated into a significant limiting factor for performing donation activities, which have an inherently short timeframe.

As part of the strategies to avoid a new collapse of the donation and transplant system, hospitals and secondary facilities are expected to create “COVID-19-free areas,” able to provide health treatment to noninfected patients, and maintain donation and procurement activities. In addition, a broader access to training and the recruitment of alternative hospital staff may also be a valid approach for improving the ability to detect, evaluate, and select potential donors.

Ten months after the initial outbreak, and despite the new increase of COVID-19 patients,⁶ the donations in our organization seem to remain stable. This tendency acknowledges the success of the measures foreseen and implemented by the DC and BTB contingency plan, which succeeded in readjusting donation activities to the resources and professionals available.

The impact of the presence of SARS-CoV-2 in the human tissues and cells is still unclear,⁷ given the lack of organ/tissue transplant-transmitted infection cases reported to date.^7,8 Thus, fully understanding the behavior and infection mechanism of the SARS-CoV-2 virus will potentially have repercussions for future risk assessment exercises and the quantification of risk consequences for both patients and professionals. These aspects should therefore be carefully analyzed, considering the probability of disease transmission dependent on the type of tissue, recovery and processing methods, which often include disinfection, sterilization, or pathogen inactivation protocols that can drastically reduce the bioburden of the processed tissues issued for clinical application. According to the current state-of-the-art of TE activities, tissues are subjected to complex processing and preservation methods, and it is unlikely that SARS-CoV-2 will survive such procedures. However, the risk of transmission must be considered for the release of tissues recovered and processed between December 2019 and March 2020, a period in which the virus could not be detected.

Despite the low demand for tissues during the outbreak’s peak, the BTB was not always able to keep a minimum stock of corneas for transplant, and the supply of other tissues (such as amniotic membrane, heart valves, or skin) could also have been jeopardized if additional urgent situations had occurred. Considering the unquestionable status of essential SoHO defined by the ECDC,⁷ a long shortage of grafts for transplant may have significant impact on patients’ quality of life. It is therefore paramount to resume donation levels, especially for tissues with a short-shelf life, to restore normal stocks and provide SoHO therapies once routine surgeries return to their normal activity.

CONCLUSIONS

Ten months after the declaration of the NHE, the volume of TE activities is still far from its normal levels. The agile adoption of a contingency plan and the effective management of minimum stocks allowed our organization to adjust their activities to the resources available. The robustness and autonomy of the BTB’s organizational model was able to ensure the control of the activities from donation to distribution, therefore safeguarding self-sufficiency at the regional level. The measures adopted as part of the contingency plan reshaped and improved many aspects of the BTBs activities, which will prevail even after the epidemic crisis has elapsed.

As for several other organizations and industries, the financial impact of the COVID-19 outbreak can compromise investments in future research and development projects and can jeopardize sustainability, which threatens to undermine the ability of public TE to provide treatment to patients, making SoHO therapies globally less available.

Considering the future occurrence of SARS-CoV-2 infection waves and similar epidemic crises, TE and health services should assess the organization of the SoHO supply chain to ensure a safe access to treatment for patients. The status of “essential therapy” recognized for SoHO⁷ should encourage TE and governments to coordinate efforts and find feasible alternatives toward ensuring at least the minimum levels of donation to meet clinical demand and sustaining basic operations in the future.

The ability of the competent authorities and TE to respond to the crisis and adapt their safety procedures may benefit from an organized network of professionals and organizations that cooperate to ensure sufficiency, optimize the use of resources at national and European level, and share knowledge with the aim of ensuring the best health care service, even during catastrophic events.