Assessment of the pneumonia severity score in community-acquired and nursing and healthcare-associated pneumonia due to COVID-19

IntroductionThe Japanese Respiratory Society (JRS) pneumonia guidelines recommend simple predictive rules, the A-DROP scoring system, for assessment of the severity of community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP). We evaluated whether the A-DROP system can be adapted for assessment of the severity of coronavirus disease 2019 (COVID-19) pneumonia.MethodsData from 1141 patients with COVID-19 pneumonia were analyzed, comprising 502 patients observed in the 1st to 3rd wave period, 338 patients in the 4th wave and 301 patients in the 5th wave in Japan.ResultsThe mortality rate and mechanical ventilation rate were 0% and 1.4% in patients classified with mild disease (A-DROP score, 0 point), 3.2% and 46.7% in those with moderate disease (1 or 2 points), 20.8% and 78.3% with severe disease (3 points), and 55.0% and 100% with extremely severe disease (4 or 5 points), indicating an increase in the mortality and mechanical ventilation rates in accordance with severity (Cochran–Armitage trend test; p = <0.001). This significant relationship between the severity in the A-DROP scoring system and either the mortality rate or mechanical ventilation rate was observed in patients with COVID-19 CAP and NHCAP. In each of the five COVID-19 waves, the same significant relationship was observed.ConclusionsThe mortality rate and mechanical ventilation rate in patients with COVID-19 pneumonia increased depending on severity classified according to the A-DROP scoring system. Our results suggest that the A-DROP scoring system can be adapted for the assessment of severity of COVID-19 CAP and NHCAP.     

REGN-COV2 antibody cocktail in patients with SARS-CoV-2: Observational study from a single institution in Japan

IntroductionA new treatment for coronavirus disease (COVID-19), REGN-COV2, a cocktail consisting of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been approved for patients at a risk of developing more severe disease.MethodsWe retrospectively reviewed patients recently diagnosed with COVID-19 with risk factors for severe infection, who were treated with the REGN-COV2 antibody cocktail between July and September 2021. The REGN-COV2 antibody cocktail was administered to patients within 7 days of disease onset, with an oxygen saturation of >93%, and with at least one comorbidity. We investigated the percentage of patients with COVID-19-related hospitalization or death, the duration of symptoms after treatment, and the adverse effects of treatment.ResultsA total of 108 patients were reviewed. Of them, 64% were aged ≥50 years, 31% had obesity, 36% had hypertension, and 18% had diabetes. In addition, 49% had multiple risk factors for severe COVID-19. Overall, 12 patients (11%) needed COVID-19-related hospitalization. No adverse effects of treatment were observed.ConclusionsThis study shows that treatment with the REGN-COV2 antibody cocktail is safe and beneficial in patients at a risk of developing severe COVID-19.     

A comparative analysis of the outcomes of patients with influenza or COVID-19 in a tertiary hospital in Belgium

IntroductionThe COVID-19 pandemic has emerged as a global health problem, associated with high morbidity and mortality rates. The aim of this study was to compare the outcomes of hospitalized patients with COVID-19 or with seasonal influenza in a teaching hospital in Belgium.MethodsIn this retrospective, single-center cohort study, 1384 patients with COVID-19 and 226 patients with influenza were matched using a propensity score with a ratio of 3:1. Primary outcomes included admission to intensive care unit (ICU), intubation rates, hospital length of stay, readmissions within 30 days and in-hospital mortality. Secondary outcomes included pulmonary bacterial superinfection, cardiovascular complications and ECMO.ResultsBased on the analysis of the matched sample, patients with influenza had an increased risk of readmission within 30 days (Risk Difference (RD): 0.07, 95% CI: 0.03 to 0.11) and admission to intensive care unit (RD: 0.09, 95% CI: 0.03 to 0.15) compared with those with COVID-19. Patients with influenza had also more pulmonary bacterial superinfections (46.2% vs 7.4%) and more cardiovascular complications (32% vs 3.9%) than patients with COVID-19.However, a two-fold increased risk of mortality (RD: ?0.10, 95% CI: 0.15 to ?0.05) was observed in COVID-19 compared to influenza. ECMO was also more required among the COVID-19 patients who died than among influenza patients (5% vs 0%).ConclusionsCOVID-19 is associated with a higher in-hospital mortality compared to influenza infection, despite a high rate of ICU admission in the influenza group. These findings highlighted that the severity of hospitalized patients with influenza should not be underestimated.     

A prospective clinical evaluation of a patient isolation hood during the COVID-19 pandemic

BackgroundHealthcare workers (HCWs) have frequently become infected with severe acute respiratory syndrome coronavirus 2 whilst treating patients with coronavirus disease 2019 (COVID-19). A variety of novel devices have been proposed to reduce COVID-19 cross-contamination.ObjectivesThe aim of the study was (i) to test whether patients and HCWs thought that a novel patient isolation hood was safe and comfortable and (ii) to obtain COVID-19 infection data of hospital HCWs.MethodsThis is a prospective cohort study of 20 patients, entailing HCW/patient questionnaires and safety aspects of prototype isolation hoods. COVID-19 data of HCWs were prospectively collected. Assessment of the hood's safety and practicality and adverse event reporting was carried out.Outcome measuresThe outcome measures are as follows: questionnaire responses, adverse event reporting, rates of infections in HCWs during the study period (20/6/2020 to 21/7/2020), and COVID-19 infections in HCWs reported until the last recorded diagnosis of COVID-19 in HCWs (20/6/2020 to 27/9/2020).ResultsOf the 64 eligible individual HCW surveys, 60 surveys were overall favourable (>75% questions answered in favour of the isolation hood). HCWs were unanimous in perceiving the hood as safe (60/60), preferring its use (56/56), and understanding its potential COVID-19 cross-contamination minimisation (60/60). All eight patients who completed the questionnaire thought the isolation hood helped prevent COVID-19 cross infection and was safe and comfortable. There were no reported patient safety adverse events. The COVID-19 attack rate from 20/6/2020 to 27/9/2020 among registered nurses was as follows: intensive care units (ICUs), 2.2% (3/138); geriatric wards, 13.2% (26/197); and COVID-19 wards, 18.3% (32/175). The COVID-19 attack rate among medical staff was as follows: junior staff, 2.1% (24/932); senior staff, 0.7% (4/607); aged care/rehabilitation, 6.7% (2/30); and all ICU medical staff, 8.6% (3/35).ConclusionsThe isolation hood was preferred to standard care by HCWs and well tolerated by patients, and after the study, isolation hoods became part of standard ICU therapy. There was an association between being an ICU nurse and a low COVID-19 infection rate (no causality implied). ICU HCWs feel safer when treating patients with COVID-19 using an isolation hood.     

Decúbito prono en pacientes COVID-19 con síndrome de distrés respiratorio agudo y ventilación mecánica invasiva

ObjectiveTo identify adverse events related to prone positioning in COVID-19 patients with severe disease and acute respiratory distress syndrome, to analyze the risk factors associated with the development of anterior pressure ulcers, to determine whether the recommendation of prone positioning is associated with improved clinical outcomes.MethodsRetrospective study performed in 63 consecutive patients with COVID-19 pneumonia admitted to intensive care unit on invasive mechanical ventilation and treated with prone positioning between March and April 2020. Association between prone-related pressure ulcers and selected variables was explored by the means of logistic regression.ResultsA total of 139 proning cycles were performed. The mean number of cycles were 2 [1-3] and the mean duration per cycle was of 22 hours [15-24]. The prevalence of adverse events this population was 84.9%, being the physiologic ones (i.e., hypo/hypertension) the most prevalent. 29 out of 63 patients (46%) developed prone-related pressure ulcers. The risk factors for prone-related pressure ulcers were older age, hypertension, levels of pre-albumin < 21 mg/dL, the number of proning cycles and severe disease. We observed a significant increase in the PaO2/FiO2 at different time points during the prone positioning, and a significant decrease after it.ConclusionsThere is a high incidence of adverse events due to PD, with the physiological type being the most frequent. The identification of the main risk factors for the development of prone-related pressure ulcers will help to prevent the occurrence of these lesions during the prone positioning. Prone positioning offered an improvement in the oxygenation in these patients.     

Prevalence of thromboembolic events and status of prophylactic anticoagulant therapy in hospitalized patients with COVID-19 in Japan

IntroductionOne of the most prominent and concerning complications associated with coronavirus disease 2019 (COVID-19) is venous and arterial thromboembolisms. The aim of the present study was to delineate the prevalence of thromboembolic events and the current status of prophylactic anticoagulation therapy in patients with COVID-19 in Japan.MethodsBetween February 1 and August 31, 2020, we performed a dual-center, retrospective cohort study based on data obtained from the medical charts of COVID-19 patients admitted to healthcare facilities in Japan. The primary outcome was any thromboembolic event including pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction, ischemic stroke and other systemic thromboemboli.ResultsDuring the study period, we extracted 628 consecutive patients admitted for COVID-19. Prophylactic anticoagulant therapy was administered in 63 (10%) patients of whom 20 (31.7%) were admitted to the intensive care unit (ICU). Thromboembolic events occurred in 18 (2.9%) patients (14.3% of patients in ICU and 2.2% of patients in the general wards). DVT were detected in 13 (2.1%) patients, PE in 11 (1.8%), and both DVT and PE in 6 (0.96%) patients. An increasing prevalence in thromboembolic events was noted with progressive clinical severity. Overall in-hospital mortality was 4.8%.ConclusionsProphylactic anticoagulation therapy was administered in only 10% of all hospitalized COVID-19 patients. The prevalence of any thromboembolic events was 2.9% in COVID-19 patients with most events occurring in severe and critical patients. Therefore, prophylactic anticoagulation therapy may be warranted in severe and critical patients but in asymptomatic to moderate patients the practice remains controversial.     

MuLBSTA score is a useful tool for predicting COVID-19 disease behavior

BackgroundThe prediction of COVID-19 disease behavior in the early phase of infection is challenging but urgently needed. MuLBSTA score is a scoring system that predicts the mortality of viral pneumonia induced by a variety of viruses, including coronavirus, but the scoring system has not been verified in novel coronavirus pneumonia. The aim of this study was to validate this scoring system for estimating the risk of disease worsening in patients with COVID-19.MethodsThis study included the patients who were treated between April 1 st and March 13 th , 2020. The patients were classified into mild, moderate, and severe groups according to the extent of respiratory failure. MuLBSTA score was applied to estimate the risk of disease worsening in each severity group and we validated the utility of the scoring system.ResultsA total of 72 patients were analyzed. Among the 46 patients with mild disease, 17 showed disease progression to moderate or severe disease after admission. The model showed a sensitivity of 100% and a specificity of only 34.5% with a cut-off value of 5 points. Among the 55 patients with mild or moderate disease, 6 deteriorated to severe disease, and the model showed a sensitivity of 83.3% and a specificity of 71.4% with a cut-off value of 11 points.ConclusionsThis study showed that MuLBSTA score is a potentially useful tool for predicting COVID-19 disease behavior. This scoring system may be used as one of the criteria to identify high-risk patients worsening to life-threatening status.     

Changes in diagnostic usefulness of the JRS scoring system in COVID-19 pneumonia by SARS-CoV-2 vaccination

IntroductionThe Japanese Respiratory Society (JRS) scoring system is a useful tool for the rapid presumptive diagnosis of atypical pneumonia in non-elderly (aged <60 years) patients. As SARS-CoV-2 vaccination progresses, COVID-19 in elderly people has markedly reduced. We investigated changes in diagnostic usefulness of the JRS scoring system in COVID-19 pneumonia between the Delta variant group (vaccination period) and non-Delta variant group (before the vaccination period).MethodsThis study was conducted at five institutions and assessed a total of 1121 patients with COVID-19 pneumonia (298 had the Delta variant). During the vaccination period, the Delta variant has spread and replaced the Alfa variant. We evaluated the vaccination period as the Delta variant group.ResultsAmong the six parameters of the JRS scoring system, matching rates of two parameters were higher in the Delta variant group than the non-Delta variant group (pre-vaccination period): age <60 years (77.5% vs 42.2%, P < 0.0001) and no or minor comorbid illness (69.1% vs 57.8%, p = 0.0007). The sensitivity of the diagnosis of atypical pneumonia in patients with COVID-19 pneumonia was significantly higher in the Delta variant group compared with the non-Delta variant group (80.2% vs 58.3%, p < 0.0001). When the diagnostic sensitivity was analyzed for different ages, the diagnostic sensitivities for the Delta variant and non-Delta variant groups were 92.6% and 95.5% for non-elderly patients and 39.1% and 32.5% for elderly patients, respectively.ConclusionsOur results demonstrated that the JRS scoring system is a useful tool for distinguishing between COVID-19 pneumonia and bacterial pneumonia in the COVID-19 vaccination period, but not before the vaccination period.     

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

ObjectivesTo 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.MethodsIn 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.ResultsOf 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.ConclusionOur 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.     

Arterial Thrombotic Events in Adult Inpatients With COVID-19

ObjectiveTo evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 (COVID-19).MethodsAll consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form.ResultsOverall, 531 COVID-19+ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19+ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P=.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19+ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001).ConclusionA dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19+ patients at risk for arterial thrombotic events.     

Predictive performance of SOFA and qSOFA for in-hospital mortality in severe novel coronavirus disease

ObjectivesThe assessment of illness severity at admission can contribute to decreased mortality in patients with the coronavirus disease (COVID-19). This study was conducted to evaluate the effectiveness of the Sequential Organ Failure Assessment (SOFA) and Quick Sequential Organ Failure Assessment (qSOFA) scoring systems at admission for the prediction of mortality risk in COVID-19 patients.MethodsWe included 140 critically ill COVID-19 patients. Data on demographics, clinical characteristics, and laboratory findings at admission were used to calculate SOFA and qSOFA against the in-hospital outcomes (survival or death) that were ascertained from the medical records. The predictive accuracy of both scoring systems was evaluated by the receiver operating characteristic (ROC) curve analysis.ResultsThe area under the ROC curve for SOFA in predicting mortality was 0.890 (95% CI: 0.826–0.955), which was higher than that of qSOFA (0.742, 95% CI 0.657–0.816). An optimal cutoff of ≥3 for SOFA had sensitivity, specificity, positive predictive value, and negative predictive value of 90.00%, 83.18%, 50.00%, and 97.80%, respectively.ConclusionsThis novel report indicates that SOFA could function as an effective adjunctive risk-stratification tool at admission for critical COVID-19 patients. The performance of qSOFA is accepted but inferior to that of SOFA.     

Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study

PurposeWe investigated the efficacy and safety of hydroxychloroquine for empirical treatment of outpatients with confirmed COVID-19.MethodsIn this prospective, single-center study, we enrolled ambulatory outpatients with COVID-19 confirmed by a molecular method who received hydroxychloroquine. The patients were divided into low- and moderate-risk groups based on the Tisdale risk score for drug-associated QT prolongation, and the QT interval was corrected for heart rate using the Bazett formula (QTc). The QTc interval was measured by electrocardiography both pretreatment (QTc1) and 4 h after the administration of hydroxychloroquine (QTc2). The difference between the QTc1 and QTc2 intervals was defined as the ΔQTc. The QTc1 and QTc2 intervals and ΔQTc values were compared between the two risk groups.ResultsThe median and interquartile range (IQR) age of the patients was 47.0 (36.2–62) years, and there were 78 men and 74 women. The median (IQR) QTc1 interval lengthened from 425.0 (407.2–425.0) to 430.0 (QTc2; 412.0–443.0) milliseconds (ms). However, this was not considered an increased risk of ventricular tachycardia associated with a prolonged QTc interval requiring drug discontinuation, because none of the patients had a ΔQTc of >60 ms or a QTc2 of >500 ms. Moreover, the median (quartiles; minimum-maximum) ΔQTc value was higher in patients in the moderate-risk group than those in the low-risk group (10.0 [−4.0–18.0; −75.0–51.0] vs. 7.0 [−10.5–23.5; −53.0–59.0 ms]) (p = 0.996). Clinical improvement was noted in 91.4% of the patients, the exceptions being 13 patients who presented with non-serious adverse drug reactions or who had severe COVID-19 and were hospitalized. Adverse effects related to hydroxychloroquine were non-serious and occurred in 52.8% (n = 80) of the patients.ConclusionsOur findings show that hydroxychloroquine is safe for COVID-19 and not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation. Additionally, hydroxychloroquine was well tolerated, and there were no drug-related non-serious adverse events leading to treatment discontinuation in the majority of patients who were stable and did not require hospitalization.     

Favipiravir for symptomatic COVID-19: A nationwide observational cohort study

IntroductionFavipiravir, an antiviral agent with activity against SARS-CoV-2, was made available to hospitals in Japan for off-label use among COVID-19 patients between 2020 and 2021.MethodsA nationwide observational cohort study was conducted on patients who received favipiravir as part of clinical care between February 2020 and December 2021. Information was collected on demographics, comorbidities, severity of illness, use of favipiravir and other medications targeting COVID-19, adverse events, clinical status at 7 and 14 days and clinical outcome one month after admission to the hospital.ResultsA total of 17,508 hospitalized patients who received favipiravir were registered from 884 hospitals. In terms of demographics, 55.9% were age ≥60 years, and 62.3% were male. At least one of the four surveyed comorbidities was present in 45.5% of the patients. The rates of clinical improvement at 7 and 14 days were 72.4％ and 87.5%, 61.4% and 76.6%, and 45.4% and 59.5% for mild, moderate, and severe diseases, respectively. The case fatality rates within a month from hospitalization were 3.3%, 12.6%, and 29.1% for mild, moderate, and severe diseases, respectively. Significant correlations were observed between death and advanced age, male sex, moderate or severe disease, diabetes, cardiovascular diseases, and immunosuppression. Commonly reported adverse events included uric acid level increase or hyperuricemia (16.8%), liver function abnormalities (6.9%), and rash (1.0%).ConclusionsFavipiravir was well tolerated among COVID-19 patients. The study provides insights into the use of this agent at hospitals across Japan in the early phase of the pandemic.     

Modified PRIEST score for identification of very low-risk COVID patients

BackgroundCOVID-19 transmission remains high around the world, and severe local outbreaks continue to occur. Prognostic tools may be useful in crisis conditions as risk stratification can help determine resource allocation. One published tool, the Pandemic Respiratory Infection Emergency System Triage Severity Score, seems particularly promising because of its predictive ability and ease of application at the bedside. We sought to understand the performance of a modified version of this score (mPRIEST) in our institution for identifying patients with a greater than minimal risk for adverse outcome (death or organ support) at 30 days after index visit.MethodsConsecutive visits at two northern Manhattan EDs with a new diagnosis of symptomatic COVID-19 were identified between November and December of 2020. Demographic variables and clinical characteristics were obtained from chart review. Outcomes were obtained from chart review and follow-up phone call.ResultsOutcomes were available on 306 patients. The incidence of death or mechanical ventilation at 30 days for patients in patients with mPRIEST above the threshold value was 43/181 (23.8%), and for patients below 1/125 (0.8%). The sensitivity of the score for adverse outcome was 97.7% (95% CI: 93.3% to 100%).ConclusionsThis data suggests the mPRIEST score, which can be calculated from clinical variables alone, has potential for use in EDs to identify patients at very low risk for adverse outcomes within 30 days of COVID diagnosis. This should be confirmed in larger formal validation studies in diverse settings.     

重症新型冠状病毒肺炎临床和肺部超声影像特点

目的探讨重症新型冠状病毒肺炎（简称"新冠肺炎"）肺部超声影像学特征，为临床诊治提供参考。 方法选择广州市第八人民医院ICU收治的29例重症新冠肺炎患者，其中重型15例，危重型14例，入ICU 24 h内进行肺部超声评分（LUS），同时收集患者性别、年龄、氧合指数（OI）和病程，计算临床肺部感染评分（CPIS）（由体温、OI、胸部X线片或CT、气道分泌物、白细胞计数组成）。 结果29例患者中男性23例（79.3%），年龄（62.59±11.91）岁，LUS（19.28±4.96）分，OI（184.24±66.18）mmHg（1 mmHg=0.133 kPa），CPIS 4（3，4）分，病程（12.48±5.34） d，其中LUS与OI呈显著负相关（r=-0.742，P=0.000），与CPIS呈显著正相关（r=0.504，P=0.005）。危重型患者的LUS及CPIS明显高于重型患者，OI则明显降低，差异均有统计学意义（P<0.05），两组间性别、年龄和病程比较差异无统计学意义（P>0.05）。348个肺部超声检查区域中主要表现为B2征象，危重型与重型患者比较，N征象明显减少（9.5% vs 23.3%），C征象明显增多（17.3% vs 4.4%），病变区域比例明显增加（90.5% vs 76.7%），差异均有统计学意义（P<0.01）；前区、侧区、后区肺部病变区域依次增加（63.8%，87.9%，98.3%），相互比较差异均有统计学意义（P<0.01）；左肺与右肺超声征象分布和病变区域比较差异无统计学意义（P>0.05）。 结论肺部超声能床旁实时评估重症新冠肺炎患者肺部病变性质、范围，为重症患者的诊断和治疗提供重要参考依据。     

Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials

PurposeThe optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19.Materials and methodsWe conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered.ResultsOut of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90–1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61–1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21–0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08–2.53).ConclusionThis systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.     

Immunogenicity and Safety of SpikoGen,an Adjuvanted Recombinant SARS-CoV-2 Spike Protein,as a Heterologous Third Booster Dose in Kidney Transplant Patients: A Single-arm Clinical Trial

PurposeStudies have found that immunocompromised patients have suboptimal responses to COVID-19 vaccines, leading to approval of a need for booster doses in this population. SpikoGen® is a subunit recombinant spike protein vaccine combined with Advax-CpG55.2? adjuvant to protect against COVID-19. Previous clinical trials found this vaccine to be tolerable, immunogenic, and efficacious in reducing the risk of COVID-19, including severe disease. However, the effects of this vaccine have not been assessed in immunocompromised patients. This study sought to assess the immunogenicity and safety of the SpikoGen vaccine as a third booster dose in patients undergoing kidney transplant who were receiving immunosuppressive therapy and had received their primary vaccination based on an inactivated whole virus platform (Sinopharm).MethodsThis single-arm trial was performed with 43 patients undergoing kidney transplant. The participants received a single booster dose of the SpikoGen vaccine 1 to 3 months after primary vaccination with 2 doses of the Sinopharm vaccine. Immunogenicity assessments were performed at baseline and 30 days after the booster dose. The primary outcomes were seroconversion rates of anti-S₁ and surrogate virus neutralizing antibodies. Safety outcomes included the incidence of solicited and unsolicited adverse events in the 7 days and 1 month after the booster dose, respectively.FindingsThe SpikoGen vaccine induced positive humoral and cellular responses 30 days after the booster dose in those patients who were seropositive or seronegative after 2 primary doses of the Sinopharm vaccine. Thirty days after the SpikoGen vaccine booster, seroconversion rates were 35.29% (95% CI, 19.75%–53.51%) to anti-S₁ and 29.41% (95% CI, 13.27%–46.57%) to surrogate neutralizing antibodies. The most common local and systemic reported solicited adverse events were injection site pain and fatigue, which were largely mild and transient. No serious adverse events were reported.ImplicationsA single booster dose of SpikoGen vaccine given 1 to 3 months after primary vaccination with 2 doses of Sinopharm vaccine induced positive humoral and cellular immune responses in immunosuppressed patients undergoing renal transplant, thereby achieving spike antibody levels predictive of protection. This study was performed as a single-center study, and it will be important for future large multicenter studies to extend these results to other immunocompromised patient groups.     

Intravenous bamlanivimab use associates with reduced hospitalization in high-risk patients with mild to moderate COVID-19

BACKGROUNDClinical data to support the use of bamlanivimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) are needed.METHODS2335 Patients who received single-dose bamlanivimab infusion between November 12, 2020, and February 17, 2021, were compared with a propensity-matched control of 2335 untreated patients with mild to moderate COVID-19 at Mayo Clinic facilities across 4 states. The primary outcome was the rate of hospitalization at days 14, 21, and 28.RESULTSThe median age of the population was 63 years; 47.3% of the bamlanivimab-treated cohort were 65 years or more; 49.3% were female and 50.7% were male. High-risk characteristics included hypertension (54.2%), BMI greater than or equal to 35 (32.4%), diabetes mellitus (26.5%), chronic lung disease (25.1%), malignancy (16.6%), and renal disease (14.5%). Patients who received bamlanivimab had lower all-cause hospitalization rates at days 14 (1.5% vs. 3.5%; risk ratio [RR], 0.41), 21 (1.9% vs. 3.9%; RR, 0.49), and 28 (2.5% vs. 3.9%; RR, 0.63). Secondary exploratory outcomes included lower intensive care unit (ICU) admission rates at days 14 (0.14% vs. 1%; RR, 0.14), 21 (0.25% vs.1%; RR, 0.25), and 28 (0.56% vs.1.1%; RR. 0.51) and lower all-cause mortality at days 14 (0% vs. 0.33%), 21 (0.05% vs. 0.4%; RR,0.13), and 28 (0.11% vs. 0.44%; RR, 0.26). Adverse events were uncommon with bamlanivimab, occurring in 19 of 2355 patients, and were most commonly fever (n = 6), nausea (n = 5), and lightheadedness (n = 3).CONCLUSIONSAmong high-risk patients with mild to moderate COVID-19, treatment with bamlanivimab was associated with a statistically significant lower rate of hospitalization, ICU admission, and mortality compared with usual care.FUNDINGMayo Clinic.     

Identifying patients with symptoms suspicious for COVID-19 at elevated risk of adverse events: The COVAS score

ObjectiveDevelop and validate a risk score using variables available during an Emergency Department (ED) encounter to predict adverse events among patients with suspected COVID-19.MethodsA retrospective cohort study of adult visits for suspected COVID-19 between March 1 – April 30, 2020 at 15 EDs in Southern California. The primary outcomes were death or respiratory decompensation within 7-days. We used least absolute shrinkage and selection operator (LASSO) models and logistic regression to derive a risk score. We report metrics for derivation and validation cohorts, and subgroups with pneumonia or COVID-19 diagnoses.Results26,600 ED encounters were included and 1079 experienced an adverse event. Five categories (comorbidities, obesity/BMI ≥ 40, vital signs, age and sex) were included in the final score. The area under the curve (AUC) in the derivation cohort was 0.891 (95% CI, 0.880–0.901); similar performance was observed in the validation cohort (AUC = 0.895, 95% CI, 0.874–0.916). Sensitivity ranging from 100% (Score 0) to 41.7% (Score of ≥15) and specificity from 13.9% (score 0) to 96.8% (score ≥ 15). In the subgroups with pneumonia (n = 3252) the AUCs were 0.780 (derivation, 95% CI 0.759–0.801) and 0.832 (validation, 95% CI 0.794–0.870), while for COVID-19 diagnoses (n = 2059) the AUCs were 0.867 (95% CI 0.843–0.892) and 0.837 (95% CI 0.774–0.899) respectively.ConclusionPhysicians evaluating ED patients with pneumonia, COVID-19, or symptoms suspicious for COVID-19 can apply the COVAS score to assist with decisions to hospitalize or discharge patients during the SARS CoV-2 pandemic.     

Analysis of older adults visiting the emergency department with fever as a suspected Covid-19 vaccine-related adverse reaction: A retrospective multicenter study

IntroductionAfter COVID-19 vaccination was initiated, the number of patients visiting the emergency department (ED) with vaccine-related adverse reactions increased. We investigated the clinical features of older adults (aged 65 years and older) visiting the ED with self-reported COVID-19 postvaccination fever.MethodsWe conducted a retrospective observational study at three EDs between March 2021 and September 2021. Patients who reported adverse reactions, fever (≥37.5 °C) and/or febrile sensation or rigors following COVID-19 vaccination were included. The demographic and clinical data of these patients were collected by reviewing their medical records.ResultsA total of 562 patients were selected, and 396 (70.5%) were female. The older adult group included 155 (27.6%) patients, and the median age was 75 (69–79 years). The older adults less frequently had a fever (≥37.5 °C) upon ED presentation (75.5% vs. 85.7%, respectively), used more emergency medical services (43.9% vs. 18.7%, respectively), and visited an ED more frequently during early hours (00:00–06:00) (31% vs. 20.1%, respectively) compared to the younger adults (p = 0.004, p < 0.001 and p = 0.036). Fewer older adults visited an ED within 2 days of fever onset (73.5% vs. 84%) (p = 0.012), and more older adults were admitted for medical conditions other than vaccine-related adverse reactions (32.9% vs. 4.2%) (p < 0.001). Older adults received more thorough testing (laboratory and imaging tests). Among the older adults, the admission rate was associated with age (p = 0.003).ConclusionOlder adults presenting with fever as an adverse reaction following COVID-19 vaccination less frequently had a fever upon visiting the ED, required more ED testing, and had higher admission rates for non-vaccination-related medical conditions.