Validation of the severe COVID-19 prognostic value of serum IL-6, IFN-λ3, CCL17, and calprotectin considering the timing of clinical need for prediction.

Although biomarkers to predict coronavirus disease 2019 (COVID-19) severity have been studied since the early pandemic, no clear guidelines on using them in clinical practice are available. Here, we examined the ability of four biomarkers to predict disease severity using conserved sera from COVID-19 patients who received inpatient care between January 1, 2020 and September 21, 2021 at the National Center for Global Health and Medicine, collected at the appropriate time for prediction. We predicted illness severity in two situations: 1) prediction of future oxygen administration for patients without oxygen support within 8 days of onset (Study 1) and 2) prediction of future mechanical ventilation support (excluding non-invasive positive pressure ventilation) or death of patients within 4 days of the start of oxygen administration (Study 2). Interleukin-6, IFN-λ3, thymus and activation-regulated chemokine, and calprotectin were measured retrospectively. Other laboratory and clinical information were collected from medical records. AUCs were calculated from ROC curves and compared for the predictive ability of the four biomarkers. Study 1 included 18 patients, five of whom had developed oxygen needs. Study 2 included 45 patients, 13 of whom required ventilator management or died. In Study 1, IFN-λ3 showed a good predictive ability with an AUC of 0.92 (95% CI 0.76-1.00). In Study 2, the AUC of each biomarker was 0.70-0.74. The number of biomarkers above the cutoff showed the possibility of good prediction with an AUC of 0.86 (95% CI 0.75-0.97). When two or more biomarkers were positive, sensitivity and specificity were 0.92 and 0.63, respectively. In terms of biomarker testing at times when prognostication may be clinically useful, IFN-λ3 was predictive of oxygenation demand and a combination of the four biomarkers was predictive of mechanical ventilator requirement.

Nasopharyngeal SARS-CoV-2 may not be dispersed by a high-flow nasal cannula.

A high-flow nasal cannula (HFNC) therapy plays a significant role in providing respiratory support to critically ill patients with coronavirus disease 2019 (COVID-19); however, the dispersion of the virus owing to aerosol generation is a matter of concern. This study aimed to evaluate if HFNC disperses the virus into the air. Among patients with COVID-19 admitted to private rooms with controlled negative pressure, we enrolled those admitted within 10 days of onset and requiring oxygenation through a conventional nasal cannula or HFNC therapy. Of the 17 patients enrolled, we obtained 22 samples (11 in the conventional nasal cannula group and 11 in the HFNC group). Viral RNA was detected in 20 nasopharyngeal swabs, and viable viruses were isolated from three nasopharyngeal swabs. Neither viral RNA nor viable virus was detected in the air sample at 0.5 m regardless of the oxygen-supplementation device. We detected viral RNA in two samples in the conventional nasal cannula group but not in the HFNC therapy group in gelatin filters located 3 m from the patient and the surface of the ventilation. This study directly demonstrated that despite viral RNA detection in the nasopharynx, viruses may not be dispersed by HFNC therapy. This warrants further research to determine if similar results can be obtained under different conditions.

Liver resection in a patient with persistent positive PCR test for coronavirus disease 2019 (COVID-19): a case report.

BACKGROUND: The perioperative mortality rate is high in patients with coronavirus disease 2019 (COVID-19), and infection control measures for medical care providers must be considered. Therefore, the timing for surgery in patients recovering from COVID-19 is difficult. CASE PRESENTATION: A 65-year-old man was admitted to a hospital with a diagnosis of moderate COVID-19. He was transferred to our hospital because of risk factors, including heavy smoking history, type 2 diabetes mellitus, and obesity (BMI 34). Vital signs on admission were a temperature of 36.1 °C, oxygen saturation > 95% at rest, and 94% on exertion with 3 L/min of oxygen. Chest computed tomography (CT) showed bilateral ground-glass opacities, predominantly in the lower lungs. Contrast-enhanced abdominal CT incidentally revealed a liver tumor with a diameter of 80 mm adjacent to the middle hepatic vein, which was diagnosed as hepatocellular carcinoma (HCC). After being administered baricitinib, remdesivir, dexamethasone, and heparin, the patient's COVID-19 pneumonia improved, his oxygen demand resolved, and he was discharged on day 13. Furthermore, the patient was initially scheduled for hepatectomy 8 weeks after the onset of COVID-19 following a discussion with the infection control team. However, 8 weeks after the onset of illness, a polymerase chain reaction (PCR) test was performed on nasopharyngeal swab fluid, which was observed to be positive. The positive results persisted till 10 and 11 weeks after onset. Both Ct values were high (≥ 31) out of 45 cycles, with no subjective symptoms. Since we determined that he was no longer contagious, surgery was performed 12 weeks after the onset of COVID-19. Notably, medical staff wearing personal protective equipment performed extended anatomical resection of the liver segment 8 ventral area in a negative-pressure room. The patient had a good postoperative course, with no major complications, including respiratory complications, and was discharged on postoperative day 14. Finally, none of the staff members was infected with COVID-19. CONCLUSIONS: We reported a case regarding the timing of surgery on a patient with persistently positive PCR test results after COVID-19, along with a literature review.

Potential usage of anterior nasal sampling in clinical practice with three rapid antigen tests for SARS-CoV-2

Introduction Anterior nasal sampling (AN) might be more convenient for patients than NP sampling to diagnose coronavirus disease. This study investigated the feasibility of rapid antigen tests for AN sampling, and the factors affecting the test accuracy. Methods This single-center prospective study evaluated one qualitative (ESP) and two quantitative (LUMI and LUMI-P) rapid antigen tests using AN and NP swabs. Symptomatic patients aged 20 years or older, who were considered eligible for reverse-transcription quantitative polymerase chain reaction using NP samples within 9 days of onset were recruited. Sensitivity, specificity, and positive and negative concordance rates between AN and NP samples were assessed for the rapid antigen tests. We investigated the characteristics that affected the concordance between AN and NP sampling results. Results A total of 128 cases were recruited, including 28 positive samples and 100 negative samples. The sensitivity and specificity of AN samples using ESP were 0.81 and 1.00, while those of NP samples were 0.94 and 1.00. The sensitivity of AN and NP samples was 0.91 and 0.97, respectively, and specificity was 1.00, for both LUMI and LUMI-P. The positive concordance rates of AN to NP sampling were 0.87, 0.94, and 0.85 for ESP, LUMI, and LUMI-P, respectively. No factor had a significant effect on the concordance between the sampling methods. Conclusions ESP, LUMI, and LUMI-P showed practical diagnostic accuracy for AN sampling compared to NP sampling. There was no significant factor affecting the concordance between AN and NP sampling for these rapid antigen tests.

Evaluation of the Detection of Pathogens in Hospitalized Patients with COVID-19 at a Tertiary Hospital in Japan.

The detection of other pathogens in patients with hospitalized coronavirus disease (COVID-19) are not frequent. Considering that data from Japan are limited, we conducted an observational study including patients with hospitalized COVID-19 at the National Center for Global Health and Medicine from January to September 2020. In total, 247 patients with COVID-19 were included in the study. Rapid diagnostic tests, such as immunochromatography, were performed in 31 patients (12.6%). The Film Array Respiratory Panel was performed in 18 (7.3%) patients, and none of the tests were positive for pathogens other than severe acute respiratory syndrome coronavirus 2. Respiratory bacterial culture was performed in 66 (26.7%) patients, with gram-positive bacteria, gram-negative bacteria and normal flora being detected in eight (12.1%), seven (10.6%), and 63 (95.5%) patients, respectively. Patients for whom cultures were performed were older, more severely ill, and more likely to have radiological evidence of pneumonia on admission. Culture was performed more frequently in the early than in the later period of the epidemic, without any differences being observed in bacterial detection rates. The proportion of viral and bacterial detection among hospitalized patients with COVID-19 in tertiary care hospitals in Japan was low. A larger cohort study is necessary to evaluate the effect of each pathogen on the clinical course of COVID-19.

Negative Results of Nucleic Acid Amplification Tests for SARS-CoV-2 in Clinical Practice May Vary among Six Molecular Assays in Patients with COVID-19.

Several commercial nucleic acid amplification tests (NAATs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. We used 6 kits available in Japan in 13 NAAT-positive specimens with crossing point values >36 and 7 NAAT-negative specimens from patients with coronavirus disease 2019 (COVID-19), and their results were compared. Specimens positive in ≥2 assays were considered true-positive and examined for concordance with the specimen results. The SARS-CoV-2 Detection Kit -Multi- (Toyobo M; Toyobo, Osaka, Japan) using extracted RNA had the highest concordance (κ = 1.00). This was followed by Cobas® SARS-CoV-2 (Roche, Basel, Switzerland) (κ = 0.79). There was a weak correlation between the number of negative results for each kit and the number of days between onset and testing (Spearman rank correlation: ρ = 0.44; P < 0.05). We believe that the variations in results among kits for specimens with low viral loads should not be problematic when these kits are used for screening infectious patients because these variations are more likely to be observed in specimens tested many days after onset (i.e., those that have lost their infectivity). However, it may be better to use a test for suspected late-stage COVID-19 with a low viral load, such as Toyobo M or Cobas.

Successful use of casirivimab/imdevimab anti-spike monoclonal antibodies to enhance neutralizing antibodies in a woman on anti-CD20 treatment with refractory COVID-19.

Management of COVID-19 patients with humoral immunodeficiency is challenging. We describe a woman with COVID-19 with multiple relapses due to anti-CD20 monoclonal antibody treatment. She was successfully treated with casirivimab/imdevimab and confirmed to have neutralizing antibodies. This case suggests that monoclonal antibodies have therapeutic and prophylactic value in patients with humoral immunodeficiency.

Multisystem Inflammatory Syndrome in Adult after First Dose of mRNA Vaccine.

A 32-year-old man in Japan experienced respiratory failure after receiving the first dose of coronavirus disease (COVID-19) vaccine. He was treated with noninvasive ventilation and corticosteroids. Serologic test results suggested previous COVID-19; therefore, he received a diagnosis of multisystem inflammatory syndrome. COVID-19 vaccination could be a trigger for this condition.

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.

Comparison of door-to-balloon time and in-hospital outcomes in patients with ST-elevation myocardial infarction between before versus after COVID-19 pandemic.

The situation around primary percutaneous coronary intervention (PCI) has dramatically changed since coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 pandemic on clinical outcomes as well as door-to-balloon time (DTBT), which is known as one of the indicators of early reperfusion, has not been fully investigated in patients with ST-elevation acute myocardial infarction (STEMI). The purpose of this study was to compare DTBT and in-hospital outcomes in patients with STEMI between before versus after COVID-19 pandemic. The primary interest was DTBT and the incidence of in-hospital outcomes including in-hospital death. We included 330 patients with STEMI who underwent primary PCI, and divided them into the pre COVID-19 group (n = 209) and the post COVID-19 group (n = 121). DTBT was significantly longer in the post COVID-19 group than in the pre COVID-19 group (p < 0.001), whereas the incidence of in-hospital death was comparable between the 2 groups (p = 0.238). In the multivariate logistic regression analysis, chest CT before primary PCI (OR 4.64, 95% CI 2.58-8.34, p < 0.001) was significantly associated with long DTBT, whereas chest CT before primary PCI (OR 0.76, 95% CI 0.29-1.97, p = 0.570) was not associated with in-hospital death after controlling confounding factors. In conclusion, although DTBT was significantly longer after COVID-19 pandemic than before COVID-19 pandemic, in-hospital outcomes were comparable between before versus after COVID-19 pandemic. This study suggests the validity of the screening tests including chest CT for COVID-19 in patients with STEMI who undergo primary PCI.

Time-course evaluation of the quantitative antigen test for severe acute respiratory syndrome coronavirus 2: The potential contribution to alleviating isolation of COVID-19 patients.

INTRODUCTION: The automated quantitative antigen test (QAT), which detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is suitable for mass screening. However, its diagnostic capability differentiated by time from onset and potential contribution to infectivity assessment have not been fully investigated. METHODS: A retrospective, observational study using nasopharyngeal swab specimens from coronavirus disease (COVID-19) inpatients was conducted using LumipulseⓇ SARS-CoV-2 antigen test. Diagnostic accuracy was examined for the early (up to 10 days after onset) and late (over 10 days after onset) stages. Time-course QAT changes and reverse-transcription quantitative polymerase chain reaction tests results were displayed as locally estimated scatterplot smoothing curve, and receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cutoff value for differentiating the early and late stages. RESULTS: We obtained 100 specimens from 68 COVID-19 patients, including 51 early-stage and 49 late-stage specimens. QAT sensitivity and specificity were 0.82 (0.72-0.90) and 0.95 (0.75-0.99) for all periods, 0.93 (0.82-0.98) and 1.00 (0.39-1.00) for the early stage, and 0.66 (0.48-0.82) and 0.93 (0.69-0.99) for the late stage, respectively. The ROC analysis indicated an ideal cutoff value of 6.93 pg/mL for distinguishing early-from late-stage specimens. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting the late stage were 0.76 (0.61-0.87), 0.76 (0.63-0.87), 0.76 (0.61-0.87), and 0.76 (0.63-0.87). CONCLUSIONS: QAT has favorable diagnostic accuracy in the early COVID-19 stages. In addition, an appropriate cutoff point can potentially facilitate rapid identification of noncontagious patients.

Does the SARS-CoV-2 rapid antigen test result correlate with the viral culture result?

Rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have advantages over viral culture in terms of cost and rapidity of testing, but they have low sensitivity. In addition, RATs tend to be negative from approximately 11 days after symptom onset. To determine whether the antigen-negative state indicates a lack of infectiousness, we assessed the association between viral culture and RAT results. Viral culture, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and rapid antigen testing were performed on stored nasopharyngeal samples with threshold cycle values < 30, based on previous RT-qPCR testing. SARS-CoV-2 was isolated by viral culture from nine samples (45%) and one sample (17%) with positive and negative RAT results, respectively. The RAT and viral culture results were both associated with the viral load level and their cutoffs were similar, but the associations were not statistically significant. RAT might be a useful indicator of infectiousness, which can be helpful to control infection. However, further studies with larger sample size are warranted to confirm this observation.

Microbiological Testing for Coronavirus Disease 2019.

Microbiological diagnosis of coronavirus disease 2019 (COVID-19) is mainly performed through nucleic acid amplification test (NAAT) and antigen test. Although NAAT is the standard diagnostic test, its use is limited by insufficient laboratory resources and long turnaround time. Point-of-care NAAT tests have been introduced to address these shortcomings, but their varied sensitivity and resource constraints remain a concern. Antigen tests require fewer resources but have low sensitivity. Nevertheless, low-sensitivity tests may be useful depending on the situation. In contrast, in some clinical phases of COVID-19, high-sensitivity tests may provide false-negative results. Therefore, the right testing strategy is needed for an accurate diagnosis. In this review, the characteristics and clinical applications of microbiological tests available in Japan (NAAT, antigen test, and antibody test) are discussed. The clinical diagnosis of COVID-19 is slightly complicated, and cases in which the infection spreads from asymptomatic infected individuals are many; hence, laboratory diagnosis is essential to prevent further transmission.

When Clinicians Should Repeat RT-PCR for SARS-CoV-2: Repeat PCR Testing in Patients with Pulmonary CT Findings Suggestive of COVID-19.

Real-time reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are occasionally repeated when clinicians suspect false-negative results, but the conditions under which repeated RT-PCR testing is warranted remain unclear. We evaluated the practice of repeat RT-PCR testing for SARS-CoV-2 in 45 patients who were retested after an initial negative PCR test. Of these, the diagnosis of coronavirus disease (COVID-19) was confirmed in four patients with typical chest computed tomography (CT) findings and in one patient without typical CT findings in whom the test result was strongly suspected to be false-positive. We recommend repeat RT-PCR testing only for patients with typical CT findings of COVID-19.

Utility of the antigen test for coronavirus disease 2019: Factors influencing the prediction of the possibility of disease transmission.

OBJECTIVES: Rapid antigen testing (RAT) for coronavirus disease 2019 (COVID-19) has lower sensitivity but high accuracy during the early stage when compared to reverse transcription quantitative polymerase chain reaction (RT-qPCR). The aim of this study was to investigate the concordance between RAT and RT-qPCR results, and their prediction of disease transmission. METHODS: This single-center retrospective observational study of inpatients with COVID-19 was conducted from March 6 to June 14, 2020. Nasopharyngeal swabs were used to perform RAT and RT-qPCR. The primary endpoint was concordance between RAT and RT-qPCR results. The secondary endpoints were the factors causing disagreement in the results and the estimated transmissibility in RT-qPCR-positive patients with mild symptoms. RESULTS: Overall, 229 samples in viral transport medium (VTM) were obtained from 105 patients. The positive and negative concordance rates for VTM were 41% vs 99% (κ = 0.37) and 72% vs 100% (κ = 0.50) for samples collected on disease days 2-9. An increased body temperature (odds ratio 0.54) and absence of drugs with potential antiviral effect (odds ratio 0.48) yielded conflicting results. RAT was associated with the ability to end isolation (OR 0.11, 95% confidence interval 0.20-0.61). CONCLUSIONS: RAT and RT-qPCR results were highly consistent for samples collected at the appropriate time and could be useful for inferring the possibility of transmissibility.

Comparison of Rapid Antigen Tests for COVID-19.

Reverse transcription-quantitative PCR (RT-qPCR)-based tests are widely used to diagnose coronavirus disease 2019 (COVID-19). As a result that these tests cannot be done in local clinics where RT-qPCR testing capability is lacking, rapid antigen tests (RATs) for COVID-19 based on lateral flow immunoassays are used for rapid diagnosis. However, their sensitivity compared with each other and with RT-qPCR and infectious virus isolation has not been examined. Here, we compared the sensitivity among four RATs by using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates and several types of COVID-19 patient specimens and compared their sensitivity with that of RT-qPCR and infectious virus isolation. Although the RATs read the samples containing large amounts of virus as positive, even the most sensitive RAT read the samples containing small amounts of virus as negative. Moreover, all RATs tested failed to detect viral antigens in several specimens from which the virus was isolated. The current RATs will likely miss some COVID-19 patients who are shedding infectious SARS-CoV-2.

Telephone consults at the Infectious Disease Outpatient Clinic during the early period of the COVID-19 epidemic.

Once novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, China in December 2019 and the first case in Japan was reported the following month, telephone inquiries to the Infectious Disease Outpatient Clinic increased. During the first wave of the epidemic, before medical measures for this emerging infectious disease were in place, the Outpatient Clinic received a significant amount of inquiries, reflecting the prevailing social turmoil. During the second wave, inquiries did not increase because a proper system of medical care was in place in hospitals and communities. Therefore, in the early stages of an emerging infectious disease, relevant information needs to be quickly consolidated and it needs to be linked to measures that are appropriate to the situation.