Capillary leak syndrome flare; Capillary leak syndrome flare; SARS-CoV-2 infection; This literature-non-study case was reported in a literature article and describes the occurrence of CAPILLARY LEAK SYNDROME (Capillary leak syndrome flare) and CONDITION AGGRAVATED (Capillary leak syndrome flare) in an 8-decade-old male patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 prophylaxis. The occurrence of additional non-serious events is detailed below.   LITERATURE REFERENCE: The patient's past medical history included Deep vein thrombosis (complication of clinical course (mid 50s)), Acute renal failure (mid-50s, oliguria), Compartment syndrome (Severe compartment syndrome of extremities in mid 50s), Syncope (Patient had weakness and had episode of syncope, four days prior to a scheduled dose of IVIG (early 70s)) in 2020, Hypotension (Patient was again hypotensive) in 2020, Influenza A virus infection (In early 2020, the patient (now in his early 70s) experienced two days of rhinorrhea, non-productive cough, and profound sweating. A nasal swab was positive for Influenza A, and he began treatment with oseltamivir), Weakness (Four days prior to a scheduled dose of IVIG, he noted weakness and had an episode of syncope), Hemoconcentration (hemoconcentrated with a hemoglobin level of 19.2 g/dl) in 2020, Hospitalization (In his mid-50s) in 2020 and Surgical intervention (in his mid-50s). Previously administered products included for Capillary leak syndrome: prednisone (100mg) in 2020, IVIG therapy (He was treated with multiple courses of IVIG therapy at a dose of 1 g/kg; his clinical course improved) in 2020, IVIG therapy (In his mid-50s and IVIG therapy at a concentration of 2 g/kg over two days every 4 weeks); for Influenza: Oseltamivir (nasal swab positive for Influenza A and began treatment with oseltamivir) in 2020. Past adverse reactions to the above products included No adverse event with IVIG therapy, IVIG therapy, Oseltamivir and prednisone. Concurrent medical conditions included Capillary leak syndrome (Initially presented in his mid-50s with the symptoms of severe hypotension, oliguria and hemoconcentration with a hemoglobin level of 23 g/dl (normal: 13.615 g/dl). The patient was later discharged and continued to have additional episodes over the next two years) and IgA MGUS (Initially presented in his mid-50s with the symptoms of severe hypotension, oliguria and hemoconcentration with a hemoglobin level of 23 g/dl (normal: 13.615 g/dl). The patient was later discharged and continued to have additional episodes over the next two years).   In 2021, the patient received third dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form. In 2021, received second dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form and first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form. On an unknown date, the patient experienced CAPILLARY LEAK SYNDROME (Capillary leak syndrome flare) (seriousness criteria hospitalization and medically significant), CONDITION AGGRAVATED (Capillary leak syndrome flare) (seriousness criteria hospitalization and medically significant) and COVID-19 (SARS-CoV-2 infection). The patient was treated with IMMUNOGLOBULINS NOS (IMMUNOGLOBULIN I.V) (intravenous) in 2021 for Capillary leak syndrome, at a dose of 1 gram per kilogram and PREDNISONE ongoing from 2021 for Capillary leak syndrome, at a dose of 60 milligram. At the time of the report, CAPILLARY LEAK SYNDROME (Capillary leak syndrome flare) and CONDITION AGGRAVATED (Capillary leak syndrome flare) was resolving and COVID-19 (SARS-CoV-2 infection) outcome was unknown.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): In 2020, Biopsy skin: Normal skin taken during the leak phase of an episode of capillary leak after influenza infection. Modest perivascular lymphocytic infiltrate localized to vessels of the superficial dermis. No significant abnormalities in vascular basement membrane zone in PAS. MXA, the surrogate type I interferon marker, was significantly upregulated in the endothelium; the staining intensity was in the +1-2/3 category. Enhanced endothelial cell staining was observed in smaller vessels, capillaries and venules throughout the dermis. C5b-9 studies also disclosed a very intense staining pattern in blood vessels throughout the dermis compatible with systemic complement pathway activation. There are three closely apposed vessels that show intense endothelial and subendothelial staining. Caspase-3, the proapoptotic marker, was also focally positive and characterized by nuclear staining of intervascular interstitial cells. In 2020, Blood albumin (Unknown-3.4 g/dL): 2.2 g/dL Low. In 2020, Hemoglobin: 19.2 g/dL hemoconcentrated (in early 70s). In 2020, Immunology test: Demonstrated that C5b-9 was positive in vessels of the mid and deeper dermis, showing granular vascular deposits localized to endothelium of capillaries, venules and arterioles; Pattern of basement membrane zone staining for immunoglobulin was likely reflective of the patient's underlying monoclonal gammopathy of IgM isotype. The patient's serum was incubated with generic endothelial cells followed by the application of fluorosceinated human anti-IgG and a positive reaction was observed. The endothelial cells exhibited a distinct oligodot nuclear staining pattern at the dilutions tested, namely 1:10 and 1:20, indicative of the presence of anti-endothelial cell antibodies. In 2020, Influenza virus test: (Positive) Positive- Influenza A. In 2021, Biopsy skin: Normal skin biopsy, Significant inflammation not seen. Basement membrane zones of the blood vessels were without reduplication, and there was no evidence of a thrombotic diathesis. Overall, significant light microscopic abnormalities were not seen and the repeat skin biopsy from late 2021 was during the recruitment phase of a mild episode of his systemic capillary leak syndrome in association with COVID-19 infection. On the repeat biopsy the type I interferon signal was essentially negative. In this image the MXA stain, the surrogate type I interferon marker, is negative. Focal microvascular deposits of C5b-9 are observed but the extent of C5b-9 is less than that noted during his more severe episode in 2020. In 2021, Hemoglobin: 17.1 g/dL hemoconcentrated. In 2021, Immunology test: Direct immunofluorescent studies showed granular deposits of IgG along the dermal epidermal junction. The staining intensity varied +1/3 to +2/3. C5b-9 was observed in endothelial cells and in a subendothelial array in deep-seated arteries and one venule. There was a predominance of CD4 T cells over those of CD8 subset with minimal staining for CD25 and Indirect immunofluorescent studies to assess for circulating anti-endothelial cell antibodies demonstrated a minimal weak staining pattern in the nucleus of endothelial cells at a dilution of 1:10; overall the assay was not conclusive for being significantly positive. In 2021, SARS-CoV-2 test: (Positive) Positive. On an unknown date, Blood albumin: 4.3 g/dL During episode free period. On an unknown date, Hemoglobin: 15 g/dL During episode free period post mid 50s hospitalization and 23 g/dL in mid 50's hospitalization.     For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter considered CAPILLARY LEAK SYNDROME (Capillary leak syndrome flare) and CONDITION AGGRAVATED (Capillary leak syndrome flare) to be related. No further causality assessment was provided for COVID-19 (SARS-CoV-2 infection).    Patient 1 in the Literature: A male patient in his 80s developed capillary leak syndrome flare after completing 3 doses of mRNA-1273 vaccine. His most recent vaccination was 4 months prior to his SARS-CoV-2 infection, confirmed with positive PCR test. History includes capillary leak syndrome, MGUS, deep vein thrombosis, acute renal failure, severe compartment syndrome of his extremities, previous influenza A infection, previous episodes of hypotension and hemoconcentration, and previous treatment with prednisone, IVIG, crystalloids, and oseltamivir. No concomitant medications were reported. On unknown date, he was clinically hypotensive and hemoconcentrated with a hemoglobin of 17.1g/dL, had marked edema in his thighs but no signs of acute compartment syndrome. Patient was admitted and treatments with IVIG and prednisone were started, which improved his condition on the 1st hospital day. A normal skin biopsy was obtained, and a 2nd biopsy during the recruitment phase of a mild episode of his systemic capillary leak syndrome in association with COVID-19 infection was warranted. Type I interferon signal was essentially negative on repeat biopsy. Focal microvascular deposits of C5b-9 are observed but the extent of C5b-9 is less than that noted during his more severe episode in 2020. Direct immunofluorescent studies showed granular deposits of IgG along the dermal epidermal junction. Indirect immunofluorescent studies showed minimal weak staining pattern of nucleus of endothelial cells.   The authors considered a positive treatment effect based on the lesser C5b-9 staining in the repeat biopsy, the minimal to absent type I interferon signaling, and negative anti-endothelial cell antibody despite significant triggers in the context of COVID-19 vaccination and COVID-19 infection.  Company Comment: This literature non-study case concerns an elderly (8 decades), male patient of unknown age with relevant history of capillary leak syndrome, MGUS, deep vein thrombosis, acute renal failure, severe compartment syndrome of his extremities, previous influenza A infection, and previous episodes of hypotension and hemoconcentration, who experienced an unexpected, medically significant event of Capillary leak syndrome aggravated after completing 3 doses of mRNA-1273 vaccine that led to hospitalization. His most recent dose was 4 months prior to his SARS-CoV-2 infection. He developed rhinorrhea and dry cough, and subsequently tested positive with SARS-CoV-2 PCR test. On unknown date, he was clinically hypotensive and hemoconcentrated with a hemoglobin of 17.1g/dL, had marked edema in his thighs but no signs of acute compartment syndrome. He was admitted. His condition improved after IVIG and prednisone treatment on the 1st hospital day. A normal skin biopsy was obtained, and a 2nd skin biopsy during the recruitment phase of a mild episode of his systemic capillary leak syndrome in association with COVID-19 infection was warranted as relatively mild symptoms occurred. Repeat biopsy showed supportive features of recurrent capillary leak syndrome given the extent of vascular C5b-9 deposition and negative type I interferon signal. Direct immunofluorescent (IF) showed deposits of IgG along the epidermal junction and Indirect IF showed a weak minimal staining pattern in the nucleus of endothelial cells. The authors considered a positive treatment effect based on the lesser C5b-9 staining in the repeat biopsy, the minimal to absent type I interferon signaling, and negative anti-endothelial cell antibody.  Patient's multiple comorbidities and current SARS-CoV-2 infection remain as confounders in this case. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report. Event's seriousness per medical judgement. Sender's Comments: This literature non-study case concerns an elderly (8 decades), male patient of unknown age with relevant history of capillary leak syndrome, MGUS, deep vein thrombosis, acute renal failure, severe compartment syndrome of his extremities, previous influenza A infection, and previous episodes of hypotension and hemoconcentration, who experienced an unexpected, medically significant event of Capillary leak syndrome aggravated after completing 3 doses of mRNA-1273 vaccine that led to hospitalization. His most recent dose was 4 months prior to his SARS-CoV-2 infection. He developed rhinorrhea and dry cough, and subsequently tested positive with SARS-CoV-2 PCR test. On unknown date, he was clinically hypotensive and hemoconcentrated with a hemoglobin of 17.1g/dL, had marked edema in his thighs but no signs of acute compartment syndrome. He was admitted. His condition improved after IVIG and prednisone treatment on the 1st hospital day. A normal skin biopsy was obtained, and a 2nd skin biopsy during the recruitment phase of a mild episode of his systemic capillary leak syndrome in association with COVID-19 infection was warranted as relatively mild symptoms occurred. Repeat biopsy showed supportive features of recurrent capillary leak syndrome given the extent of vascular C5b-9 deposition and negative type I interferon signal. Direct immunofluorescent (IF) showed deposits of IgG along the epidermal junction and Indirect IF showed a weak minimal staining pattern in the nucleus of endothelial cells. The authors considered a positive treatment effect based on the lesser C5b-9 staining in the repeat biopsy, the minimal to absent type I interferon signaling, and negative anti-endothelial cell antibody.  Patient's multiple comorbidities and current SARS-CoV-2 infection remain as confounders in this case. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report. Event's seriousness per medical judgement.