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1.
Postgrad Med J ; 98(1160): 477-482, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1927658

ABSTRACT

Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia.


Subject(s)
Hypertension , Hypokalemia , Arrhythmias, Cardiac/chemically induced , Diuretics/adverse effects , Female , Humans , Hypertension/chemically induced , Hypertension/complications , Hypertension/drug therapy , Hypokalemia/chemically induced , Hypokalemia/complications , Hypokalemia/drug therapy , Potassium/adverse effects , Sodium Chloride Symporter Inhibitors/adverse effects , Thiazides/adverse effects
2.
J Ayurveda Integr Med ; 13(1): 100365, 2022.
Article in English | MEDLINE | ID: covidwho-1838948

ABSTRACT

The ancient Indian system of medicine, Ayurveda has a treatment for symptom complexes of a variety of diseases. One such combination of Ayurvedic medications has potential for use in COVID 19 infection, and hence a prospective study was conducted with this formulation as an add-on, in COVID positive patients in a dedicated COVID hospital. The objective of the study was to evaluate the additional benefit of an Ayurvedic regime in COVID positive patients on the basis of rate of clinical improvement. The Ayurvedic formulation was administered as an add-on to Standard of Care (SoC) in patients with mild to moderate symptoms, in this prospective, open-label, comparative study. Control group received SoC only. Patients receiving Dasamoolkaduthrayam Kashaya and Guluchyadi Kwatham in tablet form in addition to the SoC showed a faster recovery from breathlessness with reduced ageusia. Patients on the treatment group could be discharged earlier than those from the control group. Addition of Dasamoolkaduthrayam Kashaya and Guluchyadi Kwatham to SoC appeared to accelerate recovery of patients hospitalized for COVID 19 infection, in terms of reduction of symptoms and duration of hospital stay.

3.
Med Clin (Engl Ed) ; 155(11): 488-490, 2020 Dec 11.
Article in English | MEDLINE | ID: covidwho-1804801

ABSTRACT

INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.


INTRODUCCIÓN: Existe controversia respecto al uso de los inhibidores de la enzima convertidora de angiotensina (IECA) o los bloqueadores de los receptores tipo I de la angiotensina II (ARA-II) para el tratamiento de la hipertensión arterial en COVID-19. Se ha sugerido que estos fármacos podrían tanto aumentar como reducir el riesgo de COVID-19 grave. PACIENTES Y MÉTODO: Estudio de cohortes retrospectivo de pacientes consecutivos de un área sanitaria, con hipertensión e infección por SARS-CoV-2. Variable de resultados: ingreso hospitalario por COVID-19 grave. RESULTADOS: Fueron diagnosticados 539 sujetos por infección por SARS-CoV-2. De estos, 157 (29,1%) eran hipertensos y se incluyeron en el estudio. Se ingresaron 69 (43,9%) pacientes por COVID-19 grave. En el análisis multivariante, la edad más elevada, la diabetes y la miocardiopatía hipertensiva se relacionaron con el riesgo de ingreso hospitalario. El tratamiento con ARA-II se asoció con un riesgo significativamente más bajo de ingreso (HR: 0,29, IC 95%: 0,10-0,88). Una tendencia similar, aunque no significativa, se encontró para los IECA. CONCLUSIÓN: el tratamiento con ARA-II o IECA no se asoció con una peor evolución clínica en pacientes hipertensos consecutivos infectados por SARS-CoV-2.

4.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

5.
Exp Clin Transplant ; 20(3): 285-292, 2022 03.
Article in English | MEDLINE | ID: covidwho-1771685

ABSTRACT

OBJECTIVES: With the declaration of the COVID-19 pandemic and the increased COVID-19 risk shown in transplant recipients, the prevalence, clinical course, and outcomes of COVID-19 infections among liver transplant recipients were assessed. MATERIALS AND METHODS: A questionnaire was designed and used to survey medical services for liver transplant recipients seen at our center in terms of COVID-19 infection. RESULTS: Twenty-five patients infected with COVID-19 were identified from 265 liver transplant recipients. Most patients were male and had COVID-19 despite quarantine at home. All patients received modified immunosuppressive drugs during infection with COVID-19 with minor changes in routine immunosuppressive therapy. Among the identified patients, 21 recovered and 4 patients died. One of the dead patients, in addition to having a liver transplant, had brain cancer with metastasis to the lungs. CONCLUSIONS: In liver transplant recipients infected with COVID-19, immunosuppressive drugs seemed to cause only mild to moderate illnesses or even helped them recover from the disease. However, more evidence is needed to prove this hypothesis. It is also recommended that transplant recipients should be warned about personal hygiene and be monitored closely by organ transplant centers.


Subject(s)
COVID-19 , Kidney Transplantation , Liver Transplantation , Humans , Immunosuppressive Agents/adverse effects , Iran/epidemiology , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Male , Pandemics , Registries , SARS-CoV-2 , Transplant Recipients , Treatment Outcome
6.
Food Funct ; 11(6): 5565-5572, 2020 Jun 24.
Article in English | MEDLINE | ID: covidwho-1721602

ABSTRACT

To date, no specific drug has been discovered for the treatment of COVID-19 and hence, people are in a state of anxiety. Thus, there is an urgent need to search for various possible strategies including nutritional supplementation. In this study, we have tried to provide a reference for protein supplementation. Specifically, 20 marine fish proteins were subjected to in silico hydrolysis by gastrointestinal enzymes, and a large number of active peptides were generated. Then, the binding abilities of these peptides to SARS-CoV-2 main protease and monoamine oxidase A were assessed. The results showed that NADH dehydrogenase could be a good protein source in generating potent binders to the two enzymes, followed by cytochrome b. In addition, some high-affinity oligopeptides (VIQY, ICIY, PISQF, VISAW, AIPAW, and PVSQF) were identified as dual binders to the two enzymes. In summary, the supplementation of some fish proteins can be helpful for COVID-19 patients; the identified oligopeptides can be used as the lead compounds to design potential inhibitors against COVID-19 and anxiety.


Subject(s)
Antiviral Agents/metabolism , Betacoronavirus/metabolism , Coronavirus Infections/virology , Dietary Supplements , Fish Proteins/metabolism , Monoamine Oxidase/metabolism , Pneumonia, Viral/virology , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Aquatic Organisms , Betacoronavirus/enzymology , COVID-19 , Coronavirus Infections/drug therapy , Decapodiformes/metabolism , Fish Proteins/chemistry , Fish Proteins/therapeutic use , Fishes/metabolism , Models, Molecular , Molecular Docking Simulation , Monoamine Oxidase Inhibitors , Pandemics , Perciformes/metabolism , Pneumonia, Viral/drug therapy , Protein Binding , Protein Conformation , SARS-CoV-2 , Salmon/metabolism , Tuna/metabolism
7.
SN Compr Clin Med ; 2(9): 1436-1443, 2020.
Article in English | MEDLINE | ID: covidwho-1700862

ABSTRACT

The outbreak of a large plaque, novel coronavirus pneumonia (NCP), which also named Coronavirus Disease 2019 (COVID-19) by the WHO, has detrimentally affected the livelihood and health of people in China. During the spread of COVID-19, colleagues who have been working at the frontline have had to face many new challenges in the treatment and prevention of NCP. Therefore, we have provided suggestions for the diagnosis, treatment, and prevention of the novel coronavirus pneumonia in the current epidemic situation based on the latest reports and the experience of doctors treating COVID-19 in our hospital. We recommend lopinavir/ritonavir as the effective drugs for antiviral treatment according to our experience in administering lopinavir/ritonavir to COVID-19 patients and the successful cases of these drugs in treating MERS and SARS, but need more clinical data to prove their efficacy in treating COVID-19.

8.
J Evid Based Integr Med ; 26: 2515690X211020685, 2021.
Article in English | MEDLINE | ID: covidwho-1691167

ABSTRACT

The retrospective cohort study aimed to evaluate the clinical outcomes of Ayurveda treatment exposure as an add-on to conventional care in early stage COVID-19 patients admitted at Samaras COVID care center, Ahmedabad, India. Conventional care included Vitamin-c, Azithromycin, and Paracetamol. Ayurveda formulations used as add-on were Dashamula and Pathyadi decoctions along with Trikatu powder, Sanshamani tablet, AYUSH-64 tablet AND Yastimadhu Ghana tablet for oral administration. Considering Add-on Ayurveda medicines as exposure of interest, patients who received Add-on Ayurveda medicines at least for 7 days were included in the exposed group while those who received only conventional care in unexposed group. Data was collected through record review and telephonic interviews. The outcomes of interest were the development of symptoms, duration of symptomatic phase in those progressing to symptomatic stage and mortality. Total 762 participants were included-[541 (71%) in the exposed group and 221 (29%) in the unexposed. Progression to symptomatic phase did not differ significantly between groups [27.6% in exposed, 24.6% in unexposed, adjusted RR 0.85; 95% CI 0.6-1.2]. The total duration of symptomatic phase among those progressing to the symptomatic stage was significantly decreased in the exposed group (x¯ = 3.66 ± 1.55 days in exposed (n = 133); x¯ = 5.34 ± 3.35 days in unexposed (n = 61), p < 0.001). No mortality was observed in either of the groups. Ayurveda Treatment as adjunctive to conventional care reduced the duration of symptomatic phase in early stage COVID-19 as compared to standalone conventional care. Add-on Ayurveda treatment has promising potential for management of early stage COVID-19.


Subject(s)
Acetaminophen/therapeutic use , COVID-19 , Medicine, Ayurvedic/methods , Plant Extracts/therapeutic use , Plant Preparations/therapeutic use , Antipyretics/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Complementary Therapies/methods , Drug Therapy, Combination/methods , Female , Hospitalization/statistics & numerical data , Humans , India/epidemiology , Male , Middle Aged , Patient Acuity , Retrospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome
9.
Mini Rev Med Chem ; 22(2): 273-311, 2022.
Article in English | MEDLINE | ID: covidwho-1666892

ABSTRACT

Due to the high mortality rate of the 2019 coronavirus disease (COVID-19) pandemic, there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, and mechanism of action of the existing drugs with potential therapeutic applications for COVID-19. Furthermore, we summarized the molecular docking stimulation of the medications related to key protein targets. These already established drugs could be further developed, and after their testing through clinical trials, they could be used as suitable therapeutic options for patients suffering from COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Metabolic Networks and Pathways/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Antiviral Agents/therapeutic use , Humans , Molecular Docking Simulation , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
10.
Clin Infect Dis ; 74(1): 24-31, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1634311

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. METHODS: We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. RESULTS: Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21-.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31-2.16, P < .001; OR 1.68, 95% CI: 2.12-8.30, P < .001, respectively). CONCLUSIONS: Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization.Bamlanivimab's role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.


Subject(s)
COVID-19 , Adolescent , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Case-Control Studies , Humans , Retrospective Studies , SARS-CoV-2
11.
PLoS One ; 16(3): e0248128, 2021.
Article in English | MEDLINE | ID: covidwho-1575679

ABSTRACT

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pandemics/prevention & control , Data Management/methods , Drug Therapy, Combination/methods , Female , Hospitalization , Humans , Male , SARS-CoV-2/drug effects
12.
Life Sci ; 284: 119201, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1574805

ABSTRACT

BACKGROUND: Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. AIM: To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. METHOD: A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. KEY FINDINGS: The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. SIGNIFICANCE: As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.


Subject(s)
COVID-19/pathology , Cytokines/metabolism , Inflammation/pathology , Spices , COVID-19/epidemiology , COVID-19/virology , Cytokine Release Syndrome/pathology , Humans , SARS-CoV-2/physiology
13.
Front Pharmacol ; 12: 610745, 2021.
Article in English | MEDLINE | ID: covidwho-1554748

ABSTRACT

Background: Pneumonia is a prevalent and complicated disease among adults, elderly people in particular, and the debate on the optimal Chinese herbal injections (CHIs) is ongoing. Our objective is to investigate the comparative effectiveness of various CHIs strategies for elderly patients with pneumonia. Methods: A comprehensive search strategy was executed to identify relevant randomized controlled trials (RCTs) by browsing through several databases from their inception to first, Feb 2020; All of the direct and indirect evidence included was rated by Network meta-analysis under a Bayesian framework. Results: We ultimately identified 34 eligible randomized controlled trials that involved 3,111 elderly participants and investigated 4 CHIs combined with Western medicine (WM) (Xiyanping injection [XYP]+WM, Yanhuning injection [YHN]+WM, Tanreqing injection [TRQ]+WM, Reduning injection [RDN]+WM), contributing 34 direct comparisons between CHIs. Seen from the outcome of Clinical effective rate and time for defervescence, patients taking medicine added with CHIs [Clinical effective rate, XYP + WM(Odd ratio (OR): 0.74, 95%Credible intervals (CrIs):0.55-0.98), YHN + WM(OR: 0.66, 95%CrI: 0.45-0.95), TRQ + WM(OR: 0.65, 95%CrI: 0.50-0.83), RDN + WM(OR: 0.60, 95%CrI: 0.40-0.89); Time for defervescence, YHN + WM(Mean difference (MD): -2.11, 95%CrI: -3.26 to -0.98), XYP + WM(MD: -2.06, 95%CrI: -3.08 to -1.09), RDN + WM(MD: -1.97, 95%CrI: -3.61 to -0.35), TRQ + WM(MD: -1.69, 95%CrI: -2.27 to -1.04)] showed statistically better effect compared with participants in the Control group (CG) who only took WM. Meanwhile, based on the time for disappearance of cough, 3 out of 4 CHIs [TRQ + WM(MD: -2.56, 95%CrI: -3.38 to -1.54), YHN + WM(MD: -2.36, 95%CrI: -3.86 to -1.00) and XYP + WM(MD: -2.21, 95%CrI: -3.72 to -1.10)] strategies indicated improvement of clinical symptoms. Only XYP + WM(MD -1.78, 95%CrI: -3.29 to -0.27) and TRQ + WM (MD: -1.71, 95%CrI: -2.71 to -0.73) could significantly shorten the time for disappearance of pulmonary rales. Conclusion: According to the statistical effect size (The surface under the cumulative ranking), we found that XYP + WM was presumably to be the preferable treatment for treating elderly patients with pneumonia compared with WM alone in terms of clinical effective rate. Our findings were based on very limited evidence and thus should be interpreted with caution. The application of the findings requires further research.

14.
Mediterr J Rheumatol ; 31(Suppl 2): 275-283, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1543144

ABSTRACT

The magnitude of the SARS-CoV-2 pandemic found health systems unprepared, not allowing for prompt evaluation, collaboration among specialities and treatment of severely ill patients admitted to intensive care units, with many of them having an unfortunate outcome. Current data demonstrate an acute immune dysregulation in severe forms of the disease. The above is concluded by clinical evolution and laboratory findings, indicating a severe inflammatory response of the innate immune system, initiating predominately with the involvement of the respiratory tract epithelial cells, occasionally progressing to thrombotic diathesis and related complications. Besides the clinical manifestations, the immune response expresses an extremely high acute phase reactants repertoire including hyperferritinemia, hyper-fibrinogenaemia, and a storm of cytokines that require an alternative view and collaboration with rheumatologists. Thrombotic diathesis in some cases may not attribute only to a possible disseminated intravascular coagulation, but also to an additional activation of adaptive immunity and the development of the antiphospholipid syndrome. Unifying speciality evaluation and treatment may improve patient outcomes by recognizing early the evolving syndromes, treating properly, in a stratifying manner, with medications that alleviate the inflammatory reaction. Corticosteroids, colchicine, hydroxychloroquine/chloroquine, and possibly potent immunosuppressants are in the armamentarium. Additionally, biologics that interrupt the innate immune dysfunction, such as IL-1, IL-6 and selective JAK inhibitors, are also used. Convalescent plasma therapy and human immunoglobulin may be restricted for those whom the proposed treatments are found inadequate. The above combined with antiretroviral medications may improve the outcome until the development of safe and effective vaccination.

15.
Lancet Respir Med ; 9(5): 511-521, 2021 05.
Article in English | MEDLINE | ID: covidwho-1537197

ABSTRACT

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Cytokine Release Syndrome , Receptors, Interleukin-6/antagonists & inhibitors , Respiratory Distress Syndrome , SARS-CoV-2/isolation & purification , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Critical Care/methods , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Drug Monitoring/methods , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , India , Male , Middle Aged , Mortality , Respiration, Artificial/methods , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Severity of Illness Index , Treatment Outcome
16.
Ann Intern Med ; 174(1): JC2, 2021 01.
Article in English | MEDLINE | ID: covidwho-1526979

ABSTRACT

SOURCE CITATION: Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. 32887691.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Practice Guidelines as Topic , Betacoronavirus , Critical Illness , Humans , Pandemics , SARS-CoV-2 , World Health Organization
17.
J Clin Med ; 10(8)2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1526828

ABSTRACT

A novel coronavirus-Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2)-outbreak correlated with the global coronavirus disease 2019 (COVID-19) pandemic was declared by the WHO in March 2020, resulting in numerous counted cases attributed to SARS-CoV-2 worldwide. Herein, we discuss current knowledge on the available therapy options for patients diagnosed with COVID-19. Based on available scientific data, we present an overview of solutions in COVID-19 management by use of drugs, vaccines and antibodies. Many questions with non-conclusive answers on the measures for the management of the COVID-19 pandemic and its impact on health still exist-i.e., the actual infection percentage of the population, updated precise mortality data, variability in response to infection by the population, the nature of immunity and its duration, vaccine development issues, a fear that science might end up with excessive promises in response to COVID-19-and were raised among scientists. Indeed, science may or may not deliver results in real time. In the presented paper we discuss some consequences of disease, its detection and serological tests, some solutions to disease prevention and management, pitfalls and obstacles, including vaccination. The presented ideas and data herein are meant to contribute to the ongoing debate on COVID-19 without pre-selection of available information.

18.
Br J Clin Pharmacol ; 87(9): 3462-3480, 2021 09.
Article in English | MEDLINE | ID: covidwho-1494604

ABSTRACT

AIM: Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and paediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provide a baseline risk assessment and identify gaps for targeted investigation. METHODS: Clinical trials have been searched and reviewed; 23 repurposed drugs and drug combinations and nine candidate vaccines have been assessed regarding the availability of relevant data in paediatrics and pregnant women and to evaluate expected or unanticipated risk. RESULTS: Thirteen of the repurposed drugs or drug combinations are indicated for use in paediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have paediatric subgroups been planned for enrolment. Data from individual case studies and RWD may suggest that subpopulations of both paediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state. CONCLUSION: In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in paediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Child , Clinical Trials as Topic , Drug Combinations , Female , Humans , Pandemics , Pregnancy , Pregnant Women , Prospective Studies , Risk Assessment
19.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
20.
J Ayurveda Integr Med ; 13(2): 100445, 2022.
Article in English | MEDLINE | ID: covidwho-1487802

ABSTRACT

This article reports the treatment outcomes of 167 COVID-19 positive patients who were treated with a stand-alone Ayurvedic therapeutic intervention. The main outcomes are quick resolution of symptoms, no deterioration in any of the cases and safe treatment for patients with multiple comorbidities. There was no observed mortality. There were no adverse events due to the Ayurvedic medications. The treatment was undertaken in an out-patient setting and at a low cost. The efficacy and safety of the treatment, and the quick resolution of symptoms were demonstrated. This shows that if COVID-19 patients are treated with Ayurvedic medicines early in the course of COVID-SARS-2 infection, Ayurveda has the potential to prevent progression and deterioration of the disease, with decreased morbidity and mortality.

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