Use of the neutrophil-to-lymphocyte ratio and an oxygen requirement to predict disease severity in patients with COVID-19

We investigated the association between complete blood count, including neutrophil-to-lymphocyte ratio (NLR) in combination with patient characteristics, and coronavirus disease (COVID-19) outcomes to identify the best prognostic indicator. We analyzed data of patients with confirmed COVID-19 from the nationwide database of the Japan COVID-19 Task Force between February 2020 and November 2021. A composite outcome was defined as the most severe condition, including noninvasive positive-pressure ventilation, high-flow nasal cannula, invasive mechanical ventilation, extracorporeal membrane oxygenation, or death. Of 2,425 patients in the analysis, 472 (19.5%) experienced a composite outcome. NLR was the best predictor of composite outcomes, with an area under the curve (AUC) of 0.81, and a sensitivity and specificity of 72.3% and 75.7%, respectively, using a cut-off value of 5.04. The combination of NLR and an oxygen requirement on admission had the highest AUC (0.88). This simple combination may help identify patients at risk of progression to severe disease.

Antibody responses to second doses of COVID-19 vaccination in lung cancer patients undergoing treatment.

BACKGROUND: Several reports have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tends to have more severe outcomes in cancer patients. Although vaccination reduces the risk of severe disease, data on antibody titers achieved by vaccination is scarce in cancer patients. METHODS: We collected 79 blood samples (69 lung cancer patients and 10 control individuals) and conducted an anti-SARS-CoV-2 antibody assay to compare the antibody titer achieved with current treatment. Sixty-eight patients (86%) received the BNT162 mRNA vaccine and 11 (14%) received the mRNA-1273 vaccine. They were categorized according to the current treatment: control individuals without cancer (cohort A), lung cancer patients who were treated with cytotoxic chemotherapy (cohort B), immunotherapy (cohort C), combination of cytotoxic chemotherapy and immunotherapy (cohort D), tyrosine kinase inhibitors (cohort E), and radiation therapy (cohort F). RESULTS: Among 69 lung cancer patients (cohort B-F), 57 (83%) had adenocarcinoma, and 66 (96%) had advanced-stage cancer. In the anti-SARS-CoV-2 antibody assay, the antibody titer was significantly lower in lung cancer patients than in control individuals (p = 0.01). The median antibody titers were 161 AU/ml in control individuals and 59.9 AU/ml in lung cancer patients. CONCLUSIONS: Antibody titers after the second vaccination were lower in cancer patients than those in healthy individuals. Our findings provide essential information for understanding the benefits and necessity of additional vaccination to prevent SARS-CoV-2 infection in lung cancer patients.

Characteristics of hospitalized patients with COVID-19 during the first to fifth waves of infection: a report from the Japan COVID-19 Task Force.

BACKGROUND: We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. METHODS: We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. RESULTS: Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9]) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p < 0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p < 0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. CONCLUSIONS: We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.

Impact of upper and lower respiratory symptoms on COVID-19 outcomes: a multicenter retrospective cohort study.

BACKGROUND: Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. METHODS: This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. RESULTS: Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11-0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43-4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. CONCLUSIONS: Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

A Novel Development of Sarcoidosis Following COVID-19 Vaccination and a Literature Review.

BNT162b2 (Pfizer/BioNTech) is a coronavirus disease 2019 (COVID-19) vaccine containing nucleoside-modified messenger RNA encoding the severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Recently, ocular complications of mRNA vaccines have been reported increasingly frequently. However, immunological adverse events due to mRNA vaccines in real-world settings are not fully known. We herein report the novel development of sarcoidosis manifested as uveitis, bilateral hilar lymphadenopathy, angiotensin-converting enzyme elevation, and epithelioid and giant cell granuloma formation in the lung soon after the first BNT162b2 injection and review the current literature, including three reported cases of sarcoid-like reaction following COVID-19 vaccination.

Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host genetics.

BACKGROUND: The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. METHODS: From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. RESULTS: Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, D-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. CONCLUSIONS: We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.

U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force.

OBJECTIVES: This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population. METHODS: We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia. RESULTS: Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio [OR] = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P <0.0001). CONCLUSION: Abnormal serum uric acid levels or a history of hyperuricemia were significantly associated with COVID-19 severity in the Japanese cohort.

Effects of mild obesity on outcomes in Japanese patients with COVID-19: a nationwide consortium to investigate COVID-19 host genetics.

BACKGROUND: Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population. METHODS: From February 2020 to May 2021, 1 837 patients aged ≥18 years were enrolled in the Japan COVID-19 Task Force. Patients with known BMI and disease severity were analyzed. Severity was defined as critical if the patient was treated in the intensive care unit, required invasive mechanical ventilation, or died. RESULTS: Class 1 obesity (25.0 ≤ BMI < 30.0 kg/m2), class 2 obesity (30.0 ≤ BMI < 35.0 kg/m2), and class 3 or 4 obesity (BMI ≥ 35 kg/m2) were present in 29%, 8%, and 3% of the cases, respectively. Multiple logistic regression analysis with known risk factors for critical illness indicated that class 2 obesity was an independent risk factor for oxygenation (adjusted odds ratio, 4.75) and critical cases (adjusted odds ratio, 1.81). Class 1 obesity and class 3 or 4 obesity were independent risk factors for oxygen administration (adjusted odds ratios 2.01 and 3.12, respectively), but not for critical cases. However, no differences in the mortality rates were observed between the BMI classes (P = 0.5104). CONCLUSION: Obesity is a risk factor for respiratory failure in Japanese patients with COVID-19, regardless of the degree of obesity. However, it may not cause severe COVID-19 in a dose-response relationship with BMI. COVID-19 patients with mild obesity may benefit from aggressive intensive care.

The Immediate Onset of Isolated and Unilateral Abducens Nerve Palsy Associated with COVID-19 Infection: A Case Report and Literature Review.

Cranial nerve palsy associated with coronavirus disease 2019 (COVID-19) is rare. We herein report the first Asian case of the immediate onset of isolated and unilateral abducens nerve palsy (ANP) accompanied with COVID-19 infection. A 25-year-old man developed diplopia one day after the COVID-19 symptom onset. Neurological examination revealed limitation of left eye abduction without ataxia and hyporeflexia. Negative anti-ganglioside antibody results and mild albuminocytological dissociation were noted. The patient was diagnosed with left ANP accompanied by COVID-19 infection. The ANP spontaneously recovered without treatment. ANP can develop during the early phase of COVID-19 infection and adversely affect patients' quality of life.

COVID-19 in a Hairy Cell Leukemia Patient: A Rare Case Report.

The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.

Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19.

BACKGROUND AND DESIGN: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. RESULTS: The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45-71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. CONCLUSIONS: Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.