Coronavirus Disease 2019 Vaccine-Induced Flare-Up of Severe Bronchial Asthma Previously Controlled With Dupilumab: A Case Report.

The widespread after-effects of the coronavirus disease 2019 (COVID-19) are still a grave threat worldwide. Among them are adverse reactions to vaccines, including those most observed following Pfizer-BioNTech (BNT162b2) vaccine administration, namely, local reactions at the injection site, fatigue, headache, myalgia, chills, arthralgia, and fever. Patients with asthma particularly present with unique adverse reactions to the BNT162b2 vaccine, notably, an exacerbation in their asthma symptoms as highlighted through the current case report. In this case, a 50-year-old woman had been undergoing treatment for bronchial asthma in the form of inhalation steroids and dupilumab, as well as systemic steroid prednisolone as maintenance therapy. She had mild injection site reactions after her first three COVID-19 vaccinations. She also experienced acute exacerbation requiring hospitalization after the fourth and fifth doses. Her symptoms resolved following steroid therapy. The close association between the timing of vaccinations and the onset of clinical symptoms suggests that the exacerbation episodes were triggered by the vaccine. Therefore, although the BNT162b2 vaccine is safe to administer in patients with bronchial asthma, cases reporting patients sensitized to the BNT162b2 vaccine developing bronchial asthma or experiencing asthma exacerbations should not be neglected. Clinicians should be aware of the possibility of flare-ups induced by repeated COVID-19 vaccinations in such patients.

Development of a new HISCL automated CXCL9 immunoassay.

C-X-C motif chemokine ligand 9 (CXCL9), a candidate biomarker, reflects type 1 (T1) inflammation pathology. Here, we report the analytical performance and clinical characteristics of a new CXCL9 reagent for a fully automated immunoassay device. We evaluated the limits of blank, detection, and quantitation (LoQ) along with other efficacy parameters, and the ability of the assay to report patient health, COVID-19 status, and the presence of asthma and/or interstitial lung diseases (ILDs). The coefficient of variation for 5-day total precision using two instruments was 7% across two controls, serum, and plasma panels. LoQ of 2.2 pg/mL suggested the efficacy of the assay in detecting T1 inflammation in plasma or serum; no cross-reactivity or interference was observed. We identified high serum CXCL9 levels in samples from patients with acute COVID-19 infections (n = 57), chronic bird-related hypersensitivity pneumonitis (n = 61), asthma (n = 194), and ILDs (n = 84) compared to healthy individuals (< 39.0 pg/mL). Furthermore, CXCL9 levels increased with age in asthma patients, and an opposite trend was observed for T2 inflammatory factors. These results suggest the utility of the automated CXCL9 immunoassay for measuring CXCL9 in clinical samples and reflect its role in T1 inflammation.

Cytokine release syndrome in a patient with non-small cell lung cancer on ipilimumab and nivolumab maintenance therapy after vaccination with the mRNA-1273 vaccine: a case report.

Background: Cytokine release syndrome (CRS) is caused by the release of inflammatory cytokines that appear during or immediately after administration of a therapeutic antibody and can cause a variety of symptoms. COVID-19 vaccination is effective in cancer patients and prevents breakthrough infections. The safety of vaccines during immune checkpoint inhibitor (ICI) therapy has been reported; however, multiple vaccinations have been developed in recent years, and it is unclear whether repeated vaccinations play a role in the development of CRS in patients receiving ICI. Case Description: A 55-year-old man with stage IV non-small cell lung cancer received ipilimumab and nivolumab maintenance therapy; adverse reactions during the first and second COVID-19 vaccinations (BNT162b2) included injection site pain and slight fever; however, the day after the third COVID-19 vaccination (mRNA-1273), he developed a high fever and lost consciousness. Brain MRI showed parietal meningitis. Cytokine levels (IL-6, sIL-2R, IL-10, IFN-γ) were elevated and Grade 2 liver and renal dysfunction were also observed. As various tests ruled out infection and a PCR test for SARS-CoV-2 was negative, a diagnosis of CRS due to COVID-19 vaccination was made. After steroid therapy, his symptoms improved dramatically. Conclusions: In this case, there was a close association between the time course after vaccination and clinical symptoms of high fever and lost consciousness. Clinicians should be aware of the possibility of vaccine-induced adverse effects such as CRS.

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum ß-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated ß-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

Lung squamous cell carcinoma with hemoptysis after vaccination with tozinameran (BNT162b2, Pfizer-BioNTech).

A 66-year-old man with squamous cell carcinoma had been receiving chemoradiation therapy after stereotactic radiotherapy for brain metastases. Atezolizumab was initiated as second-line therapy, after which the patient became progression- and recurrence-free. Four days after his second dose of tozinameran (BNT162b2, Pfizer-BioNTech), the patient developed persistent hemoptysis. The patient had no thrombocytopenia or coagulation abnormalities. Bronchoscopy revealed active bleeding from the left lingual tracheal branch. The patient was intubated and admitted to the intensive care unit because of increased bleeding. Subsequently, left bronchial artery embolization was performed using a Serescue. Hemostasis was achieved after the procedure, and the patient was discharged 7 days after the onset of hemoptysis. Vaccination against coronavirus disease has been reported to be associated with thrombosis and cerebral hemorrhage, and the hemoptysis in this case was suspected to be induced by vaccination. In summary, the benefits of vaccination exceeded the risks of adverse events in a patient with cancer. However, in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, patients should be carefully monitored for hemorrhagic events after vaccination.

Invasive pneumococcal disease affected the fatal outcome in a COVID-19 patient.

A 68-year-old man experienced fever and cough and was referred to a hospital for day 4. He had a positive reverse transcription-polymerase chain reaction result for severe acute respiratory syndrome coronavirus-2. On day 12, his PaO2/FiO2 ratio worsened to 120 and he was transferred to Sapporo Medical University Hospital for treatment using extracorporeal membrane oxygenation. Venous blood cultures were positive for Streptococcus pneumoniae, which were serotype 3, mucoid-type, and penicillin susceptible. Coinfections with coronavirus disease-2019 and invasive pneumococcal disease are rare; however, they are associated with a higher case fatality than either of the conditions manifesting alone.

Characteristics of COVID-19 patients admitted into two hospitals in sapporo, Japan: Analyses and insights from two outbreak waves.

BACKGROUND: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks. METHODS: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories. RESULTS: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old. CONCLUSIONS: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic.

Acute eosinophilic pneumonia accompanied with COVID-19: a case report.

We report a case of acute eosinophilic pneumonia (AEP) triggered by coronavirus disease 2019 (COVID-19) infection. A 77-year-old man experienced left-sided chest pain and shortness of breath. Reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) revealed a positive result, and he was treated with favipiravir, ciclesonide, and lascufloxacin, but he showed poor improvement. On the other hand, computed tomography (CT) images were atypical for COVID-19 infection, and the elevation of eosinophil was found in blood and the fluid obtained by bronchoscopy. So, we clinically diagnosed this case as AEP. Administration of prednisolone dramatically improved the patient's clinical condition and chest radiograph findings, which were consistent with the clinical course of AEP. This case suggests the importance of considering the complications of AEP when treating patients with COVID-19 infection.