Acute Vascular Complications of VA-ECMO in COVID-19 Patients. Does COVID-19 Affect the Outcome?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) through the femoral artery and vein can lead to significant vascular complications. We retrospectively studied the acute vascular complications of Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in COVID-19 patients compared to non-COVID patients during the period from January 2020 to July 2023. RESULTS: Seventy-eight patients underwent VA-ECMO for various indications from January 2020 to July 2023. The studied patients had a mean age of 59.6 ± 6.9 years for non-COVID patients (38 patients), and 62.2 ± 7.6 years for COVID patients (40 patients), with a P = 0.268. In non-COVID patients, The baseline characteristics were similar in both groups. The primary indications for ECMO were cardiac diseases, followed by respiratory failure (78.9% vs 10.5%). Conversely, in COVID patients, respiratory failure due to COVID-19 infection was the main indication (45% vs 40%). The overall incidence of general complications, including cerebrovascular stroke, acute kidney injury, intracardiac thrombi, and wound infection, was comparable in both groups (31.6% vs 45%). The overall incidence of vascular complications in both groups was 33.3%. Ipsilateral acute lower limb ischemia occurred in 5.3% vs 10% of non-COVID and COVID patients, respectively. Thrombosis of the distal perfusion catheter (DPC) occurred in 10.5% vs 15%, respectively. CONCLUSION: During the COVID-19 pandemic, an increasing number of patients required VA-ECMO due to associated respiratory failure. Patients undergoing VA-ECMO are at high risk of developing various vascular complications. COVID-19 significantly increases the risk of acute limb ischemia and distal perfusion catheter thrombosis in both upper and lower limbs. However, other VA-ECMO-related vascular complications are comparable between COVID-19 and non-COVID patients.

Comparison of the effectiveness of awake-prone positioning and high-flow nasal oxygen in patients with COVID-19-related acute respiratory failure between different waves.

OBJECTIVE: To compare the effectiveness of the awake-prone position on relevant clinical outcomes in patients with COVID-19-related acute respiratory failure requiring high-flow nasal oxygen between different waves in Argentina. METHODS: This multicenter, prospective cohort study included adult patients with COVID-19-related acute respiratory failure requiring high-flow nasal oxygen. The main exposure position was the awake-prone position (≥ 6 hours/day) compared to the non-prone position. The primary outcome was endotracheal intubation, and the secondary outcome was in-hospital mortality. The inverse probability weighting-propensity score was used to adjust the conditional probability of treatment assignment. We then adjusted for contextual variables that varied over time and compared the effectiveness between the first and second waves. RESULTS: A total of 728 patients were included: 360 during the first wave and 368 during the second wave, of whom 195 (54%) and 227 (62%) remained awake-prone for a median (p25 - 75) of 12 (10 - 16) and 14 (8 - 17) hours/day, respectively (Awake-Prone Position Group). The ORs (95%CIs) for endotracheal intubation in the Awake-Prone Position Group were 0.25 (0.13 - 0.46) and 0.19 (0.09 - 0.31) for the first and second waves, respectively (p = 0.41 for comparison between waves). The ORs for in-hospital mortality in the awake-prone position were 0.35 (0.17 - 0.65) and 0.22 (0.12 - 0.43), respectively (p = 0.44 for comparison between waves). CONCLUSION: The awake-prone position was associated with a reduction in the risk of endotracheal intubation and in-hospital mortality. These effects were independent of the context in which the intervention was applied, and no differences were observed between the different waves.

Protective Effect of Allergen Immunotherapy in Patients With Allergic Rhinitis and Asthma Against COVID-19 Infection: Observational, Nationwide, and Multicenter Study.

Background: Allergic diseases are associated with an increased susceptibility to respiratory tract infections. Although allergen immunotherapy (AIT) alters the course of allergies, there is limited evidence from clinical practice demonstrating its ability to enhance the host defense against pathogens. Objective: The aim of this study was to investigate the protective effect of AIT against viral infection in patients with allergic rhinitis (AR) and allergic asthma (AS) based on clinical evidence. Methods: A multicenter, questionnaire-based survey was conducted during a tremendous surge in COVID-19 cases between February 10, 2023, and March 15, 2023, in 81 centers across China recruiting healthy volunteers and patients with AR and AS to investigate the clinical outcomes of COVID-19 infection. Results: Of 10,151 participants recruited in the survey, 3654 patients and 2192 healthy volunteers who tested positive for COVID-19 were included in this analysis after screening. Overall, no significant differences in COVID-19 outcomes were observed between patients and healthy volunteers. An additional 451 patients were excluded due to their use of biologics as the sole add-on treatment, leaving 3203 patients in the further analysis. Of them, 1752 were undergoing routine medication treatment (RMT; the RMT group), whereas 1057 and 394 were receiving AIT and a combination of AIT and omalizumab (OMA) as adjunct therapies to RMT, respectively (AIT+RMT and AIT+OMA+RMT groups). The AIT group showed milder COVID-19 symptoms, shorter recovery periods, and a lower likelihood of hospitalization or emergency department visits than the RMT group (all P<.05). After adjusting for confounding factors, including demographic characteristics and COVID-19 vaccination, AIT remained a significant protective factor associated with shorter recovery time (adjusted odds ratio [OR] 0.62, 95% CI 0.52-0.75; adjusted P<.001) and a lower incidence of hospitalization or emergency department visits (adjusted OR 0.73, 95% CI 0.54-0.98; adjusted P=.03). Furthermore, the AIT+OMA+RMT group showed greater protection with a shorter recovery time (adjusted OR 0.51, 95% CI 0.34-0.74; adjusted P<.001) than the AIT+RMT group. Conclusions: Our multicenter observational study provides valuable clinical evidence supporting the protective effect of AIT against COVID-19 infection in patients with AR and AS.

Racial and ethnic disparities in COVID-19 hospital cost of care.

INTRODUCTION: Although studies have evaluated the hospital cost of care associated with treating patients with COVID-19, there are no studies that compare the hospital cost of care among racial and ethnic groups based on detailed cost accounting data. The aims of this study were to provide a detailed description of the hospital costs of COVID-19 based on individual resources during the hospital stay and standardized costs that do not rely on inflation adjustment and evaluate the extent to which hospital total cost of care for patients with COVID-19 differs by race and ethnicity. METHODS: This study used electronic medical record data from an urban academic medical center in Chicago, Illinois USA. Hospital cost of care was calculated using accounting data representing the cost of the resources used to the hospital (i.e., cost to the hospital, not payments). A multivariable generalized linear model with a log link function and inverse gaussian distribution family was used to calculate the average marginal effect (AME) for Black, White, and Hispanic patients. A second regression model further compared Hispanic patients by preferred language (English versus Spanish). RESULTS: In our sample of 1,853 patients, the average adjusted cost of care was significantly lower for Black compared to White patients (AME = -$5,606; 95% confidence interval (CI), -$10,711 to -$501), and Hispanic patients had higher cost of care compared to White patients (AME = $8,539, 95% CI, $3,963 to $13,115). In addition, Hispanic patients who preferred Spanish had significantly higher cost than Hispanic patients who preferred English (AME = $11,866; 95% CI $5,302 to $18,431). CONCLUSION: Total cost of care takes into account both the intensity of the treatment as well as the duration of the hospital stay. Thus, policy makers and health systems can use cost of care as a proxy for severity, especially when looking at the disparities among different race and ethnicity groups.

The winding road: Infectious disease considerations for CAR-T and other novel adoptive cellular therapies in the era of COVID-19.

Adoptive cellular therapies (ACT) are novel, promising treatments for life-threatening malignancies. In addition to the better known chimeric antigen receptor (CAR) T cells, ACTs include tumor infiltrating lymphocytes (TIL), cancer antigen-specific T cell receptors (TCRs), and CAR-NK (natural killer) cells. In key historic milestones, several adoptive therapies recently received FDA approvals, including 6 CAR-T products for the treatment of hematologic malignancies and the first TIL therapy for the treatment for metastatic melanoma. The rapid pace of clinical trials in the field and the discoveries they provide are ushering in a new era of cancer immunotherapy. However, the potential complications of these therapies are still not fully understood. In particular, patients receiving ACT may be at increased risk for severe infections due to immunocompromise resulting from their underlying malignancies, which are further compounded by the immune derangements that develop in the setting of cellular immunotherapy and/or the preconditioning treatment needed to enhance ACT efficacy. Moreover, these treatments are being readily implemented at a time following the height of the COVID-19 pandemic, and it remains unclear what additional risks these patients may face from SARS-CoV-2 and similar infections. Here, we examine the evidence for infectious complications with emerging adoptive therapies, and provide a focused review of the epidemiology, complications, and clinical management for COVID-19 in CAR-T recipients to understand the risk this disease may pose to recipients of other forms of ACT.

Impact of the COVID-19 pandemic on time to treatment, treatment patterns and outcomes among patients with acute coronary syndrome in Yogyakarta, Indonesia: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the impact of the COVID-19 pandemic on the management of acute coronary syndrome (ACS) in Yogyakarta, Indonesia with respect to time to treatment, treatment pattern and treatment outcome. DESIGN: This is a retrospective cohort study in which medical records of hospitalised patients with ACS were reviewed. SETTING: Three hospitals in Yogyakarta, Indonesia. PARTICIPANTS: Patients hospitalised with ACS during two pandemic periods (first pandemic period: March-August 2020; second pandemic period: March-August 2021) and prepandemic period (March-August 2019). OUTCOME MEASURES: Time to treatment, treatment pattern and treatment outcome. RESULTS: A total of 598 patients with ST-elevation myocardial infarction (STEMI) and 615 with non-ST-elevation ACS were identified. Of these, 313, 484 and 416 were identified during the prepandemic period, first pandemic period and second pandemic period, respectively. For STEMI, the proportion of patients with a delay from symptom onset to first medical contact (FMC) was significantly higher during the second pandemic period as compared with the prepandemic period (47.7% vs 32.0%, OR=1.84, 95% CI 1.18, 2.85). The proportion of patients with STEMI with delayed door-to-balloon (D2B) time was significantly higher during the second pandemic period as compared with the prepandemic period (99.4% vs 92.9%, OR=13.08, 95% CI 1.57, 108.73). Significantly longer mean total ischaemic time (45.85 hours vs 30.29 hours, mean difference=14.56, 95% CI 1.85, 27.28) was observed among patients with STEMI during the second year of the pandemic as compared with the prepandemic period. No significant differences between the prepandemic period and the first pandemic period were found in terms of proportion of patients with STEMI with a delay in time from symptom onset to FMC, delayed D2B time and total ischaemic time. Only Global Registry of Acute Coronary Events risk score (OR=1.04, 95% CI 1.03, 1.05) was a significant predictor of in-hospital mortality in the multivariate analysis. CONCLUSIONS: This study suggests a significant impact of the COVID-19 pandemic on time to treatment among patients with ACS. Health systems need to be well prepared to support effective and timely treatment of patients with ACS during future crisis.

Estimates of actual and potential lives saved in the United States from the use of COVID-19 convalescent plasma.

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies.

Comparative clinical trial of Langenlianqiao oral liquid and Lianhuaqingwen capsule in the treatment of mild cases of coronavirus disease 2019 (COVID-19).

OBJECTIVE: To evaluate the clinical efficacy of Langenlianqiao (LGLQ) oral liquid treatment and provide a reference basis for the clincal treatment of coronavirus disease 2019 (COVID-19). DESIGN: An experimental clinical study was conducted on three groups with confirmed diagnoses of COVID-19. SITE: This study was conducted at Changde Hospital. PARTICIPANTS: A total of 253 patients were enrolled in this study. METHODS: The patients were divided into the LGLQ treatment group (100 cases), the Lianhuaqingwen (LHQW) treatment group (100 cases) and the placebo control group (53 cases), according to the treatment each group received. The occurrence of major clinical symptoms, the duration of symptom disappearance, the number of days in hospitalisation and the duration of infection were compared among the three groups. RESULTS: Compared with the placebo control group (10.0 [1.2] d, 9.4 [1.3] d), the duration of infection and hospitalisation effectively decreased in the LGLQ group (6.8 [0.6] d, 7.4 [0.8] d) and the LHQW group (6.8 [1.0] d, 7.3 [1.0] d). Furthermore, the incidence of fatigue in the LGLQ group (4.0%) was lower compared to the LHQW group (14.0%) and the placebo control group (15.1%), but this difference was not statistically significant (P = 0.580 for LGLQ vs. LHQW, P = 0.246 for LGLQ vs. placebo). In the treatment of cough, the LGLQ group showed a significantly different effect compared to both the LHQW group (P = 0.014) and the placebo group (P = 0.016). Additionally, for dry cough specifically, LHQW was effective in reducing its incidence compared to the placebo control group (P < 0.05), while LGLQ showed no statistically significant difference from either LHQW (P = 0.39) or the placebo group (P = 0.14). However, neither the LGLQ group nor the LHQW group showed a reduction in the duration of symptom disappearance in patients with pre-existing symptoms (P > 0.05). CONCLUSIONS: Compared with the placebo control group, the LGLQ group showed an improvement in the clinical symptoms of COVID-19 and a decrease in the duration of hospitalisation and infection, which confirmed that the LGLQ treatment had the same antiviral effect as the LHQW treatment. This may provide in-depth insights for antiviral therapy research.

A qualitative study of the general practice experience of diagnosing and managing long COVID: Challenges and practical recommendations.

BACKGROUND AND OBJECTIVES: Patients with prolonged symptoms following COVID-19 infection(s) will increasingly present to general practice. Our research objective was to understand the general practice experience of diagnosing and managing long COVID and to explore recommendations for contributing to the safety and quality of the long COVID response. METHOD: A two-hour qualitative session involving 11 project stakeholders was held in March 2023. The stakeholders included general practitioners as well as representatives from four Primary Health Networks, Outcome Health and the funding body. Transcripts were analysed using qualitative content analysis. RESULTS: Key challenges and practical recommendations emerged relating to diagnosing long COVID, documentation of COVID-19 infections, ongoing management, screening tools and the need for public health messaging. DISCUSSION: General practices need more accurate definitions and information about the diagnosis of long COVID. Supporting general practitioners with information to diagnose and manage patients with long COVID is essential. General practice voices need to be heard to enhance our understanding of long COVID and inform policy decisions.

Impact of mechanical power on ICU mortality in ventilated critically ill patients: a retrospective study with continuous real-life data.

BACKGROUND: Over the past decade, numerous studies on potential factors contributing to ventilation-induced lung injury have been carried out. Mechanical power has been pointed out as the parameter that encloses all ventilation-induced lung injury-contributing factors. However, studies conducted to date provide data regarding mechanical power during the early hours of mechanical ventilation that may not accurately reflect the impact of power throughout the period of mechanical ventilatory support on intensive care unit mortality. METHODS: Retrospective observational study conducted at a single center in Spain. Patients admitted to the intensive care unit, > o = 18 years of age, and ventilated for over 24 h were included. We extracted the mechanical power values throughout the entire mechanical ventilation in controlled modes period from the clinical information system every 2 min. First, we calculate the cutoff-point for mechanical power beyond which there was a greater change in the probability of death. After, the sum of time values above the safe cut-off point was calculated to obtain the value in hours. We analyzed if the number of hours the patient was under ventilation with a mechanical power above the safe threshold was associated with intensive care unit mortality, invasive mechanical ventilation days, and intensive care unit length of stay. We repeated the analysis in different subgroups based on the degree of hypoxemia and in patients with SARS CoV-2 pneumonia. RESULTS: The cut-off point of mechanical power at with there is a higher increase in intensive care unit mortality was 18 J/min. The greater the number of hours patients were under mechanical power > 18 J/min the higher the intensive care unit mortality in all the study population, in patients with SARS CoV-2 pneumonia and in mild to moderate hypoxemic respiratory failure. The risk of death in the intensive care unit increases 0.1% for each hour with mechanical power exceeding 18 J/min. The number of hours with mechanical power > 18 J/min also affected the days of invasive mechanical ventilation and intensive care unit length of stay. CONCLUSIONS: The number of hours with mechanical power > 18 J/min is associated with mortality in the intensive care unit in critically ill patients. Continuous monitoring of mechanical power in controlled modes using an automated clinical information system could alert the clinician to this risk.

Assessment of immunological factors in COVID-19 patients treated by convalescent plasma.

Following the outbreak of COVID-19, several immunotherapy methods were used to modulate the immune responses of patients. In this study, we aimed to evaluate the immune response to COVID-19 in patients receiving convalescent plasma. In this regard, this randomized controlled trial included 30 patients who were divided into two groups according to receiving convalescent plasma or normal control plasma. Samples from both groups were collected on days 0, 1, 3, 5 and 7 after plasma infusion. We measured the expression level of TLR7/8, IRF3/7, CTLA-4, PD-1 and T cell transcription factors by Real-time PCR in the mentioned groups. Thirteen cytokines were also evaluated using flow cytometry method. Results showed that compared to the normal control plasma group, the expression levels of TLR7, 8, IRF3, 7 and PD-1 and CTLA-4, on days 3, 5 and 7 after convalescent plasma infusion, were significantly decreased. On the other hand,  Gene expression results showed that the expression levels of Tbet, RORγ3 and Foxp3 on days 3, 5 and 7 after convalescent plasma infusion were significantly increased compared to the normal control plasma group. After convalescent plasma infusion, the viral load was significantly decreased compared to the normal control plasma group. Convalescent plasma infusion also reduced the plasma cytokines levels, including IL-6, IL-10, and IL-4, and enhanced the level of IL-2, IFN- γ and perforin comparing the normal control plasma group. According to the results, the convalescent plasma infusion led to a decrease in the expression of innate immunity receptors and an increase in the expression of transcription factors of adaptive immunity. Therefore, it may be concluded that convalescent plasma infusion can modulate the immune response. To achieve a reliable consequence, further studies are required.

Cytokines and Other Laboratory Parameters of Hospitalized COVID-19 Patients that Predict Intensive Care Unit Admission.

BACKGROUND: This study aimed to investigate the roles of cytokines and other laboratory parameters in determining the need for intensive care in COVID-19 patients. METHODS: This is a retrospective observational study. Demographic, clinical, and laboratory parameters of the patients were evaluated. Thirteen cytokines were measured along with baseline laboratory tests at admission and at 48-hour intervals: IL-1ß, IFN-α, IFN-ß, TNF-α, MCP-1, IL-6, IL -8, IL-10, IL-2p70, IL-17A, IL-18, IL-23, and IL-33. RESULTS: COVID-19 was confirmed by PCR in 116 hospitalized patients. The mean age was 55.3 ± 16.4 years. Seventy-four (63.8%) of the patients were male and 42 (36.2%) were female. Twenty-two (18.9%) patients (16 male, 6 female) were transferred to the intensive care unit. A significant increase in white blood cell (WBC), neutrophil (Neu) and lymphocyte (Lym) counts, Neu/Lym ratio (NLR), lactate dehydrogenase (LDH), INR (international normalized ratio), activated prothrombin time (aPTT), D-dimer (D-D), troponin (Trop), Pro-BNP (BNP), procalcitonin (PCT), ferritin (Fer), and alanine aminotransferase (ALT) values were observed in those requiring intensive care. A significant decrease was found in albumin (Alb) levels and Lym counts. Alb levels appeared to be protective against admission to intensive care. Except for IFN- α, IL-23, and IL-33, the baseline values of other cytokines were above the threshold values. MCP-1 and IL-6 were higher in patients requiring intensive care. CONCLUSIONS: High NLR and LDH and low Alb levels, especially with an increase in MCP-1 and IL-6, were found to be the best predictors of a serious COVID-19 infection.

Comparing the impact of targeting limited driving pressure to low tidal volume ventilation on mortality in mechanically ventilated adults with COVID-19 ARDS: an exploratory target trial emulation.

BACKGROUND: An association between driving pressure (∆P) and the outcomes of invasive mechanical ventilation (IMV) may exist. However, the effect of a sustained limitation of ∆P on mortality in patients with acute respiratory distress syndrome (ARDS), including patients with COVID-19 (COVID-19-related acute respiratory distress syndrome (C-ARDS)) undergoing IMV, has not been rigorously evaluated. The use of emulations of a target trial in intensive care unit research remains in its infancy. To inform future, large ARDS target trials, we explored using a target trial emulation approach to analyse data from a cohort of IMV adults with C-ARDS to determine whether maintaining daily ∆p<15 cm H2O (in addition to traditional low tidal volume ventilation (LTVV) (tidal volume 5-7 cc/PBW+plateau pressure (Pplat) ≤30 cm H2O), compared with LTVV alone, affects the 28-day mortality. METHODS: To emulate a target trial, adults with C-ARDS requiring >24 hours of IMV were considered to be assigned to limited ∆P or LTVV. Lung mechanics were measured twice daily after ventilator setting adjustments were made. To evaluate the effect of each lung-protective ventilation (LPV) strategy on the 28-day mortality, we fit a stabilised inverse probability weighted marginal structural model that adjusted for baseline and time-varying confounders known to affect protection strategy use/adherence or survival. RESULTS: Among the 92 patients included, 27 (29.3%) followed limited ∆P ventilation, 23 (25.0%) the LTVV strategy and 42 (45.7%) received no LPV strategy. The adjusted estimated 28-day survival was 47.0% (95% CI 23%, 76%) in the limited ∆P group, 70.3% in the LTVV group (95% CI 37.6%, 100%) and 37.6% (95% CI 20.8%, 58.0%) in the no LPV strategy group. INTERPRETATION: Limiting ∆P may not provide additional survival benefits for patients with C-ARDS over LTVV. Our results help inform the development of future target trial emulations focused on evaluating LPV strategies, including reduced ∆P, in adults with ARDS.

Convalescent anti-SARS-CoV-2 plasma for the treatment of patients with COVID-19: a retrospective study RESCOVID-19.

PURPOSE: Convalescent plasma (CP) collected from people who recovered from COVID-19 became a rapidly available treatment modality in numerous countries, including the Czech Republic. The aims of our study were to evaluate the effectiveness and safety of CP in the treatment of COVID-19. METHODS: This retrospective observational study involved six Czech hospitals. This study enrolled patients with and without CP treatment who were hospitalized between April 2020 and April 2021. Propensity score matching and logistic regression analysis were performed to evaluate the influence of CP administration and its timing on the in-hospital survival of COVID-19 patients. RESULTS: A total of 1,498 patients were enrolled in the study; 406 (27%) were administered CP, and 1,092 (73%) were not treated with CP. The propensity score-matched control group consisted of 1,218 subjects. The survival of patients treated with CP was 79%, while that of patients in the matched control group was 62% (P<0.001). Moreover, the chance of survival was significantly greater when CP was administered within three days after the onset of COVID-19 symptoms than when CP was administered after four or more days (87% vs. 76%, P <0.001). In addition, adverse effects related to CP administration were recorded in only 2% of patients and were considered mild in all patients. CONCLUSIONS: Our study demonstrated that the administration of CP was safe and possibly associated with positive effects that were more pronounced if CP was administered within the first three days after the onset of COVID-19 symptoms.

Serum-derived bovine immunoglobulin treatment in COVID-19 is associated with faster resolution of symptoms: A randomized pilot clinical trial.

Effective treatment to prevent hospitalization and death in people with COVID-19 exists, but people still need interventions that alleviate symptoms without drug interactions. Oral serum-derived bovine immunoglobulins (SBI) may reduce symptoms and time-to-improvement in people with mild-to-moderate COVID-19. In this randomized, open-label, single-site study, participants with mild-to-moderate COVID-19 received SBI 5.0 g bis in die (BID) + Standard of Care (SOC) or SOC alone (2:1) for 2 weeks. After 2 weeks, 78.8% of hospitalized participants on SBI + SOC improved by World Health Organization (WHO) scale of ≥3 compared to 61.1% on SOC alone (odds ratio: OR = 2.4; p = 0.0663), with older participants (>57 years) showing more significant differences between the arms (OR = 6.1; p = 0.0109). Further, more participants on SBI + SOC reported absence of COVID-19 symptoms at Week 2 (74.2%) compared to SOC alone (43.6%; OR = 3.7; p = 0.0031), most notably the absence of dyspnea on exertion (OR = 4.4; p = 0.0047), with women exhibiting the most significant eradication of all symptoms (OR = 5.8; p = 0.0080). No difference in change of IL-6 between arms was observed. Overall, participants with mild-to-moderate COVID-19 on SBI + SOC had a shorter time-to-recovery than on SOC alone, with a significantly higher rate of complete resolution of symptoms. Dyspnea on exertion was the symptom most significantly impacted. For people with mild-to-moderate COVID-19, oral SBI could be a safe and effective intervention, devoid of drug interactions.

Efficacy of convalescent plasma in hospitalized COVID-19 patients: findings from a controlled trial.

The COVID-19 pandemic has driven the search for alternative therapies, including convalescent plasma, historically used in infectious diseases. Despite results in other diseases, its effectiveness against COVID-19 remains uncertain with conflicting results in clinical trials. A pragmatic, single-center, prospective, and open randomized controlled trial was carried out in a hospital in Brazil, with the aim of evaluating the impact of convalescent plasma on the clinical improvement of patients hospitalized with COVID-19. The World Health Organization (WHO) ordinal scale was used to measure clinical improvement, focusing on the reduction in disease severity by up to 2 points, while antibody and C-reactive protein levels were monitored over time. After hospital admission, participants were randomized 1:1 to receive convalescent plasma and standard treatment or to be part of the control group with standard treatment. Follow-up was carried out on days 1, 3, 7, 14 and/or at discharge. From January 14 to April 4, 2022, 38 patients were included, but 3 were excluded due to protocol deviations, resulting in a total of 35 patients: 19 in the control group and 16 in the plasma group. There was no significant difference in clinical improvement between the convalescent plasma group and the control group, nor in secondary outcomes. The study had limitations due to the small number of patients and limited representation of COVID-19 cases. Broader investigations are needed to integrate therapies into medical protocols, both for COVID-19 and other diseases. Conducting randomized studies is challenging due to the complexity of medical conditions and the variety of treatments available.

Biochemical rationale for transfusion of high titre COVID-19 convalescent plasma.

We aimed to model binding of donor antibodies to virus that infects COVID-19 patients following transfusion of convalescent plasma (CCP). An immunosorbent assay was developed to determine apparent affinity (Kd, app). Antibody binding to virus was modelled using antibody concentration and estimations of viral load. Assay and model were validated using reference antibodies and clinical data of monoclonal antibody therapy. A single Kd, app or two resolvable Kd, app were found for IgG in 11% or 89% of CCP donations, respectively. For IgA this was 50%-50%. Median IgG Kd, app was 0.8nM and 3.6nM for IgA, ranging from 0.1-14.7nM and 0.2-156.0nM respectively. The median concentration of IgG was 44.0nM (range 8.4-269.0nM) and significantly higher than IgA at 2.0nM (range 0.4-11.4nM). The model suggested that a double CCP transfusion (i.e. 500 mL) allows for > 80% binding of antibody to virus provided Kd, app was < 1nM and concentration > 150nM. In our cohort from the pre-vaccination era, 4% of donations fulfilled these criteria. Low and mid-range viral loads are found early post exposure, suggesting that convalescent plasma will be most effective then. This study provides a biochemical rationale for selecting high affinity and high antibody concentration CCP transfused early in the disease course.

Factors affecting symptom duration and recovery among home-treated COVID- 19 patients in Baghdad-Iraq: a cross-sectional study.

OBJECTIVE: To determine the prevalence of Long COVID among home-treated coronavirus disease-2019 cases, and the factors that may influence the duration of symptoms. METHODS: The cross-sectional study was conducted from February to July 2021 at 20 primary healthcare centres in 10 health districts of Baghdad, Iraq, after approval from the ethics review committee of the College of Medicine, Mustansiriyah University, Baghdad. Those included were adults of both genders who previously had coronavirus disease-2019 infection as diagnosed through on polymerase chain reaction test, and received supportive treatment during isolation at home. Data was collected through direct interview using a questionnaire which consisted of demographic characteristics, comorbidities, smoking history and symptoms of coronavirus disease-2019 along with their duration. Measurement of weight and height was also done for each subject. Data was analysed using SPSS 27. RESULTS: Of the 400 participants, 248(62%) were males and 152(38%) were females. The overall mean age was 40.8±12.8 years (range: 18-71 years). Of the total, 121(30.25%) subjects had persistent symptoms for >4 weeks. The mean duration of illness was 4.2±3.6 weeks (range: 1-16 weeks). The symptoms that lasted for >4 weeks were fatigue 94(23.5%), loss of smell or taste 59(14.75%), and cough 8(2%). Age, smoking status, comorbidities and the total number of initial symptoms showed a significant association with the duration of illness (p<0.05). CONCLUSIONS: A substantial number of mild to moderate coronavirus disease-2019 cases suffered from persistent symptoms. The duration of illness could have been influenced by age, comorbidities, smoking status and total number of initial symptoms.

Accessibility, Cost, and Quality of an Online Regular Follow-Up Visit Service at an Internet Hospital in China: Mixed Methods Study.

BACKGROUND: Telemedicine provides remote health care services to overcome constraints of time and space in accessing medical care. Similarly, internet hospitals in China support and provide remote health care services. Due to the COVID-19 pandemic, there has been a proliferation of internet hospitals. Many new services, including online consultations and regular online follow-up visit services, can now be accessed via internet hospitals in China. However, the accessibility, cost, and quality advantages of regular online follow-up visit services remain unclear. OBJECTIVE: This study aimed to evaluate the accessibility, costs, and quality of an online regular follow-up visit service provided by an internet hospital in China. By analyzing the accessibility, costs, and quality of this service from the supply and demand sides, we can summarize the practical and theoretical experiences. METHODS: A mixed methods study was conducted using clinical records from 18,473 patients receiving 39,239 online regular follow-up visit services at an internet hospital in 2021, as well as interviews with 7 physicians, 2 head nurses, and 3 administrative staff members. The quantitative analysis examined patient demographics, diagnoses, prescriptions, geographic distribution, physician characteristics, accessibility (travel time and costs), and service hours. The qualitative analysis elucidated physician perspectives on ensuring the quality of online health care. RESULTS: Patients were predominantly middle-aged men with chronic diseases like viral hepatitis who were located near the hospital. The vast majority were from Guangdong province where the hospital is based, especially concentrated in Guangzhou city. The online regular follow-up visit service reduced travel time by 1 hour to 9 hours and costs by ¥6 to ¥991 (US $0.86-$141.32) depending on proximity, with greater savings for patients farther from the hospital. Consultation times were roughly equivalent between online and in-person visits. Physicians provided most online services during lunch breaks (12 PM to 2 PM) or after work hours (7 PM to 11 PM), indicating increased workload. The top departments providing online regular follow-up visit services were Infectious Diseases, Rheumatology, and Dermatology. The most commonly prescribed medications aligned with the prevalent chronic diagnoses. To ensure quality, physicians conducted initial in-person consultations to fully evaluate patients before allowing online regular follow-up visits, during which they communicated with patients to assess conditions and determine if in-person care was warranted. They also periodically reminded patients to come in person for more comprehensive evaluations. However, they acknowledged online visits cannot fully replace face-to-face care. CONCLUSIONS: Telemedicine services such as online regular follow-up visit services provided by internet hospitals must strictly adhere to fundamental medical principles of diagnosis, prescription, and treatment. For patients with chronic diseases, online regular follow-up visit services improve accessibility and reduce cost but cannot fully replace in-person evaluations. Physicians leverage various strategies to ensure the quality of online care.