Moderate COVID-19 Patients Research Articles

Emergency Use of Tocilizumab in Moderate and Severe COVID-19 Patients over the Prevaccination Stage during the Pandemic in Mexico.

COVID-19 has been associated with the overactivation of the immune system; interleukin-6 (IL-6) seems to have a key role, which made its moderation to be proposed as a therapeutic blank. Tocilizumab has been used as part of treatments to modulate the immune response to infections caused by COVID-19. Material and Methods. An observational, descriptive, retrospective, and transversal study was carried out in patients diagnosed with moderate-severe COVID-19 who were hospitalized in the 251 General Regional Hospital from March to December 2020. A review of 700 files corresponding to hospitalized patients was carried out, and a sample of 70 patients who met the inclusion criteria proposed for this protocol was obtained. Among the comorbidities associated with the disease, it was found that hypertensive patients have a higher mortality rate: 62% died and so did 59% of those who needed invasive respiratory support. As regards admission tests, statistical significance was found for the figures of leukocytes, neutrophils, glomerular filtration rate, and PCR. The use of this drug benefits mainly young nonhypertensive patients with a moderate disease and preserved renal functions with no need for invasive respiratory support, regardless of other comorbidities.

RWD129 A Comparison of ICU Admission Rate and Related Cost Among Patients Taking Nirmatrelvir and Ritonavir Combination Versus Molnupiravir for Treatment of Mild to Moderate COVID-19 in the US

This study aimed to estimate the ICU admission rate and related cost in patients taking Molnupiravir versus Nirmatrelvir+Ritonavir, the oral antiviral therapies to receive Emergency Use Authorization from the US FDA in December 2021 for the treatment of mild to moderate COVID-19 patients. In this retrospective claim data study, Optum’s de-identified Clinformatics® Data Mart Database (Mainly Commercial and Medicare Advantage) is used to identify the patients who have been prescribed Molnupiravir or Nirmatrelvir+Ritonavir with NDC codes. The patient cohort is divided into two groups: one has been prescribed Molnupiravir and the other one has been prescribed Nirmatrelvir+Ritonavir. The patients in this study cohort have both medical and pharmacy claims. The study period is considered from the approval of these drugs, which is December 22nd and 23rd, 2021, to May 31st, 2022. The first fill date of the prescription for Molnupiravir and Nirmatrelvir+Ritonavir is considered the index date. All patients were followed for 30 days post index to look for any ICU admission and its related costs. The data was analyzed, and two tailed t-test and chi square test were applied. The percentage of patients who have been prescribed Molnupiravir is 25% (N= 4,851), while the patient cohort prescribed with Nirmatrelvir+Ritonavir is 75% (N= 14,479). Patients who have been prescribed Molnupiravir have a significantly higher ICU admission rate (1.2%) than patients who have been prescribed Nirmatrelvir+Ritonavir (0.2%) (P<0.001). The average cost related to ICU admission in patients who have taken Molnupiravir (mean-$15,439) does not show a difference from the cost of ICU admission in patients who have taken Nirmatrelvir+Ritonavir (mean-$13,383) (P = 0.72). This study shows that the ICU admission rate is noticeably different in the cohort of patients taking Molnupiravir compared to the Nirmatrelvir+Ritonavir combination, where ICU-related costs are almost similar in both the cohorts.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.

The role of IL-6, ferritin, and coagulopathy in COVID-19 clinical progression

Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular coagulation. However, the relationship between IL-6 and coagulopathy remains unclear in COVID-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analyzed the effect of those parameters on the worsening of COVID-19 patients. Methods A prospective cohort study was conducted in moderate and severe COVID-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate COVID-19) were included in this study. A total of 35 out of 61 severe and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 (p=0.5), −0.13 (p=0.27), 0.01 (p=0.91), and 0.03 (p=0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (&gt;60%). Conclusions In COVID-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with disease deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. Therefore, changes in IL-6 and D-dimer can predict worsening in moderate and severe COVID-19 patients.

Abstract 9842: Machine Learning-Based Prediction Model of COVID-19 Deterioration Using Wearable Core Temperature and Oxygen Saturation Sensor Data

Background: Accurate prediction of COVID-19 deterioration could enable clinicians to make optimal decisions on medical interventions or hospitalization. A machine learning-based approach using vital data is recognized as a useful tool to predict the exacerbation of infectious disease. However, in COVID-19, effective prediction models are still emerging. Here we developed an algorithm to predict clinical deterioration in non-severe COVID-19 patients using machine learning techniques with continuous core temperature (CT), SpO 2 and pulse rate (PR) data obtained via wearable sensors. Methods: Fifty mild to moderate COVID-19 patients admitted to Nishi-Kobe Medical Center between December 2020 and August 2021 were enrolled. Disease severity was judged by WHO criteria. All patients wore a Moni-Patch ®️ , a wireless CT monitoring patch and a ring-type SpO 2 monitoring device. CT, SpO 2 and PR were continuously collected to a smartphone via Bluetooth ®️ . Data from 41 patients were of sufficient duration and quality to be analyzed and preprocessed to adjust sampling windows before fed into the framework. Additional features were derived by modifying the sensor data using patients’ characteristics. To develop classifiers to distinguish a disease deteriorating into severe one, XGBoost, a gradient-boosted tree algorithm, with 3-fold cross-validation was used. Based on the algorithm, deterioration into severe disease within 24 hour was inferred every single hour using 12-hour time frame data. The area under the curve (AUC) of receiver operating characteristics was analyzed based on the classifier’s prediction threshold. Results: After the enrollment, 13 out of 41 patients developed severe diseases. At the enrollment, baseline characteristics were comparable between mild to moderate and severe disease, except for body temperature that was significantly higher in severe disease. The algorithm developed using the sensor data was able to achieve an AUC of 0.92. Conclusions: Our algorithm could well distinguished COVID-19 deteriorating into severe disease. The results indicates that machine learning approach with continuous CT, SpO 2 and PR measurement using wearable sensors is beneficial to predict the exacerbation of COVID-19.

The Impact of Demographic, Clinical Characteristics and the Various COVID-19 Variant Types on All-Cause Mortality: A Case-Series Retrospective Study.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into a pandemic affecting virtually every country in the world. We evaluated the demographic, clinical, laboratory, and all-cause mortality of moderate and severe COVID-19 patients admitted to a tertiary care hospital in Oman during the different COVID-19 waves and variant types. (2) Methods: A case-series retrospective study was carried out between 12 March 2020 and 30 June 2022. All adults over the age of 18 with laboratory-confirmed COVID-19 were enrolled. Analyses were performed using univariate and multivariate statistics. (3) Results: A total of 1462 confirmed cases enrolled with the mean age of the cohort was 55 ± 17 years with significant differences among the groups (p = 0.006). A total of 63% and 80% of the patients were males and citizens of Oman, respectively. Patients infected with the Alpha COVID-19 variant type were more likely to have acute respiratory distress syndrome (ARDS) (p < 0.001), stay longer in the hospital (p < 0.001), and get admitted to the intensive care unit (ICU) (p < 0.001). At the same time, those who had the Omicron COVID-19 type were more likely to have renal impairment (p < 0.001) and less likely to be associated with non-invasive ventilation (NIV) (p = 0.001) compared with other COVID-19 variant types. The Delta (adjusted odds ratio (aOR), 1.8; 95% confidence interval (CI): 1.22−2.66; p = 0.003) and Omicron (aOR, 1.88; 95% CI: 1.09−3.22; p = 0.022) COVID-19 variant types were associated with higher all-cause mortality when compared to the initial COVID-19 variant. Old age (aOR, 1.05; 95% CI: 1.04−1.06; p < 0.001), the presence of respiratory disease (aOR, 1.58; 95% CI: 1.02−2.44; p = 0.04), ICU admission (aOR, 3.41; 95% CI: 2.16−5.39; p < 0.001), lower eGFR (aOR, 1.61; 95% CI: 1.17−2.23; p = 0.004), and ARDS (aOR, 5.75; 95% CI: 3.69−8.98; p < 0.001) were also associated with higher mortality while NIV requirements were associated with lower odds of dying (aOR, 0.65; 95% CI: 0.46−0.91; p = 0.012). (4) Conclusions: Alpha and Delta variants were associated with a longer hospital stay, need for intensive care, mechanical ventilation, and increased mortality. Old age, cardiac renal dysfunction were commonly associated with Omicron variants. Large-scale national studies to further assess the risk factors for mortality related to COVID-19 waves are warranted.

The significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19.

This study aims at determining the significance of a novel inflammatory biomarker, presepsin, in predicting disease prognosis in patients with COVID-19. This retrospective study was concluded at the University Hospital between April and August 2020. The study involved 88 COVID-19 patients (48 men and 40 women). The patients were categorized into two groups: the patients admitted to the COVID-19 clinic, described as the moderate COVID-19 patients (Group-1; n=44), and those admitted to the internal medicine outpatient clinic, who were the mild COVID-19 patients (Group-2; n=44). The groups were compared using inflammatory markers: presepsin, C-Reactive Protein to Albumin Ratio, Neutrophil to Lymphocyte Ratio, and procalcitonin. Serum presepsin levels (195.29 vs. 52.12 pg/ml) were significantly higher in the Group-1 compared to the Group-2 (p=0.001). The gender distribution and average age were similar in both groups (p > 0.05). While ferritin, lactate dehydrogenase, D-Dimer, platelet lymphocyte ratio, C-Reactive Protein to Albumin Ratio (p=0.001), erythrocyte sedimentation ratio, C-Reactive Protein and presepsin were significantly higher in the Group-1 compared to Group-2 (p<0.05), while hemoglobin and lymphocyte were significantly lower in the Group-1 than in Group-2 (p<0.05). Serum presepsin levels were found to be significantly higher in moderate clinical group COVID-19 patients compared to mild group. Presepsin, a new inflammatory biomarker, may be useful in predicting the prognosis and early treatment of COVID-19 infection.

Evaluation of Remdesivir in Liver Functions Covid-19 Patients At Bhayangkara H.S Samsoeri Mertojoso Hospital Surabaya

Remdesivir is one of the effective anti-viral drugs used as a Covid-19 therapy at moderate, severe and critical degrees. Side effects that need to be considered in the use of remdesivir is hepatotoxicity. The active metabolite of remdesivir (GS-44152) is thought to play a role in mitochondrial damage in liver cells, inhibiting bile acid transport, and inducing oxidative stress. This study was conducted to evaluate the use of remdesivir associated with changes in liver function SGOT and SGPT. This study was retrospective observation of moderate, severe and critical COVID-19 patients receiving remdesivir with inclusion criteria of all inpatient medical records at Bhayangkara Hospital Surabaya for the period of August 2020-July 2021. The results showed that significant increase of liver enzymes occurred in SGPT (Pre 29 .50; Post 33.50) while in SGOT (Pre 33.00; Post 26.00), enzymes were significantly decreased. The decrease was greater in the SGPT (Pre 69.00; Post 47.00) and SGOT (Pre 56.00; Post 32.00) hepatoprotector groups. The use of remdesivir had no effect on liver function as indicated by an increase in SGPT value and a decrease in SGOT value, both of which were still in the normal range.

Association of thyroid dysfunction and COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis was conducted to evaluate the effect of COVID-19 on thyroid function and the role of thyroid hormones alterations in predicting the severity of COVID-19. Online databases, including Scopus, Medline/PubMed, EMBASE, Google Scholar, and Cochrane were searched up to August 2, 2022. After screening titles, abstracts, and full manuscripts, respectively, 30 reports were enrolled. The risk of bias (ROB) was evaluated using the QUADAS-2 tool. In addition, odds ratio (OR) and hazard ratio (HR) analysis for assessing the OR of abnormal thyroid function tests (TFT) in predicting the COVID-19 severity and poor outcomes. Among 30 enrolled studies, ROB of the current study is estimated low to moderate. The average number of patients in each study was 325 (range: 40-3,703), with an overall mean age of 57.6, and the female proportion of 40.4%. Overall, the pooled analysis showed that the prevalence of thyroid dysfunction among 9,707 COVID-19 cases was 15%. Among mild to moderate COVID-19 patients, 6.2% had abnormal TFT, and among patients who experienced severe to critical COVID-19, 20.8% had abnormal TFT. The pooled OR for abnormal TFT and the severity of COVID-19 obtained from 3,865 COVID-19 patients was 3.77 (2.03, 6.99). The pooled HR of TSH level of COVID-19 mortality was 1.57 (0.91, 2.72). Our results demonstrate a high prevalence of thyroid dysfunction in COVID-19, and that among patients severe cases had a 3.77-fold higher risk of abnormal TFT compared to mild to moderate COVID-19. Further studies are required to evaluate the longer-term prognostic role of thyroid dysfunction in severe COVID-19, and investigate potential therapeutic strategies.

Benefits of Cardio-Pulmonary Rehabilitation in Moderate to Severe Forms of COVID-19 Infection.

Our aim was to evaluate the benefits of cardio-pulmonary rehabilitation on severe to moderate COVID-19 patients. 25 discharged COVID-19 patients underwent a cardio-pulmonary test (CPET), a spirometry test and a measure of carbon monoxide lung diffusion capacity (DLCO) at the beginning of their rehabilitation program and after 23 ± 5 rehabilitation sessions. This rehabilitation program combined interval training exercises on a bike and resistance exercises for major muscle groups. We then compared their progress in rehabilitation to that obtained with cardiac patients. At the beginning of their rehabilitation program, COVID-19 patients presented a reduced physical capacity with a maximal aerobic capacity (VO2 max) at 71% of predicted value, a maximal workload at 70% of predicted value and an exercise hyperventilation measured by a higher VE/VCO2 slope. Exercise was mainly limited by muscle deconditioning. After rehabilitation, the VO2 max and maximal workload increased in COVID 19 patients by 18% and 26%, respectively. In patients with ischemic heart disease the post-rehabilitation gains in VO2 max and maximal workload were 22% and 25%, respectively. Moreover, exercise hyperventilation decreased by 10% in both groups. On the other hand, the intrinsic pulmonary function of COVID 19 patients improved following natural recovery. In conclusion, even if cardio-pulmonary rehabilitation is probably not the only parameter which explains the partial recovery of moderate to severe COVID-19 patients, it certainly helps to improve their physical capacity and reduce exercise hyperventilation.

Evaluation of Outcome in Patients With Moderate and Severe COVID-19 Via H-Score

Background: Due to uncontrolled lymphocyte reaction, the overproduction of cytokines in COVID-19 patients can cause sepsis-like symptoms, suggesting sepsis, cytokine release syndrome (CRS), and secondary hemophagocytic lymphohistiocytosis (sHLH). Since different therapeutic approaches are used for each diagnosis, differentiation is essential. This study aims to use H-score as a possible prognostic tool in COVID-19 patients. Methods: A sample of 64 moderate and severe COVID-19 patients was enrolled in this study. Clinical and laboratory findings were assessed. H-score was initially calculated and reevaluated among severe cases 72 hours later and among moderate cases showing severe features of COVID-19. Results: Mortality of 31.3% was reported. Laboratory findings, including triglycerides (TG), ferritin, and aspartate aminotransferase (AST) showed significantly higher initial and follow-up laboratory assessment levels in severe cases than in moderate cases. Moreover, fibrinogen was significantly higher among severe cases than moderate cases at the initial assessment, but no significant difference was reported in the second fibrinogen assessment. Conclusion: In this study, H-score was useful as a predictive tool for the initial evaluation of severe cases of COVID-19. H-score is much lower in these patients than in non-COVID-19 HLH patients may be due to the different underlying immunologic pathophysiology of COVID-19; thus, each H-score criterion must be evaluated for sensitivity and specificity in COVID-19 patients. The H-score cut-offs, H-score may be useful for diagnosing immune overreaction and determining the need for more exclusive immunomodulatory treatments.

An antibody cocktail with broadened mutational resistance and effective protection against SARS-CoV-2.

Neutralizing antibodies have been proven to be highly effective in treating mild and moderate COVID-19 patients, but continuous emergence of SARS-CoV-2 variants poses significant challenges. Antibody cocktail treatments reduce the risk of escape mutants and resistance. In this study, a new cocktail composed of two highly potent neutralizing antibodies (HB27 and H89Y) was developed, whose binding epitope is different from those cocktails that received emergency use authorization. This cocktail showed more potent and balanced neutralizing activities (IC50 0.9–11.3 ng mL−1) against a broad spectrum of SARS-CoV-2 variants over individual HB27 or H89Y antibodies. Furthermore, the cocktail conferred more effective protection against the SARS-CoV-2 Beta variant in an aged murine model than monotherapy. It was shown to prevent SARS-CoV-2 mutational escape in vitro and effectively neutralize 61 types of pseudoviruses harbouring single amino acid mutation originated from variants and escape strains of Bamlanivimab, Casirivimab and Imdevimab with IC50 of 0.6–65 ng mL−1. Despite its breadth of variant neutralization, the HB27+H89Y combo and EUA cocktails lost their potencies against Omicron variant. Our results provide important insights that new antibody cocktails covering different epitopes are valuable tools to counter virus mutation and escape, highlighting the need to search for more conserved epitopes to combat Omicron.Supporting InformationThe supporting information is available online at 10.1007/s11427-022-2166-y. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Untargeted plasma metabolomic fingerprinting highlights several biomarkers for the diagnosis and prognosis of coronavirus disease 19.

ObjectivesThe COVID-19 pandemic has been a serious worldwide public health crisis since 2020 and is still challenging healthcare systems. New tools for the prognosis and diagnosis of COVID-19 patients remain important issues.DesignHere, we studied the metabolome of plasma samples of COVID-19 patients for the identification of prognosis biomarkers.PatientsPlasma samples of eighty-six SARS-CoV-2-infected subjects and 24 healthy controls were collected during the first peak of the COVID-19 pandemic in France in 2020.Main resultsPlasma metabolome fingerprinting allowed the successful discrimination of healthy controls, mild SARS-CoV-2 subjects, and moderate and severe COVID-19 patients at hospital admission. We found a strong effect of SARS-CoV-2 infection on the plasma metabolome in mild cases. Our results revealed that plasma lipids and alterations in their saturation level are important biomarkers for the detection of the infection. We also identified deoxy-fructosyl-amino acids as new putative plasma biomarkers for SARS-CoV-2 infection and COVID-19 severity. Finally, our results highlight a key role for plasma levels of tryptophan and kynurenine in the symptoms of COVID-19 patients.ConclusionOur results showed that plasma metabolome profiling is an efficient tool for the diagnosis and prognosis of SARS-CoV-2 infection.

NUTRITIONAL STATUS OF HOSPITALIZED COVID-19 PATIENTS AND FACTORS AFFECTING THEIR DISEASE SEVERITY

Background: Individuals who are immunosuppressed and harbor co-morbid disorders are at risk of severe disease and poor prognosis for Covid-19 infection. Dietary intake gets impacted by the severity of disease and hospital stay thus creating nutritional deciencies and malnourishment among infected patients. Objective: To assess the importance of nutritional status on severity of COVID 19 disease Materials and methods: The study was a prospective cross sectional one conducted on adults with mild or moderate COVID-19 admitted to MGM Hospital, from 15th October to 15th November 2020. Written informed consent was taken. Ethical clearance was taken from the institute's ethical committee. A total of 42 mild and 58 moderate COVID-19 patients admitted in hospital were analyzed. The socio-demographic prole, anthropometric measurements, biochemical parameters and dietary intake which was noted by three-day 24-hour dietary recall were assessed in each patient. The progression of these patients was noted over the study period. The data was analyzed using descriptive statistics, frequencies, Independent T-test method and Pearson chi - square test. Results: 68% participants had co-morbidities namely Hypertension, Obesity and Diabetes Mellitus. 43% were overweight. Patients with moderate disease (patients with pneumonia and oxygen saturation between 90% to 95%), were overweight in comparison to patients with mild disease (36.2% moderate and 14.3% mild). There was a lower intake of nutrients and micro nutrients as compared to the expected daily allowance in these patients. Signicant association was seen for severity of illness with history of irregular food consumption and obesity. All of the mild cases were discharged within a week of admission. 8% of the moderate cases worsened and had prolonged stay in the hospital. There was one death in the moderate group. Conclusion: Severity of COVID-19 disease increases with comorbidities like Hypertension, Diabetes mellitus and Obesity. Meal pattern and symptoms like chest pain, nausea, vomiting and dysphagia lower the oral food intake in patients. This may contribute to malnutrition and severity of disease.

A randomized, open-label trial of combined nitazoxanide and atazanavir/ritonavir for mild to moderate COVID-19.

BackgroundThe nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19.MethodsThis is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286).ResultsThere was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492–1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV-2 viral load changes from days 2–28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341–2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251–1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797–2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva.ConclusionNitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial.Clinical trial registration[https://clinicaltrials.gov/ct2/show/NCT04459286], identifier [NCT04459286].

Production of two SARS-CoV-2 neutralizing antibodies with different potencies in Nicotiana benthamiana

Monoclonal antibodies are considered to be highly effective therapeutic tools for the treatment of mild to moderate COVID-19 patients. In the present work, we describe the production of two SARS-CoV-2 human IgG1 monoclonal antibodies recognizing the spike protein receptor-binding domain (RBD) and endowed with neutralizing activity (nAbs) in plants. The first one, mAbJ08-MUT, was previously isolated from a COVID-19 convalescent patient and Fc-engineered to prolong the half-life and reduce the risk of antibody-dependent enhancement. This nAb produced in mammalian cells, delivered in a single intramuscular administration during a Phase I clinical study, was shown to (i) be safe and effectively protect against major variants of concern, and (ii) have some neutralizing activity against the recently emerged omicron variant in a cytopathic-effect-based microneutralization assay (100% inhibitory concentration, IC100 of 15 μg/mL). The second antibody, mAb675, previously isolated from a vaccinated individual, showed an intermediate neutralization activity against SARS-CoV-2 variants. Different accumulation levels of mAbJ08-MUT and mAb675 were observed after transient agroinfiltration in Nicotiana benthamiana plants knocked-out for xylosil and fucosil transferases, leading to yields of ~35 and 150 mg/kg of fresh leaf mass, respectively. After purification, as a result of the proteolytic events affecting the hinge-CH2 region, a higher degradation of mAb675 was observed, compared to mAbJ08-MUT (~18% vs. ~1%, respectively). Both nAbs showed a human-like glycosylation profile, and were able to specifically bind to RBD and compete with angiotensin-converting enzyme 2 binding in vitro. SARS-CoV-2 neutralization assay against the original virus isolated in Wuhan demonstrated the high neutralization potency of the plant-produced mAbJ08-MUT, with levels (IC100 < 17 ng/mL) comparable to those of the cognate antibody produced in a Chinese hamster ovary cell line; conversely, mAb675 exhibited a medium neutralization potency (IC100 ~ 200 ng/mL). All these data confirm that plant expression platforms may represent a convenient and rapid production system of potent nAbs to be used both in therapy and diagnostics in pandemic emergencies.

Serum soluble Fas ligand is a severity and mortality prognostic marker for COVID-19 patients.

Finding cytokine storm initiator factors associated with uncontrolled inflammatory immune response is necessary in COVID-19 patients. The aim was the identification of Fas/Fas Ligand (FasL) role in lung involvement and mortality of COVID-19 patients. In this case-control study, mild (outpatient), moderate (hospitalized), and severe (ICU) COVID-19 patients and healthy subjects were investigated. RNA isolated from PBMCs for cDNA synthesis and expression of mFas/mFasL mRNA was evaluated by RT-PCR. Serum sFas/sFasL protein by ELISA and severity of lung involvement by CT-scan were evaluated. Also, we docked Fas and FasL via Bioinformatics software (in silico) to predict the best-fit Fas/FasL complex and performed molecular dynamics simulation (MDS) in hyponatremia and fever (COVID-19 patients), and healthy conditions. mFasL expression was increased in moderate and severe COVID-19 patients compared to the control group. Moreover, mFas expression showed an inverse correlation with myalgia symptom in COVID-19 patients. Elevation of sFasL protein in serum was associated with reduced lung injury and mortality. Bioinformatics analysis confirmed that blood profile alterations of COVID-19 patients, such as fever and hyponatremia could affect Fas/FasL complex interactions. Our translational findings showed that decreased sFasL is associated with lung involvement; severity and mortality in COVID-19 patients. We think that sFasL is a mediator of neutrophilia and lymphopenia in COVID-19. However, additional investigation is suggested. This is the first report describing that the serum sFasL protein is a severity and mortality prognostic marker for the clinical management of COVID-19 patients.

Prescribing pattern of drugs amongst COVID-19 patients in a medical college hospital

This study was conducted to studyprescribing pattern of drugs amongst mild to moderate COVID-19 patients in COVID dedicated medical college hospital in northern India. : A retrospective, descriptive study was conducted in a COVID dedicated medical college hospital at Uttar Pradesh India. Demographic data, hospitalization data, and drug utilization pattern of all laboratory confirmed mild to moderate COVID-19 patients of all age groups, either sex, and admitted between 01 July 20 to 30 September 2020 were retrieved and analyzed. Out of 767 COVID-19 patients 66.62% were male and 33.38% were female. Mean age of COVID-19 patients were 51 years. Average numbers of drug prescribed per patients were seven. Number of drug prescribed per patients increased in older COVID-19 patients and COVID-19 patients having co-morbidities. Most common prescribed drug was paracetamol (100%), followed by Vitamin C (99.08%), followed by multivitamins (97.78%), followed by protonpump inhibitors (74.84%), followed by antihistaminices in 51.89% cases followed by hydroxychloroquine and Ivermectin was prescribed in 47.84% cases. Most common antibiotic prescribed was Amoxicillin (40.94%), followed by Azithromycin (34.41%), and followed by Doxycycline (29.20%) cases. Flavipiravir was prescribed in 15.12% cases. Corticosteroids were prescribed in 16.30% cases. Drug used for admitted COVID-19 patients were diverse and were in accordance to existing guidelines.

Efficacy of Favipiravir in the Treatment of Moderate COVID-19 Patients: A Randomized, Open-label, Controlled Clinical Trial

Efficacy of Favipiravir in the Treatment of Moderate COVID-19 Patients: A Randomized, Open-label, Controlled Clinical Trial

Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial.

We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.