Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine.

OBJECTIVES: To examine the differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination. METHODS: Throughout the pandemic, we evaluated the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients over time among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants. RESULTS: A total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (percentage per 30 days [95% CI]) was slower after 3 doses (25% [23-26]) than 2 doses (36% [35-37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9-22]); 3-dose plus infection (21% [17-25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3 doses, except for sex (lower in female participants) and immunosuppressant use. Antibody waned slightly faster in older participants, females, and alcohol drinkers after 2 doses, whereas it did not differ after 3 doses across except sex. DISCUSSION: The 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection modestly enhanced its durability. The antibody levels at a given time point and waning speed after 2 doses differed across background factors; however, these differences mostly diminished after 3 doses.

Omicron BA.1 neutralizing antibody response following Delta breakthrough infection compared with booster vaccination of BNT162b2.

BACKGROUND: Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron. METHODS: Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups. RESULTS: Breakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. CONCLUSIONS: Symptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases

IMPORTANCE: Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Examination of the utility of the COVID-19 detection kit, TRC Ready® SARS-CoV-2 i for nasopharyngeal swabs.

The reverse transcription polymerase chain reaction (RT-PCR) offers high sensitivity, but has some drawbacks, such as the time required for the RNA extraction. Transcription reverse-transcription concerted reaction (TRC) Ready® SARS-CoV-2 i is easy to use and can be performed in about 40 minutes. TRC Ready® SARS-CoV-2 i and real-time one-step RT-PCR using the TaqMan probe tests of cryopreserved nasopharyngeal swab samples from patients diagnosed with COVID-19 were compared. The primary objective was to examine the positive and negative concordance rates. A total of 69 samples cryopreserved at -80° C were examined. Of the 37 frozen samples that were expected to be RT-PCR positive, 35 were positive by the RT-PCR method. TRC Ready® SARS-CoV-2 i detected 33 positive cases and 2 negative cases. One frozen sample that was expected to be RT-PCR positive was negative on both TRC Ready® SARS-CoV-2 i and RT-PCR. In addition, one frozen sample that was expected to be RT-PCR positive was positive by the RT-PCR method and negative by TRC Ready® SARS-CoV-2 i. Of the 32 frozen samples that were expected to be RT-PCR negative, both the RT-PCR method and TRC Ready® SARS-CoV-2 i yielded negative results for all 32 samples. Compared with RT-PCR, TRC Ready® SARS-CoV-2 i had a positive concordance rate of 94.3% and a negative concordance rate of 97.1%. TRC Ready® SARS-CoV-2 i can be utilized in a wide range of medical sites such as clinics and community hospitals due to its ease of operability, and is expected to be useful in infection control.

High-flow nasal cannula for severe COVID-19 patients in a Japanese single-center, retrospective, observational study: 1 year of clinical experience.

High-flow nasal cannula (HFNC) can be effective in treating type 1 respiratory failure by reducing the severity of coronavirus disease 2019 (COVID-19). The purpose of this study was to assess the reduction of disease severity and safety of HFNC treatment in patients with severe COVID-19. We retrospectively observed 513 consecutive patients with COVID-19 admitted to our hospital from January 2020 to January 2021. We included patients with severe COVID-19 who received HFNC for their deteriorating respiratory status. HFNC success was defined as improvement in respiratory status after HFNC and transfer to conventional oxygen therapy, while HFNC failure was defined as transfer to non-invasive positive pressure ventilation or ventilator, or death after HFNC. Predictive factors associated with failure to prevent severe disease were identified. Thirty-eight patients received HFNC. Twenty-five (65.8%) patients were classified in the HFNC success group. In the univariate analysis, age, history of chronic kidney disease (CKD), non-respiratory sequential organ failure assessment (SOFA) ≥ 1, oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) before HFNC ≤ 169.2, were significant predictors of HFNC failure. Multivariate analysis revealed that SpO2/FiO2 value before HFNC ≤ 169.2 was an independent predictor of HFNC failure. No apparent nosocomial infection occurred during the study period. Appropriate use of HFNC for acute respiratory failure caused by COVID-19 can reduce the severity of severe disease without causing nosocomial infection. Age, history of CKD, non-respiratory SOFA before HFNC ≤ 1, and SpO2/FiO2 before HFNC ≤ 169.2 were associated with HFNC failure.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Cumulative and undiagnosed SARS-CoV-2 infection among the staff of a medical research centre in Tokyo after the emergence of variants.

To describe the trend of cumulative incidence of coronavirus disease 19 (COVID-19) and undiagnosed cases over the pandemic through the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants among healthcare workers in Tokyo, we analysed data of repeated serological surveys and in-house COVID-19 registry among the staff of National Center for Global Health and Medicine. Participants were asked to donate venous blood and complete a survey questionnaire about COVID-19 diagnosis and vaccine. Positive serology was defined as being positive on Roche or Abbott assay against SARS-CoV-2 nucleocapsid protein, and cumulative infection was defined as either being seropositive or having a history of COVID-19. Cumulative infection has increased from 2.0% in June 2021 (pre-Delta) to 5.3% in December 2021 (post-Delta). After the emergence of the Omicron, it has increased substantially during 2022 (16.9% in June and 39.0% in December). As of December 2022, 30% of those who were infected in the past were not aware of their infection. Results indicate that SARS-CoV-2 infection has rapidly expanded during the Omicron-variant epidemic among healthcare workers in Tokyo and that a sizable number of infections were undiagnosed.

Neutralizing antibodies after three doses of the BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron-predominant wave.

OBJECTIVES: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection. METHODS: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms. RESULTS: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not. CONCLUSION: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.

Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications.

BACKGROUND & AIMS: We investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 and its complications, and we validate the results with follow-up, a Japanese Disease, Drug, Diet, Daily Life microbiome cohort, and non-Japanese data sets. METHODS: We performed shotgun metagenomic sequencing and metabolomics on stools and cytokine measurements on plasma from 112 hospitalized patients with SARS-CoV-2 infection and 112 non-COVID-19 control individuals matched by important confounders. RESULTS: Multiple correlations were found between COVID-19-related microbes (eg, oral microbes and short-chain fatty acid producers) and gut metabolites (eg, branched-chain and aromatic amino acids, short-chain fatty acids, carbohydrates, neurotransmitters, and vitamin B6). Both were also linked to inflammatory cytokine dynamics (eg, interferon γ, interferon λ3, interleukin 6, CXCL-9, and CXCL-10). Such interrelationships were detected highly in severe disease and pneumonia; moderately in the high D-dimer level, kidney dysfunction, and liver dysfunction groups; but rarely in the diarrhea group. We confirmed concordances of altered metabolites (eg, branched-chain amino acids, spermidine, putrescine, and vitamin B6) in COVID-19 with their corresponding microbial functional genes. Results in microbial and metabolomic alterations with severe disease from the cross-sectional data set were partly concordant with those from the follow-up data set. Microbial signatures for COVID-19 were distinct from diabetes, inflammatory bowel disease, and proton-pump inhibitors but overlapping for rheumatoid arthritis. Random forest classifier models using microbiomes can highly predict COVID-19 and severe disease. The microbial signatures for COVID-19 showed moderate concordance between Hong Kong and Japan. CONCLUSIONS: Multiomics analysis revealed multiple gut microbe-metabolite-cytokine interrelationships in COVID-19 and COVID-19related complications but few in gastrointestinal complications, suggesting microbiota-mediated immune responses distinct between the organ sites. Our results underscore the existence of a gut-lung axis in COVID-19.

Actual situation of handling Tokyo 2020 Games-related patients at a designated hospital during COVID-19 pandemic.

In preparation for the Tokyo 2020 Olympic and Paralympic Games, our hospital was responsible for accepting mainly media representatives, marketing partners, and other Games staff. Given that restricting our regular capacity to treat certain groups of patients could potentially result in social losses, to avoid this we made rigorous preparations for the entire hospital to accept Games-related patients. It was rational to set up a single 24-h contact point at the Emergency Department for making the decision on whether to accept the patient or not and for coordinating the patient's medical care. With respect to language support, International Health Care Center staffs were made available as interpreters on weekdays. Multilingual support was available all day via an application run on tablet devices. During a 67-day period, the hospital accepted 31 Games-related patients (mean age 43.4 years, male: female ratio 25:6). Eighteen patients were from Europe, 4 patients each were from North America and Asia, 2 each were from Central America, South America, and Africa, and 1 was from Oceania. The most common cause of visits was COVID-19, but none were severe cases. Other causes were diverse and included moderate and severe conditions. We summarized the challenges and experiences in handling Tokyo 2020 Games-related patients at a designated hospital during the COVID-19 pandemic.

Impact of inhaled ciclesonide on asymptomatic or mild COVID-19: A randomized trial.

The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study.

BACKGROUND: Polymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. The SARS-CoV-2 virus causes COVID-19, which emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity, and prolonged prothrombin time were significant factors in nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes, and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. OBJECTIVE: This study aims to access treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leukocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia. METHODS: We will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 6 on day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia. RESULTS: The study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. CONCLUSIONS: From a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37426.

Poor prognosis of patients with severe COVID-19 admitted to an infectious disease intensive care unit during the pandemic caused by the Delta variant in Japan.

During the surge of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delta variant, our institution operated an intensive care unit (ICU) for patients with severe COVID-19. The study aim was to determine the survival rate and treatment outcomes of patients with severe COVID-19 treated in the ICU during the surge. A total of 23 consecutive patients with severe COVID-19 were admitted to the ICU between August 5 and October 6, 2021. Patients received multidrug therapy consisting of remdesivir, tocilizumab, heparin, and methylprednisolone. The patients were divided into two groups based on the ordinal scale (OS): a non-invasive oxygen therapy (OS-6) group, and an invasive oxygen therapy (OS-7) group. There were 13 (57%) and 10 (43%) patients in the OS-7 and OS-6 groups, respectively. All patients were unvaccinated. Sixteen patients (70%) were male. The median age was 53 years; the median body mass index (BMI) was 30.3 kg/m2; and the median P/F ratio on admission was 96. The 30-day survival rate was 69% and was significantly poorer in the OS-7 group (54%) than in the OS-6 group (89%; p = 0.05). The prevalence of obesity (p = 0.05) and the Sequential Organ Failure Assessment (SOFA) score on admission (p < 0.01) were significantly higher in the OS-7 group. Seven patients in the OS-7 group (54%) developed bacteremia. A low P/F ratio on admission was a significant unfavorable prognostic factor (hazard ratio: 10.9; p = 0.03). The survival rate was poor, especially in patients requiring invasive oxygen therapy. More measures are needed to improve the treatment outcomes of patients with severe COVID 19.

Prolonged SARS-CoV-2 infection associated with long-term corticosteroid use in a patient with impaired B-cell immunity.

Corticosteroids are widely used to treat severe COVID-19, but in immunocompromised individuals, who are susceptible to persistent infection, long term corticosteroid use may delay viral clearance. We present a case of prolonged SARS-CoV-2 infection in a man with significantly impaired B-cell immunity due to non-Hodgkin lymphoma which had been treated with rituximab. SARS-CoV-2 shedding persisted, despite treatment with remdesivir. Viral sequencing confirmed the persistence of the same viral strain, ruling out the possibility of reinfection. Although SARS-CoV-2 IgG, IgA and IgM remained negative throughout the treatment period, after reduction of the corticosteroid dose, PCR became negative. Long-term corticosteroid treatment, especially in immunocompromised individuals, may result in suppression of cell-mediated immunity and prolonged SARS-CoV-2 infection.

Sex-associated differences between BMI and SARS-CoV-2 antibody titers following the BNT162b2 vaccine.

OBJECTIVE: This study investigated the sex-associated difference in the impact of obesity on antibody response to a COVID-19 vaccine. METHODS: This study included 2,435 health care workers who received two doses of the BioNTech, Pfizer (BNT162b2) vaccine and participated in a serological survey, during which they were tested for anti-SARS-CoV-2 spike immunoglobin G (IgG) antibodies and asked for information on height, weight, and vaccination history via a questionnaire. Multivariable linear regression analysis was used to estimate the geometric mean titers (GMT) of antibodies for each sex and BMI category. RESULTS: The relationship between BMI and anti-SARS-CoV-2 spike IgG titers markedly differed by sex (p value for interaction = 0.04). Spike IgG antibody titers tended to decrease with increasing BMI in men (p value for trend = 0.03); GMT (95% CI) were 6,093 (4,874-7,618) and 4,655 (3,795-5,708) for BMI < 18.5 and ≥30 kg/m2 , respectively. In contrast, spike IgG antibody titers did not significantly differ across BMI categories in women (p value for for trend = 0.62); GMT (95% CI) were 6,171 (5,714-6,665) and 5,506 (4,404-6,883) for BMI <18.5 and ≥30, respectively. CONCLUSIONS: Higher BMI was associated with lower titers of SARS-CoV-2 spike antibodies in men, but not in women, suggesting the need for careful monitoring of vaccine efficacy in men with obesity, who are at high risk of severe COVID-19 outcomes.

Suspected Tuberculous Pleurisy and Coronavirus Disease 2019 Comorbidity.

A 33-year-old woman with a fever, cough, and pharyngitis was admitted after left-sided pleural effusion was detected. The fever and upper respiratory symptoms were confirmed, and she was diagnosed with coronavirus disease (COVID-19) after showing a positive polymerase chain reaction (PCR) test. After thoracentesis, pleural fluid revealed elevated adenosine deaminase values and a positive QuantiFeron test; tuberculous pleurisy was thus suspected. Subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR and anti-SARS-CoV-2 Spike IgG tests were negative, suggesting that the initial PCR result had been erroneous. However, we were unable to confirm this. Data concerning COVID-19 diagnostics are insufficient at present. It is important to make comprehensive judgments regarding the diagnosis and treatment of patients as well as public health.

Coronavirus Disease 2019 (COVID-19) Breakthrough Infection and Post-Vaccination Neutralizing Antibodies Among Healthcare Workers in a Referral Hospital in Tokyo: A Case-Control Matching Study.

BACKGROUND: While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. METHODS: We describe incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected 3 matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the 2 groups. RESULTS: No COVID-19 cases occurred 1-2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2-4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and participants had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. CONCLUSIONS: Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant outbreak. The result points to the importance of infection-control measures in the post-vaccination era, irrespective of immunogenicity profile.

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease.

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.