Antibody responses to SARS-CoV-2 nucleocapsid and spike proteins in hospitalized patients with COVID-19: A multicenter,retrospective, cross-sectional study in Japan

BackgroundThere are many commercially available automated assays for assessing coronavirus disease 2019 (COVID-19) immune responses; however, owing to insufficient data, their validities remain unknown. Here, we examined antibody responses during acute-phase COVID-19 using four assays that detect anti-spike protein IgM (S-IgM), anti-nucleocapsid protein IgG (N-IgG), anti-spike protein total Ig (S-total Ig), and anti-spike protein IgG (S-IgG).MethodsWe measured antibody levels in 1154 serum samples collected from 286 hospitalized patients with confirmed COVID-19 by a gene amplification method between February and December 2020 in Japan. Sera from 860 healthcare workers were used as negative controls.ResultsThe antibody positivity rates increased on week 2, peaked, and then started to plateau by the beginning of week 3 after symptom onset. On week 1, there were some significant differences in seropositivity rates between assays (p = 0.032): 14.9% (11.0%–19.4%) for S-IgM and 8.9% (6.0%–12.7%) for N-IgG. The seropositivity for the S-total Ig (10.6% [7.3%–14.6%]) assay was considerably better than that for the S-IgG (6.9% [4.3%–10.4%]) assay, although the difference was not statistically significant (p = 0.150). The levels of S-IgM antibodies and the three others peaked on weeks 3 and 5, respectively. All four assays showed high specificities (>99%).ConclusionsAll four assays had good specificities and were suitable for seropositivity detection after week 3 of symptom onset. Assays of IgM alone or total Ig (containing IgM) were better than those of IgG alone as an adjunct serological test for early-stage COVID-19 diagnosis, albeit the use of a serological assay alone is insufficient.     

COVID-19 vaccination benefits in preventing severe disease in mild-to-moderate cases: An analysis in the first specialized hospital for COVID-19 in Japan

BackgroundIn Japan, the fourth round of coronavirus disease (COVID-19) vaccination is ongoing and is targeted at medical staff and nursing home workers, individuals aged ≥60 years, and those with comorbidities or other high-risk factors, including body mass index (BMI) ≥30 kg/m². The incidence of severe COVID-19 decreased markedly after widespread COVID-19 vaccination drives, and our hospital experienced a similar trend. We, therefore, examined the characteristics of our patients to clarify who benefited the most from vaccination.MethodsWe retrospectively investigated all patients hospitalized for COVID-19 in Osaka City Juso Hospital between March 1, 2021, and June 30, 2022. Using multivariable logistic analysis, we calculated the adjusted odds ratios (aORs) for severe disease after vaccination in the whole dataset and in subsets stratified by age, sex, BMI, smoking history, pre-hospitalization location, and comorbidities.ResultsThe analysis included 1041 patients. Multivariable logistic analysis showed that vaccination was associated with a low risk of severe disease, with an aOR of 0.21 (95% confidence interval: 0.12–0.36, p < 0.001). On stratifying the analysis according to background characteristics, lower aORs for severe COVID-19 were found for patients aged ≥60 years and for those with diabetes or hypertension. Notably, patients with BMI >30 kg/m² and those with BMI ≥18 kg/m² and ≤30 kg/m² benefited from vaccination.ConclusionsIndividuals with diabetes or hypertension and those of age ≥60 years benefited more from vaccination than did their counterparts. We recommend extending the fourth round of vaccinations to individuals with a BMI of 18–30 kg/m².     

Comparison of clinical characteristics and outcomes of COVID-19 patients undergoing early versus late intubation from initial hospital admission: A systematic review and meta-analysis

BackgroundThe true impact of intubation and mechanical ventilation in coronavirus disease 2019 (COVID-19) patients remains controversial.MethodsWe searched Pubmed, Cochrane Library, Embase, and Web of Science databases from inception to October 30th, 2021 for studies containing comparative data of COVID-19 patients undergoing early versus late intubation from initial hospital admission. Early intubation was defined as intubation within 48 h of hospital admission. The primary outcomes assessed were all-cause in-hospital mortality, renal replacement therapy (RRT), and invasive mechanical ventilation (IMV) duration.ResultsFour cohort studies with 498 COVID-19 patients were included between February to August 2020, in which 28.6% had early intubation, and 36.0% underwent late intubation. Although the pooled hospital mortality rate was 32.1%, no significant difference in mortality rate was observed (odds ratio [OR] 0.81; 95% confidence interval 0.32–2.00; P = 0.64) among those undergoing early and late intubation. IMV duration (mean 9.62 vs. 11.77 days; P = 0.25) and RRT requirement (18.3% vs. 14.6%; OR 1.19; P = 0.59) were similar regardless of intubation timing. While age, sex, diabetes, and body mass index were comparable, patients undergoing early intubation had higher sequential organ failure assessment (SOFA) scores (mean 7.00 vs. 5.17; P < 0.001).ConclusionsThe timing of intubation from initial hospital admission did not significantly alter clinical outcomes during the early phase of the COVID-19 pandemic. Higher SOFA scores could explain early intubation. With the advancements in COVID-19 therapies, more research is required to determine optimal intubation time beyond the first wave of the pandemic.     

Anti-Saccharomyces cerevisiae antibodies in patients with COVID-19

Background and study aimAnti-Saccharomyces cerevisiae antibodies (ASCA) have been described in many autoimmune diseases (AIDs). Coronavirus disease 2019 (COVID-19) could trigger AIDs. This study aimed to determine the frequency of ASCA in patients with COVID-19.Patients and methodsThis study included 88 adult patients with severe COVID-19, 51 mild COVID-19, and 160 healthy blood donors. ASCA of isotype immunoglobulin (Ig)G and IgA were detected by enzyme-linked immunosorbent assay.ResultsThe frequency of ASCA (IgG or IgA) was significantly higher in patients with severe COVID-19 (21.6 % vs 3.7 %, p < 10^?3) and in patients with mild COVID-19 than in the healthy controls (13.7 % vs 3.7 %, p = 0.03). ASCA-IgA was significantly more frequent in patients with severe COVID-19 than in healthy controls (15.9 % vs 0.6 %, p < 10^?3). ASCA-IgG was significantly more frequent in patients with mild COVID-19 than in healthy controls (13.7 % vs 3.1 %, p = 0.02). ASCA (IgG or IgA) were more frequent in severe than in mild COVID-19, but the difference was not statistically significant (21.6 % vs 13.7 %). ASCA-IgA was significantly more frequent in patients with severe than those with mild COVID-19 (15.9 % vs 0 %, p = 0.003). The mean ASCA-IgG and ASCA-IgA levels were significantly higher in patients with severe COVID-19 than in healthy controls (5.8 U/mL ± 11.8 vs 2.3 U/mL ± 2.8, p < 10^?3 and 9.2 U/mL ± 21.5 vs 3.4 U/mL ± 1.7, respectively, p < 10^?3). The mean ASCA-IgG levels were significantly higher in patients with mild COVID-19 than in healthy controls (6.2 U/mL ± 12.9 vs 2.3 U/mL ± 2.8, p < 10^?3). The mean ASCA-IgA levels were significantly higher in patients with severe than in those with mild COVID-19 (9.2 U/mL ± 21.5 vs 2.6 U/mL ± 1.2, p = 0.03).ConclusionASCA was more frequent in patients with COVID-19 than in healthy controls.     

COVID-19 symptom-onset to diagnosis and diagnosis to treatment intervals are significant predictors of disease progression and hospitalization in high-risk patients: A real world analysis

BackgroundCoronavirus disease (COVID-19) is overwhelming healthcare systems worldwide. This study aimed to elucidate factors that influence disease progression to pneumonia and hospitalization before and after antiviral treatment for COVID-19 in an outpatient setting.MethodsA total of 206 high-risk patients with COVID-19 were treated with sotrovimab, remdesivir, and molnupiravir at the Toshiwakai clinic between January 4 and April 30, 2022. Of these, 49 patients visited the Toshiwakai clinic directly and were treated immediately after diagnosis (Toshiwakai-clinic study group). The remaining patients were diagnosed elsewhere, and of these, 102 patients were quarantined at home (health-center study group) and 55 at designated facilities (quarantine-facility study group) before being referred to Toshiwakai clinic. Patients were categorized into those with mild and moderate COVID-19, based on the presence of pneumonia at the initial visit to Toshiwakai clinic.ResultsThe symptom-onset-to-diagnosis and diagnosis-to-treatment intervals were significant predictors of moderate disease. Age, dyspnea, and diagnosis-to-treatment interval at the first visit to Toshiwakai clinic were significant predictors for hospitalization even after antiviral treatment. Although the symptom-onset-to-diagnosis interval did not differ among the three study groups, the diagnosis-to-treatment and symptom-onset-to-treatment intervals were significantly longer in the health-center and quarantine-facility study groups than in the Toshiwakai-clinic study group.ConclusionThe symptom-onset-to-diagnosis and diagnosis-to-treatment intervals reflect diagnostic and interventional delays, respectively, which are closely related to the current COVID-19 clinical management protocol. Easy access to the clinics and immediate antiviral treatment after diagnosis may be the best methods to prevent disease progression and hospitalization in high-risk patients.     

Glycemic control metrics using flash glucose monitoring and hospital complications in patients with COVID-19

Background and aimsFew studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19.MethodsProspective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury.ResultsA total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70–180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04).ConclusionsBasal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.     

Diagnostic prediction of COVID-19 based on clinical and radiological findings in a relatively low COVID-19 prevalence area

BackgroundDistinguishing coronavirus disease 2019 (COVID-19) pneumonia from other lung diseases is often difficult, especially in a highly comorbid patient population in a low prevalence region. We aimed to distinguish clinical data and computed tomography (CT) images between COVID-19 and other lung diseases in an advanced care hospital.MethodsWe assessed clinical characteristics, laboratory data, and chest CT images of patients with COVID-19 and non-COVID-19 patients who were suspected of having COVID-19 between February 20 and May 21, 2020, at the University of Tokyo Hospital.ResultsTypical appearance for COVID-19 on CT images were found in 24 of 29 COVID-19 cases and 21 of 168 non-COVID-19 cases, according to the Radiological Society of North America Expert Consensus Statement (for predicting COVID-19, sensitivity 0.828, specificity 0.875, positive predictive value 0.533, negative predictive value 0.967). When we focused on cases with typical CT images, loss of taste or smell, and close contact with COVID-19 patients were exclusive characteristics for the COVID-19 cases. Among laboratory data, high fibrinogen (P < 0.01) and low white blood cell count (P < 0.01) were good predictors for COVID-19 with typical CT images in multivariate analysis.ConclusionsIn a relatively low prevalence region, CT screening has high sensitivity to COVID-19 in patients with suspected symptoms. When chest CT findings are typical for COVID-19, close contact, loss of taste or smell, lower white blood cell count, and higher fibrinogen are good predictors for COVID-19.     

Pattern of liver function and clinical profile in COVID-19: A cross-sectional study of 91 patients

Background– COVID-19 caused by SARS-CoV-2 leads to myriad range of organ involvement including liver dysfunction.AimTo analyse the liver function in patients with COVID-19 and their association with respect to age, sex, severity of disease and clinical features.Materials and methodsThis study was a cross-sectional study done at Rajendra Institute of Medical Sciences, Ranchi. 91 patients admitted with confirmed SARS-CoV-2 infection were included in this study and divided into asymptomatic, mild, moderate and severe groups. Liver function tests were compared among different severity groups.ResultsOf 91 patients with COVID-19, 70 (76.9%) had abnormal liver function. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin levels was 1–2 × ULN in 33(36.3%), 34(37.3%), 12(13.2%), 6(6.6%) cases and >2 × ULN in 20(22%), 18(19.8%), 7(7.7%) and 2 (2.2%) cases respectively. Mean AST and ALP levels among different severity groups of COVID-19 was statistically significant (p < 0.05) whereas mean ALT and total bilirubin levels was statistically non-significant (p > 0.05). There was no statistical difference between males and females with regard to abnormal liver function. Liver injury was seen in 64.3% cases of hypertension and 73.3% cases of diabetes. Fever, myalgia, headache and breathlessness were found to be correlated significantly with severity of disease.ConclusionLiver injury is common in SARS-CoV-2 infection and is more prevalent in the severe disease group. Aspartate transaminase and alkaline phosphatase are better indicators of covid-19 induced liver injury than alanine transaminase and total bilirubin.     

Increased Risk of Hospitalization in Celiac Disease With COVID-19 Infection Is Mitigated by Vaccination

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Differential white blood cell count in the COVID-19: A cross-sectional study of 148 patients

BackgroundSARS-CoV-2 infection alters various blood parameters, which may indicate disease severity and thus help in better clinical management.AimTo study the association between various hematological parameters and disease severity of COVID-19. To analyze the effects of hypertension and diabetes on neutrophil-lymphocyte ratio and neutrophil-monocyte ratio in patients suffering from COVID-19.Materials and methodsThe study was a cross-sectional study involving 148 laboratory-confirmed cases of SARS-CoV-2 infection. The patients were divided into three groups on the basis of disease severity. Various hematological parameters were analyzed. The effects of hypertension and diabetes on NLR and NMR in COVID-19 patients were evaluated.ResultsOf the 148 patients, 78.4%, 8.1% and 13.5% cases were in the mild, moderate and severe groups, respectively. Mean age was 42.63 ± 16.04 years (IQR: 29, 54.75; Range: 7–74). 58.8% patients were male while the rest (42.2%) were female. Mean TLC (cells/mm³), neutrophil (%), lymphocyte (%), monocyte (%), eosinophil (%), neutrophil-lymphocyte ratio (NLR) and neutrophil-monocyte ratio (NMR) among mild, moderate and severe COVID-19 was statistically significant (p < 0.05). Basophil (%) and lymphocyte-monocyte ratio (LMR) was statistically insignificant among the three groups. Lymphocyte (%), monocyte (%) and eosinophil (%) were negatively correlated to disease severity. Among diabetics, both NLR and NMR were statistically significant (p < 0.05). However, among hypertensive cases, only the NLR was statistically significant.ConclusionOlder age, higher TLC, neutrophilia, lymphopenia, eosinopenia, high NLR and high NMR are associated with severe COVID-19. High NLR and high NMR are indicative of severe disease among diabetic patients. High NLR also indicates severe disease among hypertensive patients.     

Applicability of lung ultrasound in the assessment of COVID-19 pneumonia: Diagnostic accuracy and clinical correlations

BackgroundThe purpose of this study was to assess the diagnostic accuracy of lung ultrasound (LUS) in determining the severity of coronavirus disease 2019 (COVID-19) pneumonia compared with thoracic computed tomography (CT) and establish the correlations between LUS score, inflammatory markers, and percutaneous oxygen saturation (SpO₂).MethodsThis prospective observational study, conducted at Târgu-Mureș Pulmonology Clinic included 78 patients with confirmed severe acute respiratory syndrome coronavirus-2 infection via nasopharyngeal real-time-polymerase chain reaction (RT-PCR) (30 were excluded). Enrolled patients underwent CT, LUS, and blood tests on admission. Lung involvement was evaluated in 16 thoracic areas, using AB₁ B₂ C (letters represent LUS pattern) scores ranging 0–48.ResultsLUS revealed bilateral B-lines (97.8%), pleural irregularities with thickening/discontinuity (75%), and subpleural consolidations (70.8%). Uncommon sonographic patterns were alveolar consolidations with bronchogram (33%) and pleural effusion (2%). LUS score cutoff values of ≤14 and > 22 predicted mild COVID-19 (sensitivity [Se] = 84.6%; area under the curve [AUC] = 0.72; P = 0.002) and severe COVID-19 (Se = 50%, specificity (Sp) = 91.2%, AUC = 0.69; P = 0.02), respectively, and values > 29 predicted the patients’ transfer to the intensive care unit (Se = 80%, Sp = 97.7%). LUS score positively correlated with CT score (r = 0.41; P = 0.003) and increased with the decrease of SpO₂ (r = −0.49; P = 0.003), with lymphocytes decline (r = −0.52; P = 0.0001). Patients with consolidation patterns had higher ferritin and C-reactive protein than those with B-line patterns (P = 0.01; P = 0.03).ConclusionsLUS is a useful, non-invasive and effective tool for diagnosis, monitoring evolution, and prognostic stratification of COVID-19 patients.     

Outcome of early-stage combination treatment with favipiravir and methylprednisolone for severe COVID-19 pneumonia: A report of 11 cases

Although the use of corticosteroids is not recommended in the World Health Organization statement for the treatment of coronavirus disease 2019 (COVID-19), steroid therapy may be indicated for critical cases in specific situations. Here, we report the successful treatment of 11 cases of severe COVID-19 pneumonia with favipiravir and methylprednisolone. All cases were severe and patients required oxygen administration or had a blood oxygen saturation ≤93% on room air. All were treated with favipiravir and methylprednisolone, and 10 of 11 patients responded well and required no further oxygen supplementation or ventilator management. This study shows the importance of the early-stage use of a combination of favipiravir and methylprednisolone in severe cases to achieve a favorable clinical outcome.