Repurposing the antioxidant and anti-inflammatory agent N-acetyl cysteine for treating COVID-19

Although several considerations have been raised suggesting a beneficial effect of N-acetyl cysteine (NAC) for the treatment of severe acute respiratory syndrome coronavirus 2 infection, there is currently no clinical evidence that NAC truly prevents coronavirus disease 2019 (COVID-19), reduces the severity of the disease, or improves the outcome. Appropriately designed clinical trials are warranted to prove or disprove a therapeutic effect of NAC for COVID-19 patients.     

Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.     

Potential therapeutic effect and methods of traditional Chinese medicine on COVID-19-induced depression: A review

COVID-19 (coronavirus) has spread all over the world with a high infection rate. Currently, there are no targeted therapeutic drugs for COVID-19 as well as for stress induced by COVID-19. The unpredictable events of COVID-19 can trigger feelings of fear, worry, or unease in people, leading to stress-related disorders such as depression and anxiety. It has been reported that individuals, including COVID-19 patients, medical staff, and ordinary people, are under both physical and psychological pressure, and many of them have developed depression or anxiety during this pandemic. Traditional Chinese medicine (TCM) has been widely used in treating depression with relatively better safety and efficacy and may have an important role in treating stress-related disorders induced by COVID-19. In this review, we collected the common TCM treatment methods including Qigong, Acupuncture, Five Elements Musical Therapy, Five Elements Emotional Therapy, and Chinese herbal medicine from the databases of PubMed and the China National Knowledge Internet to illustrate the effect of TCM on depression. The better knowledge of TCM and implementation of TCM in COVID-19 clinics may help to effectively improve depression induced by COVID-19, may assist people to maintain a healthy physical and mental quality, and may alleviate the current shortage of medical resources.     

Therapeutic potential of N-acetyl cysteine during COVID-19 epoch

N-acetyl cysteine (NAC) is a promising drug for prophylaxis and treatment of coronavirus disease 2019 (COVID-19) based on antioxidant and anti-inflammatory mechanisms. Further studies with cautious approach are needed to establish the benefits and risks before considering NAC as an adjuvant treatment for COVID-19.     

Ibuprofen use and clinical outcomes in COVID-19 patients

ObjectiveIt was recently suggested that ibuprofen might increase the risk for severe and fatal coronavirus disease 2019 (COVID-19) and should therefore be avoided in this patient population. We aimed to evaluate whether ibuprofen use in individuals with COVID-19 was associated with more severe disease, compared with individuals using paracetamol or no antipyretics.MethodsIn a retrospective cohort study of patients with COVID-19 from Shamir Medical Centre, Israel, we monitored any use of ibuprofen from a week before diagnosis of COVID-19 throughout the disease. Primary outcomes were mortality and the need for respiratory support, including oxygen administration and mechanical ventilation.ResultsThe study included 403 confirmed cases of COVID-19, with a median age of 45 years. Of the entire cohort, 44 patients (11%) needed respiratory support and 12 (3%) died. One hundred and seventy-nine (44%) patients had fever, with 32% using paracetamol and 22% using ibuprofen, for symptom-relief. In the ibuprofen group, 3 (3.4%) patients died, whereas in the non-ibuprofen group, 9 (2.8%) patients died (p 0.95). Nine (10.3%) patients from the ibuprofen group needed respiratory support, compared with 35 (11%) from the non-ibuprofen group (p 1). When compared with exclusive paracetamol users, no differences were observed in mortality rates or the need for respiratory support among patients using ibuprofen.ConclusionsIn this cohort of COVID-19 patients, ibuprofen use was not associated with worse clinical outcomes, compared with paracetamol or no antipyretic.     

Convalescent Plasma for Infectious Diseases: Historical Framework and Use in COVID-19

Convalescent plasma has emerged as a promising therapeutic agent for patients with coronavirus disease 2019 (COVID-19), has received emergency use authorization, and is being widely used during the COVID-19 pandemic. Passive antibody therapy via plasma or serum has been successfully used to treat infectious diseases for more than a century. Passive antibody administration is based on the presumption that convalescent plasma or serum contains therapeutic antibodies that can be passively transferred to the plasma recipient. There are numerous examples in which convalescent plasma has been used successfully as post-exposure prophylaxis and treatment of infectious diseases, including previous coronavirus outbreaks. In the context of the COVID-19 pandemic, convalescent plasma was demonstrated to be safe and potentially effective among patients infected with COVID-19. This review provides an overview of the historical uses of convalescent plasma therapy, summarizes current evidence for convalescent plasma use for COVID-19, and highlights future antibody therapies.     

Treatment Options for Patients With Mild-to-Moderate Coronavirus Disease 2019 in Korea

The coronavirus disease 2019 (COVID-19) continues to threaten public health in Korea although several surges have passed in the past 3 years since 2019. Although patients with mild-to-moderate COVID-19 can usually recover at home, antiviral therapy to prevent disease progression and hospitalization is beneficial for those at high risk of progressing to severe COVID-19. The purpose of this article was to review how antivirals have been rolled out for the treatment of COVID-19 and how domestic and international guidelines for their use have evolved. Several evidence-based treatment guidelines have been developed in Korea, including those derived from domestic studies. Although many different antiviral agents were nominated as promising therapeutics at the onset of the pandemic, most failed to show efficacy in clinical trials. Currently, three types of antiviral agents—nirmatrelvir-ritonavir, molnupiravir, and remdesivir—are available in Korea to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Each antiviral has its advantages and disadvantages. For most individuals, nirmatrelvir/ritonavir is preferred because of its high efficacy and convenience of administration. When serious drug interactions occur or are expected with nirmatrelvir/ritonavir administration, 3 days of remdesivir treatment is shown to be a reasonable alternative. Molnupiravir may be prescribed with caution only if no other therapeutic options are available or acceptable.     

Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19

ObjectivesDetailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19.MethodsStudy participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR.ResultsOf the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5°C) was only observed in 20 (11.6%) individuals.ConclusionsAs much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.     

In vivo oxidants and pulmonary inflammation

Endotoxemia is used as a model of the adult respiratory distress syndrome in chronically instrumented awake sheep. The toxic effects of endotoxin may be mediated through inflammatory cells and the release of toxic oxidants. N-acetylcysteine (NAC) inhibits the in vivo effects of endotoxemia in chronically instrumented unanesthetized sheep. NAC also functions as a free radical scavenger in vitro. It is possible that the protective effects of pretreatment with NAC result from NAC's ability in vivo to protect against local oxidant injury.     

Antivirals for Coexistence with COVID-19: Brief Review for General Physicians

In order to end the coronavirus disease 2019 (COVID-19) pandemic that has lasted for nearly two years, it is most necessary to introduce antiviral drugs specific to COVID-19 along with the establishment of herd immunity by vaccination. Candidates currently being studied include nucleoside analogues that inhibit replication, protease inhibitors, and entry blockers. Not only the virus itself, but also the host protein that the virus uses in its pathogenesis is the target of treatment. Although the severe acute respiratory syndrome coronavirus 2 will not be completely eradicated, if the use of antiviral drugs is established, the COVID-19 pandemic will end through coexistence with the virus.     

COVID-19 and the antiphospholipid syndrome

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic. Most COVID-19 patients are asymptomatic or have flu-like symptoms. However, around 15% of the patients may have severe disease, including unilateral or bilateral pneumonia with acute respiratory distress syndrome and progressive hypoxemia that may require mechanical ventilation assistance. A systemic inflammatory response syndrome occurs in the most severe forms of COVID-19, with multiorgan involvement which can be life threatening caused by a cytokine storm. Although what best characterizes COVID-19 are the manifestations of the respiratory system, it has been shown that it also acts at the cardiovascular level, producing coagulation abnormalities, which causes thrombotic events mainly in the arteries/arterioles, microcirculation and venous system, and potentially increased mortality risk. This multiorgan vascular disease overlaps with other known microangiopathies, such as thrombotic microangiopathy or paroxysmal nocturnal hemoglobinuria, where complement overactivation plays an important role in the pathophysiology of thrombosis. Furthermore, coagulopathy secondary to COVID-19 occurs in the context of an uncontrolled inflammatory response, reminiscent of APS, especially in its catastrophic form. This review summarizes the current knowledge regarding the relationship between COVID-19 and the APS.     

BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel

ObjectivesThe mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination.MethodsA retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed.ResultsA total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance.ConclusionsWe found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations.     

Retest positive for SARS-CoV-2 RNA of “recovered” patients with COVID-19: Persistence,sampling issues,or re-infection?

“Retest Positive” for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) from “recovered” coronavirus disease-19 (COVID-19) has been reported and raised several important questions for this novel coronavirus and COVID-19 disease. In this commentary, we discussed several questions: (a) Can SARS-CoV-2 re-infect the individuals who recovered from COVID-19? This question is also associated with other questions: whether or not SARS-CoV-2 infection induces protective reaction or neutralized antibody? Will SARS-CoV-2 vaccines work? (b) Why could some recovered patients with COVID-19 be re-tested positive for SARS-CoV-2 RNA? (c) Are some recovered pwith atients COVID-19 with re-testing positive for SARS-CoV-2 RNA infectious? and (d) How should the COVID-19 patients with retest positive for SARS-CoV-2 be managed?     

Evaluation of IGFBP5 expression and plasma osteopontin level in COVID-19 patients

PurposeThe aim of this study is to investigate insulin-like growth factor binding protein 5 (IGFBP5) expression in coronavirus disease 2019 (COVID-19) patients and its relationships with COVID-19 laboratory findings and plasma osteopontin (OPN) levels.Materials and methodsWe enrolled 60 patients with COVID-19 and 30 healthy individuals in this study. mRNA expression of IGFBP5 was measured by RT-PCR. Plasma OPN levels were measured via the ELISA method.ResultsPlasma OPN levels were higher and IGFBP5 expression levels were lower in COVID-19 patients than in the healthy individuals (p ?= ?0.0057 and p ?= ?0.0142, respectively). Critically ill patients had higher OPN and lower IGFBP5 than non-critically ill patients. Patients with affected lungs demonstrated increased OPN and decreased IGFBP5 (p ?= ?0.00032 and p ?= ?0.044, respectively). Receiver operating characteristic (ROC) analysis indicated that IGFBP5 expression and OPN levels can be used discriminate non-critically from critically ill patients (p ?= ?0.049; p ?= ?0.0016, respectively).ConclusionThis study demonstrated that patients with a poor prognosis had increased OPN and decreased IGFBP5. High values of OPN and low values of IGFBP5 may be considered as signs of disease severity. Tissue-specific IGFBP5 expression may contribute to understanding the role of IGFBP5 in the lungs in COVID-19 cases.     

Convalescent plasma transfusion for the treatment of COVID-19: Systematic review

The recent emergence of coronavirus disease 2019 (COVID-19) pandemic has reassessed the usefulness of historic convalescent plasma transfusion (CPT). This review was conducted to evaluate the effectiveness of CPT therapy in COVID-19 patients based on the publications reported till date. To our knowledge, this is the first systematic review on convalescent plasma on clinically relevant outcomes in individuals with COVID-19. PubMed, EMBASE, and Medline databases were searched upto 19 April 2020. All records were screened as per the protocol eligibility criteria. We included five studies reporting CPT to COVID-19 patients. The main findings from available data are as follows: (a) Convalescent plasma may reduce mortality in critically ill patients, (b) Increase in neutralizing antibody titers and disappearance of SARS-CoV-2 RNA was observed in almost all the patients after CPT therapy, and (c) Beneficial effect on clinical symptoms after administration of convalescent plasma. Based on the limited scientific data, CPT therapy in COVID-19 patients appears safe, clinically effective, and reduces mortality. Well-designed large multicenter clinical trial studies should be conducted urgently to establish the efficacy of CPT to COVID-19 patients.     

Biomarkers of ageing and frailty may predict COVID-19 severity

Coronavirus Disease 2019 (COVID-19) is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - the culprit of an ongoing pandemic responsible for the loss of over 3 million lives worldwide within a year and a half. While the majority of SARS-CoV-2 infected people develop no or mild symptoms, some become severely ill and may die from COVID-19-related complications. In this review, we compile and comment on a number of biomarkers that have been identified and are expected to enhance the detection, protection and treatment of individuals at high risk of developing severe illnesses, as well as enable the monitoring of COVID-19 prognosis and responsiveness to therapeutic interventions. Consistent with the emerging notion that the majority of COVID-19 deaths occur in older and frail individuals, we researched the scientific literature and report the identification of a subset of COVID-19 biomarkers indicative of increased vulnerability to developing severe COVID-19 in older and frail patients. Mechanistically, increased frailty results from reduced disease tolerance, a phenomenon aggravated by ageing and comorbidities. While biomarkers of ageing and frailty may predict COVID-19 severity, biomarkers of disease tolerance may predict resistance to COVID-19 with socio-economic factors such as access to adequate health care remaining as major non-biomolecular influencers of COVID-19 outcomes.     

Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

During the investigational use of oral N-acetylcysteine as an antidote for poisoning with acetaminophen, 11,195 cases of suspected acetaminophen overdose were reported. We describe the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Patients were categorized for analysis on the basis of initial plasma acetaminophen concentrations and the interval between ingestion and treatment. Hepatotoxicity developed in 6.1 percent of patients at probable risk when N-acetylcysteine was started within 10 hours of acetaminophen ingestion and in 26.4 percent of such patients when therapy was begun 10 to 24 hours after ingestion. Among patients at high risk who were treated 16 to 24 hours after an acetaminophen overdose, hepatotoxicity developed in 41 percent--a rate lower than that among historical controls. When given within eight hours of acetaminophen ingestion, N-acetylcysteine was protective regardless of the initial plasma acetaminophen concentration. There was no difference in outcome whether N-acetylcysteine was started zero to four or four to eight hours after ingestion, but efficacy decreased with further delay. There were 11 deaths among the 2540 patients (0.43 percent); in the nine fatal cases in which aminotransferase was measured before treatment, values were elevated before N-acetylcysteine was started. No deaths were clearly caused by acetaminophen among patients in whom N-acetylcysteine therapy was begun within 16 hours. We conclude that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion. On the basis of available data, the 72-hour regimen of oral N-acetylcysteine is as effective as the 20-hour intravenous regimen described previously, and it may be superior when treatment is delayed.     

Emergence of ancient convalescent plasma (CP) therapy: To manage COVID-19 pandemic

Since December 2019, the human populations of the 195 global countries continue experiencing grave health and life threats due to the current COVID-19 pandemic. As a result of the novelty of the pathogen, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at present there is lack of preventive as well as therapeutic options for treating and managing the infection. The use of ancient immunotherapeutic technique – the convalescent plasma (CP) therapy, may act as an immediate and available option to control the COVID-19 pandemic. This review provides a concept and understanding on the CP therapy, its potential to control SARS-CoV-2 pandemic. The CP therapy might act as an immediate saviour for society from the virus. Although the CP therapy has exert affirmative result against COVID-19 it has not been recommended for long time use in COVID-19 and this review gives support for its possible application.     

新型冠状病毒肺炎患者的骨科急诊处理经验分享(附2例报告)

目的 探讨在新型冠状病毒肺炎(COVID-19)疫情期间,合并新冠肺炎的骨科急诊患者的合理化接诊、处置流程和规范化的防护措施。方法 在新冠肺炎疫情早期接诊2例合并新冠肺炎的骨科急诊创伤患者:1例重型新冠肺炎合并股骨颈骨折,1例轻型新冠肺炎合并开放性踝关节骨折、脱位。从入院急诊开始,医务人员、患者及其家属均采取全程规范化防护措施,并将患者的新冠肺炎病情程度和骨科创伤特点有机结合、综合分析,并经院内多学科讨论后,制定出人性化、规范化的接诊、处置和防护措施:第1例患者为新冠肺炎重型,为手术的禁忌证,故采取保守治疗,即“患肢牵引制动+止痛+抗骨质疏松”;第2例患者为新冠肺炎轻型,且为开放性骨折、关节脱位,必须急诊手术,即在全程防护下行“关节复位、清创缝合术+石膏外固定”。结果 第1例患者治疗2周后,症状减轻,肺部炎性病灶已有部分吸收,最近一次核酸检测呈阴性,现持续患肢皮牵引并拟行第二次核酸检测。第2例患者已在全麻下行“关节复位、清创缝合术+石膏外固定”,伤口愈合良好,持续石膏外固定,现2次核酸检测均呈阴性,肺部炎性病灶已完全吸收,新冠肺炎也已治愈。结论 新冠肺炎疫情期间,诊治合并新冠肺炎的骨科急诊患者时,应将患者的新冠肺炎病情程度和骨科创伤特点有机结合、综合分析,以防控疫情扩散为第一原则,并经院内多学科讨论后,制定出人性化、规范化的接诊、处置流程和防护措施;有效地避免新冠肺炎院内交叉感染和聚集性扩散。