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1.
Curr Opin Rheumatol ; 32(6): 572-582, 2020 11.
Article in English | MEDLINE | ID: covidwho-2077899

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.


Subject(s)
Antimalarials/therapeutic use , Betacoronavirus , Coronavirus Infections/epidemiology , Lupus Erythematosus, Systemic/drug therapy , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Female , Humans , Lupus Erythematosus, Systemic/epidemiology , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Treatment Outcome
2.
Food Sci Nutr ; 8(8): 3971-3976, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1898719

ABSTRACT

This review focused on the use of plant-based foods for enhancing the immunity of all aged groups against COVID-19. In humans, coronaviruses are included in the spectrum of viruses that cause the common cold and, recently, severe acute respiratory syndrome (SARS). Emerging infectious diseases, such as SARS present a major threat to public health. The novel coronavirus has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. COVID-19 is usually caused a virus to which most probably the people with low immunity response are being affected. Plant-based foods increased the intestinal beneficial bacteria which are helpful and make up of 85% of the immune system. By the use of plenty of water, minerals like magnesium and Zinc, micronutrients, herbs, food rich in vitamins C, D and E, and better life style one can promote the health and can overcome this infection. Various studies investigated that a powerful antioxidant glutathione and a bioflavonoid quercetin may prevent various infections including COVID-19. In conclusion, the plant-based foods play a vital role to enhance the immunity of people to control of COVID-19.

3.
Gates Open Res ; 4: 159, 2020.
Article in English | MEDLINE | ID: covidwho-1835880

ABSTRACT

The COVID-19 pandemic has disrupted the already low resourced, fragmented and largely unregulated health systems in countries like India. It has only further exacerbated the stress on human resources for health (HRH) in many unanticipated ways. We explored the effect of COVID-19 pandemic on the health workforce in India, and analytically extrapolated the learnings to draw critical components to be addressed in the HRH policies, which can further be used to develop a detailed 'health workforce resilience' policy. We examined the existing literature and media reports published during the pandemic period, covering the gaps and challenges that impeded the performance of the health workers. Recommendations were designed by studying the learnings from various measures taken within India and in some other countries. We identified seven key areas that could be leveraged and improved for strengthening resilience among the health workforce. The system-level factors (at macro level) include developing a health workforce resilience policy, planning and funding for emergency preparedness, stakeholder engagement and incentivization mechanisms; the organization-level factors (meso level) include identifying HRH bench strength, mobilizing the health workforce, psycho-social support, protection from disease; and the individual-level factors (micro level) include measures around self-care by health workers. In keeping with the interdisciplinary nature of the associated factors, we emphasize on developing a future-ready health workforce using a multi-sectoral approach for building its strength and resilience.

4.
Crit Care Explor ; 2(6): e0139, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1795099

ABSTRACT

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, shortens mechanical ventilation duration, prevents post-ICU syndrome, and reduces healthcare costs. This narrative review acknowledges barriers and offers strategies to optimize Bundle performance in coronavirus disease 2019 patients requiring mechanical ventilation. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION: The most relevant literature, media reports, and author experiences were assessed for inclusion in this narrative review including PubMed, national newspapers, and critical care/pharmacology textbooks. DATA SYNTHESIS: Uncertainty regarding coronavirus disease 2019 clinical course, shifts in attitude, and changes in routine behavior have hindered Bundle use. A domino effect results from: 1) changes to critical care hierarchy, priorities, and ICU team composition; 2) significant personal protective equipment shortages cause; 3) reduced/restricted physical bedside presence favoring; 4) increased depth of sedation and use of neuromuscular blockade; 5) which exacerbate drug shortages; and 6) which require prolonged use of limited ventilator resources. Other identified barriers include manageable knowledge deficits among non-ICU clinicians unfamiliar with the Bundle or among PICU specialists deploying pediatric-based Bundle approaches who are unfamiliar with adult medicine. Both groups have been enlisted to augment the adult ICU work force to meet demand. Strategies were identified to facilitate Bundle performance to liberate patients from the ICU. CONCLUSIONS: We acknowledge current challenges that interfere with comprehensive management of critically ill patients during the coronavirus disease 2019 pandemic. Rapid response to new circumstances precisely requires established safety mechanisms and protocols like the ABCDEF Bundle to increase ICU and ventilator capacity and help survivors maximize recovery from coronavirus disease 2019 as early as possible.

5.
Enferm Infecc Microbiol Clin (Engl Ed) ; 2020 Sep 10.
Article in English, Spanish | MEDLINE | ID: covidwho-1620639

ABSTRACT

Major public and private laboratories have entered into a race to find an effective COVID-19 vaccine. When that vaccine arrives, the governments will have to implement vaccination programs to achieve the necessary immunization levels to prevent the disease transmission. In this context, the ethical dilemma of compulsory vaccination vs. voluntary vaccination will be raised. Underlying this dilemma, lies the problem of the ethical models on which the political decisions of governments in matters of health are based. The article proposes and argues the need to base health policy decisions on an ethical «first person¼ model, based on responsibility, that allows us to move from a normative ethic to an ethic of responsible behavior. This change in the ethical model, together with certain proposals for political action, will help us to restore institutional trust so that the necessary levels of collective immunity against COVID-19 can be achieved through the voluntary vaccination of the citizens.

6.
AIDS Rev ; 23(3): 153-163, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1579385

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious RNA coronavirus responsible for the pandemic of the coronavirus disease 2019 (COVID-19). Recent advances in virology, epidemiology, diagnosis, and clinical management of COVID-19 have contributed to the control and prevention of this disease, but re-positivity of SARS-CoV-2 in recovered COVID-19 patients has brought a new challenge for this worldwide anti-viral battle. Reverse transcription polymerase chain reaction (RT-PCR) tests of the SARS-CoV-2 pathogen is widely used in clinical diagnosis, but a positive RT-PCR result may be multifactorial, including false positive, SARS-CoV-2 RNA fragment shedding, reinfection of SARS-CoV-2, or re-activation of COVID-19. Re-infection of SARS-CoV-2 or re-activation of COVID-19 is an indicator of live viral carriers and isolation/treatment is needed, but SARS-CoV-2 RNA fragment shedding is not. SARS-CoV-2 RNA is recently reported to integrate into the host genome, but the far-reaching outcome is currently unclear. Therefore, it is critical for appropriate manipulation and prevention of COVID-19 to distinguish these causal factors of SARS-CoV-2 re-positivity. In this review article, we updated the current knowledge of SARS-CoV-2 re-positivity in discharged COVID-19 patients with a focus on re-infection and re-activation. We proposed a hypothetical flowchart for handling of the SARS-CoV-2 re-positive cases.


Subject(s)
COVID-19/pathology , RNA, Viral/analysis , Reinfection/virology , SARS-CoV-2/genetics , Virus Activation/genetics , Adaptive Immunity/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/diagnosis , Child , Child, Preschool , False Positive Reactions , Female , Humans , Infant , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
7.
Curr Neuropharmacol ; 19(12): 2250-2275, 2021.
Article in English | MEDLINE | ID: covidwho-1575288

ABSTRACT

The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin. Although bilirubin can function as an oxidant scavenger, its potent antioxidant activity reflects its ability to inactivate some isoforms of NADPH oxidase. Free bilirubin can also function as an agonist for the aryl hydrocarbon receptor (AhR); this may explain its ability to promote protective Treg activity in cellular and rodent models of inflammatory disease. AhR agonists also promote transcription of the gene coding for Nrf-2, and hence can up-regulate phase 2 induction of antioxidant enzymes, such as HO-1. Hence, it is proposed that C-Phycocyanin/PCB chiefly exert their protective effects via inhibition of NADPH oxidase activity, as well as by AhR agonism that both induces Treg activity and up-regulates phase 2 induction. This simple model may explain their potent antioxidant/antiinflammatory effects. Additionally, PCB might mimic biliverdin in activating anti-inflammatory signaling mediated by biliverdin reductase. This essay reviews recent research in which CPhycocyanin and/or PCB, administered orally, parenterally, or intranasally, have achieved marked protective effects in rodent and cell culture models of Ischemic Stroke and Multiple Sclerosis, and suggests that these agents may likewise be protective for Alzheimer's disease, Parkinson's disease, and in COVID-19 and its neurological complications.


Subject(s)
COVID-19 , Neurodegenerative Diseases , Animals , Dietary Supplements , Humans , Neurodegenerative Diseases/drug therapy , Phycobilins , Phycocyanin/pharmacology , SARS-CoV-2
8.
Commun Dis Intell (2018) ; 452021 May 27.
Article in English | MEDLINE | ID: covidwho-1524942

ABSTRACT

ABSTRACT: With COVID-19 affecting millions of people around the globe, quarantine of international arrivals is a critical public health measure to prevent further disease transmission in local populations. This measure has also been applied in the repatriation of citizens, undertaken by several countries as an ethical obligation and legal responsibility. This article describes the process of planning and preparing for the repatriation operation in South Australia during the COVID-19 pandemic. Interagency collaboration, development of a COVID-19 testing and quarantining protocol, implementing infection prevention and control, and building a specialised health care delivery model were essential aspects of the repatriation operational planning, with a focus on maintaining dignity and wellbeing of the passengers as well as on effective prevention of COVID-19 transmission. From April 2020 to mid-February 2021, more than 14,000 international arrivals travellers have been repatriated under the South Australian repatriation operations. This paper has implications to inform ongoing repatriation efforts in Australia and overseas in a pandemic situation.


Subject(s)
COVID-19/epidemiology , Infection Control/legislation & jurisprudence , Public Health/legislation & jurisprudence , Quarantine/legislation & jurisprudence , COVID-19/diagnosis , COVID-19/transmission , COVID-19 Testing/methods , COVID-19 Testing/standards , Delivery of Health Care , Humans , Infection Control/methods , International Health Regulations , Pandemics , Public Health/methods , Quarantine/methods , Risk Assessment , Risk Factors , SARS-CoV-2/isolation & purification , South Australia/epidemiology , Travel
9.
Mini Rev Med Chem ; 21(17): 2530-2543, 2021.
Article in English | MEDLINE | ID: covidwho-1504184

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering have led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials, researchers worldwide are currently using available conventional therapeutic drugs with the potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to showed promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID- 19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , SARS-CoV-2/drug effects , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/adverse effects , Alanine/pharmacology , Alanine/therapeutic use , Animals , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Humans , Randomized Controlled Trials as Topic
10.
Science ; 371(6536): 1379-1382, 2021 03 26.
Article in English | MEDLINE | ID: covidwho-1476374

ABSTRACT

Containment of the COVID-19 pandemic requires reducing viral transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by membrane fusion between the viral and host cell membranes, which is mediated by the viral spike protein. We have designed lipopeptide fusion inhibitors that block this critical first step of infection and, on the basis of in vitro efficacy and in vivo biodistribution, selected a dimeric form for evaluation in an animal model. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour cohousing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and thus may readily translate into safe and effective intranasal prophylaxis to reduce transmission of SARS-CoV-2.


Subject(s)
COVID-19/transmission , Lipopeptides/administration & dosage , Membrane Fusion/drug effects , SARS-CoV-2/drug effects , Viral Fusion Protein Inhibitors/administration & dosage , Virus Internalization/drug effects , Administration, Intranasal , Animals , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Disease Models, Animal , Drug Design , Ferrets , Lipopeptides/chemistry , Lipopeptides/pharmacokinetics , Lipopeptides/pharmacology , Mice , Pre-Exposure Prophylaxis , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Tissue Distribution , Vero Cells , Viral Fusion Protein Inhibitors/chemistry , Viral Fusion Protein Inhibitors/pharmacokinetics , Viral Fusion Protein Inhibitors/pharmacology
11.
Vaccines (Basel) ; 8(3)2020 Sep 22.
Article in English | MEDLINE | ID: covidwho-1438751

ABSTRACT

In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most recently, COVID-19. Therefore, it is important to understand the cellular and molecular mechanisms of action of vaccine adjuvants, which generally trigger the innate immune system to enhance signal transition to adaptive immunity, resulting in pathogen-specific protection. Thus, improved understanding of vaccine adjuvant mechanisms may aid in the design of "intelligent" vaccines to provide robust protection from pathogens. Various commonly used clinical adjuvants, such as aluminium salts, saponins or emulsions, have been identified as activators of inflammasomes - multiprotein signalling platforms that drive activation of inflammatory caspases, resulting in secretion of pro-inflammatory cytokines of the IL-1 family. Importantly, these cytokines affect the cellular and humoral arms of adaptive immunity, which indicates that inflammasomes represent a valuable target of vaccine adjuvants. In this review, we highlight the impact of different inflammasomes on vaccine adjuvant-induced immune responses regarding their mechanisms and immunogenicity. In this context, we focus on clinically relevant adjuvants that have been shown to activate the NLRP3 inflammasome and also present various experimental adjuvants that activate the NLRP3-, NLRC4-, AIM2-, pyrin-, or non-canonical inflammasomes and could have the potential to improve future vaccines. Together, we provide a comprehensive overview on vaccine adjuvants that are known, or suggested, to promote immunogenicity through inflammasome-mediated signalling.

12.
J Med Virol ; 93(10): 5864-5872, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432419

ABSTRACT

The aim was to investigate the association of the delivery mode and vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through the samples of vaginal secretions, placenta, cord blood, or amniotic fluid as well as the neonatal outcomes. This cross-sectional study presents an analysis of prospectively gathered data collected at a single tertiary hospital. Sixty-three pregnant women with confirmed coronavirus disease 2019 (COVID-19) participated in the study. Vertical transmission of SARS-CoV-2 was analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR) tests and blood tests for immunoglobulin G (IgG)-immunoglobulin M (IgM) antibodies. All patients were in the mild or moderate category for COVID-19. Only one placental sample and two of the vaginal secretion samples were positive for SARS-CoV-2. Except for one, all positive samples were obtained from patients who gave birth by cesarean. All cord blood and amniotic fluid samples were negative for SARS-CoV-2. Two newborns were screened positive for COVID-19 IgG-IgM within 24 h after delivery, but the RT-PCR tests were negative. A positive RT-PCR result was detected in a neof a mother whose placenta, cord blood, amniotic fluid, and vaginal secretions samples were negative. He died due to pulmonary hemorrhage on the 11th day of life. In conclusion, we demonstrated that SARS-CoV-2 can be detectable in the placenta or vaginal secretions of pregnant women. Detection of the virus in the placenta or vaginal secretions may not be associated with neonatal infection. Vaginal delivery may not increase the incidence of neonatal infection, and cesarean may not prevent vertical transmission. The decision regarding the mode of delivery should be based on obstetric indications and COVID-19 severity.


Subject(s)
COVID-19/transmission , SARS-CoV-2/isolation & purification , Adolescent , Adult , COVID-19/diagnosis , COVID-19/epidemiology , Cesarean Section , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/virology , Infectious Disease Transmission, Vertical/statistics & numerical data , Male , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Tertiary Care Centers , Vagina/virology , Young Adult
13.
Oral Dis ; 27 Suppl 3: 665-673, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1434803

ABSTRACT

We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different types of facial protection measures, including masks, needed both for the public and the healthcare workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air-purifying respirators (PAPR), and the skin health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.


Subject(s)
COVID-19 , Pandemics , Health Personnel , Humans , Personal Protective Equipment , SARS-CoV-2
14.
Int J Neuropsychopharmacol ; 24(9): 703-709, 2021 09 21.
Article in English | MEDLINE | ID: covidwho-1429234

ABSTRACT

BACKGROUND: Psychiatric patients are perceived to be especially vulnerable during a pandemic, as it increases stress and uncertainty. Several current publications have considered obsessive-compulsive disorder (OCD) patients to be particularly vulnerable during the coronavirus disease 2019 (COVID-19), and clinicians were advised to adjust treatments accordingly. The purpose of this study was to evaluate the 2- and 6-month impacts of COVID-19 on the symptom severity of OCD patients. METHODS: A cohort of OCD patients actively treated with Exposure and Response Prevention (ERP) combined with pharmacological treatment was evaluated as part of their regular psychiatric assessment twice: 113 patients were evaluated at their 2-month follow-up and 90 patients (from that cohort) were evaluated at their 6-month follow up. RESULTS: Obsessive-compulsive symptom deterioration was not present in 84% of the patients at the 2-month follow-up and 96% of the patients at the 6-month follow-up. The results were also replicated in the OCD subgroup that included patients with contamination (washers) and illness obsessions, who were believed to be particularly vulnerable considering their obsessional content. CONCLUSIONS: OCD patients (including those with obsessions related to contamination and health) who were under active ERP and pharmacological treatment did not experience exacerbated symptoms during COVID-19 at their 2- and 6-month follow-ups.


Subject(s)
COVID-19 , Obsessive-Compulsive Disorder/physiopathology , Obsessive-Compulsive Disorder/therapy , Outcome Assessment, Health Care , Symptom Flare Up , Adolescent , Adult , Aged , Cognitive Behavioral Therapy , Dopamine D2 Receptor Antagonists/therapeutic use , Female , Follow-Up Studies , Humans , Implosive Therapy , Male , Middle Aged , Obsessive-Compulsive Disorder/drug therapy , Serotonin Uptake Inhibitors/therapeutic use , Young Adult
15.
Lancet Respir Med ; 9(8): 924-932, 2021 08.
Article in English | MEDLINE | ID: covidwho-1413874

ABSTRACT

BACKGROUND: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. METHODS: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FINDINGS: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001). INTERPRETATION: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. FUNDING: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.


Subject(s)
COVID-19 , Colchicine , Administration, Oral , Ambulatory Care/methods , Ambulatory Care/statistics & numerical data , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Colchicine/administration & dosage , Colchicine/adverse effects , Double-Blind Method , Drug Monitoring/methods , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Male , Middle Aged , Outcome Assessment, Health Care , Risk Assessment , SARS-CoV-2/isolation & purification
16.
IEEE J Transl Eng Health Med ; 9: 4900711, 2021.
Article in English | MEDLINE | ID: covidwho-1411484

ABSTRACT

Viral and bacterial pathogens can be transmitted through direct contact with contaminated surfaces. Efficient decontamination of contaminated surfaces could lead to decreased disease transmission, if optimized methods for detecting contaminated surfaces can be developed. Here we describe such a method whereby thermal tracking technology is utilized to detect thermal signatures incurred by surfaces through direct contact. This is applicable in public places to assist with targeted sanitation and cleaning efforts to potentially reduce chance of disease transmission. In this study, we refer to the touched region of the surface as a "touch-point" and examine how the touch-point regions can be automatically localized with a computer vision pipeline of a thermal image sequence. The pipeline mainly comprises two components: a single-frame and a multi-frame analysis. The single-frame analysis consists of a Background subtraction method for image pre-processing and a U-net deep learning model for segmenting the touch-point regions. The multi-frame analysis performs a summation of the outputs from the single-frame analysis and creates a cumulative map of touch-points. Results show that the touch-point detection pipeline can achieve 75.0% precision and 81.5% F1-score for the testing experiments of predicting the touch-point regions. This preliminary study shows potential applications of preventing indirect pathogen spread in public spaces and improving the efficiency of cleaning sanitation.


Subject(s)
Touch Perception , Viruses , Image Processing, Computer-Assisted , Sanitation , Touch
18.
Turk J Biol ; 44(3): 168-177, 2020.
Article in English | MEDLINE | ID: covidwho-1395051

ABSTRACT

A novel coronavirus (SARS-CoV-2, formerly known as nCoV-2019) that causes an acute respiratory disease has emerged in Wuhan, China and spread globally in early 2020. On January the 30th, the World Health Organization (WHO) declared spread of this virus as an epidemic and a public health emergency. With its highly contagious characteristic and long incubation time, confinement of SARS-CoV-2 requires drastic lock-down measures to be taken and therefore early diagnosis is crucial. We analysed transcriptome of SARS-CoV-2 infected human lung epithelial cells, compared it with mock-infected cells, used network-based reporter metabolite approach and integrated the transcriptome data with protein-protein interaction network to elucidate the early cellular response. Significantly affected metabolites have the potential to be used in diagnostics while pathways of protein clusters have the potential to be used as targets for supportive or novel therapeutic approaches. Our results are in accordance with the literature on response of IL6 family of cytokines and their importance, in addition, we find that matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) with keratan sulfate synthesis pathway may play a key role in the infection. We hypothesize that MMP9 inhibitors have potential to prevent "cytokine storm" in severely affected patients.

19.
J Med Virol ; 93(2): 755-759, 2021 02.
Article in English | MEDLINE | ID: covidwho-1384219

ABSTRACT

Hydroxychloroquine sulfate (HCQ) is being scrutinized for repositioning in the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This antimalarial drug is also chronically used to treat patients with autoimmune diseases. By analyzing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS-CoV-2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS-CoV-2 infection with laboratory confirmed negative cases. Out of 26 815 SARS-CoV-2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1215 (0.36%) out of 333 489 negative patients were receiving it chronically (P = .04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS-CoV-2 infection for chronic treatment with HCQ has been 0.51 (0.37-0.70). Our data suggest that chronic treatment with HCQ confer protection against SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Pre-Exposure Prophylaxis , Adult , Aged , Antimalarials/therapeutic use , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , COVID-19/immunology , COVID-19/virology , Drug Administration Schedule , Drug Repositioning , Female , Humans , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Odds Ratio , Portugal , Registries , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
20.
Biomed Pharmacother ; 140: 111596, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1385083

ABSTRACT

Flavonoids are natural phytochemicals known for their antiviral activity. The flavonoids acts at different stages of viral infection, such as viral entrance, replication and translation of proteins. Viruses cause various diseases such as SARS, Hepatitis, AIDS, Flu, Herpes, etc. These, and many more viral diseases, are prevalent in the world, and some (i.e. SARS-CoV-2) are causing global chaos. Despite much struggle, effective treatments for these viral diseases are not available. The flavonoid class of phytochemicals has a vast number of medicinally active compounds, many of which are studied for their potential antiviral activity against different DNA and RNA viruses. Here, we reviewed many flavonoids that showed antiviral activities in different testing environments such as in vitro, in vivo (mice model) and in silico. Some flavonoids had stronger inhibitory activities, showed no toxicity & the cell proliferation at the tested doses are not affected. Some of the flavonoids used in the in vivo studies also protected the tested mice prophylactically from lethal doses of virus, and effectively prevented viral infection. The glycosides of some of the flavonoids increased the solubility of some flavonoids, and therefore showed increased antiviral activity as compared to the non-glycoside form of that flavonoid. These phytochemicals are active against different disease-causing viruses, and inhibited the viruses by targeting the viral infections at multiple stages. Some of the flavonoids showed more potent antiviral activity than the market available drugs used to treat viral infections.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Flavonoids/pharmacology , Flavonoids/therapeutic use , Virus Diseases/drug therapy , Viruses/drug effects , Animals , Cell Proliferation/drug effects , Glycosides/metabolism , Humans , Virus Diseases/metabolism
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