A systematic review and meta-analysis comparing the clinical characteristics and outcomes of COVID-19 and influenza patients on ECMO

BackgroundExtracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza.MethodsWe searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza.ResultsThe study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups.ConclusionClinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.     

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.     

Clinical characteristics of COVID-19 in Osaka,Japan: Comparison of the first–third waves with the fourth wave

BackgroundThe fourth wave of COVID-19 in Osaka Prefecture, Japan, caused a medical crisis. Here, we aim to identify the risk factors for COVID-19 severity and compare patients between the first–third waves and the fourth wave.MethodsWe performed an observational retrospective study of COVID-19 cases at the National Hospital Organization Kinki-Chuo Chest Medical Center.ResultsWe identified 404 patients (median age: 71.0 years [interquartile range: 56.0–80.0]), of whom 199 (49.1%) had mild disease, 142 (35.2%) had moderate disease, and 63 (15.6%) had severe disease. The overall mortality rate was 5.4% (22/404). Based on multivariate logistic regression analysis, cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were independent risk factors for moderate to severe disease. For every 1 mg/dL increase in C-reactive protein, 10 IU/L increase in lactate dehydrogenase, and 100 ng/mL increase in ferritin, the risk for moderate to severe disease increased by 18.3%, 12.9%, and 8.9%, respectively. Overall disease severity in the fourth wave was higher than in the first–third waves. However, there was no significant difference in mortality. Because of a shortage of beds, four of the 28 severe patients (14.3%) in the fourth wave could not be transferred to the advanced hospital.ConclusionsCardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were risk factors for moderate to severe COVID-19 in our cohort. During the fourth wave, COVID-19 severity worsened, increasing the number of patients who could not be transferred to beds for severe cases, resulting in a medical crisis in Osaka.     

Decrease in hemoglobin level predicts increased risk for severe respiratory failure in COVID-19 patients with pneumonia

BackgroundIn December 2019, the coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan, China, and has since spread throughout the world. This study aimed to investigate the association between the change in laboratory markers during the three days after pneumonia diagnosis and severe respiratory failure in COVID-19 patients.MethodsData of 23 COVID-19 patients with pneumonia, admitted to the Kumamoto City Hospital between February and April 2020 were retrospectively analyzed.ResultsAmong the 23 patients, eight patients received mechanical ventilation (MV) (MV group), and the remaining 15 comprised the non-MV group. The levels of hemoglobin (Hb) and albumin (Alb) decreased in the MV group during the three days after pneumonia diagnosis more than in the non-MV group (median Hb: 1.40 vs. ?0.10 g/dL, P = 0.015; median Alb: 0.85 vs. ?0.30 g/dL, P = 0.020). Univariate logistic regression analysis showed that the decrease in Hb was associated with receiving MV care (odds ratio: 0.313, 95% confidence interval: 0.100–0.976, P = 0.045). Receiver operating characteristic curve analyses showed that the optimal cut-off value for the decrease in Hb level was ?1.25 g/dL, with sensitivity and specificity values of 0.867 and 0.750, respectively.ConclusionsThe decrease in Hb level during the short period after pneumonia diagnosis might be a predictor of worsening pneumonia in COVID-19 patients.     

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.     

Initial Findings From the North American COVID-19 Myocardial Infarction Registry

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI).ObjectivesThe goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI.MethodsA prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization.ResultsAs of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients).ConclusionsCOVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.     

Serum gasdermin D levels are associated with the chest computed tomography findings and severity of COVID-19

BackgroundThe role of programmed cell death, especially pyroptosis and apoptosis, in unfavorable immune responses in COVID-19 remains to be elucidated.MethodsWe conducted a cross-sectional analysis to investigate the association between the serum gasdermin D (GSDMD) levels, a pyroptotic marker, and caspase-cleaved cytokeratin 18 fragment (M30), an apoptotic marker, and the clinical status and abnormal chest computed tomography (CT) findings in patients with COVID-19.ResultsIn this study, 46 patients diagnosed with COVID-19 were divided into the following three groups according to the disease severity: mild to moderate group (n = 10), severe group (n = 14), and critical group (n = 22). The serum GSDMD levels were higher in the critical group than in the mild to moderate group (P = 0.016). In contrast, serum M30 levels were lower in the critical group than in the severe group (P = 0.048). Patients who required mechanical ventilation or died had higher serum GSDMD levels than those who did not (P = 0.007). Area of consolidation only and of ground glass opacity plus consolidation positively correlated with serum GSDMD levels (r = 0.56, P < 0.001 and r = 0.53, P < 0.001, respectively).ConclusionHigher serum GSDMD levels are associated with critical respiratory status and the consolidation area on chest CT in patients with COVID-19, suggesting that excessive activation of pyroptosis may affect the clinical manifestations in patients with 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.     

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.     

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.     

SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants as potential clinical biomarkers for personalized treatment strategy selection in patients with severe COVID-19 pneumonia

BackgroundExploring the pathogenetic mechanisms behind severe lung damage in COVID-19 is crucial. In this study, we decided to focus on two molecular markers that affect surfactant metabolism and lung development: the surfactant protein B (SFTPB) and the glucocorticoid receptor (NR3C1) genes. The aim of our study was to determine the effect of SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the course of the disease in patients with COVID-19, and the treatment measures they required.MethodsThe study group included 58 patients with a diagnosis of severe “viral COVID-19 pneumonia.” Determination of SFTPB and NR3C1 gene variants was performed using the PCR-RFLP method.ResultsOur results indicate that the presence of the SFTPB gene CC genotype increases the risk of developing acute respiratory distress syndrome in patients with COVID-19 (χ² = 4.03, p = 0.045, OR = 3.90 [1.19–12.78]). However, patients with the SFTPB gene TT genotype required respiratory support for a shorter period of time. Patients with the NR3C1 gene CC genotype underwent a longer glucocorticoid therapy. Moreover, for patients with the CC genotype, a longer stay in the intensive care unit was detected before lethal outcome.ConclusionsThe obtained results confirm the influence of the SFTPB (rs11130866) and NR3C1 (rs41423247) gene variants on the therapy, course, and severity of the disease in patients with COVID-19. Of course, these results require further study, analysis, and larger, complex, systematic research.     

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies.MethodsWe administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization.ResultsResponses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis.ConclusionsThis study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.     

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.     

Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019

BackgroundCoronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19.MethodsWe retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity.ResultsA total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p < 0.001). Serum KL-6 value at peak level (371 U/mL) was used as the optimal cut-off to evaluate disease severity (sensitivity, 85.7%; specificity, 96.6%).ConclusionsSerum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity.     

Clinical outcomes of corticosteroids for COVID-19 patients at the National Center for Global Health and Medicine during the first wave of infections

BackgroundCoronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections.MethodsWe retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients’ clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group.ResultsBetween February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results.ConclusionsThere was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.     

Disease Course and Outcomes of COVID-19 Among Hospitalized Patients With Gastrointestinal Manifestations

Background & AimsOur understanding of outcomes and disease time course of COVID-19 in patients with gastrointestinal (GI) symptoms remains limited. In this study we characterize the disease course and severity of COVID-19 among hospitalized patients with gastrointestinal manifestations in a large, diverse cohort from the Unites States.MethodsThis retrospective study evaluated hospitalized individuals with COVID-19 between March 11 and April 28, 2020 at two affiliated hospitals in New York City. We evaluated the association between GI symptoms and death, and also explored disease duration, from symptom onset to death or discharge.ResultsOf 2804 patients hospitalized with COVID-19, the 1,084 (38.7%) patients with GI symptoms were younger (aOR for age ≥75, 0.59; 95% CI, 0.45-0.77) and had more co-morbidities (aOR for modified Charlson comorbidity score ≥2, 1.22; 95% CI, 1.01-1.48) compared to those without GI symptoms. Individuals with GI symptoms had better outcomes, with a lower likelihood of intubation (aHR, 0.66; 95% CI, 0.55-0.79) and death (aHR, 0.71; 95% CI, 0.59-0.87), after adjusting for clinical factors. These patients had a longer median disease course from symptom onset to discharge (13.8 vs 10.8 days, log-rank p = .048; among 769 survivors with available symptom onset time), which was driven by longer time from symptom onset to hospitalization (7.4 vs 5.4 days, log-rank P < .01).ConclusionHospitalized patients with GI manifestations of COVID-19 have a reduced risk of intubation and death, but may have a longer overall disease course driven by duration of symptoms prior to hospitalization.     

Remdesivir en pacientes trasplantados renales con neumonía por SARS-CoV-2

BackgroundRemdesivir is the only antiviral treatment that has been shown to be useful against SARS-CoV-2 infection. It shorts hospitalization time compared to placebo. Its effects in kidney transplant (KT) patients are limited to some published cases.MethodsWe performed a retrospective observational study that included all KT patients admitted between August 1st, 2020 and December 31st, 2020 with SARS-CoV-2 pneumonia who received remdesivir.The objective of this study was to describe the experience of a cohort of KT patients treated with remdesivir.DiscussionA total of 37 KT patients developed SARS-CoV-2 infection, 7 of them received treatment with remdesivir. The rest of the patients did not receive the drug due to either CKD-EPI less than 30 mL/min or they did not present clinical criteria. In addition to remdesivir, all patients received dexamethasone and anticoagulation therapy. 4 were men, the median age was 59 (53–71) years. Median time from transplantation was 43 (16–82) months. Chest X-rays of all patients showed pulmonary infiltrates and required low-oxygen flow therapy upon admission, requiring high-flow nasal therapy in 3 cases. Only 2 cases presented deterioration of the graft function, not requiring hemodialysis in any case, and all recovered renal function at hospital discharge. 2 patients rise up 1.5 times the liver function test. No patient died or required admission to the critical care unit. Median days of admission was 12 (9–27) days.ConclusionsOur study suggests that the use of remdesivir could be useful in KT patients with SARS-CoV-2 pneumonia without side effects. Additional studies are necessary with a larger number of patients to improve the knowledge of this drug in SARS-CoV-2 infection.     

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.     

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19

BackgroundPublished data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.ObjectivesThe purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre–COVID-19 cohorts.MethodsFrom March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re–myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre–COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).ResultsIn 144 ST-segment elevation myocardial infarction (STEMI) and 121 non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).ConclusionsIn this multicenter international registry, COVID-19–positive ACS patients presented later and had increased in-hospital mortality compared with a pre–COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.     

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection

BackgroundThe intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response.ObjectivesThe goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19.MethodsIn this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline.ResultsPatients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).ConclusionsPCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)