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Cureus Sep 2022Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a... (Review)
Review
Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a wide range of sequelae from mild long-term effects like headaches and fatigue to severe events like stroke and arrhythmias. Our study aimed to evaluate the long-term neurological effects of coronavirus disease 2019 (COVID-19) among patients discharged from the hospital. In this systematic review and meta-analysis, we assessed the long-term neurocognitive effects of COVID-19. Post-COVID-19 neurological sequelae were defined as persistent symptoms of headache, fatigue, myalgia, anosmia, dysgeusia, sleep disturbance, issues with concentration, post-traumatic stress disorder (PTSD), suicidality, and depression long after the acute phase of COVID-19. Data from observational studies describing post-COVID-19 neurocognitive sequelae and severity of COVID-19 from September 1, 2019, to the present were extracted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol with a consensus of three independent reviewers. A systematic review was performed for qualitative evaluation and a meta-analysis was performed for quantitative analysis by calculating log odds of COVID-19 neurocognitive sequelae. The odds ratio (OR) and 95% confidence interval (CI) were obtained and forest plots were created using random effects models. We found seven studies, out of which three were used for quantitative synthesis of evidence. Of the 3,304 post-COVID-19 patients identified, 50.27% were male with a mean age of 56 years; 20.20% had post-COVID-19 symptoms more than two weeks after the acute phase of infection. Among persistence symptoms, neurocognitive symptoms like headache (27.8%), fatigue (26.7%), myalgia (23.14%), anosmia (22.8%), dysgeusia (12.1%), sleep disturbance (63.1%), confusion (32.6%), difficulty to concentrate (22%), and psychiatric symptoms like PTSD (31%), feeling depressed (20%), and suicidality (2%) had a higher prevalence. In meta-analysis, COVID-19 patients with severe symptoms had higher odds of headache (pooled OR: 4.53; 95% CI: 2.37-8.65; p<0.00001; I: 0%) and myalgia (pooled OR: 3.36; 95% CI: 2.71-4.17; p<0.00001; I: 0%). Anosmia, fatigue, and dysgeusia had higher but non-significant odds following COVID-19. Although we had sufficient data for headache and fatigue to identify higher rates and associations following COVID-19, we could not establish relationships with other post-COVID-19 neurocognitive séqueles. Long-term follow-up may mitigate the neurocognitive effects among COVID-19 patients as these symptoms are also associated with a poor quality of life.
PubMed: 36321004
DOI: 10.7759/cureus.29694 -
Advances in Nutrition (Bethesda, Md.) Nov 2023There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed... (Meta-Analysis)
Meta-Analysis Review
There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed to provide a meta-analytic and comprehensive review on the adverse effects of all kinds of ω-3 PUFA supplementation reported in randomized controlled trials (RCTs) in human subjects. A systematic review of RCTs published between 1987 and 2023 was carried out based on searches of 8 electronic databases. All RCTs that compared the adverse effects of ω-3 PUFAs containing eicosapentaenoic acid, docosahexaenoic acid, or both compared with controls (a placebo or a standard treatment) were included. The primary outcome was the adverse effects related to ω-3 PUFA prescription. A total of 90 RCTs showed that the ω-3 PUFA group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (odds ratio [OR] = 1.257, P = 0.010), dysgeusia (OR = 3.478, P < 0.001), and bleeding tendency (OR = 1.260, P = 0.025) but lower rates of back pain (OR = 0.727, P < 0.001). The subgroup analysis showed that the prescription ω-3 PUFA products (RxOME3FAs) had higher ω-3 PUFA dosages than generic ω-3 PUFAs (OME3FAs) (3056.38 ± 1113.28 mg/d compared with 2315.92 ± 1725.61 mg/d), and studies on RxOME3FAs performed more standard assessments than OME3FAs on adverse effects (63% compared with 36%). There was no report of definite ω-3 PUFA-related serious adverse events. The subjects taking ω-3 PUFAs were at higher odds of experiencing adverse effects; hence, comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with ω-3 PUFAs. This study was registered at PROSPERO as CRD42023401169.
Topics: Humans; Randomized Controlled Trials as Topic; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Dietary Supplements
PubMed: 37567449
DOI: 10.1016/j.advnut.2023.08.003 -
The Cochrane Database of Systematic... Dec 2017The sense of taste is very much essential to the overall health of an individual. It is a necessary component to enjoy one's food, which in turn provides nutrition to an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The sense of taste is very much essential to the overall health of an individual. It is a necessary component to enjoy one's food, which in turn provides nutrition to an individual. Any disturbance in taste perception can hamper quality of life in such patients by influencing their appetite, body weight and psychological well-being. Taste disorders have been treated using different modalities of treatment and there is no consensus for the best intervention. Hence this Cochrane Review was undertaken. This is an update of the Cochrane Review first published in November 2014.
OBJECTIVES
To assess the effects of interventions for the management of patients with taste disturbances.
SEARCH METHODS
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 4 July 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017 Issue 6) in the Cochrane Library (searched 4 July 2017); MEDLINE Ovid (1946 to 4 July 2017); Embase Ovid (1980 to 4 July 2017); CINAHL EBSCO (1937 to 4 July 2017); and AMED Ovid (1985 to 4 July 2017). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for trials. Abstracts from scientific meetings and conferences were searched on 25 September 2017. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing any pharmacological agent with a control intervention or any non-pharmacological agent with a control intervention. We also included cross-over trials in the review.
DATA COLLECTION AND ANALYSIS
Two pairs of review authors independently, and in duplicate, assessed the quality of trials and extracted data. Wherever possible, we contacted trial authors for additional information. We collected adverse events information from the trials.
MAIN RESULTS
We included 10 trials (581 participants), nine of which we were able to include in the quantitative analyses (566 participants). We assessed three trials (30%) as having a low risk of bias, four trials (40%) at high risk of bias and three trials (30%) as having an unclear risk of bias. We only included studies on taste disorders in this review that were either idiopathic, or resulting from zinc deficiency or chronic renal failure.Of these, nine trials with 544 people compared zinc supplements to placebo for patients with taste disorders. The participants in two trials were children and adolescents with respective mean ages of 10 and 11.2 years and the other seven trials had adult participants. Out of these nine, two trials assessed the patient-reported outcome for improvement in taste acuity using zinc supplements (risk ratio (RR) 1.40, 95% confidence interval (CI) 0.94 to 2.09; 119 participants, very low-quality evidence). We meta-analysed for taste acuity improvement using objective outcome (continuous data) in idiopathic and zinc-deficient taste disorder patients (standardised mean difference (SMD) 0.44, 95% CI 0.23 to 0.65; 366 participants, three trials, very low-quality evidence). We also analysed one cross-over trial separately using the first half of the results for taste detection (mean difference (MD) 2.50, 95% CI 0.93 to 4.07; 14 participants, very low-quality evidence), and taste recognition (MD 3.00, 95% CI 0.66 to 5.34; 14 participants, very low-quality evidence). We meta-analysed taste acuity improvement using objective outcome (dichotomous data) in idiopathic and zinc-deficient taste disorder patients (RR 1.42, 95% 1.09 to 1.84; 292 participants, two trials, very low-quality evidence). Out of the nine trials using zinc supplementation, four reported adverse events like eczema, nausea, abdominal pain, diarrhoea, constipation, decrease in blood iron, increase in blood alkaline phosphatase, and minor increase in blood triglycerides.One trial tested taste discrimination using acupuncture (MD 2.80, 95% CI -1.18 to 6.78; 37 participants, very low-quality evidence). No adverse events were reported in the acupuncture trial.None of the included trials could be included in the meta-analysis for health-related quality of life in taste disorder patients.
AUTHORS' CONCLUSIONS
We found very low-quality evidence that was insufficient to conclude on the role of zinc supplements to improve taste acuity reported by patients and very low-quality evidence that zinc supplements improve taste acuity in patients with zinc deficiency/idiopathic taste disorders. We did not find any evidence to conclude the role of zinc supplements for improving taste discrimination, or any evidence addressing health-related quality of life due to taste disorders.We found very low-quality evidence that is not sufficient to conclude on the role of acupuncture for improving taste discrimination in cases of idiopathic dysgeusia (distortion of taste) and hypogeusia (reduced ability to taste). We were unable to draw any conclusions regarding the superiority of zinc supplements or acupuncture as none of the trials compared these interventions.
Topics: Acupuncture Therapy; Adolescent; Adult; Child; Humans; Quality of Life; Randomized Controlled Trials as Topic; Taste Disorders; Taste Perception; Zinc; Zinc Compounds
PubMed: 29260510
DOI: 10.1002/14651858.CD010470.pub3 -
Bulletin of the National Research Centre 2022In 2019, a viral and respiratory pathology called COVID-19 emerged in Wuhan, China, and spread to other continents. Its main symptoms include fever, cough, dyspnea,... (Review)
Review
BACKGROUND
In 2019, a viral and respiratory pathology called COVID-19 emerged in Wuhan, China, and spread to other continents. Its main symptoms include fever, cough, dyspnea, myalgia, anorexia and respiratory distress in the most severe cases, which can lead to death. Furthermore, manifestations in the oral cavity such as ageusia and dysgeusia, as well as lesions in other regions of the oral cavity, can be observed.
MAIN BODY
This systematic review and meta-analysis aimed to critically assess the clinical evidence on the use of photobiomodulation (PBMT) and antimicrobial photodynamic therapy (aPDT) for the treatment of oral lesions in patients infected with Sars-Cov-2. The literature extracted from electronic databases such as PubMed, Medline, CINAHL, and Google Scholar was screened for eligibility, and relevant articles were included. The review is limited to manuscripts published in English, Spanish and Portuguese language between December 2019 and October 2021. A total of 5 articles with 11 cases retracting PBMT and aPDT as therapeutic strategies for the regression of oral lesions and painful symptoms. The results show favoring the associated use of PBMT with aPDT ( = 0.004), and the isolated use of PBMT with the result of significant " = 0.005" and good confidence interval (7.18, 39.20) in ulcerative lesions, herpetic, aphthous, erythematous, petechiae and necrotic areas.
CONCLUSIONS
PBMT and aPDT could be effective in the treatment of oral lesions of patients infected with Sars-Cov-2 in a short period of time; however, more long-term randomized clinical trials studies are needed to define the therapeutic strategy.
PubMed: 35601476
DOI: 10.1186/s42269-022-00830-z -
Prostaglandins, Leukotrienes, and... Feb 2018Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far.
METHODS
A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity.
RESULTS
Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements [elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009)]. Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events [eructation (belching; p = 0.010); nausea (p = 0.044)] and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL).
CONCLUSION
RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.
Topics: Blood Glucose; Cholesterol, LDL; Dietary Supplements; Docosahexaenoic Acids; Dysgeusia; Eczema; Eicosapentaenoic Acid; Exanthema; Humans; Patient Safety; Randomized Controlled Trials as Topic
PubMed: 29482765
DOI: 10.1016/j.plefa.2018.01.001 -
Journal of Clinical Medicine Aug 2022Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin... (Review)
Review
Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin antagonist, was approved in the United States in July 2016 as a 5% (50 mg/mL) ophthalmic solution for DED management. Currently, no meta-analysis and systemic review based on relevant studies have been conducted. This study aimed to evaluate the efficacy and safety of lifitegrast in patients with DED. We systematically searched Embase, Medline, PubMed, and Web of Science for randomized controlled trials (RCTs) and nonrandomized studies evaluating lifitegrast effects on symptomatic DED. Then, inferior corneal staining score, total corneal staining score (TCSS), nasal lissamine staining score (NLSS), total lissamine staining score, ocular discomfort score (ODS), eye discomfort score (visual analog scale (VAS) score), eye dryness score (EDS), ocular surface disease index score (OSDI-S), and tear break-up time (TBUT) were assessed. Clinical global impression and safety profiles were also evaluated. The studies were pooled in a random-effects model. We included five RCTs, one case-control study, and four longitudinal or retrospective studies, comprising 3197 participants. In the meta-analysis, lifitegrast was superior to the placebo because it improved TCSS, NLSS, TBUT, ODS, eye discomfort score, EDS, and OSDI-Sin DED. However, lifitegrast showed higher risks for ocular and non-ocular treatment-emergent adverse events (TEAEs) overall or at a mild or moderate level. Nonetheless, its incidence of adverse events slightly differed from that in the placebo, especially instillation site discomforts and dysgeusia, thereby considered safe and tolerable. Claims of withdrawal during follow-up caused by TEAEs were extremely rare. Lifitegrast improves DED, although dysgeusia, installation site pain, and irritation may be a concern for some. Overall, most of the adverse events are tolerable. Lifitegrast can alleviate refractory DED and improves patients' quality of life.
PubMed: 36078948
DOI: 10.3390/jcm11175014 -
JAMA Network Open Oct 2023Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and...
IMPORTANCE
Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated.
OBJECTIVE
To evaluate the efficacy and safety of urea for the treatment of SIADH.
EVIDENCE REVIEW
A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay.
FINDINGS
Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized.
CONCLUSIONS AND RELEVANCE
In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.
Topics: Adult; Humans; Urea; Inappropriate ADH Syndrome; Vasopressins; Demyelinating Diseases; Sodium
PubMed: 37902751
DOI: 10.1001/jamanetworkopen.2023.40313 -
Brazilian Journal of Otorhinolaryngology 2015Taste is of great importance for the feeding process. Seen in this light, it is essential to investigate this sense in children as developing human beings. However,... (Review)
Review
INTRODUCTION
Taste is of great importance for the feeding process. Seen in this light, it is essential to investigate this sense in children as developing human beings. However, despite little variation in the use of tests that measure the gustatory capacity, there are still questions about the applicability and effective use of tools for quantitative assessment in children.
OBJECTIVE
To search the literature on quantitative instruments used for the evaluation of taste used in studies with children.
METHODS
A search was conducted in the PUBMED and Web of Science platforms, and subsequently, the identified articles were selected and reviewed. The descriptors and terms used were "taste," "child," "assessment," "diagnosis," and "dysgeusia". Original articles related to the theme in English, restricted to children and with no year limitation, were selected. Studies conducted in other stages of human development, exclusively or concurrently with the pediatric population; animal studies; literature review articles; dissertations and book chapters; and case studies and editorials were excluded. The data analysis was performed through a cataloging protocol created for this study, including the following points: author, research department, year, location, population/sample, age, purpose of the study, methods, and primary results.
RESULTS
5613 items were found. 5307 were excluded based on title, 248 by abstract analysis, and 43 by full text evaluation. Fifteen articles were selected for analysis; of these, six were repeated articles, and thus nine articles were selected for review.
CONCLUSION
The tests aiming at evaluation of taste were judiciously used, ensuring reliability for future research, which may employ methods similar to previous studies.
Topics: Child; Evaluation Studies as Topic; Humans; Reproducibility of Results; Taste
PubMed: 25458259
DOI: 10.1016/j.bjorl.2014.04.002 -
International Journal of... 2022With the global epidemic of coronavirus disease 2019 (COVID-19), vaccination rates are increasing globally. This study evaluated the relevant clinical manifestations of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
With the global epidemic of coronavirus disease 2019 (COVID-19), vaccination rates are increasing globally. This study evaluated the relevant clinical manifestations of vaccinated COVID-19 patients.
METHODS
We searched carefully in 11 databases such as PubMed, Embase, Scopus, Cochrane Library, Web of Science, Ovid, China National Knowledge Infrastructure Database, Wan Fang Data, Sinomed, VIP Database, and Reading Showing Database up to 26 March 2022. To search for articles that have described the characteristics of vaccinated patients including epidemiological and clinical symptoms. Statistical analysis of the extracted data using STATA 14.0.
RESULTS
A total of 58 articles and 263,708 laboratory-confirmed COVID-19 patients were included. Most of the patients in the vaccinated group had more asymptomatic infection and fewer severe illnesses. There were significant differences in ethnicity, and strain infected with COVID-19, and comorbidities (hyperlipidemia, diabetes, obesity, kidney disease, immunocompromised, cardiovascular disease, and tumor) and symptoms (fever, cough, gastrointestinal symptoms, neurological symptoms, and dysgeusia/anosmia) between vaccinated group and unvaccinated group. Oxygen support, use of steroid, days in hospital, hospital treatment, ICU treatment, death, and poor prognosis were also significantly different.
CONCLUSION
Compared with the vaccinated group, patients in the unvaccinated group had a more severe clinical manifestations. Vaccines are also protective for infected people.
Topics: Humans; Cardiovascular Diseases; China; COVID-19; Neoplasms; Research Design
PubMed: 36412572
DOI: 10.1177/03946320221141802 -
The Cochrane Database of Systematic... Nov 2023Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It... (Review)
Review
BACKGROUND
Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It remains to be evaluated for which indications and patient populations the drug is suitable.
OBJECTIVES
To assess the efficacy and safety of nirmatrelvir/ritonavir plus standard of care (SoC) compared to SoC with or without placebo, or any other intervention for treating COVID-19 or preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Scopus, and World Health Organization COVID-19 Research Database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 15 May 2023. This is a LSR. We conduct update searches every two months and make them publicly available on the open science framework (OSF) platform.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology and used the Cochrane RoB 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID-19; 2. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS-CoV-2 infection in postexposure prophylaxis (PEP); and 4. pre-exposure prophylaxis (PrEP) scenarios: SARS-CoV-2 infection, development of COVID-19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially-disadvantaged people with comorbidities, populations from low-income countries and low- to middle-income countries, and people from different ethnic and racial backgrounds.
MAIN RESULTS
As of 15 May 2023, we included two RCTs with 2510 participants with mild and mild to moderate symptomatic COVID-19 in outpatient and inpatient settings comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo. All trial participants were without previous confirmed SARS-CoV-2 infection and at high risk for progression to severe disease. Randomization coincided with the Delta wave for outpatients and Omicron wave for inpatients. Outpatient trial participants and 73% of inpatients were unvaccinated. Symptom onset in outpatients was no more than five days before randomisation and prior or concomitant therapies including medications highly dependent on CYP3A4 were not allowed. We excluded two studies due to concerns with research integrity. We identified 13 ongoing studies. Three studies are currently awaiting classification. Nirmatrelvir/ritonavir for treating people with asymptomatic or mild COVID-19 in outpatient settings Nirmatrelvir/ritonavir plus SoC compared to SoC plus placebo may reduce all-cause mortality at 28 days (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.68; 1 study, 2224 participants; low-certainty evidence) and admission to hospital or death within 28 days (RR 0.13, 95% CI 0.07 to 0.27; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC may reduce serious adverse events during the study period compared to SoC plus placebo (RR 0.24, 95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably has little or no effect on treatment-emergent adverse events (RR 0.95, 95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence), and probably increases treatment-related adverse events such as dysgeusia and diarrhoea during the study period compared to SoC plus placebo (RR 2.06, 95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably decreases discontinuation of study drug due to adverse events compared to SoC plus placebo (RR 0.49, 95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence). No studies reported improvement of clinical status, quality of life, or viral clearance. Nirmatrelvir/ritonavir for treating people with moderate to severe COVID-19 in inpatient settings We are uncertain whether nirmatrelvir/ritonavir plus SoC compared to SoC reduces all-cause mortality at 28 days (RR 0.63, 95% CI 0.21 to 1.86; 1 study, 264 participants; very low-certainty evidence), or increases viral clearance at seven days (RR 1.06, 95% CI 0.71 to 1.58; 1 study, 264 participants; very low-certainty evidence) and 14 days (RR 1.05, 95% CI 0.92 to 1.20; 1 study, 264 participants; very low-certainty evidence). No studies reported improvement or worsening of clinical status and quality of life. We did not include data for safety outcomes due to insufficient and inconsistent information. Subgroup analyses for equity For outpatients, the outcome 'admission to hospital or death' was investigated for equity regarding age (less than 65 years versus 65 years or greater) and ethnicity. There were no subgroup differences for age or ethnicity. For inpatients, the outcome 'all-cause mortality' was investigated for equity regarding age (65 years or less versus greater than 65 years). There was no difference between subgroups of age. No further equity-related subgroups were reported, and no subgroups were reported for other outcomes. Nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection (PrEP and PEP) No studies available.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death in high-risk, unvaccinated COVID-19 outpatients infected with the Delta variant of SARS-CoV-2. There is low- to moderate-certainty evidence of the safety of nirmatrelvir/ritonavir. Very low-certainty evidence exists regarding the effects of nirmatrelvir/ritonavir on all-cause mortality and viral clearance in mildly to moderately affected, mostly unvaccinated COVID-19 inpatients infected with the Omicron variant of SARS-CoV-2. Insufficient and inconsistent information prevents the assessment of safety outcomes. No reliable differences in effect size and direction were found regarding equity aspects. There is no available evidence supporting the use of nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection. We are continually updating our search and making search results available on the OSF platform.
Topics: Humans; Aged; COVID-19; SARS-CoV-2; Ritonavir; COVID-19 Drug Treatment
PubMed: 38032024
DOI: 10.1002/14651858.CD015395.pub3