Blood supply and transfusion safety during the COVID-19 pandemic

Transfusion practice and blood safety were under strain following the emergence of a new coronavirus (COV) reported in Wuhan, China, on December 8, 2019 [1].

The World Health Organization (WHO) [2] named the disease caused by the new COV: “COVID-19.”

On January 30, 2020, WHO declared the outbreak of COVID-19 constituted a Public Health Emergency of International Concern (PHEIC) [3]. On March 11, 2020, based on the high levels of global spread and the severity of COVID-19, WHO’s Director-General declared the COVID-19 outbreak a pandemic [4].

The virus causing COVID-19 is an enveloped RNA virus, high-throughput sequencing has identified COVID-19 as a beta coronavirus, genetically similar to bat coronaviruses and to share approximately 79% and 50% of its genetic sequence with the coronaviruses responsible for severe acute respiratory syndrome (SARS) in 2002 and the Middle East respiratory syndrome (MERS) in 2012, respectively, which have resulted in a high disease burden, mortality, and economic disruption [5],[6],[7]. Consequently, the new pathogen has been named SARS-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV) [8], a name that relates it to SARS-CoV and suggests the existence of severe respiratory pathology.

Early WHO estimates and classical indicators of reproduction rate (Ro) and case fatality suggest that the contagiousness and virulence of SARS-Cov-2 exceed that of recent influenza pandemics [2].

With the onset of the COVID-19 pandemic, concerns grew about the availability of sufficient and safe blood to meet patient needs. The experience of previous outbreaks of other respiratory viruses, including SARS-CoV and MERS-CoV [9],[10], indicates that the COVID-19 pandemic had significant potential to affect blood systems and transfusion medicine. There will be a substantial impact on the blood supply by reducing blood donations [11],[12],[13].

SARS-CoV-2 is a new virus; its potential for TT is uncertain [14]. Ensuring blood safety is important, especially as SARS-CoV-2 RNA is found in the blood of COVID-19 patients and blood donors, the risk of transmission of COVID-19 through the transfusion of blood and blood components remains worrying [11],[15].

In this brief review, we raise the impact of COVID-19 on the blood supply and blood collection in blood centers worldwide.

We examine whether the virus is potentially transmissible by transfusion and consider the impact of risk mitigation strategies that blood centers can employ.

For data, we have used the keywords like COVID-19, SARS-CoV-2, the impact of COVID-19 on the blood supply, impact of COVID-19 on blood collection, COVID-19 and transfusion safety, COVID-19 symptoms, the impact of MERS on blood supply, impact of SRAS on Blood supply, and H1N1 pandemic.

1. A brief overview of the impact of pandemics on the availability of blood donors and blood products

The blood product supply requires daily and frequent blood donations; however, pandemics have potentially compromised this supply [16].

During the acute respiratory syndrome (SARS) pandemic of 2003, SARS had spread to 26 countries, infected 8096 people and caused 774 deaths. Ninety-five percent of infections occurred in the Asia Pacific (AP) region.

In Beijing, the avoidance of public places and the closing of workplaces and universities had caused the unavailability of blood donors. Blood was required to be imported from other Chinese regions to satisfy patients’ clinical use [17].

At the height of the 2003 SARS outbreak in Singapore, there was a 60% decrease in blood donors with, an additional 4% deferred from donating [17].

In Hong Kong, the SARS epidemic had impacted the blood supply and the demand for blood donation had reduced by 16.9%; a drop-in blood collection was 6445 units during the SARS epidemic in 2003 [13].

During the H1N1 pandemic, in the spring of 2009, a swine-origin virus emerged among residents of Mexico. In the first week of the pandemic, a Japanese report showed a rapid decrease in blood donors (21%). This decline led to the importation of blood products from other provinces to cover the clinical use needs of patients [18].

In 2012, the outbreak Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia and other countries on the Arabian Peninsula had caused 1905 confirmed infections with 677 deaths reported as of February 24, 2017 [18]. The number of asymptomatic cases was estimated to be much higher than reported cases, which was considered a risk for blood safety. Still, no information is available on the impact of MERS-CoV on the availability of blood products but some information on the implications for transfusion safety [13],[19].

As in previous pandemics, the international organizations (WHO, ECDC, Asian Pacific Blood Network) consider that the current COVID-19 pandemic can decrease and compromise the blood supply [11],[12],[20].

2. Impact of COVID19 pandemic on the blood supply

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has caused an unprecedented health crisis that has dramatically affected the blood bank and transfusion among other health care disciplines of medicine [20].

• In China

Zhejiang Province: According to a study that assessed the impact of the COVID-19 pandemic on blood donation and blood supply in Zhejiang Province, the study has revealed that the number of whole blood donors has decreased by 67%. The success rate of donor recruitment dropped by 60%. The total supply of red blood cells (RBCs) dropped by 65%. In the first week of the epidemic, the weekly amount of RBC units issued was almost six times higher than units collected. Most of the donors who were surveyed (81.2%) indicated that they were concerned about the “possibility of contracting COVID-19 while donating blood” [21].

Hubei Province: The number of volunteer donors at mobile blood drives has significantly reduced, putting a strain on the local blood supplies and jeopardizing the bloodstock needed for clinical transfusion. The strictly implemented mobility constraints also led to a reduction in blood donation in other areas of China, and even low records were reached [22].

The Chinese Society of Blood Transfusion (CSBT) has taken various measures in response to a dramatic decrease in the total number of blood donations. These are: urgent appeal to the public for blood donations; recruitment of potential donors; using traditional and social media, such as the popular social, messaging app, and allocation of blood stocks of neighboring cities or even provinces, with efficient and convenient logistic support and management [22].

• In Hong Kong

According to the Red Cross Blood Transfusions service, 2362 blood collections were cancelled in the first five weeks of 2020 compared to 4074 in the same week in 2019. This decrease is mainly due to the advised break from public activities the closing of traditional sources of volunteer blood donors, such as schools, universities, and societies [23].

• In Singapore

According to the Singapore Red Cross website, the blood supply in the country was low and at critical levels for certain blood groups.

Since the first COVID-19 case on January 23, 2020, the blood collections have decreased by 31.9%, the blood supply has decreased by 72.5%, and mobile cancellation is about 44.4% (4/9). On February 14, 2020, the media reported on critical blood stocks, active online recruitment, widespread text messaging and the activation of an online appointment system for blood donation [24].

These initiatives resulted in a temporary increase in blood collections and blood supply of 54.7% and 21.8%, respectively. But as soon as the implementation of governmental restraint measures; the blood collections and supply dropped again, the mobile cancellation reached 99.9%.

• In Japan

The Japanese Red Cross Society (JRC) blood center for the Kanto-Koshinetsu region reported that the number of blood donors from April to October 2020 in Tokyo and surrounding pectures fell by 9%, about 45,000 donors, compared to initial estimates [25].

The JRC sent temporary blood cars to areas near train stations to search for blood donors, but the effort was insufficient to cover the shortages [25].

• In the Eastern Mediterranean Region (EMR)

Al-Riyami AZ et al. surveyed 16 centers of 15/19 countries in the region to assess the blood supply status in the early months of the pandemic [26]. A total of 75% of the centers were from national blood banks. Most centers experienced a decrease in blood supply during the first month of the pandemic, ranging from 10% to 75%. This decrease in blood supply was variable and lected the degree of community spread of the virus and the actions taken by governments. More than 12% decrease is due to the cancellation of blood drives because of the closure of universities and institutions; Public fear of contracting COVID-19 was a factor contributing to the decrease in donations in 14 countries.

Two centers did not experience a shortage of blood; they could maintain the blood supply by intensifying blood drives, organizing military clinics, and intensifying marketing and donor recruitment, including mobilizing donors among health personnel. The United Arab Emirates center used a gymnasium for blood donation while maintaining a physical distance. The Morocco center established a crisis committee at the beginning of the pandemic to monitor all regional centers' stock status and needs for consumables and reagents [26].

• In Europe

In the second stage of the global spread of the coronavirus after Asia, many European countries have reported a decrease in blood donations. Data provided by the European Blood Alliance (EBA): 15 European national and regional blood transfusion services reported a 9% (median, range 1–27%) reduction in blood and blood components collected in March and April 2020 compared to the same period in 2019, while the decrease in blood components distributed to hospitals was 12% (median, range 1–18%) [27]. Some countries expressed significant differences between blood collections from March–April 2019 and March–April 2020 and distribution of blood and blood components between March–April 2019 and March–April 2020 [27].

Croatia had the highest difference rate: −27% in blood collection and −17% in blood and blood component distribution, Slovenia with the difference of −23% in blood collections and −12% in blood and blood component distribution, while in Northern Ireland, it was reported that the difference was −18% in blood collections and −17% in blood and blood component distribution [27].

• In the United States of America

On January 21, 2020, the first case of COVID-19 in the United States was reported in Washington State. The number of confirmed cases in Washington State rapidly reached over 750 in the third week of March. On March 13, the United States of America declared the COVID-19 pandemic a national emergency [28].

According to the American Association of Blood Banks (AABB), the everyday patient needs of blood are 33,000 units [29].

Eighty percent of total blood collections are derived from mobile drives at high schools, universities, and employers in many areas. The initial weeks of the COVID-19 outbreak in the United States led to the cancellation of more than 4600 blood drives, diminishing the available blood supply by 143,600 units [30].

Washington State experienced a significant temporary drop in blood supply at the start of the pandemic; the University of Washington Medical Center reported a blood shortage as early as February 29, 2020 [28].

At the New York Blood Center, 75% of their blood supply was interrupted during the week of March 16, 2020, when schools, businesses, and religious institutions were closed [31].

Major blood suppliers and hospitals have issued emergency appeals for donations. The mass cancellation of schools and workplaces, closing off large employment campuses, cancellation of community and mobile blood drives, as well as a marked reduction in the number of donors attending scheduled appointments have resulted in a reduction in the thousands of blood donations usually collected [30].

3. Impact on blood donor availability

Experience during the SARS epidemic has shown the most significant impact on the blood supply during a pandemic is likely to be a dramatic reduction in blood donors [10]. The current pandemic's threat to the blood supply is not SARS-CoV-2 itself but rather the unintended consequences of social distancing on blood drives [30].

The reduction in blood donation results from the decrease in donors attending blood donor centers and mobile and the cancellation of large numbers of scheduled mobile sessions. There was continued difficulty in preparing new mobile sessions during this period. Anxiety and the fear of contracting COVID-19, social distancing and confinement, the close of universities and societies were deterrents to blood donation. The donor was infected or self-quarantined after exposure to infected persons or persons under investigation. The additional selection criteria, declining donors with a history of travel from infection “hot spots” and excluding contact cases, decreased blood donors. Organizations were reluctant to organize blood drives to avoid spreading the virus in the community [10],[24],[25],[26],[30].

Fear and anxiety were real among blood collection staff who might be concerned about donors' exposure, becoming sick, or self-isolating through family exposure. These factors can significantly reduce staff availability for blood collection and processing [32].

A meta-analysis estimated that the prevalence of SARS-CoV-2 infection among healthcare workers (HCWs) is about 7–11%. Thus, HCWs should strictly adhere to infection control practices during this pandemic [33].

4. Impact of the COVID-19 pandemic on blood safety

SARS-CoV-2 is a new virus; its potential for transfusion transmission is uncertain [34]. The possibility of blood transfusion, including by an asymptomatic viremic donor, concerns the scientific community.

In the early months of the Coronavirus disease – 2019 pandemic, there have been reports of persons infected with SARS-CoV-2 but did not develop symptoms of COVID-19. In some cases, the viral load of such asymptomatic persons has been equal to that of symptomatic persons, suggesting similar potential for viral transmission [35].

Several studies have estimated the rate of asymptomatic infection; it is varied between 30.8% and a median of 34.6%. In other studies, and meta-analyses, the asymptomatic individuals appear to represent approximately 15–46% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days [35],[36]. The incubation period of SARS-CoV-2 infection was modeled by several studies, with most of the estimated ranges being between 2 and 11 days, and almost all infections developed symptoms by day 14 [36],[37],[38].

Regarding the detection of SARS-CoV-2, RNAemia, several studies have proven the existence of viral RNA in COVID-19 patients, such as:

Huang et al. reported that on January 2, 2020, 41 admitted hospital patients had been identified as having a laboratory-confirmed 2019-nCoV infection. Among the 41 cases of SARS-CoV-2 RNAemia was detected in six patients (15%) [39].

Chen et al. found that the 2109-nCoV RNA was readily detected in the blood (6 of 57 Chinese patients) and all of the six patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity [40].

Andersson et al. reported that viral RNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2. The RNAemia period appears to be brief, low, and typically associated with more severe disease symptoms [41].

(a) What about SARS-CoV-2 RNA in asymptomatic blood donors?

As per the report from the Wuhan Blood Center about detection of SARS-CoV-2 RNA blood donor, the screen and retrospective testing on donor samples collected during January have found:

4 of 7425 donors were RNA-positive; 2 donors remained asymptomatic and 2 reported a febrile syndrome after donation; all 4 donors had extremely low RNA levels, and infectious virus was not confirmed [42].

From December 31, 2019 to March 17, 2020, a study has estimated the number of blood donors during the incubation period of COVID-19 among 34 provincial regions in China.

The study has found that the number of potentially infected donors during the incubation period was low, only a tiny proportion of window period cases would likely have detectable viral RNA; the infectious virus has not been circulated in the blood [43].

From February 9 to April 30, 2020, a multicenter study in Hubei Province has tested a total of 98,342 donations, including 87,095 whole blood donations and 11,247 platelet donations, by nucleic acid screening test (NAT). All donations were negative for SARS-CoV-2 RNA in the past 12 weeks [44].

Another study from the Stanford University School of Medicine researchers reports a case of a voluntary blood donor who was healthy on donation day and had detectable levels of SARS-CoV-2 RNA in plasma at least 40 days after resolution coronavirus 2019 symptoms. However, RNA levels were low, anti-SARS-CoV-2 IgG was perceptible, and the presence of infectious virus was not demonstrated [45].

(b) What about blood Recipients?

According to a Korean study, seven donors have identified COVID-19 confirmed after blood donation. Six whole blood donations were processed into multiple components, and one donation was plasma intended for fractionation. Six patients have received all six platelet units, and three red blood cell units were also transfused to three recipients. One patient died due to causes unrelated to COVID-19. No recipients of platelets or red blood cell transfusions have developed COVID-19-related symptoms or tested positive for SARS-CoV-2 RNA [46].

Cho et al. have reported a 21-year-old man with severe aplastic anemia who have received a platelet transfusion from an individual infected with SARS-CoV-2.

The platelet recipient was tested for SARS-CoV-2 using real-time reverse transcription (RT)-PCR; the result was negative. The patient had no symptoms of infection, and there was no evidence of pneumonia on the chest. The patient was tested three more times for Sars-CoV-2, all were negative [47].

Politis et al. have reported a 54-year-old patient diagnosed with acute myeloid leukemia in January 2020 who had been transfused with platelets from an asymptomatic infected donor. The patient had no symptoms of infection, and there was no evidence of pneumonia on chest computed tomography. Patient’s molecular test result for COVID-19 was negative [48].

The French National Blood Service (EFS) reported that between January 20 and May 29, 311 donations were tested, including 268 PDI (post-donation information) donations and 43 traceback donations. Three of the 268 PDI donations (1.1%) tested positive for SARS-CoV-2 RNA with high Ct values (Ct. 37). They all tested negative for SARS-CoV-2 antibodies. In addition, four immunocompromised blood recipients between 5 and 67 years old were involved in the traceback. They received between 2 and 25 blood products, including 18 red blood cells and 23 units of pathogen-reduced platelets. None of the samples tested positive for SARS-CoV-2 RNA, in particular, those corresponding to the 18 red blood units, which were not pathogen reduced [49].

Publications from international scientific societies; studies on the detection of SARS-CoV-2 RNA of COVID-19 patients or blood donors; all published cases of blood transfusion from confirmed COVID-19 positive donors; and the outcome in recipients of these products indicate that the risk of transmission of SARS-CoV-2 through blood and blood products is theoretical. Any actions taken to mitigate risk are theore precautionary [11],[36].

5. Measures to mitigate the potential risk

According to publications from international scientific societies and each country’s international and local epidemic evolution relating to SARS-CoV-2, blood establishments worldwide have put the safety measures to maintain a safe and adequate blood supply during this pandemic.

These measures were updated by the coronavirus’s recent scientific developments and evolution.

5-1 Measure strengthening and updating blood donor eligibility criteria against SARS-CoV-2 infection.

Some countries have introduced 28 days of postponement of blood donation for travellers returning from China, 21 days for travellers from other countries at risk other than China, and 21 days for contact cases. Other countries have postponed blood donors four months after returning from China [50],[51].

The AABB, the Food and Drug Administration (FDA), and the CDC (Centre of Diseases Control) do not recommend any action to be taken by blood establishments [51]. For donors with confirmed SARS-CoV-2 virus infection or who have contact with an infected person, the High Council of Public Health (HCPH) recommended reducing from 28 to14 days deferral period [52].

The WHO has recommended setting up a hemovigilance system to detect any possible cases of transmission through blood and components; quarantining blood products like Fresh Frozen Plasma (FFP) products that did not benefit from pathogen inactivation until post-donation feedback is available [11].

Other measures for donor and staff safety are taken to limit the spread of COVID-19 by ensuring enough personal protective equipment for employees and donors, ensuring appropriate social distancing, increasing disinfection of all the contacting surfaces [53].

5-2 Other measures to overcome the shortage in blood supply were focused on Encouraging blood donations through mobile blood drives, social media, or traditional media; organizing national media campaigns; creating an online system for coordination among blood centers or creating an online system that shows all blood unit inventory in real-time.

Setting up a system whereby any center suffering from a blood shortage can ask its neighbor to supply blood, providing donors with information about COVID-19 beforehand, and taking appointments to donate blood [24],[26],[53].

Managing the demand for blood and blood products in collaboration with health care services. The reduction in blood supply has been partially met by a reduction in demand due to a decrease in elective surgery and medical treatment [13].

It is estimated that in pandemic the demand for red cells will decrease by 5–25%, and frozen and fractionated products by 0–10%, with little or no change in platelet demands, maybe a decrease in the blood demand as healthcare capacity is shifted towards providing the basic healthcare support, and non-urgent clinical interventions are usually deferred [54].

Optimizing the use of available blood, and reducing unnecessary transfusions in all hospitalized patients by using patient blood management techniques, is about doing “more with less” to close the gap between supply and demand [30],[55].

Implementing patient blood management (PBM) by clinically managing and preserving patients. Beyond the beneficial effects on blood utilization, the improvements in clinical outcomes associated with PBM, including reductions in hospital-acquired infections and length of stay, could further ease the burden on an overburdened healthcare system [11],[55].

Adopting the aforementioned measures has been proven effective in some countries, especially in the first weeks of the pandemic [53].

For example, in Hong Kong, after using social networks and media, the emergency appeal for blood donation has proven effective. Thus, the number of blood collections has increased to 6401 in week 7 of 2020 compared to 4890 in the same period in 2019 [50].

In Italy, an increase in the number of collected whole blood units (53,538 whole blood units) and a decrease in red blood cell transfusion to 39,745 units were noted (positive balance of 13,793 units) one week after running a national media campaign on the importance and safety of blood donation and reorganization of hospital activity [53].

In India, Raturi et al.’s study found that deferring elective surgeries and routine procedures reduced demand and delivery of blood units. A blood component-wise reduction in the request was 14%, 11%, and 1.6% for RBCs, fresh frozen plasma and platelets, respectively, and a reduction in the RBCs issued as 17% [54].

The COVID-19 pandemic had a significant impact on the blood supply in many countries during the early stages of the pandemic. It has created a blood inventory shortage worldwide. However, the risk of transmission of the new coronavirus through blood is only theoretical. The most significant risks to blood services were the dramatic decrease in blood donations. The maintenance of the sufficiency of blood supply while minimizing respiratory transmission of SARS-CoV-19 to donors and staff while donating blood and the effective managing communications with all stakeholders including the public, blood donors, staff, hospitals, clinicians, regulators, health authorities, emergency response coordination agencies, and other blood services. An efficient communication strategy with the voluntary blood donors to motivate them for donations, with health care establishments proactively reducing blood utilization, with all stakeholders have undoubtedly helped go a long way into the blood supply management during this pandemic worldwide.