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COVID-19
Metformin mitigates insulin signaling variations induced by COVID-19 vaccine boosters in type 2 diabetes
SYNOPSIS
Studies suggest the BioNTech mRNA COVID-19 vaccine impairs glucose control and aggravates insulin resistance in human subjects with type 2 diabetes.
L. Zhai, M. Zhuang, H. Ki Wong, C. Lin, J. Zhang, G. Bao, Y. Zhang, S. Xu, J. Luo, S. Yuan, H. Leong, X. Wong, Z. Bian
The long-term effects of COVID-19 vaccines have not been well characterized. Zhai et al. conducted a longitudinal clinical trial to determine the effects of the COVID-19 vaccine in healthy controls, pre-diabetic subjects, and diabetic subjects. The corresponding author of this study Zhaoxiang Bian, is a Professor at the Hong Kong Baptist University and a leading expert in the execution of clinical trials with Chinese medicines.
A total of 180 participants receiving BioNTech mRNA COVID-19 (BNT) vaccination (60 in each of the following groups: pre-diabetes mellitus, diabetes mellitus, and healthy controls) were recruited and observed over two weeks for their changes in insulin sensitivity before and after two doses of BNT. Biomarkers were taken for immune response, glucose intolerance, and insulin resistance. Diabetic patients exhibited similar immune responses (i.e., production of IgG antibodies) as healthy controls after receiving the BNT booster. In contrast to immune responses, authors report exacerbated risks of glucose intolerance and insulin resistance after the booster shot in pre-diabetic and diabetic patients. 61.1% and 66.7% of diabetic subjects had impairment of insulin sensitivity and increased risks of cardiovascular complications, respectively. These results suggest the vaccine impairs glucose control and aggravates insulin resistance in human subjects with type 2 diabetes. Following on, animal studies were conducted to determine the mechanisms of the inhibitory action of BNT vaccination on glucose control. Compared to mice treated with saline, mice treated with the BNT vaccine (intramuscular injection at an equivalent human dosage of 4.5 μg/kg) exhibited immune responses similar as shown by the elevation of SARS-CoV-2 spike protein in serum. After the fourth dose of BNT vaccine mice exhibited impaired glucose tolerance. Based on investigated biomarkers of diabetes the authors speculate that glucose intolerance was mediated by impairment of insulin sensitivity rather than impaired insulin secretion. Researchers further showed that metformin, a common anti-diabetic medication, improved the impaired insulin signaling induced by COVID-19 vaccination in mice.
Approximately 12% (38.4 million) and 38% (97.6 million) of the US population have diabetes and prediabetes, respectively (https://www.cdc.gov/diabetes/data/statistics-report/index.html). Clinical and animal studies by Zhai et al. provide clear evidence of safety issues of the COVID-19 vaccines in diabetics or populations with metabolic conditions.
Adjuvant-dependent effects on the safety and efficacy of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus
SYNOPSIS
Global use of inactivated SARS-CoV-2 vaccines with Alum adjuvants have been used in COVID-19 pandemic response, but risk of breakthrough with novel variants and zoonotic reservoirs may lead to adverse outcomes, including VAERD.
M. Heise, J. Dillard, S. Taft-Benz, A. Knight, E. Anderson, K. Pressey, B. Parotti, S. Martinez, J. Diaz, S. Sarkar, E. Madden, G. De la Cruz, L. Adams, K. Dinnon, III, S. Leist, D. Martinez, A. Schaefer, J. Powers, B. Yount, I. Castillo, N. Morales, J. Burdick, M. Katrina Evangelista, L. Ralph, N. Pankow, C. Linnertz, P. Lakshmanane, S. Montgomery, M. Ferris, R. Baric, V. Baxter
Inactivated whole virus SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide (Alum) are among the most widely used COVID-19 vaccines globally and have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous virus infection in healthy recipients, the emergence of novel SARS-CoV-2 variants and the presence of large zoonotic reservoirs provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes including vaccine-associated enhanced respiratory disease (VAERD). To evaluate this possibility, we tested the performance of an inactivated SARS-CoV-2 vaccine (iCoV2) in combination with Alum against either homologous or heterologous coronavirus challenge in a mouse model of coronavirus-induced pulmonary disease. Consistent with human results, iCoV2 + Alum protected against homologous challenge. However, challenge with a heterologous SARS-related coronavirus, Rs-SHC014-CoV (SHC014), up to at least 10 months post-vaccination, resulted in VAERD in iCoV2 + Alum-vaccinated animals, characterized by pulmonary eosinophilic infiltrates, enhanced pulmonary pathology, delayed viral clearance, and decreased pulmonary function. In contrast, vaccination with iCoV2 in combination with an alternative adjuvant (RIBI) did not induce VAERD and promoted enhanced SHC014 clearance. Further characterization of iCoV2 + Alum-induced immunity suggested that CD4+ T cells were a major driver of VAERD, and these responses were partially reversed by re-boosting with recombinant Spike protein + RIBI adjuvant. These results highlight potential risks associated with vaccine breakthrough in recipients of Alum-adjuvanted inactivated vaccines and provide important insights into factors affecting both the safety and efficacy of coronavirus vaccines in the face of heterologous virus infections.
Child mask mandates for COVID-19: a systematic review
SYNOPSIS
Mask mandates for children during the COVID-19 pandemic varied in different locations. A risk-benefit analysis of this intervention has not yet been performed. In this study, we performed a systematic review to assess research on the effectiveness of mask wearing in children.
J. Sandlund, R. Duriseti, S. Ladhani, K. Stuart, J. Noble, T. B. Høeg
Background Mask mandates for children during the COVID-19 pandemic varied in different locations. A risk-benefit analysis of this intervention has not yet been performed. In this study, we performed a systematic review to assess research on the effectiveness of mask wearing in children.
Methods We performed database searches up to February 2023. The studies were screened by title and abstract, and included studies were further screened as full-text references. A risk-of-bias analysis was performed by two independent reviewers and adjudicated by a third reviewer.
Results We screened 597 studies and included 22 in the final analysis. There were no randomised controlled trials in children assessing the benefits of mask wearing to reduce SARS-CoV-2 infection or transmission. The six observational studies reporting an association between child masking and lower infection rate or antibody seropositivity had critical (n=5) or serious (n=1) risk of bias; all six were potentially confounded by important differences between masked and unmasked groups and two were shown to have non-significant results when reanalysed. Sixteen other observational studies found no association between mask wearing and infection or transmission.
Conclusions Real-world effectiveness of child mask mandates against SARS-CoV-2 transmission or infection has not been demonstrated with high-quality evidence. The current body of scientific data does not support masking children for protection against COVID-19.
Type 1 diabetes mellitus following COVID-19 RNA-based vaccine
SYNOPSIS
Ten days after receiving a COVID-19 vaccination, a 36-year-old female patient visited the hospital with diabetic ketoacidosis and was diagnosed with type 1 diabetes.
K. Sakurai, D. Narita, N. Saito, T. Ueno, R. Sato, S. Niitsuma, K. Takahashi, Z. Arihara
The epidemic of coronavirus disease-2019 (COVID-19) is the major public health issue in the world. COVID-19 vaccines are one of the most effective strategies against COVID-19. Here we report a 36-year-old female patient who had thirst, polydipsia, polyuria, palpitations, loss of appetite, and fatigue 3 days after the first dose of COVID-19 RNA-based vaccines without a prior history of diabetes. Ten days after vaccination, she visited our hospital with diabetic ketoacidosis and was diagnosed with type 1 diabetes. Hyperglycemia (501 mg/dL), anion gap metabolic acidosis and ketonuria were observed. The glycated hemoglobin level was 7.0%. Islet-related autoantibodies were all negative. The glucagon tolerance test revealed attenuated secretion of insulin. Human leukocyte antigen was haplotype DRB1*0405-DQB1*0401, which was associated with type 1 diabetes in Japan. The present case suggests that COVID-19 RNA-based vaccines might trigger the onset of type 1 diabetes, even in subjects without prior histories of diabetes.
Increased risk for Covid-19 in patients with Vitamin D deficiency.
SYNOPSIS
Vit D deficiency increased likelihood of being COVID-19 positive by 4.6 times.
CITATION
Katz, J., Yue, S., & Xue, W. (2020). Increased risk for COVID-19 in patients with vitamin D deficiency. Nutrition (Burbank, Los Angeles County, Calif.), 84, 111106. Advance online publication. https://doi.org/10.1016/j.nut.2020.111106
SUMMARY
This is a retrospective database analysis showing patients with vitamin D deficiency were 4.6 times more likely to be positive for COVID-19 (indicated by the ICD-10 diagnostic code COVID19) than patients with no deficiency. The association decreased slightly after adjusting for sex and malabsorption. The association decreased significantly but remained robust after adjusting for race, periodontal disease.
Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study.
SYNOPSIS
Hospitalized COVID-19 patients with diabetes had a 85.7% lower death rate when given Vit D.
CITATION
Alguwaihes AM, Al-Sofiani ME, Megdad M, Albader SS, Alsari MH, Alelayan A, Alzahrani SH, Sabico S, Al-Daghri NM, Jammah AA. Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study. Cardiovasc Diabetol. 2020 Dec 5;19(1):205. doi: 10.1186/s12933-020-01184-4. PMID: 33278893; PMCID: PMC7718833. Summary
SUMMARY
A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency. While diabetes mellitus (DM) patients have a higher mortality rate than their non-DM counterparts, hospitalized patients showed 85.7% lower mortality with vitamin D.
Nutrients, Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort.
SYNOPSIS
Observational study showing improved immune system activity if supplementation was given to Vit D insufficient and deficient patients.
CITATION
Vassiliou AG, Jahaj E, Pratikaki M, Orfanos SE, Dimopoulou I, Kotanidou A. Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort. Nutrients. 2020 Dec 9;12(12):3773. doi: 10.3390/nu12123773. PMID: 33316914; PMCID: PMC7764169.
SUMMARY
We aimed to examine whether low intensive care unit (ICU) admission vitamin D levels are associated with worse outcomes of COVID-19 pneumonia. This was a prospective observational study of SARS-CoV2 positive critically ill patients treated in a multidisciplinary ICU. Thirty (30) Greek patients were included, in whom vitamin D level was measured on ICU admission. Eighty (80%) percent of patients had vitamin D deficiency, and the remaining insufficiency. All patients who died within 28 days belonged to the low vitamin D group. Survival analysis showed that the low vitamin D group had a higher 28-day survival absence probability. Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission vitamin D levels compared to survivors. It seems plausible, therefore, that low vitamin D levels may predispose COVID-19 patients to an increased 28-day mortality risk.
Nutrients, High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study.
SYNOPSIS
An 80% decrease in death among hospitalized (late treatment) patients in the UK given Vitamin D.
CITATION
Ling SF, Broad E, Murphy R, Pappachan JM, Pardesi-Newton S, Kong MF, Jude EB. High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study. Nutrients. 2020 Dec 11;12(12):3799. doi: 10.3390/nu12123799. PMID: 33322317; PMCID: PMC7763301.
SUMMARY
This is a late treatment retrospective study showing 80% lower mortality with cholecalciferol booster therapy of 986 hospitalized patients in the UK finding that cholecalciferol booster therapy, regardless of baseline serum levels, was associated with a reduced risk of mortality in acute COVID-19 inpatients. An 80% decrease in mortality in the primary cohort (444 patients).
The Association Between the Level of Serum 25(OH) Vitamin D, Obesity, and underlying Diseases with the risk of Developing COVID‐19 Infection: A case‐control study of hospitalized patients in Tehran, Iran.
SYNOPSIS
Low levels of Vitamin D and obesity positively correlated with symptomatic COIVD
CITATION
Abdollahi, A, Sarvestani, HK, Rafat, Z, et al. The association between the level of serum 25(OH) vitamin D, obesity, and underlying diseases with the risk of developing COVID‐19 infection: A case–control study of hospitalized patients in Tehran, Iran. J Med Virol. 2021; 93: 2359– 2364. https://doi.org/10.1002/jmv.26726
SUMMARY
The aim of this study was to explore an association between the serum vitamin D level, obesity, and underlying health conditions, as well as the vulnerability to COVID‐19 in the Iranian population. A significant negative correlation was observed between the serum vitamin D level and developing coronavirus infection.
Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests.
SYNOPSIS
Italian nursing home patients given Vitamin D before being exposed to COIVD 19 had a 70% decrease in death.
CITATION
Cangiano B, Fatti LM, Danesi L, Gazzano G, Croci M, Vitale G, Gilardini L, Bonadonna S, Chiodini I, Caparello CF, Conti A, Persani L, Stramba-Badiale M, et al. Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests. Aging (Albany NY). 2020; 12:24522-24534. https://doi.org/10.18632/aging.202307
SUMMARY
The COVID-19 pandemic caused an increased mortality in nursing homes due to its quick spread and the age-related high lethality. We observed a two-month mortality of 40%, compared to 6.4% in the previous year. Increased mortality was associated with male gender, older age, no previous vitamin D supplementation and worse “activities of daily living (ADL)” scores. Our data confirms a higher geriatric mortality due to COVID-19, and mortality was inversely associated with vitamin D supplementation.
Vitamin D Status is Associated With In-hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients
SYNOPSIS
Patients with higher Vitamin D levels had significantly lower death rate.
CITATION
Angeliki M. Angelidi, Matthew J. Belanger, Michael K. Lorinsky, Dimitrios Karamanis, Natalia Chamorro-Pareja, Jennifer Ognibene, Leonidas Palaiodimos, Christos S. Mantzoros, Vitamin D Status is Associated With In-hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients, Mayo Clinic Proceedings, 2021, ISSN 0025-6196, Https://doi.org/10.1016/j.mayocp.2021.01.001.
SUMMARY
Retrospective of 144 patients in the USA admitted with laboratory-confirmed COVID-19, those with Vitamin D levels in the accepted normal range had significantly lower mortality.
Commentary: Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease
SYNOPSIS
The risk antibody‐dependent enhancement (ADE) during COVID-19 vaccine trials was sufficiently obscured in clinical trial protocols and consent forms that adequate patient comprehension of this risk is unlikely to occur, obviating truly informed consent by subjects in these trials.
CITATION
Timothy Cardozo; Ronald Veazy; Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease. International Journal of Clinical Practice. October 28, 2020; https://doi.org/10.1111/ijcp.13795
SUMMARY
COVID‐19 vaccines designed to elicit neutralizing antibodies may sensitize vaccine recipients to more severe disease than if they were not vaccinated. Vaccines for SARS, MERS and RSV have never been approved, and the data generated in the development and testing of these vaccines suggest a serious mechanistic concern: that vaccines designed empirically using the traditional approach (consisting of the unmodified or minimally modified coronavirus viral spike to elicit neutralizing antibodies), be they composed of protein, viral vector, DNA or RNA and irrespective of delivery method, may worsen COVID‐19 disease via antibody‐dependent enhancement (ADE). This risk is sufficiently obscured in clinical trial protocols and consent forms for ongoing COVID‐19 vaccine trials that adequate patient comprehension of this risk is unlikely to occur, obviating truly informed consent by subjects in these trials.
Prospects for a safe COVID-19 vaccine
SYNOPSIS
Although animal models of SARS-CoV-2 infection may elucidate mechanisms of immune protection, we need observations of enhanced disease in people receiving candidate COVID-19 vaccines to understand the risk of immune enhancement of disease. Neither principles of immunity nor preclinical studies provide a basis for prioritizing among the COVID-19 vaccine candidates with respect to safety at this time.
CITATION
Barton F. Haynes, Lawrence Corey, Prabhavathi Fernandes, Peter B. Gilbert, Peter J. Hotez, Srinivas Rao, Michael R. Santos, Hanneke Schuitemaker, Michael Watson and Ann Arvin; Science Translational Medicine 04 Nov 2020: Vol. 12, Issue 568, eabe0948 DOI: 10.1126/scitranslmed.abe0948
SUMMARY
Rapid development of an efficacious vaccine against the viral pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of the coronavirus disease 2019 (COVID-19) pandemic, is essential, but rigorous studies are required to determine the safety of candidate vaccines. Here, on behalf of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Working Group, we evaluate research on the potential risk of immune enhancement of disease by vaccines and viral infections, including coronavirus infections, together with emerging data about COVID-19 disease. Vaccine-associated enhanced disease has been rarely encountered with existing vaccines or viral infections. Although animal models of SARS-CoV-2 infection may elucidate mechanisms of immune protection, we need observations of enhanced disease in people receiving candidate COVID-19 vaccines to understand the risk of immune enhancement of disease. Neither principles of immunity nor preclinical studies provide a basis for prioritizing among the COVID-19 vaccine candidates with respect to safety at this time. Rigorous clinical trial design and post-licensure surveillance should provide a reliable strategy to identify adverse events, including the potential for enhanced severity of COVID-19 disease, after vaccination.
Impact of catch-up vaccination on aluminum exposure due to new laws and post social distancing
SYNOPSIS
Delay or catch-up vaccination due to COVID19 social distancing should be done judiciously if at all, to minimize aluminum toxicity.
CITATION
Lyons-Weiler, J. G McFarland and E La Joie. 2020. Impact of catch-up vaccination on aluminum exposure due to new laws and post social distancing; Journal of Trace Elements in Medicine and Biology Volume 62, December 2020, 126649 http://sciencedirect.
SUMMARY
This study utilized the established clearance and accumulation models to calculate expected per-body-weight whole-body toxicity of aluminum from vaccines considering for children of all ages under CDC’s Catch-Up schedule from birth to ten years, assuming social distancing for 6 months. Our updated Pediatric Dose Limit (PDL) model assumes a linear improvement in renal function from birth to two years. The results indicate that due diligence in considering alternative spacing and use of non-aluminum containing vaccines when possible will reduce whole body toxicity and may reduce risk of morbidity associated with exposure to aluminum. The study concludes that careful consideration of expected aluminum exposures during regular and Catch-Up vaccination is found to be especially important for infants and children below 2 years of age. We urge caution in the mass re-starting of vaccination under CDC’s Catch-Up schedule for children under 12 months and offer alternative strategies to minimize per-day/week/month exposure to aluminum hydroxide following the COVID-19 period of isolation.