Managing blood supplies during natural disasters, humanitarian emergencies and pandemics: lessons learned from COVID-19

Abstract

Introduction

The COVID-19 pandemic has resulted in a historic public health crisis with widespread social and economic ramifications. The pandemic has also affected the blood supply resulting in unprecedented and sustained blood shortages.

Areas Covered

This review describes the challenges of maintaining a safe and sufficient blood supply in the wake of natural disasters, humanitarian emergencies and pandemics. The challenges, which are accentuated in low- and high- income countries, span the impact on human capacity (affecting blood donors and blood collections personnel alike), disruption to supply chains, and economic sustainability. COVID-19 imparted lessons on how to offset these challenges, which may be applied to future pandemics and public health crises.

Expert Opinion

Pandemic emergency preparedness plans should be implemented or revised by blood centers and hospitals to lessen the impact to the blood supply. Comprehensive planning should address the timely assessment of risk to the blood supply, rapid donor recruitment and communication of need, measures to preserve safety for donors and operational staff, careful blood management, and resource sharing.

1. INTRODUCTION

In December 2019, a cluster of patients in Wuhan, China developed an atypical pneumonia-like illness of then unknown etiology. In early 2020, the world health organization (WHO) ascribed the outbreak to 2019 Novel Coronavirus (2019-nCoV), which was later renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1]. By March 2020, the virus had spread widely: 118,000 cases, including 4,291 deaths of Coronavirus Disease 2019 (COVID-19) had been reported in 114 countries, prompting the WHO to declare COVID-19 a pandemic[1]. At the time of writing (February 2023), over 670 million cases of COVID-19 and 6.8 million associated deaths have been reported, spanning 228 countries and territories[2]. COVID-19 is a historic public health crisis with wide ranging social and economic ramifications that remain ongoing, now three years into the pandemic. Pertinent to this review, COVID-19 has also impacted blood transfusion services and their ability to ensure an adequate and safe blood supply.

Blood transfusion is integral to disaster management; even under normal conditions, it remains one of the most common hospital procedures[3]. In the United States (U.S.) alone, red blood cell (RBC), platelet, and plasma transfusions are performed in ~3.8%, 0.5%, and 0.5% of all hospitalizations respectively[4]. Therefore, timely access to safe and sufficient blood transfusion is a priority in disaster settings. Although most patients with COVID-19 do not require transfusion support, we sought to summarize the challenges that COVID-19 has posed to blood suppliers and transfusion services, along with the solutions that were employed to contend with the pandemic. COVID-19 offers a model for disaster responsiveness, whereby the lessons that were hard-learned could prove invaluable to future outbreaks and pandemics. Many of those lessons could also apply to the management of other disasters, acknowledging that the nature of the crisis confers nuanced —or at times unique— challenges.

2. BLOOD MANAGEMENT IN HUMANITARIAN EMERGENCIES AND DISASTER SETTINGS (Table 1)

Table 1.

Overview of disasters and public health emergencies and their effects on the blood supply

Type of disaster	Impact to blood supply	Examples	Lessons Learned to optimize blood management
Natural Disaster	Immediate increase in demand for blood (i.e., burns, fractures, crush injury)	1995 Oklahoma Bombing	Ensure adequate blood supply outside of crises whereby preexisting inventories may be instrumental to address surge in demand[11]
	Damage to blood centers/collection sites (i.e., flooding, power outages)	Hurricane Ian (2022)	Transition blood collections to unaffected areas[8,12]
		Great East Japan Earthquake (2011)	Resource-sharing between blood centers[10]
	Damage to transportation infrastructure	1999 Oklahoma Tornado Outbreak	Maintain blood supply at different hospital sites given the obstacles to transportation in the wake of disaster[11]
War/Terrorism	Immediate demand for blood (i.e., soldiers, civilians)	Israeli experience with domestic disasters/acts of terrorism	Coordination, communication and centralization can be very effective model[20]
	Depletion of blood supply	2006 Lebanon War	Early recruitment of blood donors[24]
	Blood donor surge/product wastage	September 11, 2001	Disaster planning is imperative with managed/thoughtful messaging with the community to manage needs[29,30]
Outbreak/Pandemic	Blood supply shortages	2003 SARS pandemic	Reduced blood utilization (e.g., through postponement of elective procedures) can decline in available inventories[37,38]
	Decline in blood donation	H1N1 pandemic	Multimodal approaches to donor recruitment (e.g., social media, text messaging, etc.) should be used[30,32]
	Loss of personnel (i.e.; illness)	SARS-CoV-2 pandemic	Ensure safety of personnel through access to appropriate PPE to maintain blood collections, processing, and transportation[53]

There are four phases of emergency management: mitigation, preparedness, response, and recovery[5]. The mitigation phase focuses on measures to prevent or minimize the impact of the disaster. In the context of the blood supply, measures include maintenance of a stable blood inventory, consistent blood collections, and routine inventory monitoring. The preparedness phase includes disaster preparedness planning, which emphasizes communication and coordination among involved parties (i.e., blood centers, hospital transfusion services, hospital management). The response phase involves activation of disaster preparedness plans, in concert with initiation of efforts to combat the effects (direct and/or indirect) on the blood supply. Direct effects stem from the need for blood to address the surge in demand from trauma/mass injury, or reduction of blood donation in the case of outbreak[6]. Indirect effects relate to damage to infrastructure, thus disrupting blood collection, processing or distribution of blood. Finally, the recovery phase focuses on restoration of services to levels that existed prior to the event. While some challenges are shared, each disaster presents its own demands on the blood banking community[7].

3. TYPES OF DISASTERS

3.1. Natural Disasters

Natural disasters, such as floods, earthquakes, wildfires, and hurricanes, confer both direct and indirect effects to the blood supply. In the early aftermath of a natural disaster, there may be an increase in demand for blood transfusion. The injuries may be complex (e.g., burns, fractures, crush injury) requiring diverse blood products and straining extant blood bank inventories. Blood centers may also incur direct damage (e.g., debris or flooding from a storm) whereby loss or damage to critical infrastructure will impede capacity to collect or transport blood, exacerbating immediate shortages and complicating the ability to replenish the inventory[8]. For example, following the Great East Japan Earthquake of 2011, the Miyagi Red Cross was impacted by the subsequent tsunami, rendering the blood center unusable[9,10]. There are also indirect effects following natural disasters pertaining to the donor pool. In the immediate aftermath, physical damage to transportation infrastructure (e.g., roads, bridges) may immobilize communities, impeding donor access to medical facilities, blood centers and collection sites. For example, blood transport and donor access was cited as major challenges following the 1999 Oklahoma tornado outbreak as roads had been destroyed or obstructed by debris[11].

When natural disasters occur, emergency preparedness plans can help guide prompt responses, not only to help mitigate and manage destruction, but also to coordinate an adequate response to where blood need lay and initiate blood supply management. Past experience with major meteorological events has provided guidance on advanced planning for impending disasters. For example, following the Great East Japan Earthquake in 2011, healthcare providers followed previously established emergency preparedness plans, which included collaboration with local governments to promptly transport blood through damaged areas when necessary[10]. During Hurricane Ian in 2022, blood centers and blood collection drives were closed in parts of Florida, instead transitioning blood collections to unaffected parts of the country and redirecting inventories to areas situated outside of the hurricane’s projected path or away from areas where secondary flooding was expected (e.g., parts of Florida, Georgia and the Carolinas)[12,13]. In February 2023, a magnitude 7.8 earthquake struck southeastern Turkey along the border with Syria. In anticipation of need for blood, the Turkish Red Crescent promptly responded by sending their national stock of blood and plasma to affected regions as part of the emergency preparedness responses[14]. In parallel there was an appeal for blood donation[15].

3.2. Conflict, War, and Terrorism

Armed conflict, war, and terrorism are humanitarian emergencies which can introduce complex challenges to maintaining a sustainable blood supply. There may be an increased need for blood as casualties mount. Those affected include soldiers (or enemy combatants), bystander civilians, or even healthcare workers[16]. Bombs and missiles may damage facilities, including blood centers and collection sites, as well as disrupt the infrastructure by impeding the ability to transport blood to areas of need. Conflict forges a highly complex operational environment, in which the gamut of challenges extends to political instability, fragmented organization and coordination, interruption of supply lines —which may limit access to critical equipment, disposables (e.g., blood bags, infusion sets) or reagents— and financial hardship[17]. Moreover, the surge in demand for blood transfusion from conflict associated trauma does not curtail the ongoing and pervasive need for blood to contend with non-trauma related indications (e.g., obstetric care, elective surgery, anemia due to malaria, and haemoglobinopathies, etc.). Furthermore, conflict is disproportionately focused on low- and middle-income (LMICs) countries that already suffer from pre-existing deficits in the blood supply and a high dependence on replacement donations. War also introduces population shifts with internal displacement of people away from areas of active conflict, which can overwhelm medical and humanitarian services (e.g. 2023 earthquake in Turkey and Syria)[18].

There are numerous examples of war, terrorism and conflict which have been used to inform disaster responsiveness and emergency planning. In the immediate aftermath, blood donor recruitment needs to be prioritized, drawing on available approaches such as conventional (e.g., radio, TV) and social media. In parallel, there needs to be capacity to collect both at fixed sites as well as deployment of mobile blood collection teams. Emergency blood stocks can be used as a temporalizing measure coupled with support from neighboring blood centers that may be less affected by the event or conflict[17]. Israel, and countries in the WHO Eastern Mediterranean Region (Afghanistan, Egypt, Iraq, Islamic Republic of Iran, Lebanon, Syrian Arab Republic, Yemen etc.), boast the greatest number of humanitarian emergencies and offer lessons to be learned regarding blood supply management[17]. Although individualized, many countries have emergency plans in place in the event of mass casualty events, with an immediate focus on donor mobilization. For example, in 2000, Israel developed a national preparedness blood program, as a collaborative endeavor between the transfusion medicine community, the government, military representatives, and a centralized blood supplier[19,20]. The program focuses on strict control of the blood inventory at a national level as well as donor mobilization, through civilian and military donation. In mass casualty events (e.g., a bombing) there is a coordinated redistribution from a central repository to areas of need[19,20]. Studies of Israeli mass casualty events have enabled prediction of blood needs, whereby the program is able to match supply and demand, while minimizing wastage[20–22]. In Iran, the Iranian Blood Transfusion Organization crisis committee also used a centralized approach to coordinate responses and communications between the Iranian Ministry of Health, the Iranian Red Crescent, the Joint Staff of the Army of the Guardians of the Islamic Revolution, and the National Emergency Center[23]. In contrast, Lebanon has decentralized healthcare and blood systems, that include licensed and unlicensed blood banks[24]. Although, Lebanon’s response to emergencies (e.g., donor mobilization) has been positive (e.g. 2006 war), improved communication, coordination and standardization of processes and stakeholders is needed[25,26]. Centralized systems, such as the Israeli and Iranian experience, demonstrate the importance of uniformity and communication in disaster preparedness.

The response to disasters can be met with unexpected challenges, whereby past experience is instructive. As one example, shortly following the attacks on the World Trade Center, on September 11, 2001, the US government issued statements appealing for blood donation. This resulted in a national surge in blood donation during which half a million more units of blood were collected in the three months following the disaster, than the same time in prior years[27,28]. This overwhelmed the ability to collect, store, maintain, and use the donated blood, resulting in a gross excess in the numbers of units of blood, whereby almost a fifth (17%) of the blood was subsequently discarded[29–31]. Similarly, an increase in blood donation following a mass shooting in Las Vegas in 2017, resulted in over-collection and product wastage[32]. These events offer cautionary tales regarding mass appeal in the immediate aftermath of an attack or disaster. In 2002, the AABB’s Interorganizational Task Force on Domestic Disasters and Acts of Terrorism issued the Disaster Operations Handbook (DOH), to help prepare for and respond to disasters and acts of terrorism that could affect the U.S. blood supply[33]. The handbook recommends that hospitals maintain a several-day supply in preparation for inventory disruptions. When an attack occurs in a community, a blood center should assess blood needs through communication with local hospitals and emergency medical services, or through the DOH hospital medical needs assessment to calculate the expected RBC units needed[29,30]. Concurrent activation of the emergency plan should be undertaken. The AABB DOH comprises different plans for each disaster type, which can help direct media and communications to ensure the public receive clear messaging regarding the blood needs[29,33].

3.3. Economic Crises

Despite financial stability being central to medical practice, it is often omitted from the discussion of emergencies and disasters. Economic collapse has wide ranging ramifications that threaten the sustainability of a blood system. The impact may be global: funding may be reduced or absent for hospitals, patients may not be able to pay for services further reducing revenue, while potential blood donors may be deterred given the costs of transportation to donate coupled with the need to seek work. Additional effects span the inability to pay salaries for technical and collections staff, the affordability of testing, reagents and disposables, to the servicing of extant and purchase of new medical equipment. These effects were evident in the economic crisis in Lebanon (2019) where the effects on the health care system resulted in many healthcare workers going unpaid, there were medical equipment and supply shortages, and reduced hospital funding (with impending hospital closures)[34,35]. The medical supply shortages extended to blood bags (i.e., the Lebanese Red Cross procured these from international vendors).

Despite the myriad of challenges, the effects of economic uncertainty are not entirely predictable. As one example, blood donation did not decline during the economic crises in Greece (2012) and Italy (2014), despite the economic hardships encountered in both countries[16,36].

3.4. Outbreaks and Pandemics

Outbreaks and pandemics may have profound effects on the blood supply. As observed during the COVID-19 pandemic, the entire blood value safety chain, from collection to transfusion, can be affected. There may be fewer donors due to illness, abstention due to fear of infection, and/or quarantine measures that impede movement. This will adversely affect the ability to donate blood, reduce staffing (i.e., administrative, collections, technical processing) for similar reasons (e.g., illness, quarantine/lock-down measures), and limit the capacity to collect, process and distribute blood. Interruption in supply chains may impact the availability of critical reagents and supplies (e.g., blood bags), while maintenance of critical equipment may be affected.

The impact on blood donations has been reported during prior outbreaks. During the 2003 severe acute respiratory syndrome (SARS) outbreak, the reported decline in blood collections in Beijing and Hong Kong (two of the major affected cities) was 10% and 20% respectively[37,38]. Similarly, a 21% decline in blood donation was reported in Japan in the immediate phase of the 2009 H1N1 influenza pandemic[39]. Contributing factors included the suspension of mobile blood drives, transient loss of blood donors and fewer collection staff to maintain optimal blood supply. As evidenced in prior outbreaks, hospital transfusion services may also be impacted, due to loss of personnel through illness, thereby affecting the ability to perform pre-transfusion testing and issuing blood distribution[6].

Several approaches have been employed successfully during prior outbreaks to contend with blood shortages. Elective procedures were postponed during the prior SARS-CoV-1 and H1N1 pandemics, thus reducing blood utilization[37,40]. To offset the decline in blood donation, blood services appealed to the public using media, e-email, etc. During the H1N1 pandemic in Japan, following public appeal for blood donations by the Japanese Red Cross, blood collections responded and returned to normal levels within 1 week[39].

4. PLANNING

Strategic planning is imperative to safeguard the blood supply from future outbreaks. Lessons learned from prior outbreaks, provide a framework for responding to the emergence of new pathogens. With the anticipated emergence of the H5N1 strain of the avian influenza in 2009, measures were outlined to maintain a safe and adequate blood supply; these emphasized the protection of personnel, donor recruitment, access to supplies, maintenance of equipment and facilities, and functioning management system[6,41]. Measures to protect both the blood center personnel, as well as the donors include the use of personal protective equipment (PPE), such as masks and gloves, hand hygiene, screening of prospective blood donors for signs of infection, segregation and/or social distancing between donors at the collection sites or mobile drives[41]. Effective communication is imperative to maintain or increase recruitment by educating the public about the need for blood donation, while reassuring prospective donors about measures taken to protect them. Communication and coordination between blood centers and hospital transfusion services optimizes the management of extant inventories to ensure that blood product wastage is minimized[41]. Emergency preparedness plans are critical in this regard; these include measures to conserve (e.g., multi-disciplinary goals of care discussions, electronic medical record alerts when ordering, inventory dashboards, transfusion triage teams) or reduce blood needs (e.g., postponement of elective procedures), optimize resource sharing between blood centers and end-users (i.e. hospitals), and maximize safety and efficiency (e.g., standardization of blood collection and management practices) in times of strain[37].

4.1. Surveillance and risk assessment

Outbreaks may pose risk directly to transfusion recipients if the implicated pathogen is transfusion transmissible. Examples of this include the emergence of human immunodeficiency virus (HIV) in the early 1980’s and West Nile Virus in the early 2000’s[42,43]. Consequently, risk assessment is undertaken early in an outbreak to determine what —if any— mitigation measures are needed to safeguard the blood supply[44,45]. Certain attributes help to ascertain whether a given pathogen is a relevant transfusion transmitted infection (TTI). Foremost is a pathogen’s association with significant morbidity and/or mortality, as most pathogens do not warrant intervention. Second, relates to the nature of infection. Pathogens that pose greatest risk to transfusion are those with an asymptomatic phase of infection given that —in the absence of risk-based deferral and/or testing, this may escape detection at time of donation. The major TTIs for which we test routinely (e.g., HIV, hepatitis B (HBV) and hepatitis C (HCV) viruses) are illustrative of this. Third, is a high incidence and/or prevalence of the pathogen in the general and blood donor populations. If an agent is not encountered regionally, intervention may not be warranted. Instead, donor questioning, and travel-based deferral may be applied successfully, as has been the case for malaria prevention in the U.S.[46]. Fourth is a tolerance of blood storage and processing, transfusion transmissibility, and development of the cognate infection in the recipient (i.e., clinical penetrance). Many pathogens (e.g., Dengue viruses (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV)) are detectable in donors and have been shown to be transmitted to transfusion recipients[37], yet clinical infection is rarely (e.g., DENV) or yet to be reported (e.g., ZIKV, CHIKV)[47]. The risk assessment is used to determine what mitigation strategy is necessary, be it refined donor section (e.g., questioning regarding risk factors or examination for a physical sign of infection), laboratory measures (e.g., testing, pathogen reduction), or no intervention at all. Implementation of a laboratory-based intervention is complex, with scientific, regulatory, economic and even cultural/sociological considerations at play[48].

While many of the challenges posed by SARS-CoV-2/COVID-19 had been encountered during previous outbreaks, the scale —in regard to both the speed and extent of transmission—distinguishes it from any antecedent public health crises in recent times. Like many other respiratory pathogens, SARS-CoV-2 was determined not to be a relevant TTI. Rather, the challenges to the blood supply stemmed from the broader impact to human capacity, and associated supply chain disruption.

5. CHALLENGES TO BLOOD MANAGEMENT DURING THE COVID-19 PANDEMIC (Table 2)

Table 2.

COVID-19 associated challenges pertaining to blood collections and transfusion services

Challenges	Contributing factors	Potential solutions
Donor-related	Donor loss due to illness, isolation measures, fear of infection Reduced donor recruitment and sites for collection (e.g., cancelled mobile drives) Decline in blood collection	Donor recruitment efforts through conventional and social media Advertisements of critical blood shortages Measures to ensure safe donation (PPE, social distancing, regulate capacity using appointment system) Efforts to reduce blood utilization (i.e., PBM programs, postponement of elective procedures, simple transfusion over automated red cell exchange, platelet splitting, extension of platelet shelf life from 5 to 7 days[53,130])
Blood Safety	Transfusion transmissibility of novel pathogen is initially unknown	No historical accounts of respiratory pathogens being relevant TTI Hemovigilance to investigate potential clinical cases of transfusion transmission (none were found with SARS-CoV-2)
Personnel/human capacity	Transient loss of staff due to illness impacting operations at: Blood center Hospital blood bank Transportation	Ensure access to PPE Training in effective techniques for donning PPE Limit blood center capacity Social distancing Donor screening before donation (i.e., temperature, recent close contacts)
Infrastructure/supply chain disruptions	Shortages of critical supplies and reagents: Reduced production due to plant closures, temporary loss of workers due to illness	Extended use of PPE Use of alternative items Repurposing Avoid unnecessary use
Economic	Supply chain disruptions Increased demand for critical supplies that overwhelms supply, leading to a surge in prices	Maintain emergency stock of critical supplies

5.1. Donor-related challenges

Preservation of the donor pool is central to maintenance of the blood supply. Early in the COVID-19 pandemic, a decline in blood donation contributed significantly to blood shortages. The cause of this was multifactorial: lockdowns and isolation guidelines were implemented to limit the spread of disease. This included closures of schools, universities, businesses, shopping centers, and places of worship, along with cancellations of public gatherings, that notably extended to blood drives[49]. Mobile blood drives at hospitals, schools, or businesses are important recruitment opportunities for blood centers to maintain the blood supply. Their cessation blunted donor recruitment and collections while blood reserves waned. For example, in the Zhejiang province in China, there was a 67% decline in blood donors and a 60% decline in recruitment success rates for donations[50]. A similar —albeit variable— decline in donation was reported in institutions in Eastern Mediterranean Region, U.S, and Canada where the decline ranged from 10–39.5% compared to pre-pandemic[51–54]. In a survey of 42 countries, 24 of which were LMICs, respondents reported that blood donation had reportedly declined by 70.6%[55]. Although donor centers remained open, social distancing guidelines limited the capacity at collection sites, even when donors were available. In a survey of 7 European countries, 40–60% of routine donors were reported to have donated less during the COVID-19 pandemic[56]. Lockdowns and isolation further exacerbated the uncertainty, anxiety, and fear within the population. Fear of contracting COVID-19 deterred routine and first-time donors from donating blood[57]; it also prompted institutions to refuse to host blood drives, thus contributing to blood shortages[55].

Efforts were made to increase not only donors, but collected products as well. During the pandemic, the American Red Cross used advertisements, outreach (text messaging), and social media to appeal for blood donors. Additional efforts included, daily coronavirus press briefings, by the U.S. surgeon general, Dr. Jerome Adams, urging young people to donate[58]. Thus, similar to what was observed in Japan during the H1N1 pandemic, the efforts resulted in subsequent increase in donation in some parts of the U.S.[59,60]. This response to donor appeals however, was not globally experienced. For example, a German study found lower medium and long-term blood donation following the pandemic, when compared to pre-pandemic levels[61].

5.2. Blood Safety

The unknown potential for transfusion transmissibility is an immediate cause of concern with a novel pathogen. Although no respiratory virus (e.g., influenza, Middle East Respiratory Syndrome (MERS), SARS) has been designated as a relevant TTI, SARS-CoV-2’s transfusion-associated risk had yet to be determined early in the pandemic. Therefore, some blood collection establishments implemented 28-day travel deferrals for areas with SARS-CoV-2 outbreaks, along with temperature screening of donors[62]. Transfusion transmissibility was later deemed unlikely, through the evaluation of donor viral RNA levels and lack of plasma infectivity in cell culture[63]. Furthermore, no cases of transfusion-documented transmission were identified through hemovigilance.

5.3. Personnel/ Human capacity

The staff at blood centers and hospital-based transfusion services are also at risk of SARS-CoV-2 infection. Consequently, the successive waves of the COVID-19 pandemic resulted in staff shortages, limiting —in some cases, severely— the number of staff who were able to collect and process blood[53]. In hospital blood banks, this severely curtailed the capacity for compatibility testing and may have delayed the issuing of blood.

Like donors, blood center personnel also harbored anxiety regarding donor exposure, with potential transmission to their own families[53]. Fear of exposure and its adverse effect on blood donation was reported in several global surveys[54,55,64–67]. For many, the fear and uncertainty remained, even after restrictions were relaxed.

Staff illness from COVID-19 acquired through occupational exposure can be prevented through the use of PPE, such as respirators, gloves, face shields, and gowns. Challenges arose due to global shortages in PPE. In Italy, for example, high rates of SARS-CoV-2 infection among healthcare workers were ascribed to insufficient access to PPE; this led to recruitment of recently retired healthcare workers to contend with the critical staff shortage[68–70]. Other high-income countries (HICs) such as the U.S, the United Kingdom, and many European countries reported perilously low supplies of PPE early in the pandemic[71,72]. Predictably, shortages were experienced in LMICs as well. For example, PPE shortages in Yemen were vast, consequently attributed to healthcare workers illness and thus, staffing shortages[71].

In response to the PPE supply shortages, the WHO published temporary guidelines to mitigate the impact. These included extended use of PPE (i.e., beyond its manufacturer-stated expiration date), permissible re-use of PPE after cleaning and/or decontamination/sterilization. The guidelines also included prioritization of PPE to those caring directly for critically ill COVID-19 patients, patients with multidrug-resistant organisms, and/or patients posing a high infection risk to health-care workers[73].

5.4. Infrastructure/supply chain disruptions

Supply and reagent shortages were experienced due to global supply chain disruptions. The shortages spanned a wide range of products including PPE, lab coats, surface disinfectants and hand sanitizers, and products critical to blood collection and transfusion such as testing reagents and blood collection bags. The cause of the disruptions was multifactorial, including challenges associated with production/manufacture (e.g., due to plant closures and loss of personnel), or transportation limitations. Much of the world’s supply of PPE, including face masks and surgical gowns, are produced in China, where the emergence of SARS-CoV-2 was first described. The reduction in supply was inevitable, given decreased production due to illness in the Chinese workforce, later introduction of export restrictions from China, allied with an unprecedented surge in demand for those products worldwide[71]. Even when products were available, transportation services also suffered staff illness or competing priorities, thus incurring delays or cancellations of deliveries for critical supplies, including those necessary for the production of blood products[55]. In the U.S, the Food and Drug Administration (FDA) published recommendations for health care providers, laboratory directors, and other personnel to practice conservation strategies for those critically low supplies (e.g., test tubes) in order to maintain use for those where testing and use were medically necessary[29,74].

5.5. Economic

Prior to the COVID-19 pandemic, U.S. blood collection centers were already under economic strain. Contributing factors included the decline in blood utilization, through patient blood management (PBM) programs and improved adherence to evidence-based transfusion thresholds[75,76]. However, as the decentralized blood systems in the U.S rely on hospital contracts as a major source of revenue, reduced blood usage was enormously challenging[77]. Therefore, the decline in blood donation, subsequent blood shortages, and shortages of critical supplies and reagents experienced during the COVID-19 pandemic, further compounded the antecedent economic challenges. Supply chain disruptions and the shortages led to an increased demand[68]. As the demand increased, so did the cost of critical supplies; for example, by March 2020, the price of surgical masks had increased six-fold, the price of N95 respirators had trebled, and the price of surgical gowns had doubled from pre-pandemic levels[71].

6. FACTORS THAT HELPED TO OFFSET THE BLOOD SHORTAGES

Amidst the blood shortages, certain factors offset the demand for blood. For one, many elective surgical procedures were cancelled or postponed. In attempts to contain blood utilization and also prevent SARS-CoV-2 transmission, organizations such as the American College of Surgeons and the COVID-19 surgery collaborative, distributed guidelines regarding the postponement and/or cancellation of elective procedures and triage of cancer surgery patients[78,79]. Blood usage was also optimized through PBM measures. PBM minimizes the gap between supply and demand through adherence to evidence-based transfusion triggers while achieving similar or even superior clinical outcomes[80]. Conservative transfusion practices also serve to ensure that blood is available for those with unavoidable blood needs (e.g., emergency surgery, thalassemia, myelodysplastic syndrome, etc.)[53].

Lower rates of trauma also reduced blood demand during the peak of the pandemic[51]. Lockdown and isolation directives, a transition to remote work/telecommuting and fear of exposure, all contributed to people staying home, thus lowering the burden of traumatic (e.g., motor vehicle accidents) and sports-related injuries in adults and children alike[81–83]. For example, in Saudi Arabia a 21.7% decline in blood usage was reported; in Singapore, RBCs, plasma, and platelet transfusions declined by 66.5%, 58%, and 46%, respectively[51,84]. In the U.S a 72-center study reported a decline of RBC and platelet utilization by 9.9% and 13.6%, respectively[85].

7. THE ROLE OF CONVALESCENT PLASMA AND BLOOD DERIVATIVES IN COVID-19 PANDEMIC

The COVID-19 pandemic has proved enormously instructive to the use of antibody-based therapies. Convalescent plasma (CP) is the plasma collected from individuals following resolution of an infection who have subsequently developed antibodies against the infecting pathogen. Infusion of CP, which imparts passive immunity, has been used as post-exposure prophylaxis and treatment for diverse infectious diseases, including prior coronavirus outbreaks (i.e., MERS, SARS), with mixed results[86]. Early in the COVID-19 pandemic, several uncontrolled reports from China suggested that COVID-19 convalescent plasma (CCP) was safe and may confer clinical benefits such as shorter recovery times and lower mortality[59,87–89]. In the absence of alternative preventive or treatment strategies for COVID-19, this led to widespread collection and transfusion of CCP to treat COVID-19.

The number of qualified donors grew rapidly given the expanding pandemic[59,90,91]. Donors were required to satisfy both the eligibility requirements for community blood donation as well as newly established criteria for CCP (notably the presence of high-titer antibodies against SARS-CoV-2). Each country established its own criteria for CCP donation, including a minimum allowable time from resolution of COVID-19 symptoms to collection (i.e., typically 14 days)[90,92,93] to maximize the likelihood of high titer antibodies being present, while still ensuring that donors were no longer infectious. Antibody thresholds for qualification were a point of contention given the uncertainty as to what titer is optimally effective across a range of different clinical assays (formal neutralization assays are not practical given the large numbers of donor samples to be processed).

The U.S experience with CCP offers a model for the challenges surrounding implementation of antibody-based therapy in an outbreak setting. Those challenges extend well beyond the simple collection and processing of CCP, with considerations surrounding regulation, reimbursement, donor eligibility, product qualification, and evidence based practice[94]. In the U.S, the federally supported expanded access program (EAP) was devised to facilitate access to CCP for large numbers of patients in need, while still collecting data to evaluate the efficacy[59,88–93,95–100]. There are both strengths and limitations to this approach. The program ensured rapid mobilization, thus enabling unprecedented transfusion of CCP at a time when alternative therapeutic measures were lacking. However, the program did receive criticism given the uncertainty of clinically efficacy where clinical trials might have shown benefit or futility with much lower sample sizes and a fraction of the cost that was expended on the program. The criticism neglects the reality of outbreak responsiveness whereby it took months to even years before clinical trial results would become available. Those results demonstrated clinical efficacy if high-titer CCP was administered early relative to disease onset or admission[101–103].

With widespread access to transfusion of CCP already underway, observational studies and randomized clinical trials (RCT) were undertaken to evaluate the safety and clinical efficacy of CCP to treat[99,104–106] and/or prevent COVID-19[107], the findings of which were used to inform practice guidelines for CCP[105]. At least in HICs, the collective findings showed that CCP transfusion was comparably safe to standard SARS-CoV-2 non-immune plasma[97–99,108–110]. However, efficacy of use was found to be contingent upon the presence of high titers of SARS-CoV-2 antibodies, coupled with early use relative to onset of symptoms or hospital admission[99,104,111,112]. For optimal effect, CCP collection is ideally temporally and geographically proximal to when or where the patient is transfused, to increase the likelihood of matching the antibodies to the infecting virus or variant[113]. Although the role of CCP diminished following the advent of SARS-CoV-2 vaccines and therapeutics, it has still been shown to be effective in selected subpopulations, notably those with immune compromise[95,101–103,108,111,114]. Ongoing studies may contribute to uncertainties on the effect of CCP in asymptomatic or mild disease[115].

Another blood derivative that was evaluated for use during the COVID-19 pandemic was hyperimmune globulin (HIG). HIG is a concentrated polyclonal immune globulin fraction that is produced following pooling and purification of CCP from large numbers of donors[116]. The advantage of HIG is its safety profile: it is subjected to pathogen reduction technology during manufacture, rendering it very safe for transfusion[117]. Furthermore, pooling and fractionization of CCP to produce HIG ensures that the final product has a standardized antibody content. Nonetheless, the advantages that come with pooling (i.e., standardization), also represent the major limitation that precluded its widespread use. Specifically, the need for large numbers (pool sizes are often measured in the thousands of donors) and time for manufacture, rendered this impractical given the acuity of need[116]. One study failed to show significant benefit when HIG was administered in concert with remdesivir, albeit in symptomatic hospitalized COVID-19 patient[118]. A later review of five randomized clinical trials, found that HIG had little to no impact on mortality, or clinical improvement in patients with moderate to severe disease[119].

8. DIFFERENCES BETWEEN HIGH VS LOW- AND MIDDLE-INCOME COUNTRIES PERTAINING TO BLOOD MANAGEMENT CRISIS SITUATIONS

LMICs shared many of the same challenges encountered in HICs in maintaining an adequate blood supply during the COVID-19 pandemic. However, there are additional challenges that are specific to low resource settings. For one, blood availability and/or safety are longstanding systemic challenges in LMICs across Asia, Latin America, Sub-Saharan Africa, and the Middle East, where blood shortages are common[120]. Therefore, the deficit in blood supply in LMICs preceded the pandemic, but was further exacerbated given wide ranging effects on the blood safety value chain[65]. For example, government-mandated preventive measures included social isolation and physical distancing, thus reduced blood donations in LMICs, including Nigeria, Iran, and Sudan [64,66,121,122]. A high proportion of the blood in LMICs is collected from family replacement donors (i.e., friends and family of the intended recipient) or paid donors, both of which are known to be higher risk (than voluntary non-remunerated blood donors) for TTIs[54,65,67,123]. This contrasts with the US and other HICs where blood collection from paid or replacement donors is only undertaken in exceptional circumstances. Replacement donors do not provide a stable donor pool that can be mobilized rapidly in times of need. Stringent lockdown measures in LMICs impeded donation while mobile blood drives were suspended given the difficulty of maintaining infectious preventive measure in an uncontrolled (i.e., community) environment. In parallel there was loss of staff due to illness or fear, and supply chain shortages. The WHO Global status report on blood safety and availability for 2021 highlighted the disparity between HICs and LMICs. The median blood donation rates for high, upper-middle, lower-middle, and low income countries were 31.5, 16.4, 6.6 and 5.0 donations per 1000, respectively[123]. A survey investigating the impact of COVID-19 on blood availability and transfusion services in LMICs found a 10–50% decline in blood availability from pre-pandemic levels[67].

A number of measures were undertaken in LMICs to contend with the blood shortages and associated challenges imposed by the pandemic. Like in HICs, social media and advertisements were used to recruit blood donors. Some LMICs (e.g. Oman, Pakistan, Saudi Arabia, and Bahrain) reported relaxing their donor eligibility criteria to allow more individuals to donate (e.g., lowering minimum hemoglobin donation threshold from 13 to 12.5 g/dl) [54,67]. Other measures included active monitoring of blood inventories with sharing of blood between hospitals, postponement of elective surgical procedures, and adjustment of donor center hours to maximize the time available to donate. This proved effective: for example, in Iran, the collective measures increased a 3 -day (i.e., crisis level) supply to 4.5 days[64].

As occurred in HICs, there was disruption in the supply chain, limiting the availability of testing reagents, supplies, and disposables in LMIC[67]. A survey of blood centers in the WHO Eastern Mediterranean region, found that 31% of respondents had experienced reagent shortages[54]. The escalation of reagent prices throughout the pandemic, in some LMICs, exceeded the funds that were allocated to replenish those stocks.

Blood transfusion is a major treatment for a diverse set of pathologies, many of which are disproportionately focused in LMICs. For example, over 80% of patients with sickle cell disease (SCD) and thalassemia reside in LMICs[124]. Professional societies, such as British Society of Hematology and American Society of Hematology, published guidelines on how to manage these patients in the setting of blood shortages associated with the pandemic[54,125–127]. Modified practices include depletion/exchange procedures or simple transfusion over red cell exchange (RCEx) in selected patients, the use of erythropoietic simulants to reduce transfusion requirements, and consideration of hydroxyurea in patients requiring routine transfusion.

CCP has been used widely to treat COVID-19 in HICs, however, its availability in LMICs has remained limited, given preexisting challenges surrounding donor recruitment, blood collection and laboratory testing[67,91,128]. Furthermore, apheresis technology, which has been a mainstay of CCP collection in HICs is limited in LMICs due to the high costs of use, inherent to the infrastructure (i.e., equipment) requirements, and technical expertise needed for use[128].

9. Lessons learned

The spread of SARS-CoV-2 has resulted in an historic pandemic with wide ranging ramifications for health, the economy and society at large. This pandemic has imparted some important lessons on crisis and outbreak responsiveness that are specific to blood utilization and management of the blood supply (Table 3).

Table 3.

Lessons learned from COVID-19

A decline in blood Donation should be expected
	Proactive (i.e., early) recruitment of blood donors Multimodal approach to donor mobilization using conventional and social media Communication with the public about blood shortages and need for donation
	Optimization of yield from extant blood donors e.g., apheresis collections such as double red collections
	Coordination with authorities to maintain donor access to donation sites during lockdowns
	Address fears among donors and collections staff regarding personal safety and disease transmission Ensure safe donation facilities; social distancing, limit capacity Encourage donation appointments/discourage walk-ins to limit Screen donors for illness (i.e., temperature monitoring)
Transient loss of personnel can impact blood collection and processing
	Establish safe collection/working environments for staff Adequate PPE and hand sanitizer Education on appropriate donning techniques Social distancing with separators between donors
	Address potential staffing loss (i.e., due to illness) Plan for staff reassignment or training of other non-essential staff Develop clear supportive policies for sick leave; encourage staff to self-report illness
	Encourage/strengthen moral with routine acknowledgement of efforts, and incentives to recruit and retain laboratory staff
Blood supply management in blood centers and hospital blood banks
	Active monitoring of inventory to (1) replenish stocks and (2) minimize wastage
	Activate a system allowing for blood sharing between institutions.
	Mitigate demand (i.e., PBM, postponement of elective procedures)
	Continuous communication with clinicians/blood users; regular inventory updates
	Ensure blood availability for transfusion dependent conditions (e.g. sickle cell disease, thalassemia, hematologic malignancies)
	Consideration for simple transfusion over red cell exchange in sickle cell disease
	Extending platelet shelf life from 5 to 7 days
	Consider reduced platelet dose (i.e., platelet splitting)
Potential shortages in reagents and critical supplies
	Maintain an emergency stock of critical reagents
	Communicate with distributors to maintain access
	Establish allocation protocols for reagents to avoid critical shortages
	Establish guidelines for PPE availability in times of shortages Consider extended use of PPE in critical situations Consider reprocessing of PPE Consider use of alternative item in place of traditional PPE if necessary
Planning or disaster preparedness is critical
	Develop emergency blood inventory plans
	Continuous involvement of clinicians and hospital administration of blood supply status
	Prompt inclusion of PBM programs to reduce blood utilization prior to critical shortages
	Develop systems to enable rapid adoption of recommended changes in accordance with national, local and/or institutional guidelines

1. Crisis brings a predictable decline in the blood supply, with limited ability for replenishment. Maintenance of a sustainable blood inventory with continued blood donation are imperative to minimizing the impact. Communication with routine and first-time blood donors about the importance and need for donation is crucial in maintaining an adequate blood supply.

2. Mitigation strategies are necessary to offset the blood shortages. Those which have been proven effective include postponement of high-use elective procedures and implementation of PBM programs. Lockdowns and isolation directives have also helped reduce blood use through the reduction of traumatic injuries.

3. Supply chain disruptions and infrastructure disturbances result in shortages of PPE and testing reagents. The pandemic has emphasized the importance of maintaining sufficient stock of critical supplies, while also establishing emergency inventories, such as reagents.

4. The blood center and transfusion service workforce are also at risk for illness underscoring, the need for protective measures such as PPE and social distancing during blood collection.

5. Antibody-based therapies may be useful in the early phases of an outbreak when alternative management options are few. However, early obstacles include the early determination of efficacy with donor and blood product qualification. The research on CCP during the COVID-19 pandemic could help streamline its use in future pandemics. Clinical trials, while ideal for informing practices, have limited utility in the early phases of a pandemic.

6. Disaster management planning is critical. The establishment of emergency plans in concordance with communication is essential to the maintenance of blood supplies. Communication is needed between blood centers and the public to encourage blood donation in times of shortages, to evaluate blood needs in each institution and promote resource sharing, as necessary. Additionally, systems should be established early to engage blood bank managers and clinical staff thus facilitating the rapid adoption of recommendations to comply with national, local and/or institutional guidelines.

10. CONCLUSION

The COVID-19 pandemic has imparted many lessons spanning emergency blood supply management to the use of antibody-based therapies to treat infectious diseases. The pandemic is not over, the lessons that were hard learned may be used to contend with future pandemics, outbreaks and public health emergencies.

11. EXPERT OPINION

The challenges encountered during the COVID-19 pandemic are likely to be encountered again. There are numerous antecedent examples of outbreaks that threatened the blood supply, either directly (e.g., HIV, WNV) or indirectly (i.e., through changes that impacted routine collection practices). Nonetheless, the COVID-19 pandemic has provided invaluable guidance on managing blood supplies in the face of a major outbreak or pandemic. Important lessons highlight that emergency preparedness pertaining to blood collection and donor mobilization is imperative.

Advances in blood management consequent to the pandemic, include growth and maturation of PBM programs, which encourage evidence-based transfusion practices thus reducing blood utilization. Second, blood centers and hospital transfusion services developed sophisticated lines of communication, which were important to the ongoing assessment of blood inventories, blood allocation, and resource sharing. Third, rapid adaptation to the growing threat enabled timely implementation of mitigation measures to ensure a safe donation experience for staff and donors alike (i.e., PPE measures, social distancing, separators between donations, etc.). Finally, there was unprecedented access to CCP at a time when alternative therapies for COVID-19 were lacking. New knowledge pertaining to the optimal use of CP allied with its practical implementation could be applied to future pandemics.

Despite this new breadth of knowledge, there remain opportunities for improvement, in anticipation of future crises. Foremost, are ways to mobilize donor rapidly, while balancing collection with wastage. Second, disruption in the supply chain risks critical shortages of reagents. This underscores the need to avoid reliance on single source (i.e., there is a need to re-distribute risk). The example of PPE production in China during the pandemic offers a case study in this regard. Third, CP was adopted early for clinical use, despite limited data pertaining to how it might be applied optimally for the treatment of COVID-19. By contrast, clinical trials were slow to launch. Mechanisms to expedite the research apparatus (i.e., design, funding, and logistical support) are critically needed so that efficacy data become available at a time when they are most useful.

Blood supply management continues to evolve. Each emerging pathogen introduces new challenges. Fortunately, transfusion transmission did not transpire. That may not hold true for the next emerging pathogen whereby proactive strategies (e.g. active surveillance and mitigation) are needed to address looming infectious threats[129].

Article Highlights:

• COVID-19 has posed complex challenges to the global blood supply spanning reductions in blood donation, loss of key personnel, supply chain disruptions, economic strains, and initial uncertainty regarding blood transfusion safety

• There are effective measures to reduce blood utilization in the face of blood shortages

• Disaster management planning is critical and can mitigate the impact to the blood supply

• The COVID-19 pandemic has imparted new knowledge on the optimal use, efficacy, and implementation of antibody-based therapies (e.g. convalescent plasma)

• The lessons from COVID-19 pertaining to blood supply management can be applied to new outbreaks and other public health crises