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finally. kind of. hope this delivers some news we can use.

Evaluation of Serum Zinc Levels Response to Treatment of Covid 19 Positive Patients (April 9)
https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=1
NCT04339556 Active, not recruiting. Conditions: Covid19; Zinc Deficiency.
"Primary Outcome Measures :
The effect of serum zinc levels of patients on the course of the disease and response to treatment is examined. [ Time Frame: 45 days ]
serum zinc levels (mcg/dL) will be measured in peripheral blood."

apr 15 update: grabbed this additional study info from the web cache:

"Study Design
Study Type : Observational [Patient Registry]
Estimated Enrollment : 25 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 45 Days
Official Title: Zinc Levels in Covid-19 Positive Patients
Actual Study Start Date : March 20, 2020
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 3, 2020

Intervention Details:
Other: Zinc levels
Since covid 19 and zinc act on the same receptor in the body, the effect of serum levels of patients on the course of the disease and response to treatment is examined.

Study Population
Serum zinc levels of women between 18 and 45 years old who are covid positive and hospitalized in our hospital will be examined.
Criteria
Inclusion Criteria:
covid positive women
not use zinc pills
Exclusion Criteria:
covid negative women
have zinc metabolism disease

Locations
Turkey
Pinar Yalcin Bahat
Istanbul, İ̇stanbul, Turkey, 34000

More Information
Responsible Party: Pınar Yalcin bahat, Principal Investigator, Kanuni Sultan Suleyman Training and Research Hospital
ClinicalTrials.gov Identifier: NCT04339556 History of Changes *
Other Study ID Numbers: zinccovid19
First Posted: April 9, 2020 Key Record Dates
Last Update Posted: April 9, 2020

* https://clinicaltrials.gov/ct2/history/NCT04339556
No history records found for NCT ID: NCT04339556"

i am not sure why the study subjects would have been constrained to younger, hospitalized and female cases.

aaaand, gone. easy come easy go. NCT04339556 no longer appears in the trial registry.

i hope researchers bother to design and implement the trials that would credibly tease out the answer to this question:

COVID-19 Pandemic: Can Maintaining Optimal Zinc Balance Enhance Host Resistance? (April 1)
https://www.preprints.org/manuscript/202004.0006/v1

thank you cleveland clinic:

COVID-19 Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ) (April 13)
https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=2

now if we could throw baseline and post-treatment serum level assessments into the mix (NCT04339556???), that would be even better.
and an arm that received 100 mg daily zinc (divided doses to avoid nausea and improve overall absorption/retention).
i also have questions about potential impacts of high dose iron-favouring vit c on zinc absorption/retention. maybe the timing will be sufficient mitigation? without digging in to refresh, i am not sure.
we'll see what we get!

first impression, this one seems designed not to achieve results of any particular significance...:

• Influence of Zinc and Vitamin D3 Supplementation on Survival in Elderly Institutionalized Individuals With CoV-2 SARS Infection (ZnD3-Cov-Vici) (April 17)
  https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=3
  ClinicalTrials.gov Identifier: NCT04351490
  
  Brief Summary:
  Mortality from Covid-19 increases with age, reaching 14.8% from the age of 80. The severity of the infection is linked to the acute respiratory distress syndrome (ARDS) which requires intensive care. ARDS is the consequence of the reactional inflammatory storm that damages the lungs.
  
  Aged subjects are particularly prone to zinc and vitamin D deficiency. These two micronutrients are able to modulate the immune response by reducing the inflammatory storm.
  
  The hypothesis is that supplementation with zinc and vitamin D would reduce the inflammatory reaction which worsens ARDS and leads to the death of subjects infected with Covid-19.
  
  Study Design
  Study Type : Interventional (Clinical Trial)
  Estimated Enrollment : 3140 participants
  Allocation: Randomized
  Intervention Model: Parallel Assignment
  Masking: None (Open Label)
  Primary Purpose: Treatment
  Official Title: Influence of Zinc and Vitamin D3 Supplementation on Survival in Elderly Institutionalized Individuals With CoV-2 SARS Infection
  Estimated Study Start Date : April 2020
  Estimated Primary Completion Date : July 2020
  Estimated Study Completion Date : July 2020
  
  Arm.............................................Intervention/treatment
  Experimental: Group supplementation...Dietary Supplement: Zinc gluconate
  ..................................................Zinc gluconate capsule 15 mg x 2 per day during 2 months
  
  ..................................................Dietary Supplement: 25-OH cholecalciferol
  ..................................................25-OH cholecalciferol drinkable solution 10 drops (2000 IU) per day during 2 months
  No Intervention: Group usual treatment
  
  Outcome Measures
  
  Primary Outcome Measures :
  Survival rate in asymptomatic subjects at inclusion [ Time Frame: Two months after inclusion ]
  
  Secondary Outcome Measures :
  Survival rate in symptomatic subjects at inclusion [ Time Frame: Two months after inclusion ]
  Survival rate in overall subjects [ Time Frame: Two months after inclusion ]
  symptomatic subjects and asymptomatic subjects
  
  Cumulative incidence of Covid-19 infection in asymptomatic subjects at inclusion [ Time Frame: Within two months after inclusion ]
  
  Eligibility Criteria
  Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
  Sexes Eligible for Study: All
  Gender Based Eligibility: Yes
  Accepts Healthy Volunteers: No
  Criteria
  Inclusion Criteria: Institutionalized
  Exclusion Criteria:
  Life expectancy < 1 month independently of Covid-19 infection (overall subjects)
  Known hypercalcemia
  History of renal lithiasis

questions:

• no pre or post serum or plasma level assessment for zinc or 25-OH D3?

• is there no interest in assessing whether any observed efficacy may correlate to level improvements achieved, if any?

• no cofactor assessment?

• re exclusions - really, still stuck on calcium alone?

i feel like some of the methodological questions raised above have already been described in at least one prior publication. i'll see if i can find the article i'm thinking of. without having it at my fingertips, the memory feels old. i know scoping is needed but sometimes wish that researchers wouldn't bother asking a research question without having the resources available to address said question at least somewhat thoroughly.

some things i like about this study (with caveats):

• zinc pills vs zinc lozenges. should help guard against taste-related issues potentially associated with suboptimal intervention adherence.

• 15 mg elemental zinc at a time. should maximize single dose absorption and guard against side effects from nausea.
  (that said i have not refreshed on the relative utility of zinc gluconate in comparison to other forms. also, i am still not sure 30 mg per day will be enough, especially in the context of any kind of long term background tissue deficit. without serum or plasma assessments, we won't know either).

• 2000 IU vit d3 per day over 2 months. i like this cautious input.
  (but still would like it better if we knew more about levels and mineral status going in as well as having the ability to assess dose response and potential correlation with background mineral status)

design would be even better if it incorporated:
separate intervention arms for zinc alone, D3 alone, and zinc/D3 combo

jimmylegs wrote: ↑Fri Apr 17, 2020 8:15 am first impression, this one seems designed not to achieve results of any particular significance...:

• Influence of Zinc and Vitamin D3 Supplementation on Survival in Elderly Institutionalized Individuals With CoV-2 SARS Infection (ZnD3-Cov-Vici) (April 17)
  https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=3
  ClinicalTrials.gov Identifier: NCT04351490
  
  Brief Summary:
  Mortality from Covid-19 increases with age, reaching 14.8% from the age of 80.

In my state, the 80+ age group represents 10% of covid19 cases yet 55% of fatalities. With 11,766 cases and 613 deaths reported due to covid19 at the time of this posting, this is a 28.7% mortality rate for the 80+ age group.

ouch! source FYI - 14.8% likely incorporates some regional variation

https://scholar.google.ca/scholar?as_yl ... as_sdt=1,5

The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020
"72,314 individuals diagnosed with COVID19 as of February 11, 2020, were included in the analysis. ... The ≥80 age group had the highest case fatality rate of all age groups at 14.8%."

Vitamin D Insufficiency is Prevalent in Severe COVID-19 (Apr 28)
https://www.medrxiv.org/content/10.1101 ... 1.full.pdf

"VDI was defined as serum 25OHD < 30 ng/mL... Among ICU subjects, 11 (84.6%) had VDI, vs. 4 (57.1%) of floor subjects. Strikingly, 100% of ICU patients less than 75 years old had VDI (n=11; Table 2). Among these, 64.6% (n=7) had critically low 25OHD (<20ng/mL) and three had <10 ng/mL. ... "

ouch. i prefer to be sufficiently well-nourished to readily maintain serum levels of at least 50 ng/ml...

"...VDI and COVID-19 share prevalence patterns for hypertension, diabetes, obesity, advanced age, and male sex (Table 3). VDI can contribute to our understanding of COVID-19 health disparities: VDI is highly prevalent in dark-skinned persons (82.1% of African Americans vs. 41.6% overall). ... In Europe, COVID-19 has been severe in Italy, Spain and Greece, but much less so
in Scandinavian countries – this precisely recapitulates VDI data showing that Italy, Spain and Greece have VDI rates of 70-90%, vs. 15-30% in Norway and Denmark. Scandinavian diets contain more vitamin D due to higher fatty fish intake and dairy products supplementation with vitamin D."

Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review) (April 14)
https://www.spandidos-publications.com/ ... .2020.4575

"In view of the emerging COVID‑19 pandemic caused by SARS‑CoV‑2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID‑19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin‑converting enzyme 2 (ACE2), known to be the receptor for SARS‑CoV‑2. Improved antiviral immunity by zinc may also occur through up‑regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti‑inflammatory activity by inhibiting NF‑κB signaling and modulation of regulatory T‑cell functions that may limit the cytokine storm in COVID‑19. Improved Zn status may also reduce the risk of bacterial co‑infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID‑19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID‑19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator‑induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required."

yes please, science
up to 11 studies at https://clinicaltrials.gov/ct2/results? ... ity=&dist=

re https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=1
would be nice if a zinc arm by itself was planned. with pre and post plasma zinc evaluation for all arms.

interesting potential links between COVID vulnerability, nutrition and MS:

• New challenges from Covid-19 pandemic: an unexpected opportunity to enlighten the link between viral infections and brain disorders (Apr 25)
  https://link.springer.com/content/pdf/1 ... 4444-z.pdf
  
  "...Many Covid-19 patients present with loss of taste and olfaction [1], even after the acute phase of infection [2]. Hyposmia is a common symptom of different neurodegenerative and neuropsychiatric disorders [6] and has been associated with levels of interleukin-6 (IL-6), an inflammatory biomarker deeply investigated in brain disorders [7]. Of note, IL-6 action is blocked by tocilizumab, a drug currently used to inhibit cytokine storm in Covid-19 patients [8]. A recent study revealed creactive protein levels above the low-grade inflammation threshold (> 3 mg/l) for three out of four patients presenting with loss of taste and olfaction, which were reported to be more intense and long-lasting than those in common cold disease [2].
  Therefore, accumulating evidence suggests systemic inflammation may be a potential pathway to explain neurological sequelae of Covid-19, a hypothesis which should be investigated more in depth..."

not ms, but one result each (all three RCTs, i note) from three quick scans for research investigating effects of zinc therapy on IL-6, CRP and olfactory impairment:

• Efficacy of zinc supplementation on serum calprotectin, inflammatory cytokines and outcome in neonatal sepsis – a randomized controlled trial (2016)
  https://www.tandfonline.com/doi/abs/10. ... 16.1220524
  
  "...Serum zinc levels were considerably increased in the zinc group after supplementation. There was significant decline in concentrations of serum calprotectin, TNF-α and IL-6 (p < 0.05) in the zinc group. In the control group also, serum calprotectin and IL-6 levels were found to be decreased significantly after antibiotic treatment (p < 0.05), while TNF-α showed insignificant reduction. Kaplan–Meier analysis was performed to assess the survival time between the groups. The mortality was lower in the zinc group compared to the control group 5 versus 11, p= 0.12..."

• The effect of zinc supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials (2018)
  https://www.sciencedirect.com/science/a ... 9918303777
  
  "... The results of the meta-analysis displayed a significant reduction in circulating CRP levels (WMD: − 1.68 mg/l; 95% CI: − 2.4 to − 0.9, P = <0.001) following zinc supplementation..."

• Double-blind, Placebo-controlled Trial of Zinc Picolinate for Taste Disorders (2009)
  https://www.tandfonline.com/doi/abs/10. ... 0260046517
  
  "... No significant difference was noted between the treatment and placebo groups in terms of improvement in subjective symptoms or whole-mouth taste sensation. However, assessment of taste using the filter paper disk method showed significantly better improvement for the group given zinc, and the serum zinc level was also significantly higher in this group than in the placebo control group."

for that last one above, modest zinc improvement in the treatment group (~71 to ~81 ug/dl) with insignificant subjective improvement suggests that higher daily dosage perhaps over a longer period may have been required to achieve more pronounced status and associated effects. perhaps with another cofactor in the mix as well? TBD.

considering the zinc requirement in vitamin a utilization, i had a look at research linking vitamin a and olfactory function.

• Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: A double‐blind, placebo‐controlled, randomized clinical trial† (2012)
  https://onlinelibrary.wiley.com/doi/abs ... lary.23405

from that study, doesn't look like there's a strong link. however, the authors failed to test subjects' serum levels, so we can't know whether the trial failed in spite of optimal serum vit a levels. the authors speculate that the lack of effect may have been a result of their chosen daily dose (10,000IU ie a healthy maintenance dose) vs doses used by other researchers (50,000IU - 150,000IU ie therapeutic megadose). there is no mention of zinc in this article; given the known zinc requirement for proper vit a utilization, perhaps the researchers should have been looking not only at the participants' vit a status, but at their zinc status as well.

circling back to the ms context:

• Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis (1991)
  https://www.sciencedirect.com/science/a ... 289190073G
  
  "...Our results indicate that increased CSF levels of the cytokines IL-6 and TNFα occur frequently in MS... "

• High sensitivity measurement of CRP and disease progression in multiple sclerosis (2005)
  https://n.neurology.org/content/65/1/153.short
  
  "... CRP values were similar in patients with MS and in healthy controls but higher during MS relapses than in remission (p = 0.010). CRP levels were lower during treatment with high-dose interferon beta 1a than placebo (p = 0.035) and higher during first 12 months of study in patients who progressed by year 4 compared with stable patients (p = 0.007)."

i wonder if i look back over my own files, whether i have enough data on IL-6 and/or CRP levels to show any correlation with my long history of zinc testing?? could be interesting.

yes please, science:

• Investigate Oral Zinc as a Prophylactic Treatment for Those at Risk for COVID-19 (May 26)
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247979/
  
  "...Because of the strong link between ACE2 and SARS-CoV-2 infection, inhibitors of ACE2 have been discussed as potential therapeutic agents against COVID-19.2 , 3 We believe there already might be a safe, potential inhibitor of ACE2 function that could constrain the ability of SARS-CoV-2 to infect cells—and that is the trace mineral zinc. Given that zinc supplements are widely used, proven safe in moderate doses, and available without prescription, we propose that there is an urgent need to determine if zinc can be an effective prophylactic treatment against COVID-19.
  ...
  Normal serum levels of zinc are around 12 μM, and the AREDS formula, which provides 80 mg of zinc daily, was able to increase serum zinc by 17% within 1 year.15 It should be studied to determine if this increase in zinc can prevent or limit disease duration for those particularly vulnerable to COVID-19.
  ...
  Whether or not any benefit from oral zinc can be demonstrated, we warn users strongly against taking more zinc than provided by the AREDS 2 formula and developing a false sense of security by using oral zinc. Social distancing and meticulous hand hygiene remain of the utmost importance in limiting the spread of COVID-19 and should continue to be the primary strategy against the SARS-CoV-2 pandemic.
  
  In summary, investigating oral zinc supplementation for the prevention of COVID-19 should commence immediately."

note re dosage and cautioning based on false sense of security - ideally researchers will also caution based on zinc's known relationship with copper, and consider subjects' copper status in the context of any oral zinc RCT.

• Zinc toxicity (1990)
  https://academic.oup.com/ajcn/article-a ... 25/4695142

note re realistic expectations - zinc is unlikely to prevent infection, but has potential to boost immune system capacity to deal more effectively with infection.

• Zinc supplementation for prevention of acute respiratory infections in infants: A randomized controlled trial (2014)
  https://link.springer.com/article/10.10 ... 014-0503-z

Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic (Apr 4)
https://www.sciencedirect.com/science/a ... 1620302254

"Highlights
•A significant amount of the world's population will contract COVID-19 infection.
•Individual risk assessment and management strategies are crucial.
•Metabolic status determines the clinical severity of COVID-19, from asymptomatic to death.
•Important factors include diet, nutrition, age, sex, health, lifestyle, and environment.
...
1. Introduction
2. Personal hygiene and social distancing determine the individual risk of SARS-CoV-II infection
3. The host metabolic status determines the clinical course of COVID-19
4. The host macro- and micronutrient status as the preventive measures for COVID-19
(Vitamins D, A, C, Selenium & Zinc)
5. Potential therapeutic options for COVID-19
6. Concluding remarks
"...individual assessment for the possible dietary, nutritional, lifestyle, and environmental risks, together with the proper risk management, is the sensible way to deal with the pandemic of SARS-CoV-II."

jimmylegs wrote: ↑Sun May 31, 2020 9:45 am Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic (Apr 4)
https://www.sciencedirect.com/science/a ... 1620302254

Excellent! Thank you.

yw - good to see hygiene and distancing as top strategic priorities, with diet and nutrition reflected as contributors to metabolic status (including, i would argue, microbiomes) as a determinant of COVID 19 clinical course in the event an individual is infected.

preprint: ASSESSING THE ROLE OF ZINC IN COVID-19 INFECTIONS AND MORTALITY: IS ZINC DEFICIENCY A RISK FACTOR FOR COVID-19? (Jun 14)
https://www.medrxiv.org/content/10.1101 ... 1.full.pdf

A negative correlation between the Zinc deficiency prevalence estimate for the countries and the reported cases of COVID-19 was consistently observed at all three time-points analyzed that covered pre infections peak, i.e.,8 April 2020, and post infections peak, i.e., 12 and 26 May 2020 (see Table 2). ...

An exploratory estimation of the correlation for COVID-19 affected countries of the world that had seemingly comparable exposure to disease, population structure, and health care response as on 12th May 2020 ... and accounted for 63.7% of total cases ... seemed reassuring. For these eleven countries, the Zn deficiency prevalence was exponentially correlated to cases per million (R2 = 0.3301) and more strongly to deaths per million (R2 = 0.4307) suggesting a supposedly robust correlation.

Carefully designed studies investigating the basis of increased vulnerability of target groups and the elderly could help devise better strategies for future COVID-19 treatment. If the observed correlation is to be believed as having cause and effect relationship, it may be predicted that the inherently or transiently higher Zinc levels resulting from supplementation or medication may be associated with higher COVID-19 infections and mortality in patients. A scrutiny of the COVID-19 patients’ data for potential Zinc status alteration, such as resulting from the intake of vitamin C, organic acids, animal protein, phytate content along with Zinc supplementation and the administration of Zn status altering drugs such as Hydroxychloroquine would shed light on the biological significance of the observed covariation of the Zinc deficiency prevalence with COVID-19 cases and mortality in different target populations and its potential preventive role. So, more evidence-gathering follow-up exercises for the closer scrutiny of the COVID-19 patients' medical records, including the micronutrient supplementation and food consumption details is advisable to ascertain the role of Zinc deficiency in COVID-19 pandemic and potentially find an early solution to COVID-19.