Sex: F
Vaccine: VARZOS
Symptoms: Gomori methenamine silver stain, Gram stain negative, Haematocrit decreased, Haemoglobin decreased, Hypersensitivity pneumonitis
Clinical narrative: Cryptogenic organizing pneumonia/ acute organizing pneumonia; Bilateral interstitial pneumonitis; Shortness of breath; Low grade fever; Bilateral peripheral infiltrates/ bilateral peripheral ground glass infiltrates; Bilateral peripheral ground-glass opacities; Trans-bronchial biopsies showed acute and chronic inflammation; This case was reported in a literature article and described the occurrence of cryptogenic organizing pneumonia in a 67-year-old female patient who received Herpes zoster (Shingles vaccine) for prophylaxis.  The patient's past medical history included diverticulitis (the patient's surgical history was significant for diverticulitis status post partial colectomy and status post hysterectomy), colectomy partial, hysterectomy, covid-19 (about eight months ago prior to this presentation) and ex-smoker (smoked for about 15 years but quit about six months prior to presentation). Previously administered products included Moderna vaccine (was fully vaccinated with the Moderna vaccine four months prior to the presentation). Concurrent medical conditions included hypertension, hyperlipidemia and coronary artery disease. Concomitant products included acetylsalicylic acid (Aspirin), citalopram, iron, hydrochlorothiazide, levothyroxine sodium (Synthroid), vitamins nos (Multivitamin), olmesartan medoxomil (Benicar), bupropion hydrochloride (Wellbutrin Xl), icosapent (Vascepa) and bifidobacterium infantis (Align).   On an unknown date, the patient received Shingles vaccine. On an unknown date, between 1 and 2 weeks after receiving Shingles vaccine, the patient experienced cryptogenic organizing pneumonia (serious criteria hospitalization and GSK medically significant), interstitial pneumonitis (serious criteria hospitalization and GSK medically significant), shortness of breath (serious criteria hospitalization), low grade fever (serious criteria hospitalization), bilateral pulmonary infiltrates (serious criteria hospitalization), lung opacity (serious criteria hospitalization) and lung inflammation (serious criteria hospitalization). The patient was treated with prednisone. On an unknown date, the outcome of the cryptogenic organizing pneumonia, shortness of breath, low grade fever, lung opacity and lung inflammation were unknown and the outcome of the interstitial pneumonitis and bilateral pulmonary infiltrates were recovered/resolved.   The reporter considered the cryptogenic organizing pneumonia, interstitial pneumonitis, shortness of breath, low grade fever, bilateral pulmonary infiltrates, lung opacity and lung inflammation to be related to Shingles vaccine.  Additional information was provided as follows: This case was reported in a literature article and described occurrence of Organizing Pneumonia, in a 67 years old female patient, who was vaccinated with unspecified Shingles vaccine (Manufacturer unknown) for prophylaxis.  The patient's past medical history was significant for coronary artery disease, hypertension and hyperlipidemia. The patient's surgical history was significant for diverticulitis status post partial colectomy and status post hysterectomy. The patient had COVID-19 about eight months ago prior to this presentation. The patient had no pulmonary symptoms at that time and did not require any hospitalization and recovered fully. The patient was fully vaccinated with the Moderna vaccine four months prior to the presentation. The patient smoked for about 15 years but quit about six months prior to presentation. The patient's home medications included aspirin, citalopram, iron, hydrochlorothiazide, Synthroid, multivitamin, Olmesartan (Benicar), bupropion (Wellbutrin XL), icosapent ethyl (Vascepa), and Align (probiotic). The patient had no known prior lung disease. No information on patient's family history or current condition was provided. On an unspecified date, about 4 weeks prior to presentation, the patient received unspecified Shingles vaccine (Route and site of administration unspecified; batch number not provided, dosage unknown). The age at vaccination was not provided. On an unspecified date, about 4 weeks after the vaccination, the patient presented to the hospital with shortness of breath of over two to three weeks prior to hospitalization. The patient stated that, since receiving VZV (Varicella zoster vaccine) vaccine, the patient started getting progressive shortness of breath and had constitutional symptoms with low-grade fever. The patient's chest X-ray and CT scans in the emergency room showed bilateral pathy peripheral infiltrates and bilateral peripheral ground-glass opacities respectively. On physical examination, the patient's temperature was 35.9-degree Celsius, and oxygen saturation was 93%. Other vital signs were normal. The physical examination was normal. The patient's lungs were clear to auscultation and there was no evidence of any skin rashes. Laboratory data included a WBC count of 14,800, 88% neutrophils, 4% bands, 6% lymphocytes and 5.8% eosinophils. Hemoglobin and hematocrit were 11.1 g/dL and 30.6% respectively, Platelet count was 542,000, lactic acid was 0.5, and procalcitonin level was less than 0.05, CRP was less than 5. The patient's nasopharyngeal swab for COVID-PCR test on two occasions was negative. Sedimentation rate was 80. Rheumatoid factor was less than 10. ANA was slightly positive at 40, which was nonspecific. The IgE level was 5.5. Arterial blood gas showed a pH of 7.51 with pCO2 of 31, PaO2 of 51 and O2 saturation of 86% on room air. COVID-19 antibody titers were positive at 106 AU/mL due to a prior COVID-19 infection eight months ago. Chest X-ray and CT scans showed bilateral peripheral ground glass infiltrates. The differential diagnosis included acute or chronic eosinophil pneumonia, cryptogenic organizing pneumonia (COP), COVID-19-related acute or chronic interstitial pneumonitis, chronic interstitial lung disease and hypersensitivity pneumonitis. The patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and trans-bronchial biopsies (TBBx). BAL showed 3% epithelial cells, 40% macrophages, 40% neutrophils, 0% lymphocytes and only 12% eosinophils. TBBx showed acute and chronic inflammation as well as alveolar spaces filled with young fibroblast consistent with organizing pneumonia. The findings were consistent with acute organizing pneumonia. GMS and PAS stains were negative for any fungi. AFB stains were also negative. Cytology was negative for any malignant cells. A diagnosis of acute organizing pneumonia due to the varicella-zoster virus vaccine was made based on the temporal relationship, laboratory data, and bronchoscopy findings. The patient was started on oral prednisone. A follow-up CT scan after 12 weeks of prednisone therapy showed complete resolution of bilateral interstitial pneumonitis. Chest X-ray following therapy showing complete clearing of bilateral infiltrates. This case has been considered as serious due to hospitalization. Treatment was unknown. Outcome of the event was not reported. The authors commented, "Our patient is a 67-year-old female with no known prior lung disease who presented with progressive onset of shortness of breath for about two to three weeks in duration. Her chest X-ray and CT scan showed bilateral pulmonary infiltrates with ground-glass appearance and peripheral distribution. The patient underwent extensive evaluation. Nasopharyngeal swab for COVID-19 by PCR was negative twice. Her CRP level was also normal. Given the negative COVID-19 PCR at the time of presentation as well as normal CRP levels, it was highly unlikely that she had acute COVID-19 pneumonia. Post-COVID-19 interstitial lung disease was also felt unlikely especially since her current illness started eight months after she had the COVID-19. She did not have any pulmonary symptoms at the time of her COVID-19 infection. The patient denied any history of exposure to any chemicals, irritants, or any other noxious stimulus to suggest any form of hypersensitivity pneumonitis. The possibility of acute versus chronic eosinophilic pneumonia was also raised given the 5.8% eosinophils in the peripheral blood. However, BAL only showed 12% eosinophils. Eosinophils greater than 25% in BAL are required for the diagnosis of acute or chronic eosinophilic pneumonia. TBBx did not show any eosinophilic infiltration or granulomas to suggest eosinophilic pneumonia or hypersensitivity pneumonitis. GMS and PAS stains were negative for any fungi. AFB stains were also negative. Cytology was negative for any malignant. TBBx showed acute and chronic inflammations as well as alveolar spaces filled with young fibroblasts. These findings were highly consistent with a diagnosis of acute organizing pneumonia. Recombinant zoster vaccine (RZV) is designed to restore both cell- and humoral-mediated immunity. The formulation is a combination of glycoprotein E (gE) along with a liposomal-based adjuvant called AS01. This combination consistently enhances T-cell responses in addition to antibody production. The most common side effects include injection site reactions such as pain, redness, and swelling. Systemic side effects include myalgia, fever, headache, shivering, fatigue, and gastrointestinal symptoms. A 10-year review of post-marketing safety experience showed that 93% of adverse reactions were nonserious. Injection site reactions were the most reported adverse experience. Most of the adverse reactions were reported within two weeks of vaccination. The exact mechanism of action for acute lung injury following VZV vaccination is not known. We believe that it may be due to an exaggerated immune response. Adjuvants themselves do not mount an immune response, but they help in the production of an intense response against inoculated antigens. This helps in reducing frequency and dosing to attain acquired preventive immunity. The adjuvant used in VZV vaccination is AS01, which could have caused an exaggerated immune response, causing an acute lung injury that leads to organizing pneumonia".  The authors concluded, "Recombinant zoster vaccine (RZV) is generally safe and more than 90% effective in preventing the reactivation of herpes zoster in older age. The majority of the side effects are mild at the site of local injection or systemic, such as low-grade fever, myalgias or fatigue. These side effects normally abate by seven days. Secondary organizing pneumonia as described in our case report is the first serious pulmonary side effect of vaccination. Onset was insidious with symptoms starting within one to two weeks of vaccination and progressing over the next three to four weeks. The pathology findings revealed organizing pneumonia, and symptoms completely resolved after treatment. It is felt that this could be a hyperimmune response to the adjuvants used in the vaccine". The article corresponding to this case is not available for regulatory submission due to copyright restriction.