Molnupiravir in COVID-19: A systematic review of literature.
Diabetes & metabolic syndrome. 2021;(6):102329
BACKGROUND AND AIMS Molnupiravir is a newer oral antiviral drug that has recently been tested in COVID-19. We aim to conduct a systematic review of literature to find out the efficacy and safety of molnupiravir in patients with COVID-19. METHODS We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar from inception until October 15, 2021, using MeSH keywords. Ongoing trials of molnupiravir in COVID-19 were additionally searched from the ClinicalTrials.Gov and ctri.nic.in/Clinicaltrials. We retrieved all the available granular details of phase 1 to 3 studies of molnupiravir in COVID-19. Subsequently we reviewed the results narratively. RESULTS Two phase 1 double-blind, randomized, placebo-controlled (DBRPC) studies of molnupiravir showed that 1600 mg daily dose is safe and tolerable, without any serious adverse events up to 5.5 days. One phase 2 DBPRC study found significantly lower time to clearance (RNA negativity) with molnupiravir 800 mg twice daily compared to the placebo (log-rank p value = 0.013) in mild to moderate COVID-19. Interim report of one phase 3 DBRPC study in non-hospitalized COVID-19 found a significant reduction in the risk of hospital admission or death by 50% (p = 0.0012). However, no significant benefit was observed with molnupiravir in the later stage of moderate to severe COVID-19. CONCLUSION Molnupiravir is first oral antiviral drug to demonstrate a significant benefit in reducing hospitalization or death in mild COVID-19 and could be an important weapon in the battle against SARS-CoV-2. However, its role in moderate to severe COVID-19 is questionable and more studies are needed.
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis of Early COVID-19 and Treated at Home Within 3 Days or After 3 Days of Symptom Onset with Prescribed and Non-Prescribed Treatments Between November 2020 and August 2021.
Medical science monitor : international medical journal of experimental and clinical research. 2021;:e935379
BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.
Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.
Diabetes/metabolism research and reviews. 2021;(3):e3388
BACKGROUND Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.
Diabetes Increases Severe COVID-19 Outcomes Primarily in Younger Adults.
The Journal of clinical endocrinology and metabolism. 2021;(9):e3364-e3368
CONTEXT Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. OBJECTIVE To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. DESIGN SETTING AND PARTICIPANTS We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. MAIN OUTCOME MEASURE(S): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. RESULTS Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]). CONCLUSIONS Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.
Risk of COVID 19 in patients with inflammatory bowel diseases compared to a control population.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021;(3):263-270
BACKGROUND It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19. OBJECTIVES This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders. METHODS This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed. RESULTS 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28-0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03-0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02-1.17). CONCLUSION IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.
[Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19].
Revista espanola de geriatria y gerontologia. 2021;(5):259-267
INTRODUCTION Elderly patients with COVID-19 has a worse clinical evolution, being more susceptible to develop serious manifestations. The differences between the elderly and very elderly population, mortality and associated prognostic factors of SARS-CoV-2 infection have not been enough studied yet. METHODS An observational study of 416 elderly patients admitted consecutively to Hospital General Universitario de Ciudad Real for COVID-19 respiratory infection from March 1st to April 30th, 2020. Data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions and clinical outcomes during the hospitalization and after discharge, until June 15, 2020 with the aim of analyzing mortality, and associated prognostic factors. RESULTS The mean age was 84.43±5.74 years old; elderly patients (75-84 years) were 50.2% of the sample and very elderly (≥85 years) the remaining 49.8%. In Cox regression model, mortality rate was higher in very elderly group (HR = 2.58; 95% CI: 1.23-5.38; P = .01), hypertensive (HR = 3, 45; 95% CI: 1.13-10.5; P = .03) and chronic kidney disease patients (HR = 3.86; 95% CI: 1.3-11.43; P = .02). In contrast, calcium antagonists (HR = 0.27; 95% CI: 0.12-0.62; P = .002) and anticoagulant therapy during hospitalization (HR = 0.26; 95% CI: 0.08 0, 83; P = .02) were associated with a longer time free of mortality. CONCLUSIONS Mortality rate was higher in very eldery patients compared with eldery; and in hypertensive and chronic kidney disease patients. Anticoagulation therapy and calcium chanel bloquers treatment during hospitalization were associated with a higher survival in the short-term follow-up in patients hospitalized with COVID-19.
The Effect of Vitamin C on Pathological Parameters and Survival Duration of Critically Ill Coronavirus Disease 2019 Patients: A Randomized Clinical Trial.
Frontiers in immunology. 2021;:717816
INTRODUCTION Vitamin C has been reported to have beneficial effects on patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of vitamin C supplementation on pathological parameters and survival duration of critically ill patients with COVID-19. METHODS This clinical trial was conducted on 120 hospitalized critically ill patients infected with COVID-19. The intervention group (n = 31) received one capsule of 500 mg of vitamin C daily for 14 days. The control group (n = 69) received the same nutrition except for vitamin C supplements. Measurement of pathological and biochemical parameters was performed at baseline and after 2 weeks of the intervention. RESULTS Following 2 weeks of vitamin C supplementation, the level of serum K was significantly lower in the patients compared with the control group (3.93 vs. 4.21 mEq/L, p < 0.01). Vitamin C supplementation resulted in a higher mean survival duration compared with that of the control group (8 vs. 4 days, p < 0.01). There was a linear association between the number of days of vitamin C intake and survival duration (B = 1.66, p < 0.001). The vitamin C supplementation had no effect on blood glucose, mean arterial pressure, arterial blood gas (ABG) parameters, Glasgow Coma Scale (GCS), kidney function, cell blood count (CBC), hemoglobin (Hb), platelet (Plt), partial thromboplastin time (PTT), albumin, hematocrit (Hct), and other serum electrolytes including sodium (Na), calcium, and phosphorus (P). CONCLUSION The present study demonstrated the potential of vitamin C supplementation in enhancing the survival duration of critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION https://www.irct.ir/trial/55074, identifier IRCT20151226025699N5.
Persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19: a hospital-based longitudinal study.
Virology journal. 2021;(1):134
BACKGROUND The persistence of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RNA in the body fluids of patients with the novel coronavirus disease 2019 (COVID-19) may increase the potential risk of viral transmission. There is still uncertainty on whether the recommended quarantine duration is sufficient to reduce the risk of transmission. This study aimed to investigate the persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19. METHODS In this hospital-based longitudinal study, 100 confirmed cases of COVID-19 were recruited between March 2020 and August 2020 in Guilan Province, north of Iran. Nasopharyngeal, blood, urine, and stool samples were obtained from each participant at the time of hospital admission, upon discharge, 1 week after discharge, and every 2 weeks until all samples were negative for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) assay. A survival analysis was also performed to identify the duration of viral persistence. RESULTS The median duration of viral RNA persistence in the nasopharyngeal samples was 8 days from the first positive RT-PCR result upon admission (95% CI 6.91-9.09); the maximum duration of viral shedding was 25 days from admission. Positive blood, urine, and stool RT-PCR results were detected in 24%, 7%, and 6% of the patients, respectively. The median duration of viral persistence in the blood, urine, and stool samples was 7 days (95% CI 6.07-7.93), 6 days (95% CI 4.16-8.41), and 13 days (95% CI 6.96-19.4), respectively. Also, the maximum duration of viral persistence in the blood, urine, and stool samples was 17, 11, and 42 days from admission, respectively. CONCLUSION According to the present results, immediately after the hospitalized patients were discharged, no evidence of viral genetic materials was found. Therefore, appropriate treatments were selected for the patients at this hospital. However, we recommend further investigations on a larger sample size in multi-center and prospective randomized controlled trials (RCTs) to evaluate the effects of different drugs on the shedding of the virus through body secretions.
Diabetic retinopathy is independently associated with increased risk of intubation: A single centre cohort study of patients with diabetes hospitalised with COVID-19.
Diabetes research and clinical practice. 2021;:108529
In our study of 187 patients with diabetes hospitalised with COVID-19 we observed a more than 5 fold increased risk of intubation in patients with diabetic retinopathy. Further studies are required to understand the mechanisms that explain the associations between retinopathy and other indices of microangiopathy with severe COVID-19.
Blood glucose levels should be considered as a new vital sign indicative of prognosis during hospitalization.
Diabetes & metabolic syndrome. 2021;(1):221-227
BACKGROUND AND AIMS The measurement of vital signs is an important part of clinical work up. Presently, measurement of blood glucose is a factor for concern mostly when treating individuals with diabetes. Significance of blood glucose measurement in prognosis of non-diabetic and hospitalized patients is not clear. METHODS A systematic search of literature published in the Electronic databases, PubMed and Google Scholar was performed using following keywords; blood glucose, hospital admissions, critical illness, hospitalizations, cardiovascular disease (CVD), morbidity, and mortality. This literature search was largely restricted to non-diabetic individuals. RESULTS Blood glucose level, even when in high normal range, or in slightly high range, is an important determinant of morbidity and mortality, especially in hospitalized patients. Further, even slight elevation of blood glucose may increase mortality in patients with COVID-19. Finally, blood glucose variability and hypoglycemia in critically ill individuals without diabetes causes excess in-hospital complications and mortality. CONCLUSION In view of these data, we emphasize the significance of blood glucose measurement in all patients admitted to the hospital regardless of presence of diabetes. We propose that blood glucose be included as the "fifth vital sign" for any hospitalized patient.