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.

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force.

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. CONCLUSION: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

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.

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.

Frequency and Significance of Coinfection in Patients with COVID-19 at Hospital Admission.

Objective Viral pneumonia is not rare in community-acquired pneumonia (CAP). Mixed or secondary pneumonia (coinfection) can be seen in viral pneumonia; however, its frequency in coronavirus disease 2019 (COVID-19) has only been investigated in a few studies of short duration, and its significance has not been fully elucidated. We investigated the frequency and significance of co-infection in patients with COVID-19 over a 1-year study period. Methods Coinfection was investigated via multiplex polymerase chain reaction (PCR), culture of respiratory samples, rapid diagnostic tests, and paired sera. We used logistic regression analysis to analyze the effect of coinfection on severity at admission and Cox proportional-hazards model analysis to analyze the effect of coinfection on need for high-flow nasal cannula, invasive mandatory ventilation use, and death, respectively. Patients We retrospectively investigated 298 patients who suffered CAP due to severe acute respiratory syndrome coronavirus-2 infection diagnosed by PCR and were admitted to our institution from February 2020 to January 2021. Results Primary viral pneumonia, and mixed viral and bacterial pneumonia, accounted for 90.3% and 9.7%, respectively, of COVID-19-associated CAP, with viral coinfection found in 30.5% of patients with primary viral pneumonia. Influenza virus was the most common (9.4%). Multivariable analysis showed coinfection not to be an independent factor of severity on admission, need for high-flow nasal cannula or invasive mandatory ventilation, and mortality. Conclusion Viral coinfection was common in COVID-19-associated CAP. Severity on admission, need for high-flow oxygen therapy or invasive mandatory ventilation, and mortality were not affected by coinfection.

Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: study protocol.

INTRODUCTION: The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale. METHODS AND ANALYSIS: In this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives. ETHICS AND DISSEMINATION: This trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.

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.

[Other treatments : Covid-19]

Summary In patients with COVID-19, appropriate supportive care should be given and further treatment should be considered. Excessive host immunoreactivity to the virus is responsible for the severity of the disease, and steroids and biologics may be effective in some cases. In some cases, steroids and biologics are effective. COVID-19 may be associated with mixed infections and cross Infections during the course of the disease, so careful observation and effective preventive measures are important.

Clinical course and findings of 14 patients with COVID-19 compared with 5 patients with conventional human coronavirus pneumonia.

OBJECTIVE: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. METHODS: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. RESULTS: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients' symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients' clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. CONCLUSION: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality.

High incidence of false-positive results of IgG antibody against SARS-CoV-2 with rapid immunochromatographic antibody test due to human common cold coronavirus infection.

We experienced a 72-year-old man who developed laboratory-confirmed human coronavirus HKU1 pneumonia. PCR testing for SARS-CoV-2 from a nasopharyngeal specimen was negative twice, and rapid immunochromatographic antibody test (RIAT) using a commercially available kit for IgM and IgG against SARS-CoV-2 showed him turning positive for IgG against SARS-CoV-2. We then performed RIAT in stored serum samples from other patients who suffered laboratory-confirmed human common cold coronaviruses (n = 6) and viruses other than coronavirus (influenza virus, n = 3; rhinovirus, n = 3; metapneumovirus, n = 1; adenovirus, n = 1) admitted until January 2019. Including the present case, four of 7 (57%) showed false-positive RIAT results due to human common cold coronaviruses infection. Two of the 4 patients showed initial negative to subsequent positive RIAT results, indicating seroconversion. RIAT was positive for IgG and IgM in viruses other than coronavirus in 2 (25.0%) and 1 (12.5%) patient. Because of high incidence of false positive RIAT results, cross antigenicity between human common cold coronaviruses and SARS-CoV-2 can be considered. Results of RIAT should be interpreted in light of epidemics of human common cold coronaviruses infection. Prevalence of past SARS-CoV-2 infection may be overestimated due to high incidence of false-positive RIAT results.

[Antibody Response as Assessed by A Rapid Immunochromatographic Assay in Patients with COVID-19 Pneumonia Caused by the Novel Coronavirus, SARS-CoV-2]

An immunochromatographic assay that has been developed for the detection of antibodies in blood-derived specimens is raising expectations for the diagnosis of COVID-19, the disease caused by the novel corona virus SARS-CoV-2. Herein, we studied the interval from symptom onset to the first positive results of the immunochromatographic assay for IgM and IgG antibodies in 52 patients with a definitive diagnosis of COVID-19 (disease confirmed by the PCR test). Furthermore, we also examined the test results in 35 patients with acute fever and pneumonia who were negative by the PCR test. All patients with a definitive diagnosis of COVID-19 were confirmed to be antibody-positive. The mean time from symptom onset to the first positive result for IgM antibody was 11.9 days (minimum: 5, median: 11), and that to the first positive result for IgG antibody was 11.2 days (minimum: 5, median: 11). No significant difference was observed between the tests for IgM and IgG antibodies in terms of the percentage of positive patients or the interval from first onset to the first positive test result. There were no patients in whom the test for IgM became positive before the test for IgG. In 45 patients (87%), both IgM and IgG became positive at the same time, and in the remaining 7 patients (13%), the test for IgG became positive before that for IgM. Of 35 patients with acute fever and pneumonia who tested negative by the PCR test for SARS-CoV-2, not COVID-19, 6 (17.1%) and 1 (2.8%) showed positive results for anti-IgG antibody and anti-IgM antibody, respectively. Our study results were quite limited, and we do not intend to conduct a performance evaluation of the reagents contained in the detection kits. Assessment of antibody detection reagents for the immunochromatographic assay, which can be used as a complementary test to PCR, is expected in the future;however, the findings should be reviewed carefully.

[Predictors of Severe COVID-19 Pneumonia]

In patients with COVID-19, age over 50 years is also considered as an indication for antiviral drug therapy, in addition to hypoxemia. At this time, it still remains unclear as to which clinical markers can be considered as being predictive of severe COVID-19 pneumonia with hypoxemia. We categorized 49 patients with COVID-19 pneumonia into the following 4 groups by the clinical manifestations: stage A: no symptoms, and no viral pneumonia on chest computed tomography (CT);stage B: symptom (s) present, but no viral pneumonia on CT;stage C: viral pneumonia on CT, but no hypoxemia;stage D: viral pneumonia on CT, with hypoxemia. The clinical background characteristics that were correlated with the disease severity were the patient age, presence/absence of complications, smoking history, and presence/absence of fever and diarrhea, but multivariate analysis identified only smoking history as being significantly predictive of stage D disease. The lymphocyte count, serum CRP level, serum ferritin level and incidence of consolidation on CT were significantly different between patients with stage C and stage D disease. Therefore, we propose five predictors of severe COVID-19 pneumonia, namely, smoking history, lymphocyte count 1,200 μL, serum ferritin 400 ng/mL, serum CRP 2.5 mg/dL, and presence of consolidation on CT. The interval (in days) from the onset of symptom (s) to the first negative result of PCR for SARS-CoV2 was well correlated with the number of these risk factors in each patient (p�E�E.0001�E�E