Testing, treatment, foundational considerations and masks: The Sars-Covid2 episode with Jena S. Griffith, RDN, IHC, part 2

Uncategorized Jul 11, 2020

TESTING: PCR & ANTIBODY STRENGTHS AND WEAKNESSES

CHAPTER MARKERS:
  • Diagnosing thru RT PCR [02:17]
  • Potential False-Positive Rate Among the 'Asymptomatic Infected Individuals' in Close Contacts of COVID-19 Patients [04:58]
  • COVID symptoms [12:54]
  • Treatment [16:30]
  • Similarity of Zinc deficiency and COVID19 [24:19]
  • Study about Vit D nutrition [27:57]
  • Integrative medicine clinicians journal COVID [40:53]
  • European gastroenterology journal internally applied ultraviolet light as a novel approach [44:59]
  • MATH Protocol [46:16]
  • Daily emotional well-being during the COVID-19 pandemic [48:12]
  • Study about mask/ respiratory influenza [53:02]
  • Cluster randomized trial [53:29]
  • Policy review non-pharmaceutical measure [54:16]
  • Commentary Lisa Brosseu at al. [54:37]
  • Recommendation of the use of cloth masks[56:57]
  • New England journal of medicine [59:01]
  • Zach bush interview coronavirus [1:00:43]
  • Wuhan COVID 19 data Q and A [1:01:00]
  • Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area [1:06:00]

 

 

Key takeaway: “Symptoms are the largest indication and should drive behavior”

Struyf T, Deeks JJ, Dinnes J, et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database Syst Rev. 2020;7:CD013665. Published 2020 Jul 7. DOI:10.1002/14651858.CD013665

 
Fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present.
 
The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. 
  
 

A. Antibody testing:  

Deeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020;6:CD013652. Published 2020 Jun 25. DOI:10.1002/14651858.CD013652
 
Our findings come mainly from 38 studies that provided results based on the time since people first noticed symptoms.
 
The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later when RT-PCR tests are negative or are not done. Antibody tests are likely to have a useful role in detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days of post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes.
 
Antibody tests one week after the first symptoms only detected 30% of people who had COVID-19. Accuracy increased in week 2 with 70% detected, and was highest in week 3 (more than 90% detected). Little evidence was available after week 3. Tests gave false-positive results in 2% of those without COVID-19.
 
Results from IgG/IgM tests three weeks after symptoms started suggested that if 1000 people had antibody tests, and 50 (5%) of them really had COVID-19 (as we might expect in a national screening survey):
 
- 58 people would test positive for COVID-19. Of these, 12
people (21%) would not have COVID-19 (false-positive
result).
- 942 people would test negative for COVID-19. Of these, 4
people (0.4%) would actually have COVID-19 (false-negative
result).
-If we tested 1000 healthcare workers (in a high-
risk setting) who had had symptoms, and 500 (50%) of
them really had COVID-19: - 464 people would test positive
for COVID-19. Of these, 7 people (2%) would not have
COVID-19 (false-positive result).
- 537 people would test negative for COVID-19. Of these, 43
(8%) would actually have COVID-19 (false-negative results


B. PCR testing: PCR testing 

1a.  Explicitly stated by the CDC from the start that the RT- PCR test does not rule out bacterial infection or co-infections from other viruses. Page 2 of the 6/12/2020 CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel Instruction Manual. 


https://www.fda.gov/media/134922/download states: “Positive results are indicative of active infection with 2019-nCoV but do not rule out bacterial infection or co-infection with other viruses. 


This link is a lengthy discussion of the validity of the PCR test, fully referenced. https://www.greenmedinfo.com/blog/does-2019-coronavirus-exist. However, the major points presented here:

The agent detected may not be the definite cause of the disease (we’ll come back to this one soon)

Somewhere between March 14-March 16th the CDC changed their language as below:
 
1b. From Stephen Bustin, a professor at Anglia Ruskin University, UK, arguably the world’s top expert on quality control TR-PCR says on this podcast, The InfectiousMyth
·       The amount of DNA extracted from a patient’s sample can vary widely.
·       Most tests have a different definition of what they’re looking for.
 
2. Tahamtan A, Ardebili A. Real-time RT-PCR in COVID-19 detection: issues affecting the results. Expert Rev Mol Diagn. 2020;20(5):453-454. DOI:10.1080/14737159.2020.1757437 
 
An important issue with the real-time RT-PCR test is the risk of eliciting false-negative and false-positive results. It is reported that many ‘suspected’ cases with typical clinical characteristics of COVID-19 and identical specific computed tomography (CT) images were not diagnosed [4]. 
 
3.  Younes, N.; Al-Sadeq, D.W.; AL-Jighefee, H.; Younes, S.; Al-Jamal, O.; Daas, H.I.; Yassine, H.M.; Nasrallah, G.K. Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2. Viruses 2020, 12, 582.
 
 
 
 
 
5. A study came out that made headlines showing an 80% false-positive rate but was withdrawn without explanation: https://pubmed.ncbi.nlm.nih.gov/32133832/
 
 
Bottom line: There is false-negative and false-positive potential for the gold standard PCR diagnostic testing for CoVid. However, at the time of this publishing, this testing was still the best option. Moreover, no testing is ever perfect and this should be a clear public health message. 
 
 
 

TREATMENT OR FOUNDATIONAL NUTRITION CONSIDERATIONS:

A. Orthomolecular medicine defined. 
 
B. Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?. Med Drug Discov. 2020;5:100028. DOI:10.1016/j.medidd.2020.100028
 
High-dose intravenous VC has also been successfully used in the treatment of 50 moderate to severe COVID-19 patients in China. The doses used varied between 10 g and 20 g per day, given over a period of 8–10 h. Additional VC bolus may be required among patients in critical conditions. The oxygenation index was improving in real-time and all the patients eventually cured and were discharged [18]. In fact, high-dose VC has been clinically used for several decades and a recent NIH expert panel document states clearly that this regimen (1.5 g/kg body weight) is safe and without major adverse events [19].
 
Because the development of efficacious vaccines and antiviral drugs takes time, VC and other antioxidants are among currently available agents to mitigate COVID-19 associated ARDS. Given the fact that high-dose VC is safe, healthcare professionals should take a close look at this opportunity. Obviously, well-designed clinical studies are absolutely needed to develop standard protocols for bedside use.
 
C.  (Several Vitamin D papers available by search PubMed for "CoVid and Vitamin D”) Review Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths
 
Through several mechanisms, vitamin D can reduce the risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines.
 
Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing the risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer is low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration.
 
To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For the treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
 
 
D. Alipio, Mark, Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19) (April 9, 2020). Available at SSRN: 
 
One of the first Vitamin D studies looking at 212 patients and highest Vit D levels with least severity in disease: 
Of the 212 cases of COVID-19, the majority had an ordinary clinical outcomes. Mean serum 25(OH)D level was 23.8 ng/ml. Serum 25(OH)D level was lowest in critical cases, but highest in mild cases. 
 
E. MATH Protocol for serious cases. https://covid19criticalcare.com/
Methylprednisolone (IV)
Ascorbic acid (Vit C) 
Thiamine (Vit B1)
Heparin (anticoagulant) 
 
Presented to White House 4 different times;  These leading critical care specialists at academic centers and major hospitals have formed the Front Line Covid-19 Critical Care Alliance (former Working Group).  
 
Based on available research, the experience in China reflected by the Shanghai expert commission, and their decades-long professional experiences in Intensive Care Units around the country, these experts have since developed the MATH+ Hospital Treatment Protocol for Covid-19 for patients presenting with low oxygen rates, breathing difficulties, or other symptoms of the disease in hospitals. The five critical care experts have since been joined by other physicians, who recognize the value of their protocol and are assisting in getting word of it out to help other doctors, hospitals, medical, and governmental officials save lives during this extraordinary pandemic.  
 
MATH+ is designed for use earlier in the disease course, as soon as a patient requires supplemental oxygen. The results achieved to date with this more aggressive treatment approach for COVID-19 have lead the group to predict that early adoption of MATH+ will reduce ICU admissions, obviate the need for mechanical ventilators, and most importantly, save the lives of many who would not likely survive on supportive care.
 
 
F. SF Yanuck, J. Pizzorno, H Messier, KN Fitzgerald. From Integrative Medicine: A Clinicians Journal: Evidence Supporting a Phased Immuno-Physiological Approach to Covid-19 From Prevention Through Recovery.  
 
 
This paper reviews 4 phases of Covid, how to target support foundational as well as inflammatory and antioxidant support. It reviews specific immune mechanisms and support that can be used for a comprehensive treatment approach. 
 
4 phases: 
1. Prevention - support is focused on immune surveillance efficiency and reduction of baseline levels of inflammation, to improve outcomes if the patient becomes infected,
2. Infection - support emphasizes immune activity against infection,
3. Escalating Inflammation - support is focused on anti-inflammatory measures, and
4. Recovery - support is focused on resolving inflammation, inhibiting fibrosis and other forms of tissue damage, curtailing losses of function, and restoring and reoptimizing function. 
 
Foundational support: 
+ Eliminating factors that can drive non-purposeful inflammation and related dysregulation impacts on immune function. 
+ Sleep
+ Stress
+ Glycemic control
+ Dietary factors
+ Microbiome balancing 
+ Exercise
+ Supporting levels of vitamins and minerals
+ Anti-inflammatory support 
+ Antioxidant support 
 
 
 
G.  Victoria Yunez Behm, MS,CNS, LDN;  Jeffrey Blumberg, PhD; Corinne Bush, MS, CNS; Rajesh Grover, PhD; Deanna Minich, PhD; FACN, CNS; Roger Newton, PhD, FACN, FAHA; David Perlmutter, MD; Dana Reed, MS, CNS, LDN; Stephen Sinatra, MD; Michael Stroka, JD, MS, CNS, LDN. (May 26, 2020). Personalized Nutrition & the Covid Era: A Rapid Review for Health Professionals, recommendations from the American Nutrition Association. 
 
This paper reviews cytokine inhibitors that could be potentially supportive of immune resilience, viral enzyme targets and food-based influencers, nutrients & bioactive compounds, etc
 
 
H. Minnich and Hanaway. The Functional Medicine Approach to COVID-19: Nutrition and Lifestyle Practices for Strengthening Host Defense. 
 
I.  A novel approach to treating COVID 19 using nutrition and oxidative therapies. Brownstein et al. Free PDF: https://cf5e727d-d02d-4d71-89ff-9fe2d3ad957f.filesusr.com/ugd/adf864_8979940e4aed4fd9a62eb3554a59cd5f.pdf
 
At present, there is no published cure, treatment, or preventive for COVID-19 except for a recent report on dexamethasone for seriously ill patients. A novel treatment program combining nutritional and oxidative therapies was shown to successfully treat the signs and symptoms of 100% of 107 patients diagnosed with COVID-19. Each patient was treated with an individualized plan consisting of a combination of oral, IV, IM, and nebulized nutritional and oxidative therapies which resulted in zero deaths and recovery from COVID-19.
 
J. Iddir, M., Brito, A., Dingeo, G., Fernandez Del Campo, S., Samouda, S., La Frano, M., and Bohn, T. (2020). Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Nutrients 2020, 12(6),1562; 
 
 
K. Recovery rate comment based on: 
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239–1242. DOI:10.1001/jama.2020.2648 (cited 2.3% fatality rate)
 
HOWEVER, this data is constantly moving. For more up to date numbers consider: 
 
AND 
 
For example, this paper showed a case fatality rate of 0.2% in Germany to 7.7% in Italy. 
Lazzerini M, Putoto G. COVID-19 in Italy: momentous decisions and many uncertainties. Lancet Glob Health. 2020;8(5):e641-e642. DOI:10.1016/S2214-109X(20)30110-8  https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(20)30110-8/fulltext 
 
Data is confounded by whether patients died WITH the disease or the disease overall. It will likely be many months before data and numbers stop moving overall. 
 
 
L. UV light via intubation does not appear to be used, just studied by scientists at Cedar Sinai Medical Center
 
Rezaie, A., Leite, G., Park., J., Kim,S., Weisman, S., Melmed G., Barlow, G., Morales,W., Celly, S., Parodi,G., Sakhaie,S., Melmed, Z., Ybarra, E., Mathur, R., Pimentel, M.. Internally Applied Ultraviolet Light as A Novel Approach for Effective and Safe Anti-Microbial Treatment  
 

MASKS

A.  Chou R, Dana T, Jungbauer R, Weeks C, McDonagh MS. Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review [published online ahead of print, 2020 Jun 24]. Ann Intern Med. 2020; M20-3213. DOI:10.7326/M20-3213
 
39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies.
 
Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain.
 
B. bin-Reza, F., Chavarrias, V., Nicoll, A., and Chamberland., M. (2012) The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence. Influenza Other Respir Viruses.  6(4): 257–267. Published online 2011 Dec21.  DOI: 10.1111/j.1750-2659.2011.00307.x PMID: 22188875
 
Conclusion: None of the studies established a conclusive relationship between mask/respirator use and prevention of influenza transmission.
 
 
C. MacIntyre CR, Seale H, Dung TC, et al., A cluster-randomized trial of cloth masks compared with medical masks in healthcare workers. BMJ Open 2015;5:e006577
 
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 an increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. 
 
 
“We know that wearing a mask outside health care facilities offers little if any, protection from infection. Public health authorities define a significant exposure to Covid-19 as face-to-face contact within 6 feet with a patient with symptomatic Covid-19 that is sustained for at least a few minutes (and some say more than 10 minutes or even 30 minutes).
 
The chance of catching Covid-19 from a passing interaction in a public space is therefore minimal. In many cases, the desire for widespread masking is a reflexive reaction to anxiety over the pandemic.”

E. Commentary by: Dr. Lisa M Brosseau, (national expert on respiratory protection and infectious diseases) and Dr. Margaret Sietsema, PhD (expert on respiratory protection and an assistant professor at the University of Illinois at Chicago.)

Link: https://www.cidrap.umn.edu/news-perspective/2020/04/commentary-masks-all-covid-19-not-based-sound-data

 
F. Review on CDC website at:  https://wwwnc.cdc.gov/eid/article/26/5/19-0994_article  Policy Review Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings—Personal Protective and Environmental Measures. 
 
Conclusion on face masks: no significant reduction in viral transmission with the use of face masks
 
 
G. Dr. Michael Osterholm podcast: 
https://www.cidrap.umn.edu/sites/default/files/public/downloads/special_episode_masks_6.2.20_0.pdf
 
Page 23 of pdf: 
Finally, regardless of all the “yes, the use of cloth masks offer critical protection to users” or “no they don’t” statements, there is the fact that only one study has been conducted that was a randomized trial of cloth masks compared with surgical masks.
 
It was carried out in healthcare workers, not the general public. In short, the study found that those that wore the cloth masks had 13 times more infection outcomes than those that wore surgical masks. The authors of this study also found that cloth mask users versus the surgical mask users had 6.6 times higher risk of influenza-like illness and 1.7 times higher risk of a lab-confirmed respiratory virus infection.
 
The filtration testing of the surgical mask material found a penetration rate of 44%, meaning that 44% of the particles came through the mask, and for the cloth mask it was 97%. This means that in the filtration studies only 3% of the particles in that test were stopped by the cloth material.
 
The authors concluded that cloth masks should not be recommended for healthcare workers, particularly in high-risk settings. If they are not recommended for healthcare workers per the result of this study, the only one ever done comparing surgical and cloth masks, how can cloth face mask use be expected to reduce the incidence of COVID-19 to one-twelfth of what it would otherwise?
 
 
H. A compilation of why masks have been socially controversial looking at conflicting recommendations by country: Feng S, Shen C, Xia N, Song W, Fan M, Cowling BJ. Rational use of face masks in the COVID-19 pandemic. Lancet Respir Med. 2020;8(5):434-436. doi:10.1016/S2213-2600(20)30134-X 
 
 
I. Kim MN. What Type of Face Mask Is Appropriate for Everyone-Mask-Wearing Policy amidst COVID-19 Pandemic?. J Korean Med Sci. 2020;35(20):e186. Published 2020 May 25. doi:10.3346/jkms.2020.35.e186
 
In conclusion, a surgical mask is the best type for a person wearing a mask to prevent droplet transmission, with or without symptoms. A cotton mask rather than a HEPA mask can be the last resort for the person without respiratory symptoms
 
J. Greenhalgh T, Schmid MB, Czypionka T, Bassler D, Gruer L. Face masks for the public during the COVID-19 crisis. BMJ. 2020;369:m1435. Published 2020 Apr 9. DOI:10.1136/bmj.m1435
 
In conclusion, in the face of a pandemic, the search for perfect evidence may be the enemy of good policy. As with parachutes for jumping out of aeroplanes,38 it is time to act without waiting for randomized controlled trial evidence.39 
 
A recently posted preprint of a systematic review came to the same conclusion.40 Masks are simple, cheap, and potentially effective. We believe that worn both in the home (particularly by the person showing symptoms) and also outside the home in situations where meeting others is likely (for example, shopping, public transport), they could have a substantial impact on transmission with a relatively small impact on social and economic life.
 

PENDING PAPERS ON PUB MED NOT YET AVAILABLE AT TIME OF PUBLISHING ON MASK EFFICACY: 

 
A. Quintana-Díaz MA, Aguilar-Salinas CA,. Universal Masking During Covid19 Pandemic - Current Evidence and Controversies. Rev Invest Clin. 2020;72(3):144-150. DOI:10.24875/RIC.20000196
 
B. Szarpak L, Smereka J, Filipiak KJ, Ladny JR, Jaguszewski M. Cloth masks versus medical masks for COVID-19 protection. Cardiol J. 2020;27(2):218-219. DOI:10.5603/CJ.a2020.0054
 
C. Law SK, Leung AWN, Xu C. Are face masks useful for limiting the spread of COVID-19?. Hong Kong Med J. 2020;26(3):267-268. DOI:10.12809/hkmj208566 https://pubmed.ncbi.nlm.nih.gov/32536613/
 
 
 

 

 
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