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Vitamin D Supplementation in Neonatal and Infant MIS-C Following COVID-19 Infection.
Rizzi, M, Avellis, V, Messina, A, Germano, C, Tavella, E, Dodaro, V, Vitale, R, Revelli, A, Zola, P, Picone, S, et al
International journal of molecular sciences. 2024;(7)
Abstract
To date, the SARS-CoV-2 pandemic still represents a great clinical challenge worldwide, and effective anti-COVID-19 drugs are limited. For this reason, nutritional supplements have been investigated as adjuvant therapeutic approaches in disease management. Among such supplements, vitamin D has gained great interest, due to its immunomodulatory and anti-inflammatory actions both in adult and pediatric populations. Even if there is conflicting evidence about its prevention and/or mitigation effectiveness in SARS-CoV-2 infection, several studies demonstrated a strict correlation between hypovitaminosis D and disease severity in acute COVID-19 and MIS-C (multisystem inflammatory syndrome in children). This narrative review offers a resume of the state of the art about vitamin D's role in immunity and its clinical use in the context of the current pandemic, specially focusing on pediatric manifestations and MIS-C. It seems biologically reasonable that interventions aimed at normalizing circulating vitamin D levels could be beneficial. To help clinicians in establishing the correct prophylaxis and/or supportive therapy with vitamin D, well-designed and adequately statistically powered clinical trials involving both adult and pediatric populations are needed. Moreover, this review will also discuss the few other nutraceuticals evaluated in this context.
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Prevalence and predictors of suboptimal glycemic control among patients with type 2 diabetes mellitus in northern Thailand: A hospital-based cross-sectional control study.
Yeemard, F, Srichan, P, Apidechkul, T, Luerueang, N, Tamornpark, R, Utsaha, S
PloS one. 2022;(1):e0262714
Abstract
BACKGROUND Suboptimal glycemic control among patients with type 2 diabetes mellitus (DM) is a significant public health problem, particularly among people living with poor education and economic statuses, including those with a unique dietary culture. This study aimed to estimate the prevalence and identify the factors associated with suboptimal glycemic control among patients with type 2 DM during the coronavirus disease-2019 (COVID-19) pandemic. METHODS A hospital-based cross-sectional study was used to elicit information from DM patients attending six hospitals located in Chiang Rai Province, northern Thailand, between February and May 2021. A validated questionnaire and 5 mL blood specimens were used as the research tools. Glycated hemoglobin (HbA1c) greater than 7.0% among DM patients at least two years after diagnosis was defined as suboptimal glycemic control. Chi-square tests and logistic regression were used to identify the associations between variables at the significance level α = 0.05. RESULTS A total of 967 patients were recruited for this study; 54.8% 530 had suboptimal glycemic control, 58.8% were female, 66.5% were aged 50-69 years, and 78.5% were married (78.5%). Six variables were found to be associated with suboptimal glycemic control in multivariable logistic regression. Participants aged <49, 50-59, and 60-69 years had 3.32 times (95% CI = 1.99-5.53), 2.61 times (95% CI = 1.67-4.08), and 1.93 times (95% CI = 1.26-2.95) greater odds of having suboptimal glycemic control, respectively, than those aged ≥70 years. Married individuals had 1.64 times (95% CI = 1.11-2.41) greater odds of having suboptimal glycemic control than those ever married. Participants who consumed sticky rice had 1.61 times (95% CI = 1.19-2.61) greater odds of having suboptimal glycemic control than those who did not consume sticky rice in daily life. Participants who had been diagnosed with DM for 11-20 years and ≥21 years had 1.98 times (95% CI = 1.37-2.86) and 2.46 times (1.50-4.04) greater odds of having suboptimal glycemic control, respectively, than those who had been diagnosed ≤ 10 years. Participants who had experienced forgetting to take their medication had 2.10 times (95% CI = 1.43-3.09) greater odds of having suboptimal glycemic control than those who did not, and those who had their medical expenses covered by the national scheme had 2.67 times (95% CI = 1.00-7.08) greater odds of suboptimal glycemic control than those who self-paid. CONCLUSION Effective health interventions to control blood glucose among DM patients during ongoing treatment are urgently required. The interventions should focus on patients aged less than 69 years, marital status, forgetting to take their medication, and a longer time since diagnosis, including reducing their sticky rice consumption. The effects of copayments should also be considered.
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Evaluating the Findings of the IMPACT-C Randomized Clinical Trial to Improve COVID-19 Vaccine Coverage in Skilled Nursing Facilities.
Berry, SD, Goldfeld, KS, McConeghy, K, Gifford, D, Davidson, HE, Han, L, Syme, M, Gandhi, A, Mitchell, SL, Harrison, J, et al
JAMA internal medicine. 2022;(3):324-331
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IMPORTANCE Identifying successful strategies to increase COVID-19 vaccination among skilled nursing facility (SNF) residents and staff is integral to preventing future outbreaks in a continually overwhelmed system. OBJECTIVE To determine whether a multicomponent vaccine campaign would increase vaccine rates among SNF residents and staff. DESIGN, SETTING, AND PARTICIPANTS This was a cluster randomized trial with a rapid timeline (December 2020-March 2021) coinciding with the Pharmacy Partnership Program (PPP). It included 133 SNFs in 4 health care systems across 16 states: 63 and 70 facilities in the intervention and control arms, respectively, and participants included 7496 long-stay residents (>100 days) and 17 963 staff. INTERVENTIONS Multicomponent interventions were introduced at the facility level that included: (1) educational material and electronic messaging for staff; (2) town hall meetings with frontline staff (nurses, nurse aides, dietary, housekeeping); (3) messaging from community leaders; (4) gifts (eg, T-shirts) with socially concerned messaging; (5) use of a specialist to facilitate consent with residents' proxies; and (6) funds for additional COVID-19 testing of staff/residents. MAIN OUTCOMES AND MEASURES The primary outcomes of this study were the proportion of residents (from electronic medical records) and staff (from facility logs) who received a COVID-19 vaccine (any), examined as 2 separate outcomes. Mixed-effects generalized linear models with a binomial distribution were used to compare outcomes between arms, using intent-to-treat approach. Race was examined as an effect modifier in the resident outcome model. RESULTS Most facilities were for-profit (95; 71.4%), and 1973 (26.3%) of residents were Black. Among residents, 82.5% (95% CI, 81.2%-83.7%) were vaccinated in the intervention arm, compared with 79.8% (95% CI, 78.5%-81.0%) in the usual care arm (marginal difference 0.8%; 95% CI, -1.9% to 3.7%). Among staff, 49.5% (95% CI, 48.4%-50.6%) were vaccinated in the intervention arm, compared with 47.9% (95% CI, 46.9%-48.9%) in usual care arm (marginal difference: -0.4%; 95% CI, -4.2% to 3.1%). There was no association of race with the outcome among residents. CONCLUSIONS AND RELEVANCE A multicomponent vaccine campaign did not have a significant effect on vaccination rates among SNF residents or staff. Among residents, vaccination rates were high. However, half the staff remained unvaccinated despite these efforts. Vaccination campaigns to target SNF staff will likely need to use additional approaches. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04732819.
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Ferritin - from iron, through inflammation and autoimmunity, to COVID-19.
Mahroum, N, Alghory, A, Kiyak, Z, Alwani, A, Seida, R, Alrais, M, Shoenfeld, Y
Journal of autoimmunity. 2022;:102778
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While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed.
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Individual outcome prediction models for patients with COVID-19 based on their first day of admission to the intensive care unit.
Rigo-Bonnin, R, Gumucio-Sanguino, VD, Pérez-Fernández, XL, Corral-Ansa, L, Fuset-Cabanes, M, Pons-Serra, M, Hernández-Jiménez, E, Ventura-Pedret, S, Boza-Hernández, E, Gasa, M, et al
Clinical biochemistry. 2022;:13-21
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BACKGROUND Currently, good prognosis and management of critically ill patients with COVID-19 are crucial for developing disease management guidelines and providing a viable healthcare system. We aimed to propose individual outcome prediction models based on binary logistic regression (BLR) and artificial neural network (ANN) analyses of data collected in the first 24 h of intensive care unit (ICU) admission for patients with COVID-19 infection. We also analysed different variables for ICU patients who survived and those who died. METHODS Data from 326 critically ill patients with COVID-19 were collected. Data were captured on laboratory variables, demographics, comorbidities, symptoms and hospital stay related information. These data were compared with patient outcomes (survivor and non-survivor patients). BLR was assessed using the Wald Forward Stepwise method, and the ANN model was constructed using multilayer perceptron architecture. RESULTS The area under the receiver operating characteristic curve of the ANN model was significantly larger than the BLR model (0.917 vs 0.810; p < 0.001) for predicting individual outcomes. In addition, ANN model presented similar negative predictive value than the BLR model (95.9% vs 94.8%). Variables such as age, pH, potassium ion, partial pressure of oxygen, and chloride were present in both models and they were significant predictors of death in COVID-19 patients. CONCLUSIONS Our study could provide helpful information for other hospitals to develop their own individual outcome prediction models based, mainly, on laboratory variables. Furthermore, it offers valuable information on which variables could predict a fatal outcome for ICU patients with COVID-19.
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Mini review ATF4 and GRP78 as novel molecular targets in ER-Stress modulation for critical COVID-19 patients.
Shahriari-Felordi, M, Alikhani, HK, Hashemian, SR, Hassan, M, Vosough, M
Molecular biology reports. 2022;(2):1545-1549
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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in more than 4.4 million deaths worldwide as of August 24, 2021. Viral infections such as SARS-CoV2 are associated with endoplasmic reticulum (ER) stress and also increased the level of reactive oxygen species. Activating transcription factor 4 (ATF4) is preferentially translated under integrated stress conditions and controls the genes involved in protein homeostasis, amino acid transport and metabolism, and also protection from oxidative stress. The GRP78, regulated either directly or indirectly by ATF4, is an essential chaperone in the ER and overexpressed and appears on the surface of almost all cells during stress and function as a SARS-CoV2 receptor. In this mini-review article, we briefly discuss the effects of SARS-CoV2 infection on the ER stress, and then the stress modulator functions of ATF4 and GRP78 as novel therapeutic targets were highlighted. Finally, the effects of GRP78 inhibitory components as potential factors for targeted therapies for COVID-19 critical cases were discussed.
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Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial.
Bravo, L, Smolenov, I, Han, HH, Li, P, Hosain, R, Rockhold, F, Clemens, SAC, Roa, C, Borja-Tabora, C, Quinsaat, A, et al
Lancet (London, England). 2022;(10323):461-472
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BACKGROUND A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019. METHODS This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395). FINDINGS 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups. INTERPRETATION Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant. FUNDING Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations.
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Postvaccination SARS-CoV-2 infection among healthcare workers: A systematic review and meta-analysis.
Chandan, S, Khan, SR, Deliwala, S, Mohan, BP, Ramai, D, Chandan, OC, Facciorusso, A
Journal of medical virology. 2022;(4):1428-1441
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Healthcare workers (HCWs) remain on the front line of the battle against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) infection and are among the highest groups at risk of infection during this raging pandemic. We conducted a systematic review and meta-analysis to assess the incidence of postvaccination SARS-CoV-2 infection among vaccinated HCWs. We searched multiple databases from inception through August 2021 to identify studies that reported on the incidence of postvaccination SARS-CoV-2 infection among HCWs. Meta-analysis was performed to determine pooled proportions of COVID-19 infection in partially/fully vaccinated as well as unvaccinated individuals. Eighteen studies with 228 873 HCWs were included in the final analysis. The total number of partially vaccinated, fully vaccinated, and unvaccinated HCWs were 132 922, 155 673, and 17 505, respectively. Overall pooled proportion of COVID-19 infections among partially/fully vaccinated and unvaccinated HCWs was 2.1% (95% confidence interval [CI] 1.2-3.5). Among partially vaccinated, fully vaccinated and unvaccinated HCWs, pooled proportion of COVID-19 infections was 2.3% (CI 1.2-4.4), 1.3% (95% CI 0.6-2.9), and 10.1% (95% CI 4.5-19.5), respectively. Our analysis shows the risk of COVID-19 infection in both partially and fully vaccinated HCWs remains exceedingly low when compared to unvaccinated individuals. There remains an urgent need for all frontline HCWs to be vaccinated against SARS-CoV-2 infection.
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Elucidating important structural features for the binding affinity of spike - SARS-CoV-2 neutralizing antibody complexes.
Sharma, D, Rawat, P, Janakiraman, V, Gromiha, MM
Proteins. 2022;(3):824-834
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The coronavirus disease 2019 (COVID-19) has affected the lives of millions of people around the world. In an effort to develop therapeutic interventions and control the pandemic, scientists have isolated several neutralizing antibodies against SARS-CoV-2 from the vaccinated and convalescent individuals. These antibodies can be explored further to understand SARS-CoV-2 specific antigen-antibody interactions and biophysical parameters related to binding affinity, which can be utilized to engineer more potent antibodies for current and emerging SARS-CoV-2 variants. In the present study, we have analyzed the interface between spike protein of SARS-CoV-2 and neutralizing antibodies in terms of amino acid residue propensity, pair preference, and atomic interaction energy. We observed that Tyr residues containing contacts are highly preferred and energetically favorable at the interface of spike protein-antibody complexes. We have also developed a regression model to relate the experimental binding affinity for antibodies using structural features, which showed a correlation of 0.93. Moreover, several mutations at the spike protein-antibody interface were identified, which may lead to immune escape (epitope residues) and improved affinity (paratope residues) in current/emerging variants. Overall, the work provides insights into spike protein-antibody interactions, structural parameters related to binding affinity and mutational effects on binding affinity change, which can be helpful to develop better therapeutics against COVID-19.
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COVID-19-associated-mucormycosis: possible role of free iron uptake and immunosuppression.
Tabassum, T, Araf, Y, Moin, AT, Rahaman, TI, Hosen, MJ
Molecular biology reports. 2022;(1):747-754
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COVID-19-associated-mucormycosis, commonly referred to as the "Black Fungus," is a rare secondary fungal infection in COVID-19 patients prompted by a group of mucor molds. Association of this rare fungal infection with SARS-CoV-2 infection has been declared as an endemic in India, with minor cases in several other countries around the globe. Although the fungal infection is not contagious like the viral infection, the causative fungal agent is omnipresent. Infection displays an overall mortality rate of around 50%, with many other secondary side effects posing a potential threat in exacerbating COVID-19 mortality rates. In this review, we have accessed the role of free iron availability in COVID-19 patients that might correlate to the pathogenesis of the causative fungal agent. Besides, we have analyzed the negative consequences of using immunosuppressive drugs in encouraging this opportunistic fungal infection.
