Early Prediction of COVID-19 Patient Survival by Targeted Plasma Multi-Omics and Machine Learning

The recent surge of coronavirus disease 2019 (COVID-19) hospitalizations severely challenges healthcare systems around the globe and has increased the demand for reliable tests predictive of disease severity and mortality. Using multiplexed targeted mass spectrometry assays on a robust triple quadrupole MS setup which is available in many clinical laboratories, we determined the precise concentrations of hundreds of proteins and metabolites in plasma from hospitalized COVID-19 patients. We observed a clear distinction between COVID-19 patients and controls and, strikingly, a significant difference between survivors and nonsurvivors. With increasing length of hospitalization, the survivors’ samples showed a trend toward normal concentrations, indicating a potential sensitive readout of treatment success. Building a machine learning multi-omic model that considers the concentrations of 10 proteins and five metabolites, we could predict patient survival with 92% accuracy (area under the receiver operating characteristic curve: 0.97) on the day of hospitalization. Hence, our standardized assays represent a unique opportunity for the early stratification of hospitalized COVID-19 patients.     

Current scenario of COVID-19 in pediatric age group and physiology of immune and thymus response

COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0–18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March (https://www.worldometers.info/coronavirus). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.     

Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity

ObjectivePrecise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death.MethodsThis retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization.ResultsOf a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death.ConclusionFT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.     

Predictive monitoring and therapeutic immune biomarkers in the management of clinical complications of COVID-19

The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), appears with a wide spectrum of mild-to-critical clinical complications. Many clinical and experimental findings suggest the role of inflammatory mechanisms in the immunopathology of COVID-19. Hence, cellular and molecular mediators of the immune system can be potential targets for predicting, monitoring, and treating the progressive complications of COVID-19. In this review, we assess the latest cellular and molecular data on the immunopathology of COVID-19 according to the pathological evidence (e.g., mucus and surfactants), dysregulations of pro- and anti-inflammatory mediators (e.g., cytokines and chemokines), and impairments of innate and acquired immune system functions (e.g., mononuclear cells, neutrophils and antibodies). Furthermore, we determine the significance of immune biomarkers for predicting, monitoring, and treating the progressive complications of COVID-19. We also discuss the clinical importance of recent immune biomarkers in COVID-19, and at the end of each section, recent clinical trials in immune biomarkers for COVID-19 are mentioned.     

MicroRNA-425-5p modulates osteoporosis by targeting annexin A2

The disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.

     

d-Alanine as a biomarker and a therapeutic option for severe influenza virus infection and COVID-19

Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain insufficient. We explored the potential of d-amino acids, rare enantiomers of amino acids, as biomarkers for assessing disease severity and as protective nutrients against severe viral infections. In mice infected with influenza A virus (IAV) and in patients with severe COVID-19 requiring artificial ventilation or extracorporeal membrane oxygenation, blood levels of d-amino acids, including d-alanine, were reduced significantly compared with those of uninfected mice or healthy controls. In mice models of IAV infection or COVID-19, supplementation with d-alanine alleviated severity of clinical course, and mice with sustained blood levels of d-alanine showed favorable prognoses. In severe viral infections, blood levels of d-amino acids, including d-alanine, decrease, and supplementation with d-alanine improves prognosis. d-Alanine has great potentials as a biomarker and a therapeutic option for severe viral infections.     

Clinical characteristics,risk factors,and rate of severity of a nationwide COVID-19 Saudi cohort

ObjectiveTo evaluate COVID19 patients’ clinical characteristics, risk factors, and COVID-19 severity at baseline and over one month following hospitalization.Design, setting, and participantsThis prospective cohort study of 598 Saudi COVID19 patients recruited from 4 major medical institutions nationwide between June 01, 2020, and February 28, 2021. Patients were stratified into different demographic characteristics and COVID-19 severity scale.ResultsOf the 598 hospitalized adult COVID19 patients (mean [range] age, 57 [46 to 65] years; 59% male), 300 (50.16%) had severe clinical COVID-19. Comorbidity was high among hospitalized patients (73.5 %), with diabetes mellitus (n=; 46%) and hypertension (n=; 41%) being the most common prevalent. In a multivariate logistic regression model, patient demographics and clinical factors such as age (odds ratio [OR], 1.014 per year; 95% CI, 1.003–1.025), male sex (OR, 1.63; 95% CI, 1.02–2.62), diabetes mellitus (OR, 1.63; 95% CI, 1.06–2.49), obesity (OR, 1.93; 95% CI, 1.26–2.94), oxygen saturation<92% (OR, 4.83; 95% CI, 2.96–7.86), and high neutrophil to lymphocyte ratio (OR, 3.74 per unit; 95% CI, 1.96–7.14) were independently associated with higher COVID-19 severity. Moreover, more than 60% of male patients and middle-aged patients (40–60 years) were associated with the use of COVID-19 medications, including favipiravir and dexamethasone, during their hospital stay. Additionally, the rate of invasive mechanical ventilation was the highest in female patients (61.5%) and in middle-aged patients (46.2%). However, the death rate was slightly higher in males (56%) than in female patients and in elderly patients (52%). In Cox proportional analysis, age associated with increased risk of 60-days mortality (Hazard ratio; HR, 1.05 per year; 95% CI, 1.018–1.098). Additionally, the Riyadh region associated with more COVID-19 cases required invasive respiratory support (57.7%) and Jeddah was associated with more deceased COVID-19 cases (44%).ConclusionsThe data shows that comorbidity is associated with hospitalization among COVID-19 patients, which indicates the level of severity. Infection during the winter season (November), male gender, elderly, and those with pre-existing diabetes mellitus or obesity were associated with higher COVID-19 clinical severity.     

Advances and gaps in SARS-CoV-2 infection models

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to recapitulate COVID-19 demographic variables such as comorbidities and age.

In February of 2020, the World Health Organization (WHO) R&D Blueprint convened a group of experts to develop preclinical models of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Since its inception, the goal of this WHO COVID Modeling group (WHO-COM) has been to accelerate the development of Coronavirus Disease 2019 (COVID-19) vaccines and therapeutics by rapidly sharing data among member scientists worldwide. In addition, concerns were raised at that time about the possibility of vaccine-associated enhanced respiratory disease (VAERD) or antibody-dependent enhancement (ADE) after vaccination or infection. In September of 2020, the WHO-COM published a review on COVID-19 animal models [1], which reflected the state-of-the art at that time, with the vast majority of publications authored by members of the group.Preclinical studies in nonhuman primates (NHPs) of COVID-19 vaccines that are currently being deployed [2–5] proved remarkably predictive of the outcome of clinical efficacy studies. In particular, NHP studies not only predicted high clinical efficacy of these vaccines but also suggested immune correlates of protection. Moreover, preclinical studies accurately predicted that protection against severe pneumonia would be easier to achieve than protection against viral replication in nasal mucosa. These observations confirm the value and importance of the use of animal models for COVID-19.In 2021, with several vaccines rolling out worldwide and the detection of variants of concern (VOCs), the development of preclinical models of SARS-CoV-2 infection and their role in COVID-19 research has entered into a new phase. This paper provides an update from the WHO-COM regarding advances in preclinical models. In particular, we discuss how animal model research has provided insight into VOC pathogenesis and correlates of protection and has helped therapeutic development. Finally, we discuss the current status of VAERD research and the race to develop models that recapitulate COVID-19 demographic variables such as comorbidities and age.     

SARS-CoV-2 infection and oxidative stress: Pathophysiological insight into thrombosis and therapeutic opportunities

The current coronavirus disease 2019 (COVID-19) pandemic has presented unprecedented challenges to global health. Although the majority of COVID-19 patients exhibit mild-to-no symptoms, many patients develop severe disease and need immediate hospitalization, with most severe infections associated with a dysregulated immune response attributed to a cytokine storm. Epidemiological studies suggest that overall COVID-19 severity and morbidity correlate with underlying comorbidities, including diabetes, obesity, cardiovascular diseases, and immunosuppressive conditions. Patients with such comorbidities exhibit elevated levels of reactive oxygen species (ROS) and oxidative stress caused by an increased accumulation of angiotensin II and by activation of the NADPH oxidase pathway. Moreover, accumulating evidence suggests that oxidative stress coupled with the cytokine storm contribute to COVID-19 pathogenesis and immunopathogenesis by causing endotheliitis and endothelial cell dysfunction and by activating the blood clotting cascade that results in blood coagulation and microvascular thrombosis. In this review, we survey the mechanisms of how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces oxidative stress and the consequences of this stress on patient health. We further shed light on aspects of the host immunity that are crucial to prevent the disease during the early phase of infection. A better understanding of the disease pathophysiology as well as preventive measures aimed at lowering ROS levels may pave the way to mitigate SARS-CoV-2-induced complications and decrease mortality.     

Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review

Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st_, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.     

Fungal Infections in COVID-19 Intensive Care Patients

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.     

COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management

Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3–7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients.     

微量元素硒在对抗COVID-19中的作用研究进展

自新型冠状病毒肺炎（corona virus disease 2019，COVID-19）疫情爆发以来，严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome-coronavirus 2， SARS-CoV-2）引起的各类临床表现和后续并发症受到了广泛关注。有研究发现，COVID-19死亡率具有地域差异性，中度或重度缺硒地区感染人群常常具有更高的死亡率，因此硒可能在对抗COVID-19中具有一定的作用。总结了硒缺乏COVID-19患者的临床表现、硒对抗COVID-19的临床效应、以及硒对抗COVID-19的作用机制等方面的研究进展。从目前的研究结果来看，硒在应对感染SARS-CoV-2以及避免过激免疫反应导致的细胞因子风暴过程中具有积极作用，但仍然缺乏临床试验研究证据。     

Association of glycosylated haemoglobin HbA1c levels with outcome in patients with COVID-19: A Retrospective Study

Patients with hyperglycemia tend to be susceptible to Coronavirus disease 2019 (COVID-19). However, the association of HbA1c level with outcome of COVID-19 patients was unclear. We performed a retrospective study of 2880 cases of COVID-19 admitted in Tongji Hospital, Wuhan, China, among which 922 had detected the HbA1c levels. We found that COVID-19 patients with either lower levels of HbAlc (3%-4.9%) or higher levels of HbAlc (≥6%) were associated with elevated all-cause mortality. Meanwhile, we observed that HbAlc levels were highly correlated with haemoglobin (Hb) and total cholesterol (TC) (P < .0001), moderately correlated with albumin (ALB) and high-sensitive C reaction protein (hs-CRP) (0.0001 < P<.001), and relatively low correlated with low-density lipoprotein cholesterol (LDL-C) (.001 < P<.01). These associated cofactors might together contribute to the clinical outcome of COVID-19 patients. Furthermore, the mortality was higher in COVID-19 patients with newly diagnosed diabetes mellitus (DM) compared with COVID-19 patients with history of DM. Moreover, in patients with history of DM, the mortality was decreased in patients treated with anti-hyperglycaemic drugs. In summary, our data showed that the in-hospital mortality was increased in COVID-19 patients with lower or higher levels of HbAlc. Meanwhile, initiation of appropriate anti-hyperglycaemic treatment might improve the clinical outcome in COVID-19 patients.     

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study

ObjectiveCancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history.MethodsThis is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes.ResultsOf 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19–attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers.ConclusionThese data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.     

Association between Statin Use and Short-Term Outcome Based on Severity of Ischemic Stroke: A Cohort Study

Background

Statins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity.

Methods

A total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0–5) at 3 months after onset using multivariable logistic regression models.

Results

A total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38–0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81–1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31–0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57–0.92) at 3 months in the non-minor stroke group.

Conclusions

Statin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.     

Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study

BackgroundPeople infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity.Methods and findingsThis analysis comprises an observational cohort of 329 HIV–seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) (p < 0.001). Diabetes, age >55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed.ConclusionsIn summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04403880","term_id":"NCT04403880"}}NCT04403880.

Shelly Karuna and co-workers study variations in neutralizing antibody responses after SARS-CoV-2 infection.     

Association of disease severity and death outcome with vaccination status of admitted COVID-19 patients in delta period of SARS-COV-2 in mixed variety of vaccine background

To understand the effectual role of COVID-19 vaccination, we must analyze its effectiveness in dampening the disease severity and death outcome in patients who acquire infection and require hospitalization. The goal of this study was to see if there was an association between disease progression in admitted COVID-19 patients and their prior vaccination exposure. A prospective cohort study based on 1640 admitted COVID-19 patients were carried between June 2021 and October 2021. Depending on vaccination exposure they were divided into vaccinated (exposed) and unvaccinated (unexposed) groups, excluding partially vaccinated patients. Disease severity was assessed at admission on severity index scale. Disease progression to mortality or need of mechanical ventilation and survival were taken as outcome. Absolute difference with 95%CI and Risk Ratio were calculated using cross tabulation, Chi square test and multivariable logistic regression analysis. Among 1514 total analyzed cohort (median age, 53 years [IQR, 17,106]; 43.7% from 46 to 65 years of age group, 56.2% males,33.4% with no comorbid factor for disease progression) 369(24.4%) were vaccinated breakthrough cases and 1145(75.6%) were unvaccinated controls. 556(36.7%) progressed to death or mechanical ventilation, 958(63.3%) patients survived and were discharged home. Disease progression to death or mechanical ventilation was significantly associated with decreased likelihood of vaccination (24.9% among vaccinated breakthrough vs 40.5% unvaccinated controls, [Absolute difference ?15.6% 95%CI (?10.2% to ?20.6%); RR 0.615 95%CI (0.509, 0.744); p <.001]). This association was stronger for old age population and for increase time span between second dose of vaccine and onset of symptoms. There was no statistically significant difference among different types of vaccination and occurrence of outcome when compared to unvaccinated controls (RR 0.607(0.482, 0.763); 0.673(0.339, 1.33) and 0.623(0.441, 0.881) for Inactivated virus vaccine, mRNA and Adenovirus vector-based vaccine respectively. The patients who were fully vaccinated against SARS-COV-2 die or shift to mechanical ventilation less frequently than unvaccinated COVID-19 admitted patients.     

Theoretical benefits of yogurt-derived bioactive peptides and probiotics in COVID-19 patients – A narrative review and hypotheses

The world is currently facing a frightening coronavirus disease-2019 (COVID-19) epidemic. Severity of COVID-19 presentation is highly variable among infected individuals with increasingly recognized risk factors. Although observational studies suggested lower COVID-19 severity in populations consuming fermented foods, no controlled study investigated the role of diet. Yogurt, a fermented dairy product, exhibits interesting properties related to the presence of bioactive peptides and probiotics that may play a beneficial role in COVID-19 presentation and outcome. Peptides contained in yogurt are responsible for angiotensin-converting enzyme-inhibitory, bradykinin potentiating, antiviral, anti-inflammatory, antithrombotic, and antioxidant effects. The types and activity of these peptides vary widely depending on their amino acid sequence, on the probiotics used in yogurt production and on intestinal digestion. Additionally, probiotics used in yogurt exhibit direct angiotensin-converting enzyme-inhibitory, antiviral and immune boosting activities. Since COVID-19 pathogenesis involves angiotensin II accumulation and bradykinin deficiency, yogurt bioactive peptides appear as potentially beneficial. Therefore, epidemiological investigations and randomized controlled clinical trials to evaluate the exact role of yogurt consumption on COVID-19 manifestations and outcome should be encouraged.