She tested positive for SARS-CoV-2; She tested positive for SARS-CoV-2; COVID-19 pneumonitis; severe sepsis; positive for aspergillus/ Galactomannan serum antigen was positive; This is a literature report.  A 63-year-old female with COPD, rheumatoid arthritis on abatacept, prednisone, & methotrexate (MTX), and Sweet syndrome presented to the ED (emergency department) with acute non-exertional chest pain, palpitations, and dyspnea at rest. She denied fevers or chills but reported diarrhea and vomiting. She had no history of or exposure to COVID-19 and had completed her 2-dose mRNA SARS-CoV-2 vaccination 45 days prior. On presentation she was in respiratory distress, hypotensive, tachycardic, and tachypneic. She was saturating at 86% on room air, requiring supplemental O2. Physical exam was significant for scattered bilateral wheezes. CBC showed no leukocytosis. CRP was elevated. Lactic acid, ferritin and LDH were within normal limits. Ddimer was higher than the age-adjusted cutoff; CTA of the chest revealed no PE but showed bilateral ground glass opacities with consolidations. She tested positive for SARS-CoV-2. She was admitted for severe sepsis from COVID-19 pneumonitis and started on dexamethasone and remdesivir. SARS-CoV-2 IgG antibodies were positive. Given her immunocompromised status, bronchoscopy with BAL was performed and revealed copious thick secretions. Gram stain and bronchial brushings were negative for bacterial etiologies. Lavage culture was positive for aspergillus antigen and cytology revealed markedly enlarged reactive cells. Galactomannan serum antigen was positive. She was discharged on day 9 with a prolonged course of voriconazole. She had residual dyspnea on exertion but did not require supplemental O2. A nasal swab to test for variant strains was still pending. DISCUSSION: The COVID vaccine proved effective in preventing severe COVID-19 infections but trials excluded immunocompromised patients. This case of infection despite vaccination and detectable IgG titers reveals suboptimal protection. From data on pre-existing vaccines in immunocompromised patients, MTX is known to reduce immunogenicity. Our patient remained on immunosuppressants after vaccination, which may have contributed to her subsequent viral and fungal infections. Rheumatology guidelines suggest holding MTX for one to two weeks after vaccination to improve vaccine response. Employing this strategy will maximize immunogenicity against SARS-CoV-2 in immunocompromised patients. CONCLUSIONS: Recommends vaccinating patients with rheumatological conditions against SARS-CoV-2. This case highlights individual patient factors to consider in the battle against COVID-19 in immunosuppressed patients. Non-viral infections must also be considered despite the ongoing pandemic. Determining protective antibody titers can guide booster vaccine recommendations.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; 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 , COVID-19 pneumonia, Sepsis , Aspergillus test positive cannot be completely excluded. The impact of this report on the benefit-risk profile of the Pfizer product and on the conduct of the study is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, ethics committees, and investigators, as appropriate.