Pre-Vaccination Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Seroprevalence in Workers at Three Japanese Hospitals.

BACKGROUND: Antibody testing is essential for accurately estimating the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to investigate the influence of background factors on seroprevalence by testing for anti-SARS-CoV-2 antibodies in blood samples obtained from the staff of three hospitals. METHODS: This cross-sectional observational study was conducted from June 8 to July 4, 2020, as part of a mandatory health examination. Leftover blood samples collected during the health examinations at each hospital were used to test for the presence of anti-SARS-CoV-2 antibodies. The Elecsys Anti-SARS-CoV-2 RUO assay was used for antibody detection. The relationship between staff age, gender, body mass index, blood pressure, work environments with different exposure risks, place of residence, and campus location and seroprevalence was investigated. The data were anonymized prior to analysis. RESULTS: A total of 3,677 individuals were included in the study, comprising 2,554 females (69.5%) and 1,123 males (30.5%). Anti-SARS-CoV-2 antibody (immunoglobulin G) was detected in 13 participants (0.35%). Seroprevalence was slightly higher in males than females (0.62% vs. 0.23%, P=0.08). By occupation, anti-SARS-CoV-2 antibodies were found in 6 (0.75%) physicians, 6 (0.31%) nurses, and one individual (0.11%) in the medical personnel group, with slightly higher levels in physicians. No significant difference was noted in the seroprevalence in terms of all background factors. CONCLUSIONS: Our study shows that the background factors do not impact seropositivity rates. Thorough daily infection control and adherence to recommended health guidelines were found to reduce infection risk.

Evaluation of a carbapenem antimicrobial stewardship program and clinical outcomes in a Japanese hospital.

INTRODUCTION: Microorganisms can evolve and become resistant to antimicrobials, and this is known as antimicrobial resistance (AMR). Inappropriate use of antibiotics contributes to AMR, and antimicrobial stewardship programs have been developed to mitigate AMR. The Appropriate Use of Carbapenems Program was implemented in March 2019 in a university hospital and its effect was evaluated. METHODS: We conducted a prospective audit and feedback on carbapenems at the time of prescription daily. Additionally, we compared a monthly survey of the total days of therapy (DOTs) per 1000 patient-days for carbapenems, piperacillin/tazobactam, and fluoroquinolones. The susceptibility of Pseudomonas aeruginosa to meropenem, piperacillin/tazobactam, and levofloxacin was tested before (January 2018 to February 2019) and after (March 2019 to December 2020) the intervention. RESULTS: The monthly median DOTs of carbapenem usage decreased after the intervention; carbapenem use immediately declined during the intervention period. The monthly median DOTs of piperacillin/tazobactam and fluoroquinolones also decreased and continued to decline significantly after the intervention. Susceptibility of P. aeruginosa to meropenem, piperacillin/tazobactam, and levofloxacin did not change significantly during the study. CONCLUSION: The implementation of the Appropriate Use of Carbapenems Program was effective in reducing the use of broad-spectrum antibiotics and maintaining the antibiotic susceptibility of P. aeruginosa.

A patient with Castleman's disease initially manifesting symmetrical synovitis with pitting oedema.

Castleman's disease (CD), especially multicentric CD (MCD) has been known to manifest a variety of clinical features such as fatigue, anaemia, fever, and hypergammaglobulinaemia. Here, we report a 72-year-old female patient who had complicated severe synovitis, as an initial manifestation of the disease, lastly diagnosed as MCD. Initially, she had been diagnosed as remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome because of bilateral leg pitting oedema with significant C-reactive protein and matrix metalloproteinase-3 elevation but no disease-specific autoantibodies. Promptly, corticosteroid and additionally weekly methotrexate were introduced, but her leg oedema and inflammatory findings did not adequately come to be a remission. A lymph node biopsy from the groin region was performed because multiple lymph node swelling in ultrasound examination appeared even after introducing treatments, which revealed mixed-type CD. Multiple lymphadenopathies were observed in the axilla and inguinal region; finally, we diagnosed her as idiopathic MCD and introduced tocilizumab, which significantly improved leg oedema as well as inflammatory findings. As is shown in this case, manifestations included in RS3PE syndrome could be one of the clinical phenotypes in MCD, which should be considered as a differential diagnosis of MCD.

A case of anti-MDA5 antibody-positive dermatomyositis developing reversible cerebral vasospasm syndrome successfully treated by multi-immunosuppressant combination including mycophenolate mofetil.

A 39-year-old woman admitted with multiple joint pain, hand rashes, and shortness of breath was diagnosed with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) with interstitial pneumonia (IP). Because of progressive dyspnoea and hypoxaemia, her IP was considered rapidly progressive interstitial lung disease. Initially, prednisolone 60 mg/day, cyclosporine A (CyA), and intravenous cyclophosphamide (IVCY) were initiated. A few days following the initiation of treatment, she experienced massive thunderclap headache, which was diagnosed as reversible cerebral vasospasm syndrome based on the findings of contraction in cerebral arteries with brain magnetic resonance imaging. Treatment with CyA and IVCY was discontinued, and diltiazem and mycophenolate mofetil (MMF) were initiated as an alternative immunosuppressant. Considering IVCY as the cause of Reversible cerebral vasospasm syndrome based on her clinical course, tacrolimus was commenced, which improved both DM and IP. DM patients who are anti-MDA5 antibody-positive are considered to have poor prognosis and require aggressive immunosuppressive treatments. In patients experiencing adverse events with standard IVCY, MMF with high-dose steroids and alternative calcineurin inhibitor should be considered.

Clinical and Microbiological Features of Asymptomatic SARS-CoV-2 Infection and Mild COVID-19 in Seven Crewmembers of a Cruise Ship.

Objective To describe the clinical features and clinical course of individuals diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild coronavirus disease (COVID)-19. Patients The study participants consisted of 7 crewmembers of the passenger cruise-liner, Diamond Princess, who were admitted to our hospital after becoming infected with SARS-CoV-2 aboard the ship. Methods The data on patient background and biochemical test results were obtained from the patients' medical records. All patients had a chest X-ray, and a throat swab and sputum samples were sent for culture on admission. Results The median age of the 7 patients, of whom 4 were male and 3 were female, was 39 years (range: 23-47 years). On admission, none of them had fever, but 4 (57%) had a cough. None of them showed any signs of organ damage on laboratory testing. Chest X-ray showed pneumonia in one individual, which resolved spontaneously, while the other 6 had normal chest X-ray findings. Culture of throat swabs and sputum samples revealed that 4 patients (57%) had bacterial upper respiratory infections (Haemophilus influenzae, Klebsiella pneumoniae, and Staphylococcus aureus). The period from a positive polymerase chain reaction (PCR) test to negative conversion ranged from 5 to 13 days, with a median of 8 days. Conclusion Healthy young adults without risk factors who acquire SARS-CoV-2 infection may have an asymptomatic infection or may experience mild COVID-19. In addition to obesity, an older age, underlying illness, and being overweight can lead to a risk of exacerbation; thus, hospital management for such individuals may be desirable. Culturing respiratory samples may be useful for diagnosing secondary bacterial pneumonia.

Haemophilus influenzae Non-type b Infection in an Adult Patient with Systemic Lupus Erythematosus.

A 40-year-old man with systemic lupus erythematosus taking consecutive oral corticosteroids developed a high-grade fever and disorder of consciousness following acute rhinitis. Haemophilus influenzae type f (Hif) was found and isolated from the blood and cerebrospinal fluid by culture, leading to a diagnosis of meningitis. The prevalence of H. influenzae type b (Hib) infections has decreased due to routine immunization. As a result, the prevalence of invasive non-Hib, including Hif infection, is increasing as a common H. influenzae infection in children and adults. Physicians should be aware of non-Hib H. influenzae infection, even though the Hib vaccine is widely used in Japan.

Three Novel COVID-19 Pneumonia Cases Successfully Treated With Lopinavir/Ritonavir.

Following the first case of Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov-2), in Wuhan, China, in December 2019, it has spread worldwide. An outbreak in Japan occurred on a cruise ship, and this was followed by community-acquired COVID-19. Herein, we report three cases of COVID-19 that presented pneumonia following admission to Kitasato University Hospital. Patients were admitted based on the positive result of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for COVID-19 nucleic acid. All patients were diagnosed as suffering from non-severe COVID-19 pneumonia and were successfully treated with Lopinavir/Ritonavir (LPV/r). LPV/r could be an option for treating non-severe COVID-19 pneumonia in general and even in elderly patients.

Differential influences of Fc gamma receptor blocking on the effects of certolizumab pegol and infliximab on human monocytes.

OBJECTIVES: To compare the effects of certolizumab pegol (CZP) and infliximab (IFX) on human monocytes. METHODS: Highly purified monocytes from healthy donors were cultured with CZP, IFX, control IgG1, or polyethylene glycol (PEG) at pharmacological attainable concentrations in culture medium with 10% autologous normal human serum (NHS) or with fetal bovine serum (FBS) for 24 h, after which the supernatants were replaced by fresh culture medium containing LPS. After additional 24 h of incubation, the supernatants were assayed for TNF-α and IL-6. In some experiments, the cells were harvested after 1 h of stimulation with LPS for analysis of mRNA for TNF-α by quantitative PCR. RESULTS: Pre-incubation of monocytes with CZP or IFX reduced the production of TNF-α in subsequent cultures stimulated by LPS in a dose-dependent manner. The suppressive effects of IFX on the TNF-α production were significantly diminished, but those of CZP were rather enhanced, in cultures with autologous NHS compared with in cultures with FBS. Addition of IgG, but not IgG F(ab')2 fragments, significantly inhibited the suppressive effects of IFX on the production of TNF-α and IL-6, whereas either IgG or IgG F(ab')2 fragments had no significant influences on the suppressive effects of CZP. Furthermore, pre-incubation with CZP or IFX significantly inhibited the expression of mRNA for TNF-α and IL-6 in monocytes compared with PEG or IgG. CONCLUSION: These results indicate that the mechanism of action of CZP is different from that of IFX. Thus, CZP suppresses the production of proinflammatory cytokines independently of Fc receptors, whereas the suppressive effects of IFX on human monocytes are almost totally dependent on the interaction with Fc receptors.

Effects of CTLA4-Ig on human monocytes.

BACKGROUND: Abatacept, a CTLA4-Ig fusion protein attenuates T cell activation by inhibiting the CD80/86-CD28 costimulatory pathway that is required for the proper T cell activation and thus displays beneficial effects in the treatment of rheumatoid arthritis (RA). Although some studies have disclosed the in vitro effects of this biological agent on the immune-competent cells, the precise mechanisms of action in RA still remain unclear. The current studies were therefore undertaken to explore the effects of abatacept on monocytes in detail. METHODS: Monocytes from healthy donors were cultured in the presence of staphylococcal enterotoxin B (SEB) with pharmacologically attainable concentrations of abatacept or control IgG-Fc. The expression of CD80 and CD86 and the induction of apoptosis of monocytes were measured by flow cytometry. The expression of CD80 and CD86 messenger RNA (mRNA) was determined by quantitative RT-PCR. RESULTS: Abatacept promoted apoptosis of SEB-stimulated monocytes. The induction of apoptosis of monocytes by these biological agents was reversed by the addition of IgG, but not IgG-F(ab')2 fragments. Furthermore, abatacept significantly suppressed the expression of CD80, but not that of CD86 at protein levels. Finally, abatacept significantly suppressed the expression of mRNA for CD80 of monocytes stimulated with SEB, but not that of CD86. CONCLUSIONS: These results demonstrate that one of the mechanisms of action of abatacept involves the induction of apoptosis of monocytes, which involves interaction with Fc receptor on monocytes. Moreover, the data also demonstrate that abatacept selectively suppresses the expression of CD80 at mRNA levels.

Transverse myelitis extended to disseminated encephalitis in systemic lupus erythematosus: Histological evidence for vasculitis.

A 42-year-old woman was admitted due to systemic lupus erythematosus complicated with glomerulonephritis and pulmonary hypertension. During the treatment for these complications, she presented motor paresis and sensory loss caused by transverse myelitis. In spite of methyl prednisolone pulse therapy, she further developed acute confusional state due to disseminated encephalitis and fell into respiratory arrest. On laboratory examination, elevation of anti-NR2 antibodies in serum as well as in cerebrospinal fluid was noted. Although she recovered from the disseminated encephalitis after extensive treatment with high doses of corticosteroid and intravenous cyclophosphamide, she suddenly died of pulmonary hypertension. Autopsy findings confirmed the presence of liquefaction necrosis in the entire circumference of the whole spinal cord along with intimal hyperplasia and obliteration of the small arteries, accompanied by mononuclear cell infiltration and disruption of internal elastic lamina. It is therefore most likely that our patient developed longitudinal transverse myelitis through spinal cord vasculitis, which extended to brainstem and brain parenchyma, leading to the development of disseminated encephalitis.

A very rare case of primary meningococcal arthritis in an adult male.

We report here a very rare case of primary meningococcal arthritis of the knee joint without clinical features associated with meningococcemia, meningitis, or meningococcal complications. The patient suffered from diabetes mellitus and had experienced two episodes of joint trauma. Intravenous infusion of ampicillin/sulbactam for 18 consecutive days was successful.

Effects of anti-IL-6 receptor antibody on human monocytes.

OBJECTIVE: To explore the effects of anti-IL-6 receptor antibody, tocilizumab on function of human monocytes. METHODS: Monocytes from healthy donors were cultured in the presence of staphylococcal enterotoxin B (SEB) with pharmacologically attainable concentrations of tocilizumab or control IgG. The expression of IL-6 mRNA was determined using quantitative RT-PCR. The expression of CD80 and CD86 and the induction of apoptosis of monocytes were measured using flow cytometry. RESULTS: Tocilizumab promoted apoptosis of SEB-stimulated monocytes. The induction of apoptosis of monocytes by tocilizumab were reversed by addition of IgG, but not IgG F(ab')2 fragments. Tocilizumab significantly suppressed the expression of CD80, but not that of CD86, on SEB- stimulated monocytes. Finally, tocilizumab significantly suppressed the expression of mRNA for IL-6 of monocytes stimulated with SEB. CONCLUSIONS: These results demonstrate that one of the mechanism of action of tocilizumab involves the induction of apoptosis of monocytes, which requires interaction with Fc receptor on monocytes. Moreover, the data also indicate that tocilizumab inhibit IL-6 production of monocytes at mRNA levels.

[An adult case of acute pericarditis and glomerulonephritis associated with human parvovirus B19 infection].

We report herein on a 52-year-old Japanese woman with acute pericarditis and glomerulonephritis associated with human parvovirus B19 infection, who had no significant medical history. The patient was admitted for progressive edema and upper abdominal pain. On physical examination, she had hypertension, generalized edema and upper abdominal tenderness. Urinalysis revealed protein (1+), and occult blood (+/-), with cellular casts. Echocardiography revealed pericardial effusion measuring 3-9mm in diameter. A serological test showed elevation of serum IgM antibodies for parvovirus B19. At the end of two weeks, generalized edema and glomerulonephritis improved spontaneously, and pericardial effusion was resolved three weeks after admission. This case would appear to be a very rare case indicating a direct relationship between human parvovirus B19 infection and acute pericarditis in a healthy adult patient.