The patient was a 54-year-old man with a history of type 2 diabetes controlled without medication. He had no known immunodeficiency or past episodes of recurrent infections. He did not smoke or consume alcohol. He had not received vaccination for either COVID-19 or N. meningitidis. He had no known sick contact within the last few months. The patient had no recent trauma.
In August 2021, he developed fever and cough (herein after referred to as day 1). On day 2, a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 by reverse transcription-polymerase chain reaction (PCR) returned positive. On day 4, he developed dyspnea and was admitted to a nearby hospital. He was hypoxic on admission, and he received supplemental oxygen and was started on intravenous dexamethasone 6.6 mg once daily and intravenous remdesivir 100 mg once daily (first dose: 200 mg). Despite treatment, respiratory failure deteriorated. On day 7, the patient was transferred to our hospital for further treatment.
On presentation, he was alert, afebrile with a body temperature of 36.8 C, tachypneic with a respiratory rate of 28/min, and had an oxygen saturation of 93 % with a 10-L/min non-rebreathing mask. He complained of severe cough with excess purulent sputum, which was considered an atypical presentation of COVID-19. He had no headache on admission or during the clinical course. Respiratory investigation revealed diffuse bilateral coarse crackles. Physical examination was otherwise normal. Abnormal skin lesions or neck stiffness were not observed. Blood pressure was 171/109 mmHg and pulse rate was 85 beats/min. Laboratory tests showed lymphopenia with an absolute lymphocyte count of 241/muL (reference range (RR), 1000-4800/muL), normal level of leukocytes (4300/muL; RR, 3100-8400/muL), elevated D-Dimer level of 1.4 mug/mL (RR < 1.0 mug/mL), elevated lactate dehydrogenase level of 472 IU/L (RR 124-222 IU/L), elevated C-reactive protein level of 5.63 mg/dL (RR < 0.3 mg/dL), and elevated ferritin level of 360.0 ng/mL (RR < 160 ng/mL). Chest X-ray showed bilateral consolidation.
The patient was intubated and treated with neuromuscular blockade and prone positioning. He received dexamethasone for 10 days and remdesivir for 5 days. He developed a new onset of fever on day 8, and respiratory failure deteriorated from day 8 to day 10. Elevated leukocytes (10,300/muL, RR 3100-8400/muL) and C-reactive protein level (14.59 mg/dL, RR < 0.3 mg/dL) were detected on day 10. A large amount of purulent sputum was noted; a sputum sample was collected for Gram staining and culture. Gram staining results (Fig. 1) revealed a large number of gram-negative diplococci phagocytosed by numerous neutrophils. No other pathogen was detected upon Gram staining. Based on the Gram staining findings and the clinical course, bacterial pneumonia was diagnosed, and intravenous cefepime (1 g every 8 h) was initiated. The culture was dominated by gram-negative diplococci, identified as N. meningitidis by the ID-test HN-20 Rapid system (Nissui, Tokyo, Japan). The blood culture results were negative. Antimicrobial drug susceptibility tests for N. meningitidis were performed using the Etest (bioMerieux, Lyon, France). Antimicrobial susceptibility was interpreted according to the guidelines of the European Committee on Antimicrobial Susceptibility Testing. The isolate was susceptible to ceftriaxone (minimal inhibitory concentration [MIC] < 0.016 mug/mL), minocycline (MIC = 0.064 mug/mL), chloramphenicol (MIC = 0.50 mug/mL, and meropenem (MIC = 0.016 mug/mL), and was resistant to benzylpenicillin (MIC = 0.25 mug/mL) and ciprofloxacin (MIC = 0.125 mug/mL). Based on the sputum culture and Gram staining results, N. meningitidis pneumonia was diagnosed. Antibiotic treatment was switched to intravenous ceftriaxone (2 g every 24 h) on day 14 and was administered for 6 days.
A sample was sent to the Tokyo Metropolitan Institute of Public Health for further testing. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI Biotyper; Bruker Daltonics Inc., Billerica, MA, USA) detected N. meningitidis. Typing was performed for serogroups A, B, C, W, and Y by PCR, which were all negative. The PCR to detect the phytoene synthase gene (ctrB) was also negative. Owing to the lack of crtB, it was typed as non-serogroupable. Multilocus sequence typing was performed according to the protocols on the Public databases for molecular typing and microbial genome diversity (PubMLST) website (https://pubmlst.org). The sequence type was assigned as ST-11026, a member of the ST-32 complex.
His clinical course improved gradually, and the patient was extubated on day 15. Fever and purulent sputum resolved on day 16, and the patient remained afebrile for the rest of the hospital course. Potential immunodeficiency was considered, and testing was performed. The human immunodeficiency virus test results were negative. Complement C3 and C4, and CH50 values tested on day 13 were normal. On day 25, the patient was transferred to another hospital for rehabilitation.