Age: 67.0
Sex: M
Vaccine: FLUX
Symptoms: Epstein-Barr virus infection, Epstein-Barr virus test positive, Fungal test positive, General physical health deterioration, HIV antibody negative
Clinical narrative: Acute EBV pneumonia; Acute pneumonia; Sinus tachycardia; Sepsis; Frequent premature ventricular complexes; Left basilar atelectasis; Infiltrates throughout the posterior right upper lobe, middle lobe, and posteromedial right lung base; Interstitial pulmonary edema; Positive fungal culture for Aspergillus fumigatus was later isolated; Light growth Methicillin-Resistant Staphylococcus aureus; This literature case was received on 15-Jan-2024 and concerned a 67-year-old, male patient.  The objective of this literature article was to highlight the importance of recognizing Epstein-Barr virus (EBV) as a potential cause of the severe respiratory syndrome and that it could present as a nidus for superimposed infections.   The patient's concurrent conditions included chronic obstructive pulmonary disease (COPD) and atrial fibrillation. The patient's concomitant medications included oxygen for chronic obstructive pulmonary disease, warfarin for atrial fibrillation, diltiazem for rate control, azithromycin, and ceftriaxone, for unreported indication. The patient's historical condition included remote motor vehicle accident. The patient's historical procedure included cardioversion and splenic repair/ embolization. It was also reported that the patient had two previous hospitalizations during the past few months, initially being for new onset atrial fibrillation and cardioversion and lastly being one month prior to presentation for presumed COPD exacerbation and atrial fibrillation with a rapid ventricular response. The patient was tobacco user.   On an unspecified date, the patient was vaccinated with influenza vaccine (brand not specified; dose, route of administration, anatomical location and indication: not reported). The batch number was not reported.  On an unspecified date, reported as about two weeks after receiving influenza vaccine, the patient experienced progressive shortness of breath, chills, general malaise, gradually worsening dyspnea, fever, and dry cough.  On an unspecified date, the patient visited the emergency department where the investigations included blood pressure stable at 125/76 mmHg, he was tachycardic with a heart rate of 124 bpm, febrile at 39.3 Celsius, and placed on 4L oxygen. Initial blood work was significant for elevated lactic acid of 2.7 mmol/l, aspartate transaminase/ alanine aminotransferase (AST/ALT) 71/93, units/L, white blood cell count (WBCs) of 3.8 k/uL with 9.1 % lymphocytes, low platelets of 111k/uL and an international normalized ratio (INR) of 3.4, but a negative respiratory viral panel. Electrocardiogram (EKG) showed sinus tachycardia with frequent premature ventricular complexes at a ventricular rate of 127 bpm. Physical exam was significant for expiratory wheeze and decreased air entry bilaterally. Chest x-ray and chest computed tomography (CT) scan showed left basilar atelectasis and new infiltrates throughout the posterior right upper lobe, middle lobe, and posteromedial right lung base. The patient was admitted to the hospital regular floors, and the treatment included nebulizers, diltiazem, levofloxacin at the dose of 75 mg, and prednisone at the dose of 40 mg. Presumptive diagnosis was bronchitis exacerbation with pneumonia.  On an unspecified date, reported as during the night, the patient's respiratory status worsened as he required a high-flow nasal cannula and was upgraded to the intensive care unit (ICU). The investigations included arterial blood gas that showed a pH of 7.47 with a pCO2 of 30.1 mmHg and pO2 of 78.3 mmHg. Treatment were broadened to include vancomycin and ceftriaxone with levofloxacin transitioned to azithromycin.  On an unspecified date, on the third day of admission as reported, the patient's hypoxic respiratory failure worsened, and he was intubated and placed on ventilatory support.  On an unspecified date, CT chest abdomen pelvis was repeated and revealed worsening interstitial pulmonary edema with an increase in dependent atelectasis and consolidation, especially throughout the dependent right lung, reactive mediastinal lymphadenopathy, and splenomegaly. All antibiotics were discontinued, except for azithromycin, after consulting with infectious diseases. The investigations on this date included obtaining nasopharyngeal washing swab with respiratory viral culture, and the patient's monospot test was positive, serology for Epstein-Barr virus, the EBV viral capsid antigen (VCA) IgM and EBV VCA IgG returned positive, cytomegalovirus (CMV) blood polymerase chain reaction (PCR) was negative, and HIV Ab/Ag screen was also negative. The patient's hemodynamic status worsened and he required vasopressors support, believed to be secondary to his sepsis. The echocardiogram showed an ejection of 65% with no other significant cardiac abnormalities.  On an unspecified date, on the seventh day of admission as reported, a bronchoscopy revealed a copious amount of thick tannish colored secretions with no apparent endobronchial lesions or bleeding or foreign bodies. EBV PCR of the bronchoalveolar lavage (BAL) revealed positive EBV, the analysis of bacterial cultures and fungal panel from BAL showed light growth methicillin-resistant Staphylococcus aureus and positive fungal culture for Aspergillus fumigatus was later isolated.  On an unspecified date, on the eighth day of admission as reported, the patient's condition continued to deteriorate. The patient was diagnosed with acute EBV pneumonia.  On an unspecified date, on the ninth day of admission as reported, the patient died. The causes of death were EBV infection, sinus tachycardia, 'premature ventricular contractions', 'partial atelectasis', 'lung infiltration', acute pneumonia, sepsis, 'pulmonary edema', 'Aspergillus fumigatus bronchopulmonary infection', and 'Methicillin-resistant Staphylococcus aureus infection'. It was unknown if an autopsy was performed.   The reporter did not provide a causality assessment.  All events were considered to be serious due to the seriousness criteria of hospitalization and fatal outcome. Additionally, the events of acute pneumonia, sepsis, 'pulmonary edema', 'Aspergillus fumigatus bronchopulmonary infection', and 'Methicillin-resistant Staphylococcus aureus infection' were considered to be medically significant by Physician within Seqirus' Pharmacovigilance Department.  In conclusion, severe lung involvement in the setting of acute EBV infection is an unusual complication and is rarely reported. It is unclear whether lung involvement is the result of direct viral invasion of lung tissue, or it represents an immunological reaction, which made it a diagnostic and therapeutic challenge.   The literature citation:   Company comment: The objective of this literature article was to highlight the importance of recognizing Epstein-Barr virus (EBV) as a potential cause of the severe respiratory syndrome and that it could present as a nidus for superimposed infections. A 67-year-old patient developed Epstein-Barr virus infection, acute pneumonia, sinus tachycardia, sepsis, premature ventricular contractions, left basilar atelectasis, lung infiltration, interstitial pulmonary edema, Aspergillus fumigatus bronchopulmonary infection, and methicillin-resistant Staphylococcus aureus infection more than two weeks after receiving the suspect product influenza vaccine. The patient's significant concurrent conditions included chronic obstructive pulmonary disease and atrial fibrillation. Based on underlying medical history, implausible temporal relationship, and biological implausibility, causal role of the suspect vaccine is assessed as not related.; Sender's Comments: The objective of this literature article was to highlight the importance of recognizing Epstein-Barr virus (EBV) as a potential cause of the severe respiratory syndrome and that it could present as a nidus for superimposed infections. A 67-year-old patient developed Epstein-Barr virus infection, acute pneumonia, sinus tachycardia, sepsis, premature ventricular contractions, left basilar atelectasis, lung infiltration, interstitial pulmonary edema, Aspergillus fumigatus bronchopulmonary infection, and methicillin-resistant Staphylococcus aureus infection more than two weeks after receiving the suspect product influenza vaccine. The patient's significant concurrent conditions included chronic obstructive pulmonary disease and atrial fibrillation. Based on underlying medical history, implausible temporal relationship, and biological implausibility, causal role of the suspect vaccine is assessed as not related.; Reported Cause(s) of Death: Acute EBV pneumonia; Acute pneumonia; Sinus tachycardia; Sepsis; Frequent premature ventricular complexes; Left basilar atelectasis; Infiltrates throughout the posterior right upper lobe, middle lobe, and posteromedial right lung base; Interstitial p