| Abstract|| |
BACKGROUND: Asymptomatic/presymptomatic COVID-19 affected individuals who may appear healthy during blood donor screening can donate blood despite being infective. Most blood donors in India are relatives/friends/acquaintances of patients, who under peer pressure overlook the donor selection process, which can significantly impact the transfusion safety.
AIMS: The prevalence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) antibodies among blood donors was assessed, along with the possible transmissibility of SARS-CoV-2 virus in transfusion recipients of blood components prepared from sero-reactive blood donors.
SETTINGS AND DESIGN: A prospective cross-sectional study was conducted among eligible blood donors from November-2020 to April 2021.
METHODS: 1500 blood donors were tested for SARS-CoV-2 IgG antibodies. Sero-reactive donors were followed-up telephonically to inquire about risk factors prior to donation or appearance of COVID-19 related symptoms postdonation. Patients transfused with blood components from seroreactive donors were also followed up for posttransfusion symptoms suggestive for COVID-19. Descriptive analysis was done for the donor and patient follow-up data.
RESULTS: A total of 452 (30.1%) donor were reactive, with median S/CO ratio of 2.8 (interquartile range 1.5–5.5). Risk factors such as travel, contact, or quarantine were significantly higher among reactive donors. History of diabetes and/or hypertension was associated with seroreactivity. Total 516 patients were transfused with blood components from these seroreactive donors. Three patients developed fever after transfusion, one of which was found to be PCR positive after 4 days of transfusion.
CONCLUSION: Sero-reactivity rate among blood donors was lower than the general population. Optimum blood donor screening strategies can help decrease the possibility of blood collection from infected blood donors.
Keywords: Blood donors, COVID-19, epidemiology, transfusion transmissibility
|How to cite this URL:|
Chaurasia R, Patidar GK, Pandey HC, Palanisamy S, Gupta V, Chopra S, Coshic P. Epidemiology of severe acute respiratory syndrome-related coronavirus 2 antibodies in healthy blood donors and their follow-up. Asian J Transfus Sci [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajts.org/preprintarticle.asp?id=356899
| Introduction|| |
The outbreak of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) was reported in December 2019 from Wuhan, Hubei Province, China. SARS-CoV-2, which is an enveloped RNA virus of coronavirus family is the causative agent of COVID-19. Approximately 80% of those infected are expected to have mild or no symptoms and recover from the disease without needing hospital treatment at all. COVID-19 has been known to primarily spread through droplet infection and direct contact with infected individuals. Although other routes of transmission such as feco-oral and blood transfusion have been implicated, the evidence to support the same are lacking as of now., In the light of the knowledge that the presence of virus can be detected in the bloodstream even when the oral swabs are negative, the transmission of SARS-CoV-2 through transfusion of blood and blood components remains a possibility and thence potential threat to the patients who are transfused with blood and blood components from asymptomatic blood donors.,
In a retrospective study done by Chang et al., 4 asymptomatic donors were found to be positive for the presence of viral RNA in blood stream but they did not able to find the transfusion transmissibility of the virus. Another study performed by Kwon et al., seven blood donors were found to be positive for SARS-CoV-2 RNA and no recipient of blood components from these donors diagnosed with SARS-CoV-2 infection. However, these previous studies could not provide sufficient evidence to recommend any pretransfusion screening of blood donors for COVID-19 antibodies.
In India, over 34 million conﬁrmed positive cases and 0.46 million deaths have been reported till November 25, 2021. In India, still large number of donors are relatives or friends or acquaintances of patients, accompanying them to the hospitals., These donors sometimes under peer pressure may overlook the donors screening process and donate blood which may affect the overall transfusion safety. With the increased number of COVID-19 cases, the possibility of asymptomatic yet infective blood donors among these kinds of replacement blood donors cannot be ruled out completely. Even after almost 2 years of pandemic till now the information about seroprevalence of asymptomatic blood donors and the transfusion transmissibility of SARS-CoV-2 virus is limited. Hence, in this study, we assessed the prevalence of SARS-CoV-2 antibodies among healthy blood donors along with the possible transmissibility of SARS-CoV-2 virus in transfusion recipients who were transfused with blood components prepared from the seropositive blood donors.
| Methods|| |
This cross-sectional study was conducted on a pilot basis with 1500 blood donors being tested for the serological status of SARS-CoV-2 antibodies in a tertiary care institute in North India from November 2020 to April 2021. The study was approved by the Institutional Ethics Committee (IEC-878/03.01.2020).
Selection and description of participants
Blood donors were selected for whole blood donation in accordance with the donor selection criteria laid by the Drug and Cosmetic Act and the donor selection criteria during the COVID-19 pandemic as laid by the National Blood Transfusion Council (NBTC), India., Blood donors with a history of close contact for <28 days of known COVID-19 positive patients were excluded from the study process. Consent was taken for enrollment in the study process, which included testing and follow-up as follows:
Severe acute respiratory syndrome-related coronavirus 2 antibodies testing
6 ml blood sample was collected in EDTA vial for blood grouping and after performing blood grouping the plasma from rest of the sample was used for testing of SARS-CoV-2 antibodies. Testing for SARS CoV-2 antibodies (IgG) was performed using Chemiluminescence immunoassay (ADVIA Centaur® SARS-CoV-2 IgG (COV2G) assay, Siemens Healthcare Diagnostics Inc. NY, USA).
Seroreactive donors were contacted telephonically (at least on 2 occasions 24 h apart) after all the samples were tested for the SARS CoV2 IgG antibodies. On telephonic conversation, donors were inquired about any contact history with COVID-19 infective personnel/travel to areas with a high risk of transmission, alongside any history of symptoms suggestive of COVID-19 (fever or chills/cough/shortness of breath or difficulty breathing/fatigue/muscle or body aches/headache/new loss of taste or smell/sore throat/congestion or runny nose/nausea or vomiting/diarrhea) that occurred 14 days before or after donation, which the blood donor might have hidden at the time of blood donation. Contacted blood donors were also requested to report to the blood center, where they were counseled and repeat sample was collected for confirmation of the SARS CoV-2 antibodies (IgG). Repeat testing was also performed by the same procedure as previous.
If the blood components from seroreactive donors were transfused, such patients were contacted telephonically (at least 2 occasions 24 h apart) at least after 14 days of transfusion. Patients (transfusion recipients) were asked about any signs and symptoms suggestive of COVID-19 within 14 days of blood components transfusion. Patients were also requested to report to blood centre, where they would be counselled and repeat samples were collected for confirmation of the SARS CoV-2 antibodies (IgG). The testing was performed by the same procedure as donor's blood sample was tested.
Details of donor demographics such as age, gender, address (urban/rural), type of blood donors (voluntary/replacement), first time/repeat donors, results of blood grouping were collected initially from the blood bank management software. And on a telephonic conversation with seroreactive blood donors, history of travel to COVID-19 affected areas or contact with COVID-19 affected patient along with any history of isolation/quarantine, or chloroquine prophylaxis for COVID-19, presence of comorbidities and history of signs and symptoms suggestive of COVID-19 was collected.
Initially details (name, registration number, contact details, number, and type of blood components transfused) of all transfused patients from blood component of COVID-19 seroreactive blood donors were collected from hospital information system. Later, the patient's COVID-19 infectious status was inquired telephonically.
Data collected were entered and analyzed using SPSS version 20.0 (Armonk, NY: IBM Corporation). Comparative analysis was performed for blood donors who were tested positive and negative for SARS CoV2 IgG antibodies. Descriptive analysis was done for the donor and patient follow-up data.
| Results|| |
A total of 1500 donors who were selected for blood donation were enrolled in the study. Of these, 452 (30.1%) donors were found to be positive for SARS-CoV-2 IgG antibodies [Figure 1]. The demographics and epidemiological characteristics of the positive and negative blood donors were compared in [Table 1]. The median value for signal-to-cut-off ratio for SARS-CoV-2 IgG antibodies in seroreactive blood donors was 2.8 (interquartile range 1.5–5.5). The frequency distribution of blood donors with their signal-to-cut-off ratio for SARS-CoV-2 IgG assays is shown in [Figure 2]. No correlation of signal-to-cut-off ratio was observed with the risk factors as travel history, contact history, and isolation/quarantine.
|Figure 1: Flow chart for the donor follow-up, details of blood components prepared, and patient follow-up. *13 units split into pediatric bags, @prepared as fresh plasma|
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|Table 1: Demographics and epidemiological characteristics of the blood donors|
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|Figure 2: Frequency distribution of blood donors with their signal-to-cut-off ratio for severe acute respiratory syndrome-related coronavirus 2 IgG assays|
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All 452 seroreactive donors were followed up after a mean duration of 63 days (range 40–87 days) from the day of donation, of which 324 (71.7%) donors responded and the rest 128 (28.3%) did not respond twice to the phone calls made. None of the blood donors who responded to the phone calls gave a history of risk factors for COVID-19 that they might have missed during donors screening or signs and symptoms suggestive of COVID-19 following blood donation. Of all responsive blood donors, 11 (3.4%) reported back to the blood centers for counseling and repeat testing [Figure 1]. Of these, only 1 blood donor was found to repeat reactive, whereas others were negative for SARS CoV-2 IgG antibodies, the results of baseline and repeat testing is shown in [Table 2].
|Table 2: Signal is cut-off ratio for severe acute respiratory syndrome-related coronavirus 2 IgG assay during repeat testing of blood donors|
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Of the 452 donors tested reactive for SARS CoV2 IgG antibody, blood components were prepared from 435 blood units, as 9 units were discarded due to TTI reactivity and other 8 units due to under-collection or leakage during blood component processing [Figure 1]. Blood components that were prepared from these units were then traced back to its transfusion recipient. The mean duration to follow-up was 75 (range 46–98) days after transfusion. A total of 516 patients were identified, which included, 327 (63.37%) males, with the majority of the patients in age below 30 years of age. The majority of these patients 152 (29.5%) were admitted to hematology/oncology ward followed by emergency medicine department 88 (17.1%), pediatrics 47 (9.1%), trauma 46 (8.9), cardiology (8.1%), and others 141 (27.3%). At the time of hospital admission, all patients were screened negative for COVID-19 using reverse transcription–polymerase chain reaction (RT-PCR) or cartridge-based nucleic acid amplification test assays. Of these, 282 patients responded to phone calls, and history suggestive of COVID-19 was taken. The remaining 234 patients could not be contacted as 83 patients expired and 151 did not respond the phone calls. Three patients gave history was suggestive of fever along with other signs/symptoms. The details of these patients are shown in [Table 3]. One of the patients who complained of fever and cough was found to COVID-19 positive after 4 days of transfusion for E gene and N2 gene by Xpert SARS COV-2 assay.
|Table 3: Details of the patients who gave history of fever after blood transfusion|
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| Discussion|| |
During the initial breakout of COVID-19 cases, various strategies were adopted to mitigate the theoretical risk of transfusion-transmission of SARS-CoV-2 through blood donation from presymptomatic or asymptomatic yet infective individuals. These strategies included a 28-day deferral of donors with a history of travel to covid affected areas/containment zones, history of contact to contact, self-isolation/quarantine due to close contacts of infected individuals. Alongside donors were also requested to report any signs or symptoms suggestive of COVID-19 after blood donation to rule out the possibility of infective blood donors. The assessment of the serological status for COVID-19 is a useful tool to determine whether blood donors/healthy individuals have been previously infected by SARS-CoV-2, thus estimating the overall effectiveness of the donor screening strategies and improving them to increase transfusion safety.
Some of the asymptomatic or presymptomatic or recovered blood donors who may appear healthy during the donor screening process may continue to donate blood despite being infective. The situation may be even worse in our scenario as unlike the developed world most the blood donors in our country are often family members or acquaintances from different socioeconomic and sociocultural backgrounds, who accompany the patients to the hospitals. These donors, under peer pressure, may overlook the donors screening process and donate blood which may affect the overall transfusion safety. In this study, we assessed the seroprevalence of IgG antibodies among 1500 blood donors on a pilot basis and then followed these seroreactive donors and the transfusion recipients for the blood components prepared from these donors. We detected an overall seroprevalence of (30.1%) among blood donors, which was lower compared to the seroprevalence among the general population (50.76%) during the same phase of the pandemic in the same area. The lower rate of seroprevalence could be due to additional screening for travel- and contact-related deferral criteria for COVID-19. However, the seroprevalence rates observed by us were higher in comparison to the other seroprevalences among the blood donors reported by other countries during November and December 2020.,,,, This could be attributed to differences in the epidemiological profile of the COVID-19 positive populations in our country. In our study majority of the blood donors were males, with equivalent proportions of first-time and repeat donors, from the urban areas of the country with no major difference from the pre-COVID era among the age/gender, urban/rural population. AlthoughVassallo et al. pointed out changes in the demographic profile of the blood donors during the pandemic.
In our study, a positive association among the seroreactive blood donors with the history of quarantine, travel/contact even after 28 days of deferral was observed. Our results show that introducing a questionnaire for the assessment of travel/contact risk for SARS CoV2 has helped in reducing the risk of asymptomatic or presymptomatic COVID-19 individuals in the donor pool but has not eliminated the risk of acceptance of such donors. Since the Donor History Questionnaire (DHQ) is dependent on the individuals understanding and perception of the items presented in the questionnaire, where the donors do their own risk assessment and may or may not discloses the accurate information regarding the risk factors. Moreover, the DHQ also has a relatively high rate of noncompliance, which may affect the overall effectiveness of the DHQ. Similar reports have also been reported for various situations., In our study, we also noticed that donors who had controlled hypertension or diabetes mellitus had higher rates of seroreactivity which could be due to the risk profile of such individuals for contracting the SARS-COV2 infection.
These seroreactive donors were also followed up telephonically for any additional risk factors which could have been initially omitted/missed by the blood donors. Two-thirds of the donors responded to the phone calls for follow-up, none of these donors gave a history of signs and symptoms suggestive of COVID-19. Since the follow-up donors were limited only to the responsive donors, the possibility of at-risk donors could not be ruled out. Donors who also did not respond to the phone calls could be the ones who deliberately omitted the history of contact/travel/risk factors due to peer pressure during the process of blood donation. Thus educating donors regarding their health and its implication on the transfusion safety is also of necessary in addition to the introduction of the additional questions in the DHQ.
Signal is cut-off values (S/CO) of SARS-CoV2 IgG antibodies have been correlated with the level of the neutralization antibodies, where a specific cut-off was used to classify it as high titer for collection of convalescent plasma. The S/CO ratio for SARS-CoV2 IgG assay for reactive donors was found below 5 in majority of the blood donors (72%) in our study, indicating low levels of neutralizing antibodies in these donors. Reason for low s/co levels was not analyzed as time to infection/exposure with contact/travel was not known. We also could not find any association of the S/CO values specifically for contact or history of travel to covid affected areas or any history of isolation/quarantine.
Most of the donors who responded and reported back to the blood center were found to repeat negative/nonreactive despite higher S/CO values on initial testing. Only one donor was found to be reactive, however, the S/CO was quite low compared to the baseline value (S/CO decreased from 8.3 to 1.4). This finding was concordant to the studies evaluating the antibody levels of COVID-19 positive patients, where asymptomatic COVID-19 tend to have a weaker immune response or earlier disappearance of antibodies compared to the serologic responses of a severe or critically ill patients.,,,,
Apart from a few cases reports/observational studies, knowledge regarding the transfusion transmissibility of COVID-19 has not been investigated using longitudinal follow of the transfused individuals who received blood components from seroreactive donors.,,, In this study we performed a follow-up of patients using a simple telephone conversation to inquire about the signs and symptoms suggestive of COVID-19. We followed 282 patients of the 516 who were transfused with blood components from seroreactive donors, where we identified 3 patients who gave history suggestive COVID-19 following transfusion. Of these 3 patients, the possibility of COVID-19 following transfusion was excluded in 2 patients due to the timing of signs/symptoms and/or associated complaints, one patient who a known case of acute myeloid leukemia was found to be positive for SARS CoV-2 after 4 days of a transfusion of 1 unit of the red blood cells unit. Since the remaining blood components from the implicated donor units were issued to fractionation agency, confirmation of RNAemia from the remining blood units was not done, and possibility of transfusion transmission cannot be ruled out, which is one the major limitation of this study. Along with that, there could be a possibility that the patient may have acquired infection before admission, or during admission. As the hospital policy was to admit all the patients only after negative COVID-19 test report and the COVID-19-positive and negative patients were admitted in different wards with separately designated staff. So, it is less likely that the patient got infected from direct exposure during hospital stay. Hence, the remaining possibilities that the patient could be in window period at the time of admission or transfusion transmission of the infection cannot be ruled out.
| Conclusion|| |
Seroprevalence of IgG antibodies against SARS-CoV2 assay was lower among blood donors than the general population during the same phase of the pandemic. History of travel to high-risk areas or close contact of COVID-19 or history of quarantine were identified as common risk factors for seroreactivity. For reducing the chances of blood collection from asymptomatic yet infective blood donors, donor education along with optimal screening strategies should be emphasized. Although transfusion transmissibility of SARS-CoV-2 virus could not be established in this study, further studies with longitudinal follow-up of donors using NAT assays are required.
Financial support and sponsorship
The study was funded by the Institutional Research Committee as intramural funds.
Conflicts of interest
There are no conflicts of interest.
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Gopal Kumar Patidar,
Department of Transfusion Medicine, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]