Sex: M
Vaccine: COVID19-2
Symptoms: Blood immunoglobulin G, Blood immunoglobulin M, COVID-19, Drug ineffective, Forced expiratory volume
Clinical narrative: COVID-19 (Delta VOC and mixture of both Delta and the newly emerged Omicron BA.1 VOCs); COVID-19 (Delta VOC and mixture of both Delta and the newly emerged Omicron BA.1 VOCs); This is a literature report for the following literature source(s):  A 76-year-old male patient received BNT162b2 (BNT162B2), in 2021 as dose 1, single (Batch/Lot number: unknown), in 2021 as dose 2, single (Batch/Lot number: unknown) and in 2021 as dose 3 (booster), single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history included: "Lung transplant", start date: 2013, stop date: 2013, notes: bilateral lung transplantation; "Idiopathic pulmonary fibrosis" (unknown if ongoing). Concomitant medication(s) included: PREDNISONE taken for immunosuppressant drug therapy; TACROLIMUS taken for immunosuppressant drug therapy; BELATACEPT taken for immunosuppressant drug therapy. The following information was reported: DRUG INEFFECTIVE (hospitalization, medically significant), COVID-19 (hospitalization, medically significant) all with onset Nov2021, outcome "recovering" and all described as "COVID-19 (Delta VOC and mixture of both Delta and the newly emerged Omicron BA.1 VOCs)". The patient underwent the following laboratory tests and procedures: Blood immunoglobulin G: (2021) undetectable levels; (2021) undetectable levels; (Nov2021) >200000, notes: Units:[arb'U] high passive Spike IgG antibody levels; (2022) 35695, notes: Units:[arb'U]; Blood immunoglobulin M: (2021) undetectable levels, notes: epidemiologically dominant at the time of sampling; (2022) undetectable levels; Forced expiratory volume: (2021) reduced from baseline; at the time of discharge; (2022) near baseline at the time of 2nd discharge; Gene sequencing: (Nov2021) revealed mutations consistent with the Delta VOC, notes: which was epidemiologically dominant at the time of sampling; (2022) SARS-CoV-2 mutational signatures consistent with, notes: the presence of two unique VOCs. Delta (believed to be remaining from his initial infection) and Omicron BA.1 (secondary infection) were identified (genotyping of the second PCR-positive specimen); (2022) revealed mutations specific to Delta and, notes: Omicron BA.1 were found on independent reads. While a total of eight fragment analysis targets are used in genotyping, only three are highlighted here to demonstrate the difference in Omicron BA.1 and Delta VOCs. ORF1A detects the 3 amino acid deletion from ORF1A: Del3675_3677. Spike recurrently deleted region (RDR)1 and 2 detect S:Del69_70 and mutations in the 140-160 amino acid range, respectively. The Delta variant has a 2 amino acid deletion in Spike region 2 (S:Del157_158), while Omicron has a 3 amino acid deletion (S:Del143_145). These data, paired with information from WGS, reveal no mutagenic signatures were identified to suggest recombination between the two lineages in this case; SARS-CoV-2 test: (Nov2021) Positive; (Jan2022) Positive. Therapeutic measures were taken as a result of drug ineffective, covid-19.  Clinical course: This case was detected in the medical literature. SARS-CoV-2 coinfections with variant genomic lineages identified by multiplex fragment analysis. Frontiers in Genetics. 2022;13:942713 on 03 Nov 2022. This spontaneous case was reported in the medical literature by a physician and concerns a 76-years-old male patient who experienced serious adverse drug reaction of COVID-19 associated with tacrolimus, prednisone, and belatacept. This patient underwent bilateral lung transplantation 8 years prior due to idiopathic pulmonary fibrosis presented with fever and respiratory symptoms in November 2021 consistent with COVID-19. SARS-CoV-2 PCR was positive upon admission. Viral genotyping revealed mutations consistent with the Delta VOC which was epidemiologically dominant at the time of sampling. The patient's immunosuppressive regimen included prednisone, tacrolimus, and monthly belatecept (belatacept) infusions. He had received three doses of the Pfizer/BioNTech COVID-19 vaccine prior to presentation (from Jan-Nov 2021). The patient was initially treated with Casirivimab/Imdevimab (Regeneron) followed by dexamethasone and remdesivir for 5 and 10 days, respectively. He was discharged without supplemental oxygen but reported continued exertional dyspnea and reduced forced expiratory volume (FEV1) from baseline. Forty-five days later (early January 2022), he returned with fever, worsening shortness of breath, and productive cough. Respiratory RT-PCR was again positive for SARS-CoV-2, but given the proximity to prior infection, was initially thought to be a result of persistent viral shedding and alternative etiologies were sought. The patient was treated for hospital acquired pneumonia with piperacillin-tazobactam and vancomycin, and with methylprednisolone for acute cellular rejection. However, genotyping of the second PCR-positive specimen identified SARS-CoV-2 mutational signatures consistent with the presence of two unique VOCs. Delta (believed to be remaining from his initial infection) and Omicron BA.1 (secondary infection) were identified. Following confirmation of active COVID-19, a course of Dexamethasone and Remdesivir was recommended. With discontinued antibiotics and tapered steroids, the patient was discharged without supplemental oxygen and a FEV1 near baseline. Laboratory findings. This patient's initial SARS-CoV-2 PCR-positive specimen contained only Delta VOC sequences, while the positive specimen from the subsequent admission contained mutational signatures consistent with a mixture of both Delta and the newly emerged Omicron BA.1 VOCs. At the time of both infections, the patient had undetectable levels of nucleocapsidspecific IgG of IgM antibodies (IgMsp), often see among patient groups receiving immunosuppressive therapies. As part of his management, the patient was given monoclonal antibody therapy (casirivimab and imdevimab for Delta), resulting in very high passive Spike IgG antibody levels (>200000 AU) which quickly diminished over the months following administration. Thus, he was later given prophylactic monoclonal antibodies (tixagevimab with cilgavimab). Given the patient's immunosuppressed and coinfected status, author wanted to determine if there was any evidence of recombination between the detected VOCs. WGS revealed mutations specific to Delta and Omicron BA.1 were found on independent reads using WGS. While a total of eight fragment analysis targets are used in genotyping, only three are highlighted here to demonstrate the difference in Omicron BA.1 and Delta VOCs. ORF1A detects the 3 amino acid deletion from ORF1A: Del3675_3677. Spike recurrently deleted region (RDR)1 and 2 detect S:Del69_70 and mutations in the 140-160 amino acid range, respectively. The Delta variant has a 2 amino acid deletion in Spike region 2 (S:Del157_158), while Omicron has a 3 amino acid deletion (S:Del143_145). These data, paired with information from WGS, reveal no mutagenic signatures were identified to suggest recombination between the two lineages in this case. Patient had undetectable levels of IgMsp and IgG antibody levels (35695 AU). Later on IgG was undetectable. Immunocompromised patients can experience prolonged SARS-CoV-2 infections in the setting of a lack of protectivity immunity despite vaccination. As circulating SARS-CoV-2 strains become more heterogeneous, concomitant infection with multiple SARS-CoV-2 variants has become an increasing concern. Immunocompromised patient populations represent potential reservoirs for the emergence of novel SARSCoV-2 variants through mutagenic change or coinfection followed by recombinatory events. Identification of SARS-CoV-2 coinfections is challenging using traditional next generation sequencing pipelines; however, targeted genotyping approaches can facilitate detection. Follow-up information has been requested.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: The efficacy of a drug varies from patient to patient and can be affected by different factors, however a contributory role of the suspect drug BNT162B2 (COMIRNATY) to the reported events Drug ineffective and COVID-19 cannot be ruled out., Linked Report(s) :PFIZER INC-202201308525 Same Article/drug/event and different patient.