The World Health Organization declared the outbreak a global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) on March 11, 2020. COVID-19 became a global concern as it spreads easily and quickly through close contact through respiratory droplets containing infectious virus particles. Over past 2 year, there have been literature available to suggest that the red blood cell (ABO) blood group have a role in the immunopathogenesis of SARS-CoV-2 infection.[1,2,3,4] ABO blood group clinically is the most important. Deleers et al. showed that ABO isoagglutinin titer levels are significantly lower among COVID-19 patients as compared to the control groups indicating higher degree of infection.
An ABO discrepancy exists when the result of an ABO red blood cell typing, or forward type, does not agree with reverse type. They arise from intrinsic problems with either red cells or serum or from the technical errors in performing the test. Group I discrepancies are the most common ones and are due to weakly reacting or missing antibodies leading to unexpected reactions in the reverse grouping. Here, we document the two cases of absence anti-A and anti-B antibodies in two COVID patients, with the photographic representation of the immunohematological workups.
A 68-year-old gentleman was diagnosed with SARS-COVID-19 infection with computed tomography (CT) chest score was 12/25 on April 25, 2021. The disease severity was classified as moderate disease as per AIIMS/ICMR-COVID-19 National Task Force/Joint Monitoring Group (Dte. GHS) Ministry of Health and Family Welfare, Government of India, issue dated May 17, 2021. He was started with remdesivir, methylprednisolone, ceftriaxone, doxycycline, and ivermectin along with enoxaparin for managing the SARS-COVID-19 infection. As a part of routine investigations, his blood group was A Rh D negative on forward grouping and Group AB on reverse grouping [Figure 1]. The technical errors were ruled out and the discrepancy was confirmed by repeating the test twice with fresh sample by both conventional tube technique (CTT) and column agglutination technology (CAT). The patient's serum when incubated with freshly prepared pooled A and B cells at the room temperature for 30 min was uneventful. Cold enhancement at 4°C for 30 min also gave a negative reaction with B cells. From the previous medical records, patient's blood group was A Rh D negative; with no ABO discrepancies. Salivary inhibition test was not done due to active COVID-19 infection. The direct and indirect antiglobulin tests were negative performed by CAT. As the grouping discrepancy was inconclusive, the patient was planned for AB group convalescent plasma transfusion when required. Nevertheless, he recovered without any transfusion support.
Considering the age of the patient, the blood grouping was repeated 3 months after recovery from COVID-19 infection to resolve the grouping discrepancy. The blood group of the patient was irrefutably noted as A1 Rh D negative both through forward and reverse grouping [Figure 1].
A 65-year-old female was diagnosed with SARS-COVID 19 infection on April 18, 2021. Her CT score was 13/25. She was also categorized to have moderate disease. She had received methylprednisolone, favipiravir, ivermectin, piperacillin and tazobactum, and enoxaparin sodium for SARS-COVID 19 infection. One month later, she presented with 5 days history of pain and swelling over the left cheek and headache. Imaging studies were suggestive of invasive fungal sinusitis. Potassium hydroxide mount and fungal culture was positive for mucormycosis. She underwent bilateral functional endoscopic sinus surgery. Her repeat SARS-COVID-19 infection testing at time of surgery was negative. She received amphotericin B (liposomal), ceftriaxone, and \ posaconazole during her postoperative period.
Her blood group during pretransfusion workup for surgery was B Rh D Positive on forward grouping and group AB on reverse grouping [Figure 1]. Historical blood group was verified and the workup was completed in similar lines to first case. The missing ABO antibodies in serum were confirmed in this patient also. The direct and indirect antiglobulin tests were negative performed by CTT.
Considering the similar age of this patient and post-COVID-19 infection complication, blood grouping was repeated after 45 days. The blood group was unambiguously noted as B positive both through forward and reverse grouping [Figure 1].
All the tests performed for the immunohematological work up for both the patients were as per the standard operating procedure of the department.
The cases reported here are of first known patients with COVID-19 infection showing ABO discrepancies (Type I), transitory absence of anti-A and anti-B antibodies during the infective period. ABO discrepancies are recognized when the reactions obtained in the forward type disagree with the reverse typing. The discrepancy may arise because of technical errors or clinical conditions of the patients.
The alertness regarding the ABO discrepancy due to loss/weakening of ABO antibodies is not just for educational interest but it also helps in guiding towards the underlying conditions. The above two described cases all the systemic illnesses were ruled out which could cause Type I ABO discrepancy and neither they had received any transfusion support in the past. There have been published literature, COVID-19 and development of auto-immune hemolytic anemia (AIHA) especially cold agglutinin disease among the patients.[8,9] The AIHA was also ruled out as Direct Coombs Test (DCT) and auto-control were persistently negative for both the case and patient's blood group was performed prior to initiation of any medications. The temporary absence of antibodies could only be due to SARS-CoV-2 infection. There has been literature evidence on ABO blood group having influence on COVID-19 disease severity.[1,2,3,4,10] Hence, it was planned to repeat the blood grouping for both the patient's during the follow-up with minimum interval of 28 days, as the half-life of antibodies remain between 17.5 and 26 days. The ABO blood group of such patients should be cautiously reported. They should be asked to repeat the blood group upon recovery from the infection completely. With respect to the transfusion support, universal donor groups, i.e., O for red cells and AB for plasma containing products can be used.
Two possible explanations for ABO discrepancy following SARS-CoV-2 infection as available in the literature are Anti-A and/or anti-B antibodies serve as viral neutralizing antibodies by binding to A and/or B antigens expressed on the viral envelope and thereby preventing infection of target cells and the SARS-CoV-2 S protein is bound by human anti-A antibodies, which may block the interaction between the virus and angiotensin-converting enzyme 2 receptor, thereby preventing entry into the lung epithelium. Both the mechanism might reduce the level of antibodies among the affected patients, as antibodies reappeared following full-recovery. A study by Deleers et al. showed that isoagglutinins are comparatively less in COVID-19 as compared to the nonaffected individuals. The study showed that COVID-19 infection only affects ABO isoagglutinins only as anti-xenoantigens antibodies level remained unchanged. The limiting factor of this study could be, it reports isolated two individual's patients finding, which may be associated with novel coronavirus, requiring further studies exploring this finding of ABO discrepancy.
COVID-19 infection is known to intermingle with the ABO antigen and antibodies in an affected individual. The cases signify the importance of a full clinical history and ABO typing including both forward and reverse typing should be performed routinely.
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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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1. Liu N, Zhang T, Ma L, Zhang H, Wang H, Wei W, et al The impact of ABO blood group on COVID-19 infection risk and mortality: A systematic review and meta-analysis Blood Rev. 2021;48:100785.
2. Goel R, Bloch EM, Pirenne F, Al-Riyami AZ, Crowe E, Dau L, et al ABO blood group and COVID-19: A review on behalf of the ISBT COVID-19 working group Vox Sang. 2021;116:849–61
3. Fan Q, Zhang W, Li B, Li DJ, Zhang J, Zhao F. Association between ABO blood group system and COVID-19 susceptibility in Wuhan Front Cell Infect Microbiol. 2020;10:404.
4. Zhang Y, Garner R, Salehi S, La Rocca M, Duncan D. Association between ABO blood types and coronavirus disease 2019 (COVID-19), genetic associations, and underlying molecular mechanisms: A literature review of 23 studies Ann Hematol. 2021;100:1123–32
5. Cooling LRoback JD, Grossman BJ, Harris T, Hillyer CD. ABO, H, and Lewis blood groups and structurally related antigens Technical Manual. 201117th Maryland, United States AABB:363–87
6. Deleers M, Breiman A, Daubie V, Maggetto C, Barreau I, Besse T, et al COVID-19 and blood groups: ABO antibody levels may also matter Int J Infect Dis. 2021;104:242–9
7. AIIMS/ICMR-COVID-19. . Clinical Guidance for Management of Adult COVID-19 Patients Ministry of Health & Family Welfare, Government of India. 2021Last accessed on 2021 Oct 11 Available from: https://www.icmr.gov.in/pdf/covid/techdoc/COVID_Management_Algorithm_17052021.pdf
8. Jacobs J, Eichbaum Q. COVID-19 associated with severe autoimmune hemolytic anemia Transfusion. 2021;61:635–40
9. Ahmadnezhad M, Mosleh M, Ferdowsi S, Mohammadi S, Eshghi P, Oodi A. Cold agglutinin associated with COVID-19 infection in a thalassemia patient with multiple alloantibodies: A case of cold hemagglutinin disease (CAD) with complex antibody detection Hematol Transfus Cell Ther. 2021;43:361–3
10. Pendu JL, Breiman A, Rocher J, Dion M, Ruvoën-Clouet N. ABO blood types and COVID-19: Spurious, anecdotal, or truly important relationships? A reasoned review of available data Viruses. 2021;13:160.