Covid Studies
Select the Studies Section
SARS-CoV-2 Virus
SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2 2021 https://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/
In the current study, we show that S protein alone can damage vascular endothelial cells (ECs) by downregulating ACE2 and consequently inhibiting mitochondrial function.
Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein. 2021 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250780
The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control. Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions.
Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities.
Asymptomatic SARS-CoV-2
Covid-19: Asymptomatic cases may not be infectious, Wuhan study indicates. Dec. 2020 https://www.bmj.com/content/371/bmj.m4695.full
A mass screening programme of more than 10 million residents of Wuhan, China, performed after SARS-CoV-2 was brought under control, has identified 300 asymptomatic cases of covid-19, none of which was infectious.
Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis. December 2020. https://jammi.utpjournals.press/doi/full/10.3138/jammi-2020-0030
The relative risk (RR) of asymptomatic transmission was 42% lower than that for symptomatic transmission (combined RR 0.58; 95% CI 0.34 to 0.99, p = 0.047).
Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy — Springfield, Missouri, May 2020 https://www.cdc.gov/mmwr/volumes/69/wr/mm6928e2.htm
The CDC uses this study to affirm that masks prevent the spread of SARS-CoV-2 because 2 symptomatic hair stylists did not transfer virus to 139 clients.
What I find interesting is that hair stylist (A) spread to her 4 close contacts outside of work, while hair stylist (B), did not spread to her 2 close contacts. This confirms what prior research has found, not everyone with symptomatic infection spreads virus and transmits infection mask or no mask.
“Six close contacts of stylists A and B outside of salon A were identified: four of stylist A and two of stylist B. All four of stylist A’s contacts later developed symptoms and had positive PCR test results for SARS-CoV-2. These contacts were stylist A’s cohabitating husband and her daughter, son-in-law, and their roommate, all of whom lived together in another household. None of stylist B’s contacts became symptomatic.”
COVID Vaccine Safety Pregnancy
COVID-19 vaccine response in pregnant and lactating women: a cohort study. March 2021. https://www.ajog.org/article/S0002-9378(21)00187-3/pdf
Not a safety study, main endpoint is antibody production. 131 women in the trial, all health care workers. 84 of whom are pregnant, with 13 who delivered. Funding by NIH, NIAID, Gates Foundation, Musk Foundation.
Of 13 women who delivered, 2 babies ended in NICU, which is slightly more than 2 times the national average for NICU admission. 88% of women had side effects after the first dose. 57% had side effects after 2nd dose. No information about well-being of infants, it’s not a safety study, but is marketed as a safety study by NPR.
COVID Vaccine Safety
New-Onset Neurologic Symptoms and Related Neuro-Oncologic Lesions Discovered After COVID-19 Vaccination: Two Neurosurgical Cases and Review of Post-Vaccine Inflammatory Responses. Einstein, Evans. June 2021.
We report two cases of new-onset neurological symptoms after the COVID-19 vaccination. In both cases, further diagnostic testing revealed neuro-oncologic processes that required neurosurgical intervention. Administration of these vaccines was unrelated to the oncologic diagnoses themselves. However, these two independent processes both came to the clinical forefront following vaccination. We hypothesize that the inflammatory response to the COVID vaccine may have played a role in increasing clinical symptoms in these patients, potentially in relation to the COVID-19 spike protein.
Reports of death after COVID-19 vaccination. April 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html
Over 167 million doses of COVID-19 vaccines were administered in the United States from December 14, 2020, through April 5, 2021. During this time, VAERS received 2,794 reports of death (0.00167%) among people who received a COVID-19 vaccine.
Rapid Response to BMJ: Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots 2021 https://www.bmj.com/content/372/bmj.n699/rr-6
CoViD Vaccines and thrombotic events: Possibility of mRNA translation and spike protein synthesis by platelets?
Immune thrombocytopenia (ITP) is an autoimmune condition characterized by low platelet counts manifested by spontaneous purpura, petechia, haematomas or fatal subarachnoid, intracerebral, or other internal bleeding. ITP secondary to CoViD-19 have been reported in many patients with CoViD-19 [2] and coagulopathy have been a major contributing factor to the high mortality associated with CoViD-19.
Besides SARS-CoV-2, various other pathogens are known to induce ITP, notably Helicobacter pylori, H3N2 influenza virus and the Dengue virus. It has been proposed that the antibodies produced by the body to clear the virus have a potential cross reactivity with surface antigens on platelets or megakaryocytes. This molecular mimicry had been proposed in the past as a classic mechanism responsible for the vaccine associated ITP. Antibody bound platelets and megakaryocytes undergo reticuloendothelial phagocytosis and a direct lysis by cytotoxic T-cells leading to thrombocytopenia [3].
Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine. 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499017/
The rationale is that, following an infection, the immune responses raised against the pathogen can cross-react with human proteins that share peptide sequences (or structures) with the pathogen, in this way, leading to harmful autoimmune pathologies. Accordingly, lungs and airways dysfunctions associated with SARS-CoV-2 infection might be explained by the sharing of peptides between SARS-CoV-2 spike glycoprotein and alveolar lung surfactant proteins.
COVID Vaccine Efficacy
Obesity may hamper SARS-CoV-2 vaccine immunogenicity. Feb 2021. https://www.scribd.com/document/497798033/OBESITY-MAY-HAMPER-SARS-CoV-2-VACCINE-IMMUNOGENICITY
“These findings imply that females, lean and young people have an increased capacity to mount humoral immune responses compared to males, overweight and the older population.”
“Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers – a Danish cohort study” 2021 https://www.medrxiv.org/content/medrxiv/early/2021/03/09/2021.03.08.21252200.full.pdf
Results: No protective effect was observed for LTCF residents after first dose.
According to the table in the study, both health care workers and nursing home patients experienced higher incidence of covid cases compared to unvaccinated, 40% higher and 100% higher in nursing home residents, and health care workers.
BMJ Letter Rapid Response Re: previous study: “Why don’t Covid-19 vaccine trials report statistics for the first 14 days?” Allan S. Cunningham. 2021 https://www.bmj.com/content/372/bmj.n728/rr-0
Recently a pediatric colleague sent me this preprint link to a Danish cohort study of the Pfizer Covid-19 vaccine in long-term care facility residents and healthcare workers. (https://www.medrxiv.org/content/10.1101/2021.03.08.21252200v1 ) It showed real-world effectiveness of two doses of the mRNA vaccine: 64% and 90% VE in the two groups respectively beyond seven days after the second dose.
However, from 0 to 14 days after the first dose the risk of Covid-19 infection was actually increased in vaccine recipients: in the LTCF residents VE was -40%, CI -62% to -2%; among healthcare workers VE was -104%, CI -118% to -91%.(Table 2)…..By contrast, statistics for the 0 to 14 days after the first dose were not reported in the randomized trials of the Pfizer, Moderna, or AstraZeneca vaccines. (Polack et al, NEJM 2020;383:2603. Baden et al, NEJM 2021;384:403. Voysel et al, Lancet 2021;397:92) Why not? Are the manufacturers hiding negative data?
BMJ Letter Rapid Response: “Will covid-19 vaccines save lives? Current trials aren’t designed to tell us” Indrani Roy 2021 https://www.bmj.com/content/371/bmj.m4037/rr-20
“Here I would like to bring attention to an urgent and very important issue of its indirect effect. Apart from the direct side effect after vaccination, if any; the secondary effect that might be caused due to mutation of the virus after mass vaccination needs attention too.
For Brazil, vaccination started in mid-January and a sharp rise in cases is observed since mid-February. Such a steep rise in deaths in Brazil that happened for the last one month never happened in the whole period of pandemic. It already reached twice the height of previous peaks [3]. Globally, the cases started increasing after 5 weeks of a steady decline and coincidentally, the period of rise matches when major vaccination programmes were initiated worldwide.”
Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of ‘real-world’ vaccination outcomes from Israel. Feb. 2021. https://www.medrxiv.org/content/medrxiv/early/2021/02/03/2021.02.01.21250957.full.pdf
“After initial injection case numbers increased to day 8 before declining to low levels by day 21. Estimated vaccine effectiveness was pretty much 0 at day 14 but then rose to about 90% at day 21 before levelling off.”
Natural Immunity
“Naturally-acquired immunity in Syrian Golden Hamsters provides protection from re-exposure to emerging heterosubtypic SARS-CoV-2 variants B.1.1.7 and B.1.351” 2021. https://www.biorxiv.org/content/10.1101/2021.03.10.434447v1
“Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection” 2021 https://pubmed.ncbi.nlm.nih.gov/33408181/
Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: implications for COVID-19 epidemiology. March 2021. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab147/6179975?
Here, we examined the replication kinetics of SARS-CoV-2 in the human respiratory epithelium in the presence or absence of rhinovirus. We show that human rhinovirus triggers an interferon response that blocks SARS-CoV-2 replication.
Retracted Studies
“Decrease in Hospitalizations for COVID-19 after Mask Mandates in 1083 U.S. Counties“ 2020. https://www.medrxiv.org/content/10.1101/2020.10.21.20208728v2
Withdrawal: The authors have withdrawn this manuscript because there are increased rates of SARS- CoV-2 cases in the areas that we originally analyzed in this study. New analyses in the context of the third surge in the United States are therefore needed and will be undertaken directly in conjunction with the creators of the publicly-available databases on cases, hospitalizations, testing rates. Etc.
RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext
Effectiveness of Surgical and Cotton Masks in Blocking SARS–CoV-2: A Controlled Comparison in 4 Patients. July 2020. https://www.acpjournals.org/doi/10.7326/M20-1342
“In conclusion, both surgical and cotton masks seem to be ineffective in preventing the dissemination of SARS–CoV-2 from the coughs of patients with COVID-19 to the environment and external mask surface.”
Retraction notice: We had not fully recognized the concept of limit of detection (LOD) of the in-house reverse transcriptase polymerase chain reaction used in the study (2.63 log copies/mL), and we regret our failure to express the values below LOD as “<LOD (value).” The LOD is a statistical measure of the lowest quantity of the analyte that can be distinguished from the absence of that analyte. Therefore, values below the LOD are unreliable and our findings are uninterpretable.
Excess Deaths
Between March 1, 2020, and January 2, 2021, the US experienced 2 801 439 deaths, 22.9% more than expected, representing 522 368 excess deaths. Deaths attributed to COVID-19 accounted for 72.4% of US excess deaths.
Excess deaths not attributed to COVID-19 could reflect either immediate or delayed mortality from undocumented COVID-19 infection, or non–COVID-19 deaths secondary to the pandemic, such as from delayed care or behavioral health crises. Death rates from several non–COVID-19 diseases (eg, heart disease, Alzheimer disease) increased during surges. The model does not adjust directly for population aging, which could contribute to an overestimate of excess deaths. Other study limitations include reliance on provisional data, inaccurate death certificates, and modeling assumptions.
Non–COVID-19 excess deaths by age and gender in the United States during the first three months of the COVID-19 pandemic. Dec. 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547600/
There have been more excess deaths in several age group and gender cohorts during the first three months of the pandemic, beyond direct deaths directly attributable to COVID-19. These non–COVID-19 excess deaths are most apparent in the 25- to 44-year age group for women and 15- to 54-year age group for men. Further research is needed to assess the cause of such excess deaths and introduce safeguards to reduce such deaths in the future.
Only 38% of all-cause excess deaths in adults aged 25 to 44 years recorded during the pandemic were attributed directly to COVID-19.
Antibody Dependent Enhancement
Sometimes called immune enhancement, Antibody Dependent Enhancement is a paradoxical immune enhancement observed in animals and people vaccinated against certain viruses which results in a heightened or worse course of disease when they come in contact or were challenged with the wild virus.
The Dengue vaccine in the Philippines was withdrawn from use after hundreds of vaccinated children died from this same type of immune enhancement.
Breakthrough COVID Cases
70 fully vaccinated Delawareans have contracted COVID-19, and one death
39 fully vaccinated people infected with COVID-19 in Sonoma County
CORRECTION: COVID death in Miss. was not vaccine-related
A COVID-related death in Mississippi is attributed to a “breakthrough case” where someone in the state contracted COVID-19 after receiving a vaccine.
141 vaccine “breakthrough cases” have been identified in S.C. as of April 5
Georgia woman contracts breakthrough COVID-19 infection after vaccination
246 fully vaccinated Michiganders got COVID-19 between January and March, state reports (and 3 died)
Dozens in Central Florida contract COVID-19 after being fully vaccinated
Of 1.2 million fully vaccinated people in Washington state, 100 have gotten COVID-19
Dunn: Utah’s had 97 ‘breakthrough’ COVID-19 cases, but the vaccine is still working
Washington confirms ‘breakthrough’ COVID-19 cases after vaccination
Of the potential 102 cases of patients who tested positive for COVID-19 after vaccination, two died, the state said. But the majority had mild or no symptoms.
Vaccinated Minnesota nurse stuck in Mexico after testing positive for COVID
COVID Treatments
The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article. 2021 https://www.nature.com/articles/s41429-021-00430-5#Tab1
Random effects meta-analysis with pooled effects showed 79% improvement for early treatment RR 0.21 and CI [0.11-0.37]
Random effects meta-analysis with pooled effects showed 46% improvement for late treatment RR 0.54 and CI [0.40-0.72]
The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial. 2021 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30464-8/fulltext
Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials.
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) 2020 https://rcm.imrpress.com/article/2020/2153-8174/RCM2020264.shtml
Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine.
Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019. 2021 https://journal.chestnet.org/article/S0012-3692(20)34898-4/fulltext
Ivermectin treatment was associated with lower mortality during treatment of COVID-19, especially in patients with severe pulmonary involvement.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. June 2020 https://www.sciencedirect.com/science/article/pii/S0166354220302011
We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey October 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533663/
Vitamin D insufficiency was present in 93.1% of the patients with severe-critical COVID-19.Serum 25(OH) vitamin D was independently associated with mortality in COVID-19 patients.
The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis. Jan. 2021. https://www.medrxiv.org/content/10.1101/2021.01.04.21249219v1
Prescribing vitamin D supplementation to patients with COVID-19 infection seems to decrease the mortality rate, the severity of the disease, and serum levels of the inflammatory markers.
Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. November 2020. https://www.nature.com/articles/s41598-020-77093-z
The prevalence of vitamin D deficiency was 32.96% and 96.82% respectively in Group A (asymptomatic patients) and Group B (critically ill patients). Out of total 154 patients, 90 patients were found to be deficient in vitamin D.
Vitamin D level is markedly low in severe COVID-19 patients. Inflammatory response is high in vitamin D deficient COVID-19 patients. This all translates into increased mortality in vitamin D deficient COVID-19 patients. As per the flexible approach in the current COVID-19 pandemic authors recommend mass administration of vitamin D supplements to population at risk for COVID-19.
Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. Sept. 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239799
Masks
Association of State-Issued Mask Mandates and Allowing On-Premises Restaurant Dining with County-Level COVID-19 Case and Death Growth Rates — United States, March 1–December 31, 2020. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e3.htm
According to the Table, there was a less than 2 percent difference in cases growth rates related to mask mandates.
CAL-OSHA Regulations: “Cloth face covers are not protective equipment and do not protect the person wearing a cloth face cover from COVID-19” https://dir.ca.gov/dosh/coronavirus/COVID-19-Infection-Prevention-in-Logistics.pdf
“A cluster randomised trial of cloth masks compared with medical masks in healthcare workers” 2015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420971/
Conclusions: This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated.
“Cloth masks: Dangerous to your health?” 2015 https://www.sciencedaily.com/releases/2015/04/150422121724.htm
Respiratory infection is much higher among healthcare workers wearing cloth masks compared to medical masks, research shows. Cloth masks should not be used by workers in any healthcare setting, authors of the new study say.
“A cluster randomised trial of cloth masks compared with medical masks in healthcare workers” 2014. https://pubmed.ncbi.nlm.nih.gov/25903751/
“Results: The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%.”
“Face masks to prevent transmission of influenza virus: A systematic review” 2010.
None of the studies reviewed showed a benefit from wearing a mask, in either HCW or community members in households (H). See summary Tables 1 and 2 therein.
“Use of surgical face masks to reduce the incidence of the common cold among health care workers in Japan: A randomized controlled trial” 2009 https://pubmed.ncbi.nlm.nih.gov/19216002/
Conclusions: Face mask use in health care workers has not been demonstrated to provide benefit in terms of cold symptoms or getting colds. A larger study is needed to definitively establish noninferiority of no mask use.
Children & COVID (and Vaccines)
Why are we vaccinating children against COVID-19?. September 2021
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437699/pdf/main.pdf
A novel best-case scenario cost-benefit analysis showed very conservatively that there are five times the number of deaths attributable to each inoculation vs those attributable to COVID-19 in the most vulnerable 65+ demographic. The risk of death from COVID-19 decreases drastically as age decreases, and the longer-term effects of the inoculations on lower age groups will increase their risk-benefit ratio, perhaps substantially.
Among a cohort of 305 patients aged 4 to 60 years, older children (10-17 years old; n = 185), young adults (18-24 years old; n = 46), and adults (≥25 years old; n = 29) all had higher expression of ACE2 in the nasal epithelium compared with younger children (4-9 years old; n = 45), and ACE2 expression was higher with each subsequent age group after adjusting for sex and asthma.
Understanding the age divide in COVID-19: Why are children overwhelmingly spared? June 2020. Understanding_the_age_divide_in_COVID-19_Why_are_c (1)
Among the first 149,082 US cases (through 4/2/2020), only 2,572 (~1.7%) were infants, children, and adolescents <18yo (children <18yo make up 22% of 112 the US population). A systematic review of literature showed that children accounted for 1- 5% of diagnosed cases.
Spread of SARS-CoV-2 in the Icelandic Population June 2020. https://pubmed.ncbi.nlm.nih.gov/32289214/
Children under 10 years of age were less likely to receive a positive result than were persons 10 years of age or older, with percentages of 6.7% and 13.7%, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8% of those 10 years of age or older.
Effect of the new SARS-CoV-2 variant B.1.1.7 on children and young people February 2021. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00030-4/fulltext
“Media reports of increases in admissions to hospital and more serious illness in children and young people have resulted in public confusion and implicated the B.1.1.7 variant as a more pathogenic infection within this group. This uncertainty has necessitated a public statement from the Royal College of Paediatrics and Child Health.”
“Importantly, we have found no evidence of more severe disease having occurred in children and young people during the second wave, suggesting that infection with the B.1.1.7 variant does not result in an appreciably different clinical course to the original strain. These findings are in keeping with early national data. Severe acute respiratory COVID-19 remains an uncommon occurrence in children and young people.”
Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. October 2020 https://adc.bmj.com/content/archdischild/early/2020/11/30/archdischild-2020-320338.full.pdf
Factors proposed to explain the difference in severity of COVID-19 in children and adults include those that put adults at higher risk and those that protect children. The former include: (1) age-related increase in endothelial damage and changes in clotting function; (2) higher density, increased affinity and different distribution of angiotensin converting enzyme 2 receptors and transmembrane serine protease 2; (3) pre-existing coronavirus antibodies (including antibody-dependent enhancement) and T cells; (4) immunosenescence and inflammaging, including the effects of chronic cytomegalovirus infection; (5) a higher prevalence of comorbidities associated with severe COVID-19 and (6) lower levels of vitamin D. Factors that might protect children include: (1) differences in innate and adaptive immunity; (2) more frequent recurrent and concurrent infections; (3) pre-existing immunity to coronaviruses; (4) differences in microbiota; (5) higher levels of melatonin; (6) protective off-target effects of live vaccines and (7) lower intensity of exposure to SARS-CoV-2.
Kawasaki Disease, Multisystem Inflammatory Syndrome in Children: Antibody-Induced Mast Cell Activation Hypothesis, June 2020. https://www.pediatricsresearchjournal.com/articles/kawasaki-disease-multisystem-inflammatory-syndrome-in-children-antibody-induced-mast-cell-activation-hypothesis.html
The observed symptoms for MIS-C and KD are consistent with Mast Cell Activation Syndrome (MCAS) characterized by inflammatory molecules released from activated mast cells. Based on the associations of KD with multiple viral and bacterial pathogens, we put forward the hypothesis that KD and MIS-C result from antibody activation of mast cells by Fc receptor-bound pathogen antibodies causing a hyperinflammatory response upon second pathogen exposure.
Vitamin D contributes to mast cell stabilization. 2017 https://pubmed.ncbi.nlm.nih.gov/27998003/
The data demonstrate that VitD is required to maintain the stability of mast cells. The deficiency of VitD results in mast cell activation.
COVID-19 Mortality
Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey October 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533663/
Vitamin D insufficiency was present in 93.1% of the patients with severe-critical COVID-19.Serum 25(OH) vitamin D was independently associated with mortality in COVID-19 patients.
The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis. Jan. 2021. https://www.medrxiv.org/content/10.1101/2021.01.04.21249219v1
Prescribing vitamin D supplementation to patients with COVID-19 infection seems to decrease the mortality rate, the severity of the disease, and serum levels of the inflammatory markers.
Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. November 2020. https://www.nature.com/articles/s41598-020-77093-z
The prevalence of vitamin D deficiency was 32.96% and 96.82% respectively in Group A (asymptomatic patients) and Group B (critically ill patients). Out of total 154 patients, 90 patients were found to be deficient in vitamin D.
Vitamin D level is markedly low in severe COVID-19 patients. Inflammatory response is high in vitamin D deficient COVID-19 patients. This all translates into increased mortality in vitamin D deficient COVID-19 patients. As per the flexible approach in the current COVID-19 pandemic authors recommend mass administration of vitamin D supplements to population at risk for COVID-19.
Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. Sept. 2020. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239799