SARS-CoV-2 positive; SARS-CoV-2 positive; This is a literature report.  The authors present delta variant vaccine breakthrough cases in a father and son, with hospitalization of the father, which occurred despite a high level of IgG detected in the patient's serum, and resolution of symptoms within 24 hours following monoclonal antibody (mAb) therapy. A 63-year-old man (Patient A) with a history of mild hypertension, benign prostatic hypertrophy, and a body mass index of 27, was found to be SARS-CoV-2 positive by reverse transcription polymerase chain reaction (RT-PCR) on 03Jun2021. His 25-year-old son (Patient B), whom he had seen the previous weekend, had developed upper respiratory symptoms and headaches 6 days earlier, and also had a SARS-CoV-2 positive PCR on 03Jun2021. Although Patient A was asymptomatic at the time of testing, he developed nasal congestion, headache, and a dry cough the following day. These symptoms became more pronounced over the next few days and were associated with extreme fatigue and lassitude. His partial oxygen saturation (SPO2) was consistently above 98% by self-monitoring, except for a transient drop to 95%. Both patients had previously received two doses of COVID-19 vaccine BNT162B2 (Pfizer-BioNTech, Lot numbers: EM9810, EN6207) 22 days apart in Mar2021 and Apr2021. After 4 days of symptoms following his diagnosis, Patient A presented to hospital. His vital signs were stable, and he was afebrile. A SARS-CoV-2 IgG semi-quantitative anti-spike protein antibody was a strong positive at 178 AU/ml (negative less than 5AU/ml), suggesting a strong immune response to the vaccine. He received mAb infusion (bamlanivimab/etesevimab) and was discharged. He reported feeling a returned sense of well-being with complete resolution of symptoms by the next morning. The close contacts of both patients remained asymptomatic and were negative by repeat SARS CoV-2 PCR testing. The SARS-CoV-2 positive clinical specimens (nasopharyngeal swabs) were further tested by RT-PCR and next-generation sequencing (NGS). COVID-DX software (Biotia) was used to detect genetic variants, define PANGO lineage, and assess clade-level phylogenetic analysis. NGS testing of Patient A identified the B.1.617.2 lineage with 35 mutations detected, including 9 in the spike protein. Patient B had a similar phylogenetic and variant profile to Patient A (B.1.617.2 lineage, with 7/12 shared S-gene mutations). Notably, the authors detected two spike protein deletions in Patient A that were not present in-Patient B [H69_V70del (ATACATG21764A) and Y145del (TTTA21990T)]. Phylogenetic analysis and SARS-CoV-2 viral genome coverage with genetic variants of Patient A. NGS using NEBNext ARTIC SARS-CoV-2 FS Library Prep Kit and Illumina NextSeq 550 platform resulted in 3.4 million reads (with 99% coverage of the genome at 10X depth, 4880x mean target coverage). RT-PCR (N1) prior to NGS testing resulted in the following cycle threshold (Ct) values: 31.3 (Patient A) and 25.2 (Patient B). The clinical sample was identified as B.1.617.2 lineage (clade 20A). The phylogenetic tree was generated using COVID-DX and Nextclade (version 4-22-2021). The plot showed the depth of sequencing that was recovered across the genome. The authors detected 35 mutations, including 12 ORF1ab, 9 spike protein, and 3 nucleocapsid genes in reference to the Wuhan wild-type strain (NC_045512.2). The spike protein mutations include: C21618G (T19R), ATACATG21764A (H69_V70del), TTTA21990T (Y145del), T22917G (L452R), C22995A (T478K), A23403G (D614G), C23604G (P681R), A24783G (N1074S), G25352T (V1264L). The percent of the SARS-CoV-2 genome recovered from the sample and genetic variants identified compared to the reference genome (Wuhan wild-type strain) are indicated (top) with no coverage (pink), and higher callable coverage (blue) shown. The proportion of known genetic variants of SARS-CoV-2 strains as reported from across the world. The patients provided informed consent to provide specimen and clinical metadata, and the samples were processed. Interestingly, the two vaccine breakthroughs in the same family with similar variant profiles of the SARS-CoV-2 virus may be related to host genetics or the specific mutations of a shared virus. At hospitalization, the patient described no fever, no loss of smell or taste, and no shortness of breath, presenting a clinical picture related to Delta variant cases. Despite his SARS CoV-2 IgG being strongly positive, he was treated with mAb (bamlanivimab/etesevimab) and his symptoms resolved quickly. The mAb therapy potentially influenced the patient's clinical course as within 12 hours of receiving this therapy the patient got better and within 24 hours, he was completely free of all symptoms he had been suffering within the previous three days. Genomic surveillance of novel variants in SARS-CoV-2 positive cases, especially vaccine breakthrough cases, as well as collection of related clinical metadata and therapeutic outcomes, will be necessary to fight the virus as it continues to evolve.; Sender's Comments: Based on the information provided, known drug safety profile and plausible temporal association, the causality between BNT162B2 and the Vaccination failure , COVID-19 cannot be completely excluded.,Linked Report(s) : PFIZER INC-202101382355 Same article/drug/event; different patients