Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study.

BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

Association of the quantitative oral health status of patients with COVID-19 with their organ status and immunity: A single-centre observational study.

OBJECTIVES: To evaluate the prevalence of oral complications in patients with severe COVID-19; investigate the association between their oral health, organ status, and immunity; and determine whether the resazurin disc test is an effective substitute for the Oral Assessment Guide. RESEARCH METHODOLOGY/DESIGN: A single-centre observational study. SETTING: Intensive care unit with restricted access specialising in extracorporeal membrane oxygenation for COVID-19 treatment. MAIN OUTCOME MEASURES: We investigated the oral health of 13 patients with COVID-19 receiving extracorporeal membrane oxygenation therapy between April and December 2021 using the Oral Assessment Guide and colour reactive resazurin disc test. The Sequential Organ Failure Assessment and Prognostic Nutritional Index were used to assess organ status and immunity, respectively. The correlation of oral health status with organ status and immunity was investigated. RESULTS: High bacterial levels, revealed by the resazurin disc test, were associated with elevated Oral Assessment Guide scores, indicating oral health deterioration, particularly in terms of teeth and dentures. Increased Sequential Organ Failure Assessment scores and decreased Prognostic Nutritional Index were correlated with poor oral health, revealed by the Oral Assessment Guide and resazurin disc test. CONCLUSION: Poor oral health is an important risk factor for severe COVID-19 complications in patients admitted to an intensive care unit. The Oral Assessment Guide and resazurin disc test can evaluate oral conditions; however, the resazurin disc test is quantitative and does not require salivary specimens to be transferred outside the patient ward for evaluation. The resazurin disc test can be a useful substitute for the Oral Assessment Guide in intensive care units with restricted access. IMPLICATIONS FOR CLINICAL PRACTICE: The resazurin disc test can be used for quantitative assessment of patients' oral condition in isolation wards. Multidisciplinary management of patients with COVID-19 should be promoted and involve oral healthcare providers such as dentists and dental hygienists.

Daily combined measurement of platelet count and presepsin concentration can predict in-hospital death of patients with severe coronavirus disease 2019 (COVID-19).

The purpose of this study was to classify patients with severe COVID-19 into more detailed risk groups using coagulation/fibrinolysis, inflammation/immune response, and alveolar/myocardial damage biomarkers, as well as to identify prognostic markers for these patients. These biomarkers were measured every day for eight intensive care unit days in 54 adult patients with severe COVID-19. The patients were classified into survivor (n = 40) and non-survivor (n = 14) groups. Univariate and multivariate analyses showed that the combined measurement of platelet count and presepsin concentrations may be the most valuable for predicting in-hospital death, and receiver operating characteristic curve analysis further confirmed this result (area under the curve = 0.832). Patients were consequently classified into three groups (high-, medium-, and low-risk) on the basis of their cutoff values (platelet count 53 × 103/µL, presepsin 714 pg/mL). The Kaplan-Meier curve for 90-day survival by each group showed that the 90-day mortality rate significantly increased as risk level increased (P < 0.01 by the log-rank test). Daily combined measurement of platelet count and presepsin concentration may be useful for predicting in-hospital death and classifying patients with severe COVID-19 into more detailed risk groups.

Sepsis-Associated Delirium: A Narrative Review.

Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD.

Diagnostic significance of secondary bacteremia in patients with COVID-19.

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

SARS-CoV-2 is localized in cardiomyocytes: a postmortem biopsy case.

A 72-year-old patient was admitted to the intensive care unit due to acute respiratory distress syndrome caused by COVID-19. On day 20, the patient experienced shock. The electrocardiogram showed ST segment elevation in leads V3-V6 and severe left ventricular dysfunction with an ejection fraction of 35%-40%. The left ventricle showed basal hypokinesis and apical akinesis, while the creatine kinase level was normal, indicating Takotsubo cardiomyopathy. On day 24, the patient died of multiple organ failure. In post-mortem biopsy, SARS-CoV-2 antigen was detected in cardiomyocytes by immunostaining. Moreover, SARS-CoV-2 RNA was detected in heart tissue. We need to further analyse the direct link between SARS-CoV-2 and cardiomyocytes.

The Association between the Oral-Gut Axis and the Outcomes of Severe COVID-19 Patients Receiving Extracorporeal Membrane Oxygenation: A Case-Control Study.

The novel conceptual disease model, the oral-gut axis, which represents the immunomodulatory mutual relationship between oral and gut microbial compartments, has been attracting attention in relation to systemic health issues. We investigated whether this unique crosstalk influences the systemic condition of patients with COVID-19 infections who received extracorporeal membrane oxygenation (ECMO) in the intensive care unit (ICU) during April and December 2020. In this case-control study, patients were divided into two groups according to their survival (total entry size, n = 21; survivors, n = 13; non-survivors, n = 8). Patients were evaluated using the oral assessment guide from Fukuoka University (OAG-F) and the Bristol Stool Form Scale (BSFS) to examine the oral and fecal conditions. A blood-based inflammatory factor, the neutrophil-to-lymphocyte ratio (NLR), was used as an indicator of systemic immunity. The high total OAG-F scores were associated with both elevated BSFS and NLR values, and a mutually positive correlation between BSFS and NLR was observed. This indicated an interplay between oral deterioration, gut dysbiosis, and the impairment of immunity. Furthermore, oral deterioration was more frequently observed in non-survivors on day 14 of ICU admission. In addition, on days 7 and 21 of ICU admission, impaired immunity, reflected by an elevated NLR, was observed in non-survivors. However, the distribution of the gut microbiome-reflected by increased BSFS values-with the time it was examined was not directly observed in non-survivors. Taken together, these findings suggested that oral-gut health may be specifically associated with mortality in COVID-19 patients receiving ECMO in the ICU.

Oral Health of COVID-19 Patients Using Extracorporeal Membrane Oxygenation: A Clinical Study of 19 Cases.

The oral health of coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is an important issue in treatment of respiratory failure. We retrospectively investigated the oral health history of severe COVID-19 patients who received extracorporeal membrane oxygenation (ECMO) from April 2020 to December 2020 using the oral assessment guide from Fukuoka University (OAG-F). Nineteen consecutive patients (median age: 62 years) were divided into two groups according to survival (survivors, n = 12; non-survivors, n = 7). A univariate analysis revealed no significant differences between the groups in sex, age, body mass index (BMI), or the number of remaining teeth, whereas the ECMO assistance of non-survivors (median: 34 days) was prolonged in comparison to survivors (median: 8 days; p < 0.05). Among the factors of OAG-F, significant differences were observed between the groups in the conditions of the saliva, mucous membrane, and gingiva. The total scores in non-survivors (median: 19) were significantly higher in comparison to survivors (Median: 15.5), suggesting that the frequency of oral health deterioration was higher in non-survivors (p < 0.05). Taken together, these findings suggest that poor oral health is associated with mortality in COVID-19 patients receiving ECMO in the ICU.

Coronavirus disease (COVID-19) associated delayed-onset fulminant myocarditis in patient with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

A healthy 35-year-old man was admitted to a rural hospital with coronavirus disease (COVID-19). During 14 days of hospitalization, he had no symptoms and was not given supplemental oxygen. About 3 weeks after discharge, he was re-admitted to the same hospital with new-onset continuous fever and general weakness. At the time of his second admission, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RT-PCR was performed on a retro-nasal swab and the result was negative. Four days after admission, the patient was transferred to our intensive care unit (ICU) following deterioration of his respiratory and haemodynamic conditions, where he received mechanical ventilation, intra-aortic balloon pumping, and veno-arterial extracorporeal membrane oxygenation. A nasopharyngeal swab was obtained again at ICU admission, but RT-PCR was negative for SARS-CoV-2. All antibody titres measured against other viruses were low. Blood cultures were negative, and no bacteria were observed in sputum samples. However, SARS-CoV-2 RNA was detected by RT-PCR from sections obtained by myocardial biopsy. The patient's final diagnosis was delayed-onset SARS-CoV-2-induced fulminant myocarditis (FM). We strongly suggested that one of the proposed mechanisms of COVID-19-related myocardial injury will be the direct invasion of SARS-CoV-2 into cardiomyocytes even if delayed-onset. And this is the first case of delayed-onset FM in which diagnosis of active myocarditis was proven by pathological examination following endomyocardial biopsy and SARS-CoV-2 was detected in the myocardium by RT-PCR.

[Characteristics of coagulation/fibrinolysis abnormalities in severe novel coronavirus disease 2019 (COVID-19) patients —Case series—]

[Hiroyasu Ishikura *, Junichi Maruyama, Yuhei Irie, Yoshito Izumiya, Mako Naito, Megumi Koie, Kodai Hoshino, Yoshihiko Nakamura Summary: This time, the coagulation line of severe new coronavirus 2019 (COVID-19) patients We report some findings on the melting anomaly. There were 6 cases, and only 1 case decreased the platelet count below 10 × 10 4 /mm 3 within 8 days after admission to the ICU. The prothrombin time-international normalized ratio (PT-INR) was almost normal throughout the course, and the activated partial thromboplastin time (APTT) exceeded the upper limit of normal in 5 cases, but did not significantly extend except 1 case. On the other hand, FDP and D-dimer remained above the normal upper limit during the course of time, and in 2 cases, marked re-elevation occurred after the 7th day of illness. Based on the above, in severe COVID-19 patients, despite the infection, coagulation and fibrinolysis abnormalities did not appear to be “fibrinolysis-suppressive”, but rather “fibrinolysis-promoting”. Of the 6 cases, 4 cases were diagnosed with DIC based on the Japanese Association for Acute Medicine criteria (JAAM) disseminated intravascular coagulation (DIC) diagnostic criteria, and recombinant human soluble tronmodulin (rhsTM) was administered, and 3 cases were completed. At that point, he left the DIC.] 石倉宏恭 * ，丸山隼一，入江悠平，泉谷義人，内藤麻巳子，鯉江めぐみ， 星野耕大，仲村佳彦 要約：今回，重症新型コロナウィルス 2019（Coronavirus disease 2019: COVID-19）患者の凝固線溶 異常について，若干の知見を得たので報告する．症例は 6 症例で，ICU 入室から 8 日間の経過で血 小板数が 10×10 4 /mm 3 未満に低下したのは 1 例のみであった．prothrombin time-international normalized ratio（PT-INR）は経過を通じて概ね正常で，activated partial thromboplastin time（APTT）は経過中 5 例で正常上限を上回ったが，1 例を除き大きく延長する事は無かった．一方，FDP と D-dimer は経 過中，正常上限を超えて推移し，2 例は第 7 病日以降に著明な再上昇を来した．以上より，重症 COVID-19 患者は感染症にも関わらず，凝固線溶異常は「線溶抑制型」でなく，あたかも「線溶亢 進型」の様相を呈していた．6 例中 4 例が Japanese Association for Acute Medicine criteria（JAAM） disseminated intravascular coagulation（DIC）診断基準で DIC と診断され，遺伝子組換え型ヒト可溶性 トロンモジュリン（rhsTM）が投与され，3 例が投与終了時点で DIC から離脱した．