Search

The purpose of this review was to conduct a comparative assessment of the concepts of therapy for pediatric patients with COVID-19 in the framework of global clinical practice. A structural analysis of the range of drugs and treatment strategies in the context of etiotropic, pathogenetic, and symptomatic therapy has shown that in the global context and in real clinical practice, the etiotropic-pathogenetic approach based on information about the effectiveness of individual medical technologies prevails today. It has been established that eight international nonproprietary/grouping names are present in international practice as means of etiotropic therapy for pediatric patients with COVID-19, and 18 positions are used for pathogenetic therapy. In terms of frequency of occurrence, the leading positions are occupied by remdesivir and the combination of nirmatrelvir with ritonavir, as well as dexamethasone and tocilizumab. The paper emphasizes the relevance of research in the field of evaluating the effectiveness of individual treatment regimens as well as the analysis of the delayed consequences of pathology suffered in childhood under the conditions of using various approaches to pharmacotherapy. [ABSTRACT FROM AUTHOR]

Background: Patients with coronavirus disease 2019 (COVID-19) undergoing maintenance hemodialysis have a poor prognosis and limited treatment options. Methods: This paper outlines the impact of COVID-19, its treatment, and the efficacy of vaccines in Japanese patients undergoing hemodialysis with a review of the literature. Results: Patients undergoing dialysis in dialysis facilities are at greater risk of exposure to severe acute respiratory syndrome coronavirus 2 than the general population due to limited isolation capabilities. Therefore, vaccines are expected to be effective for patients undergoing dialysis. In addition, effective use of available medications is important because treatment options are limited. Conclusions: Efforts should be made to prevent the spread of the infection to high-risk patients undergoing dialysis while ensuring the effective use of vaccines. [ABSTRACT FROM AUTHOR]

Background/Objectives: Molnupiravir (MOV), an oral antiviral COVID-19 treatment, was introduced in the Czech Republic in December 2021 for COVID-19 patients at a high risk of progression to severe disease requiring hospitalization. In this observational, retrospective study, we aimed to describe the characteristics and healthcare resource utilization in non-hospitalized, adult COVID-19 patients prescribed MOV in the Czech Republic between 1 January and 30 April 2022. Methods: A total of 621 patients were included and followed up with for 28 days. Results: The median age was 68.0 (20–99) years, 77.8% were overweight or obese, 14.1% smoked, and 85.7% were vaccinated. The overall cumulative incidence (95% CI) of all-cause hospitalization was 0.71 (0.37; 1.24) per 1000 person years or 1.9%, with similar rates across sexes, age groups, BMI category, multimorbidity category, polypharmacy category, and COVID-19 vaccination status. Among patients reported hospitalized, oxygen-based resources were not observed, and no deaths occurred. Conclusions: These data describe the characteristics and healthcare resource utilization in Czech MOV-treated patients whose clinical characteristics may put them at increased risk of severe disease. [ABSTRACT FROM AUTHOR]

Background/Objectives: Upper-limb function of chronic stroke patients declined when outpatient rehabilitation was interrupted and outings restricted, owing to the novel coronavirus infection (COVID-19) pandemic. We investigated whether these patients recovered upper-limb function post-resumption of outpatient rehabilitation. Methods: In this observational study, 43 chronic stroke hemiparesis patients with impaired upper extremity function were scored for limb function via the Fugl-Meyer assessment of the upper extremity (FMA-UE) and the Action Research Arm Test (ARAT) after a structured interview, evaluation, and intervention. Scores at 6 and 3 months pre- and 3 months post-rehabilitation interruption were examined retrospectively; scores immediately and at 3 and 6 months post-resumption of care were examined prospectively. The amount of change for each time period and an analysis of covariance were performed with time as a factor, changes in the FMA-UE and the ARAT scores as dependent variables, and statistical significance at 5%. Results: The time of evaluation significantly impacted the total score, as well as part C and part D of FMA-UE and total, pinch, and gross movement of the ARAT. Post-hoc tests showed that the magnitude of change in limb-function scores from immediately to 3 months post-resumption was significantly higher than the change from 3 months pre- to immediately post-interruption for the total score and part D of the FMA-UE, as well as grip and gross movement of the ARAT (p < 0.05). Conclusions: Upper-limb functional decline in chronic stroke patients, caused by the COVID-19 pandemic-related therapy interruption and outing restrictions, was resolved approximately 3 months post-resumption of rehabilitation therapy. Our data can serve as reference standards for planning and evaluating treatment for chronic stroke patients with inactivity-related impaired upper-limb function. [ABSTRACT FROM AUTHOR]

During the pandemic, assisted reproductive treatments suffered from major disruptions in their terms due to the restrictions imposed. The objective of this study is to evaluate the level of anxiety of women whose treatments were either suspended or delayed. Methods: Descriptive cross-sectional study conducted between April and May 2020. The State-Trait Anxiety Inventory was applied by telephone in a Spanish adapted version. The research also included social, personal, and work aspects which may be involved in the challenging situation. Results: A total of 115 patients participated in the study (73.7%). Women showed a mean in trait anxiety of 17.79 (SD = 8.80) and a mean in state anxiety of 19.95 (SD = 9.08). Neither the type of treatment nor the time of infertility were predictors of trait anxiety or state anxiety. Greater age pressure and more worry were associated to greater trait and state anxiety (p < 0.001). The most common emotional reactions to discontinuation of fertility treatments were sadness and anxiety. Conclusions: Discontinuation of fertility treatments due to confinement restrictions had a negative impact on the mental health of women who were following a process of assisted reproduction treatment, increasing their levels of emotional distress and anxiety. [ABSTRACT FROM AUTHOR]

New-onset atrial fibrillation (NOAF) is the most frequently encountered cardiac arrhythmia observed in patients with COVID-19 infection, particularly in Intensive Care Unit (ICU) patients. The purpose of the present review is to delve into the occurrence of NOAF in COVID-19 and thoroughly review recent, pertinent data. However, the causality behind this connection has yet to be thoroughly explored. The proposed mechanisms that could contribute to the development of AF in these patients include myocardial damage resulting from direct virus-induced cardiac injury, potentially leading to perimyocarditis; a cytokine crisis and heightened inflammatory response; hypoxemia due to acute respiratory distress; disturbances in acid-base and electrolyte levels; as well as the frequent use of adrenergic drugs in critically ill patients. Additionally, secondary bacterial sepsis and septic shock have been suggested as primary causes of NOAF in ICU patients. This notion gains strength from the observation of a similar prevalence of NOAF in septic non-COVID ICU patients with ARDS. It is plausible that both myocardial involvement from SARS-CoV-2 and secondary sepsis play pivotal roles in the onset of arrhythmia in ICU patients. Nonetheless, there exists a significant variation in the prevalence of NOAF among studies focused on severe COVID-19 cases with ARDS. This discrepancy could be attributed to the inclusion of mixed populations with varying degrees of illness severity, encompassing not only patients in general wards but also those admitted to the ICU, whether intubated or not. Furthermore, the occurrence of NOAF is linked to increased morbidity and mortality. However, it remains to be determined whether NOAF independently influences outcomes in critically ill COVID-19 ICU patients or if it merely reflects the disease's severity. Lastly, the management of NOAF in these patients has not been extensively studied. Nevertheless, the current guidelines for NOAF in non-COVID ICU patients appear to be effective, while accounting for the specific drugs used in COVID-19 treatment that may prolong the QT interval (although drugs like lopinavir/ritonavir, hydrochlorothiazide, and azithromycin have been discontinued) or induce bradycardia (e.g., remdesivir). [ABSTRACT FROM AUTHOR]

(1) Background: Long COVID syndrome (LCS) is a heterogeneous long-standing condition following COVID-19 infection. Treatment options are limited to symptomatic measures, and no specific medication has been established. Hyperbaric oxygenation (HBO) has been found to have a positive impact on the treatment of COVID-19 infection. This study evaluates both the feasibility and outcome of supportive HBO in patients with LCS. (2) Methods: Within 17 months, 70 patients with proven LCS were prospectively included. Each patient underwent a cycle of 10 subsequent HBO treatment sessions administered for 75 min at 2.2 atmospheres. Evaluation of the patients was performed before the first and after the last HBO session and 3 months afterwards. Statistical evaluation was based on an intention-to-treat analysis using Fisher's exact test and Student's t-test for paired samples. (3) Results: In total, 59 patients (33 females, 26 males; mean age: 43.9 years; range: 23–74 years; median: 45.0) were evaluable. After HBO, a statistically significant improvement of physical functioning (p < 0.001), physical role (p = 0.01), energy (p < 0.001), emotional well-being (p < 0.001), social functioning (p < 0.001), pain (p = 0.01) and reduced limitation of activities (p < 0.001) was confirmed. (4) Conclusions: Physical functioning and both the physical and emotional role improved significantly and sustainably, suggesting HBO as a promising supportive therapeutic tool for the treatment of LCS. [ABSTRACT FROM AUTHOR]

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020–2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir–ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir–ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19. [ABSTRACT FROM AUTHOR]

Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study's data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise. [ABSTRACT FROM AUTHOR]

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients. [ABSTRACT FROM AUTHOR]

Mortality in COVID-19 is mainly associated with respiratory failure, cytokine storm, and macrophage activation. Oxygenation and anti-inflammatory effects of Hyperbaric Oxygen Therapy (HBOT) suggest that it is a promising adjunct treatment for COVID-19. Repeated sessions of HBO with standard COVID-19 therapy were used to reduce the inflammation and increase oxygenation. We evaluated the safety and efficacy of HBOT in avoiding the replacement ventilation and/or ECMO and its effect on the inflammatory process. Twenty-eight moderate-to-severe COVID-19 patients were randomized into control or HBOT group. HBOT patients participated in 5 hyperbaric sessions (60 min). Before and after each session blood gas levels and vital parameters were monitored. Blood samples were collected for extended biochemical tests, blood morphology and immunological assays. There were 3 deaths in the control, no deaths in the HBOT group. No adverse events leading to discontinuation of HBOT were observed and patients receiving HBOT required lower oxygen delivery. We observed decrease in CRP, ferritin and LDH and increase in CD3 in HBOT group compared to control. This study confirmed the feasibility and safety of HBOT in patients with COVID-19 and indicated HBOT can lead to alleviation of inflammation and partial restoration of T cell responses. [ABSTRACT FROM AUTHOR]

Early therapies to prevent severe COVID-19 have an unclear impact on patients with hematological malignancies. The aim of this study was to assess their efficacy in this group of high-risk patients with COVID-19 in preventing hospitalizations and reducing the SARS-CoV-2 shedding. This was a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted the data of patients with hematologic malignancies and COVID-19 who received and did not receive early COVID-19 treatment between 23 December 2021, and May 2022. We used a Cox proportional hazard model to assess whether receiving any early treatment was associated with lower rates of hospitalization and reduced viral shedding. Data from 88 patients with hematologic malignancies were extracted. Among the patients, 55 (62%) received any early treatment, whereas 33 (38%) did not. Receiving any early therapy did not significantly reduce the hospitalization rate in patients with hematologic malignancies (HR 0.51; SE 0.63; p-value = 0.28), except in the vaccinated non-responders subgroup of patients with negative anti SARS-CoV-2 antibodies at the time of infection, who benefited from early therapies against SARS-CoV-2 (HR 0.07; SE 1.04; p-value = 0.001). Moreover, no difference on viral load decay was observed. In our cohort of patients with hematologic malignancies infected with SARS-CoV-2, early treatment were not effective in reducing the hospitalization rate due to COVID-19, neither in reducing its viral shedding. [ABSTRACT FROM AUTHOR]

Background: Molnupiravir is approved for the treatment of adult patients with mild to moderate COVID-19. The main goal of the treatment is to reduce hospitalization and mortality rate. This study aimed at the all-cause hospitalization and all-cause death assessment in patients at high risk of severe COVID-19 treated with molnupiravir. Methods: This was a prospective, observational single center study. Non-hospitalized patients with SARS-CoV-2 infection, COVID-19 symptoms with the onset of up to 5 days, and at high risk of severe COVID-19 illness received molnupiravir based on attending physician decisions. Results: In total, 107 patients were enrolled. Adverse events were reported in 28.0% of patients, with nausea and abdominal pain being the most commonly observed. No treatment-emergent AEs resulted in therapy discontinuation. Overall, 15 patients required hospitalization. During the observation, 2.8% (n = 3) of patients subsequently died. All deaths were considered to be related to COVID-19 complications. Age over 65 years, heart failure, and ischemic heart disease showed a significant correlation with the severe course of COVID-19. Conclusion: Molnupiravir may be perceived as an alternative treatment for patients with immunosuppression and advanced chronic kidney disease. Nevertheless, further studies are required to conclusively establish a role for molnupiravir in future COVID-19 treatment recommendations. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis, like COVID-19, is most often a pulmonary disease. The COVID-19 pandemic has severely disrupted tuberculosis services in myriad ways: health facility closures, lockdowns, travel bans, overwhelmed healthcare systems, restricted export of antituberculous drugs, etc. The effects of the shared risk on outcomes of the two diseases is not known, particularly for the first year of the pandemic, during the period before COVID-19 vaccines became widely available. Objective: We embarked on a systematic review to elucidate the consequences of tuberculosis on COVID-19 outcomes and of COVID-19 on tuberculosis outcomes during the pre-vaccination period of the pandemic. Methods: The systematic review protocol is registered in PROSPERO. We conducted an initial search of PubMed, Embase, Web of Science, WHO coronavirus database, medRxiv, bioRxiv, preprints.org, and Google Scholar using terms relating to COVID-19 and tuberculosis. We selected cohort and case–control studies for extraction and assessed quality with the Newcastle-Ottawa scale. Results and Conclusion: We identified 2108 unique abstracts published between December 2019 and January 2021. We extracted data from 18 studies from 8 countries. A total of 650,317 persons had a diagnosis of COVID-19, and 4179 had a diagnosis of current or prior tuberculosis. We explored links between tuberculosis and COVID-19 incidence, mortality, and other adverse outcomes. Nine studies reported on mortality and 13 on other adverse outcomes; results on the association between tuberculosis and COVID-19 mortality/adverse outcomes were heterogenous. Tuberculosis outcomes were not fully available in any studies, due to short follow-up (maximum of 3 months after COVID-19 diagnosis), so the effects of COVID-19 on tuberculosis outcomes could not be assessed. Much of the rapid influx of literature on tuberculosis and COVID-19 during this period was published on preprint servers, and therefore not peer-reviewed. It offered limited examination of the effect of tuberculosis on COVID-19 outcomes and even less on the effect of COVID-19 on tuberculosis treatment outcomes. [ABSTRACT FROM AUTHOR]

The current pandemic due to the SARS-CoV-2 virus has caused irreparable damage globally. High importance is placed on defining current therapeutics for Coronavirus Disease 2019 (COVID-19). In this review, we discuss the evidence from pivotal trials that led to the approval of effective therapeutics in the treatment and prevention of COVID-19. We categorize them as effective outpatient and inpatient management strategies The review also attempts to contextualize the efficacy of therapeutics to the emerging variants. Vaccines, which remain the most effective prevention against hospitalization and deaths is not included in this review. [ABSTRACT FROM AUTHOR]

Background: COVID-19 disease, which typically presents with respiratory symptoms, can trigger intestinal inflammation through SARS-CoV-2 replication in the gastrointestinal tract. Supplementation with probiotics may have beneficial effects on gut inflammation due to their analgesic and anti-inflammatory properties. The primary objective of our study was to evaluate the efficacy of a mix of three probiotic strains (Bifidobacterium lactis LA 304, Lactobacillus salivarius LA 302, and Lactobacillus acidophilus LA 201; Lactibiane Iki®) in the reduction in fecal calprotectin in patients with COVID-19 pneumonia, compared to a control group. The secondary aim was to evaluate the reduction in oxygen support and length of hospital stay in patients taking the probiotic mix. Patients and Methods: We conducted a prospective randomized controlled trial at Fondazione Policlinico Gemelli, Rome. We enrolled patients with COVID-19 interstitial pneumonia. One group received the probiotic mix twice a day for 10 days in addition to the standard COVID-19 therapy, and a second group received standard COVID-19 therapy without probiotics. We administered oxygen support (through Ventimask or Optiflow®) on days (D) 1, 3, 5, 7 and 10, and the level of fecal calprotectin between D3–D5 and D7–D10. Results: A total of 80 patients (44 M/36 F; mean age: 59.8 ± 17.3) were enrolled with a mean value of calprotectin at enrollment of 140 mg/dl. At D7–10, the probiotic group showed a 35% decrease in fecal calprotectin compared to 16% in the control group, a decrease in C-reactive protein (CRP) of 72.7% compared to 62%, and a slight but not significant decrease in oxygen support compared to the control group. Conclusion: Supplementation with a mix of probiotics for 10 days in patients with COVID-19 interstitial pneumonia significantly reduces inflammatory markers. [ABSTRACT FROM AUTHOR]

(1) Background: Until now, several reports about pregnant women with confirmed coronavirus disease 2019 (COVID-19) have been published. However, there are no comprehensive systematic reviews collecting all case series studies on data regarding adverse pregnancy outcomes, especially association with treatment modalities. (2) Objective: We aimed to synthesize the most up-to-date and relevant available evidence on the outcomes of pregnant women with laboratory-confirmed infection with COVID-19. (3) Methods: PubMed, Scopus, MEDLINE, Google scholar, and Embase were explored for studies and papers regarding pregnant women with COVID-19, including obstetrical, perinatal, and neonatal outcomes and complications published from 1 January 2020 to 4 May 2020. Systematic review and search of the published literature was done using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). (4) Results: In total, 11 case series studies comprising 104 pregnant women with COVID-19 were included in our review. Fever (58.6%) and cough (30.7%) were the most common symptoms. Other symptoms included dyspnea (14.4%), chest discomfort (3.9%), sputum production (1.0%), sore throat (2.9%), and nasal obstruction (1.0%). Fifty-two patients (50.0%) eventually demonstrated abnormal chest CT, and of those with ground glass opacity (GGO), 23 (22.1%) were bilateral and 10 (9.6%) were unilateral. The most common treatment for COVID-19 was administration of antibiotics (25.9%) followed by antivirals (17.3%). Cesarean section was the mode of delivery for half of the women (50.0%), although no information was available for 28.8% of the cases. Regarding obstetrical and neonatal outcomes, fetal distress (13.5%), pre-labor rupture of membranes (9.6%), prematurity (8.7%), fetal death (4.8%), and abortion (2.9%) were reported. There are no positive results of neonatal infection by RT-PCR. (5) Conclusions: Although we have found that pregnancy with COVID-19 has significantly higher maternal mortality ratio compared to that of pregnancy without the disease, the evidence is too weak to state that COVID-19 results in poorer maternal outcome due to multiple factors. The number of COVID-19 pregnancy outcomes was not large enough to draw a conclusion and long-term outcomes are yet to be determined as the pandemic is still unfolding. Active and intensive follow-up is needed in order to provide robust data for future studies. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) shows high incidence of thromboembolic events in humans. In the present study, we aimed to evaluate if anticoagulation prior to COVID-19 infection may impact clinical profile, as well as mortality rate among patients hospitalized with COVID-19. The study was based on retrospective analysis of medical records of patients with laboratory confirmed SARS-CoV-2 infection. After propensity score matching (PSM), a group of 236 patients receiving any anticoagulant treatment prior to COVID-19 infection (AT group) was compared to 236 patients without previous anticoagulation (no AT group). In 180 days, the observation we noted comparable mortality rate in AT and no AT groups (38.5% vs. 41.1%, p = 0.51). Similarly, we did not observe any statistically significant differences in admission in the intensive care unit (14.1% vs. 9.6%, p = 0.20), intubation and mechanical ventilation (15.0% vs. 11.6%, p = 0.38), catecholamines usage (14.3% vs. 13.8%, p = 0.86), and bleeding rate (6.3% vs. 8.9%, p = 0.37) in both groups. Our results suggest that antithrombotic treatment prior to COVID-19 infection is unlikely to be protective for morbidity and mortality in patients hospitalized with COVID-19. [ABSTRACT FROM AUTHOR]

The outburst of inflammatory response and hypercoagulability are among the factors contributing to increased mortality in severe COVID-19 cases. Pentoxifylline (PTX), a xanthine-derived drug registered for the treatment of vascular claudication, has been reported to display broad-spectrum anti-inflammatory and immunomodulatory properties via adenosine A2A receptor (A2AR)-related mechanisms, in parallel to its rheological actions. Prior studies have indicated the efficacy of PTX in the treatment of various pulmonary diseases, including the management of acute respiratory distress syndrome of infectious causes. Therefore, PTX has been proposed to have potential benefits in the treatment of SARS-CoV-2 symptoms, as well as its complications. The aim of this review is to discuss available knowledge regarding the role of PTX as a complementary therapeutic in SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The recent respiratory virus known as SARS-CoV-2 has caused millions of deaths worldwide, causing great uncertainty due to the lack of a specific treatment, which has been mitigated by the use of various drugs traditionally used against other types of pathologies. Pregnancy presents special physiological conditions that expose the pregnant woman and the foetus to greater risk. Pregnant women are often excluded from trials due to possible risk of toxicity or side effects, resulting in a lack of knowledge about the use of drugs and treatments during pregnancy. The main objective of this review was to compile existing knowledge about currently available drug treatments for COVID-19 in pregnant women. The review report met the criteria of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) review protocol and was registered with the registration number CRD42021251036. The electronic databases searched were Scopus, PubMed, CINAHL and SciELO. Finally, 22 articles were included, resulting in an analysis of drugs with an acceptable safety profile in the treatment of pregnant women with COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: Remdesivir is currently approved for the treatment of COVID-19. The recommendation for using remdesivir in patients with COVID-19 was based on the in vitro and in vivo activity of this drug against SARS-CoV-2. Methods: This was a prospective observational study conducted on a population of patients hospitalized for COVID-19. The primary endpoint of this study was the impact of remdesivir-containing therapy on 30-day mortality; the secondary endpoint was the impact of remdesivir-containing therapy on the need for high-flow oxygen therapy (HFNC), non-invasive ventilation (NIV), or mechanical ventilation. The data were analyzed after propensity score matching. Results: A total of 407 patients with SARS-CoV-2 pneumonia were consecutively enrolled. Out of these, 294 (72.2%) were treated with remdesivir and 113 (27.8%) were not. Overall, 61 patients (14.9%) were treated during hospitalization with HFNC, NIV, or mechanical ventilation, while 30-day mortality was observed in 21 patients (5.2%). Univariate analysis of patients treated with remdesivir or not showed no differences in 30-day mortality (4% vs. 6%, p = 0.411) in the two study groups. Cox regression analysis, after propensity score matching, showed that therapies, including remdesivir-containing therapy, were not statistically associated with 30-day survival or mortality. The Kaplan–Meier curves of 30-day survival in patients treated with remdesivir or not before (p = 0.24) and after (p = 0.88) propensity score matching showed no differences between the two study groups. Finally, patients treated with remdesivir or not showed the same need for HFNC/NIV or mechanical ventilation. Conclusions: This real-life experience of remdesivir use in hospitalized patients with COVID-19 was not associated with significant increases in rates of survival or reduced use of HFNC/NIV or mechanical ventilation compared with patients treated with other therapies not including remdesivir. [ABSTRACT FROM AUTHOR]

Introduction: Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID-19 and the mechanisms of action of Ig led to the consideration of this adjunctive therapy, including in patients with respiratory failure due to the SARS-CoV-2 infection. This manuscript reports the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID-19. Methods: A panel of multidisciplinary experts defined the clinical phenotypes of COVID-19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. Results: Three different phenotypes of COVID-19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune paralysis (late phase) and patients with sepsis due to a hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panelists considered its use in the late phase and patients with sepsis/septic shock by bacterial superinfection appropriate. Conclusion: As with other immunotherapies, IVIg adjunctive therapy may have a potential role in the management of COVID-19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness. [ABSTRACT FROM AUTHOR]

Background: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. Methods: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. Results: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). Conclusions: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography. [ABSTRACT FROM AUTHOR]

Background: Our aim was to investigate the impact of therapeutics with antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mortality of older adults affected by coronavirus disease 2019 (COVID-19), taking into consideration the time interval from symptoms onset to drugs administration. Methods: Data from 143 COVID-19 patients over 65 years of age admitted to the Humanitas Clinical and Research Center Emergency Department (Milan, Italy) and treated with Lopinavir/ritonavir (LPV/r) or Darunavir/cobicistat (DVR/c) associated to Hydroxychloroquine (HCQ) were retrospectively analyzed. Statistical analysis was performed by using a logistic regression model and survival analysis to assess the role of different predictors of in-hospital mortality, including an early (<6 days from symptoms onset) vs. late treatment onset, signs and symptoms at COVID-19 presentation, type of antiviral treatment (LPV/r or DVR/c) and patients' age (65–80 vs. >80 years old). Results: Multivariate analysis showed that an older age (OR: 2.54) and dyspnea as presenting symptom (OR: 2.01) were associated with higher mortality rate, whereas cough as presenting symptom (OR: 0.53) and a timely drug administration (OR: 0.44) were associated with lower mortality. Survival analysis demonstrated that the timing of drug administration had an impact on mortality in 65–80 years-old patients (p = 0.02), whereas no difference was seen in those >80 years-old. This impact was more evident in patients with dyspnea as primary symptom of COVID-19, in whom mortality decreased from 57.1% to 38.3% due to timely drug administration (OR: 0.5; p = 0.04). Conclusions: There was a significant association between the use of a combined antiviral regimen and HCQ and lower mortality, when timely-administered, in COVID-19 patients aged 65–80 years. Our findings support timely treatment onset as a key component in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Because the optimal treatment for COVID-19 is still unknown, it is important to explore every potential way of improving the chances of survival for COVID-19 patients. The aim of the study was to analyze the effectiveness of convalescent plasma on COVID-19 patients. The study population consisted of 78 patients diagnosed with COVID-19, selected from the SARSTer national database, who received convalescent plasma. The impact on clinical and laboratory parameters was assessed. A clinical improvement was observed in 62 (79%) patients, and 10 (13%) patients died from COVID-19. No side effects of the convalescent plasma treatment were observed. When plasma was administered earlier than 7 days from diagnosis, the total hospitalization time was shorter (p < 0.05). Plasma efficacy was inferior to remdesivir in endpoints such as the necessity and duration of oxygen therapy, the duration of hospitalization, and mortality rate, and inferior to other drugs in the case of the duration of hospitalization and the necessity of constant oxygen therapy, but comparable in most other measured endpoints. A comparison of a 30-day mortality rate in patients who received plasma and remdesivir (4/25, 16%) and who received only plasma (6/53, 11%) showed no significant difference. Convalescent plasma efficacy is inferior to remdesivir when treating COVID-19 patients but the addition of remdesivir to plasma does not improve the treatment effectiveness. In most endpoints, plasma was comparable to other treatment options. In our opinion, convalescent plasma may be used as a supportive treatment in COVID-19 patients because of the low frequency of adverse effects and availability, but must be given as early from the diagnosis as possible. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a challenge for all participants in the healthcare system. At the beginning of the pandemic, many physicians asked themselves what risk their patients, especially those with chronic diseases, were exposed to. We present an overview of all patients with multiple sclerosis (MS) and SARS-CoV-2 infection published in the literature so far. In total, there are publications on 873 SARS-CoV-2 positive MS patients and information on the outcome can be given for 700 patients. With regard to the different disease modifying therapies (DMTs), by far the most cases were described under anti-CD20 treatment (n = 317). The mortality rate of all MS patients was 4% and a further 3% required invasive or non-invasive ventilation. When looking at the severe and fatal cases, it is particularly noticeable that patients without DMTs, with previous cardiovascular diseases, or with a severe degree of disability are at risk. Immunosuppressive therapy itself does not appear to be a substantial risk factor. Rather, it is reasonable to assume that the therapies could be protective, either directly, by mitigating the cytokine storm, or indirectly, by reducing the disease activity of MS. [ABSTRACT FROM AUTHOR]

The receptor for advanced glycation end products (RAGE), a well-known player of diabetes mellitus (DM)-related morbidities, was supposed to be involved in coronavirus disease-19 (COVID-19), but no data exist about COVID-19, DM, and the soluble RAGE (sRAGE) forms. We quantified total sRAGE and its forms, the endogenously secretory esRAGE and the membrane-cleaved cRAGE, in COVID-19 patients with and without DM and in healthy individuals to explore how COVID-19 may affect these molecules and their potential role as biomarkers. Circulating sRAGE and esRAGE were quantified by enzyme-linked-immunosorbent assays. cRAGE was obtained by subtracting esRAGE from total sRAGE. sRAGE, esRAGE, cRAGE, and the cRAGE/esRAGE ratio did not differ between DM and non-DM patients and had the same trend when compared to healthy individuals. Levels of total sRAGE, cRAGE, and cRAGE/esRAGE ratio were upregulated, while esRAGE was downregulated. The lack of difference between DM and non-DM COVID-19 patients in the levels of sRAGE and its forms supports the hypothesis that in COVID-19 the RAGE system is modulated regardless of glycemic control. Identifying how sRAGE and its forms associate to COVID-19 prognosis and the potential of RAGE as a therapeutic target to control inflammatory burden seem of relevance to help treatment of COVID-19. [ABSTRACT FROM AUTHOR]