There isn’t any proof that the Bacille Calmette-Guérin vaccine (BCG) protects folks towards an infection with COVID-19 virus. Two medical trials addressing this query are underway, and WHO will consider the proof when it’s obtainable. In the absence of proof, WHO doesn’t advocate BCG vaccination for the prevention of COVID-19. WHO continues to advocate neonatal BCG vaccination in nations or settings with a excessive incidence of tuberculosis.
There is experimental proof from each animal and human research that the BCG vaccine has non-specific results on the immune system. These results haven’t been nicely characterised and their medical relevance is unknown.
Since December of 2019 COVID-19 is a quickly spreading virus presently infecting over 1,000,000 people worldwide, over 250,000, and over 6,000 deaths in the United States as of 03/31/2020.1
Presently there are not any FDA accepted remedies or immunizations towards COVID-19; nonetheless, the FDA has granted an EUA for the therapy of hospitalized sufferers with hydroxycholorquine.2
Depending on case sequence the anticipated case fatality fee for COVID-19 with out therapy is between 0.5-10% with the most definitely vary between 1-3% which is>>10x the anticipated case fatality fee of seasonal influenza.
Several research have reported anecdotal and promising preliminary knowledge on the therapy of Coronavirus. Based on the restricted proof from these research, pre-exposure prophylaxis, or post-exposure prophylaxis could also be useful.3-21
Due to the nature of the work in the Pentagon a number of important people are unable to apply efficient social distancing measures with a view to guarantee their mission important jobs for continuity of authorities and nationwide protection.
Any treatment, therapy protocol, or epidemiological management measure which seems protected preliminarily and could be carried out have to be examined and put into apply instantly with a view to defend senior leaders and different mission important personnel.
2. EUA Hydroxychloroquine sulfate Health Care Provider Fact Sheet, model date 3/28/2020 – connected in research paperwork.
3. Colson P, et al. Chloroquine and hydroxychloroquine as obtainable weapons to fightCOVID-19. International Journal of Antimicrobial Agents https://doi.org/10.1016/j.ijantimicag.2020.105932
4. Zhou D, et al. COVID-19: a advice to look at the impact of hydroxychloroquine in stopping an infection and development, Journal of Antimicrobial Chemotherapy, https://doi.org/10.1093/jac/dkaa114
5. Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the therapy of novel coronavirus pneumonia. Expert consensus on chloroquine phosphate for the therapy of novel coronavirus pneumonia Chinese Journal of Tuberculosis and Respiratory Diseases 43, no. 0. https://www.ncbi.nlm.nih.gov/pubmed/32075365.
6. Yao X, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. https://www.ncbi.nlm.nih.gov/pubmed/32150618.
7. Cortegiana, et al. A scientific evaluate on the efficacy and security of chloroquine for the therapy of COVID-19. J Crit Care. 2020 Mar 10. https://www.sciencedirect.com/science/article/pii/S0883944120303907.
8. Hydroxychloroquine medical trial (NCT04261517). https://clinicaltrials.gov/ct2/show/NCT04261517?cond=covid-19&draw=8.
9. WHO. Clinical administration of extreme acute respiratory an infection when novel coronavirus (nCoV) an infection is suspected. Accessed 2020 Mar 12. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory- infection-when-novel-coronavirus(ncov)-infection-is-suspected.
10. CDC. Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19). Accessed 2020 Mar 12. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html .
11. Gross AE, Bryson ML. Oral Ribavirin for the Treatment of Noninfluenza Respiratory Viral Infections: A Systematic Review. Ann Pharmacother. 2015 Oct;49(10):1125-35. https://www.ncbi.nlm.nih.gov/pubmed/26228937.
12. Arabi YM, et al. Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study. Clin Infect Dis. 2019 Jun 25. https://www.ncbi.nlm.nih.gov/pubmed/31925415.
13. Mo Y, Fisher D. A evaluate of therapy modalities for Middle East Respiratory Syndrome. J Antimicrob Chemother. 2016 Dec;71(12):33403350. https://www.ncbi.nlm.nih.gov/pubmed/27585965.
14. Darunavir/cobicistat medical trial (NCT04252274). https://clinicaltrials.gov/ct2/show/NCT04252274.
15. Wang M, et al. Remdesivir and chloroquine successfully inhibit the lately emerged novel coronavirus (2019-nCoV) in vitro. Cell Research. 2020 30;269-71. https://www.nature.com/articles/s41422-020-0282-0.
16. Gamino-Arroyo AE, et al. Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness. Clin Infect Dis. 2019 Dec 69;11:1903-11. https://academic.oup.com/cid/article/69/11/1903/5308603.
17. Yao TT, et al. A Systematic Review of Lopinavir Therapy for SARS Coronavirus and MERS Coronavirus-A Possible Reference for Coronavirus Disease-19 Treatment Option. J Med Virol. 2020 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/32104907.
18. Young BE, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. 2020 Mar 3. https://jamanetwork.com/journals/jama/fullarticle/2762688
19. Li Y, et al. Extraordinary GU-rich single-strand RNA recognized from SARS coronavirus contributes an extreme innate immune response. Microbes Infect. 2013 Feb;15(2):88-95. https://www.ncbi.nlm.nih.gov/pubmed/23123977
20. Xiaoling X, et al. Effective therapy of Severe COVID-19 Patients with Tocilizumab. [Pre-print – not peer reviewed]. http://chinaxiv.org/abs/202003.00026.
21. NephJC (nephrology on-line journal membership) detailed evaluate with hyperlinks to society statements. Accessed 2020 Mar 16. http://www.nephjc.com/news/covidace2.
The main purpose of this research is to find out whether or not pre-exposure prophylaxis decreases the incidence of COVID-19 infections amongst personnel, and the secondary purpose is to find out whether or not post-exposure prophylaxis decreases the severity of sickness and speeds the return to work of personnel.
The Pentagon Medical Facilities consist of 2 separate medical clinics and a pair of separate dental clinics that collaborate on each day actions. Operational personnel with particular medical necessities similar to aviators and Personnel Reliability Program (PRP) personnel are sometimes seen in the Pentagon Flight Medicine Clinic whereas different personnel are seen in the DiLorenzo Tricare Health Clinic Pentagon.
Based on the EUAs for hydroxychloroquine & chloroquine, that are in important nationwide scarcity, and inpatient therapy protocols, hydroxychloroquine and chloroquine present potential for therapy of sufferers hospitalized for COVID-19. We suspect that therapy of early or asymptomatic uncovered sufferers with chloroquine could lower an infection charges or restrict an infection severity if pre-treated or handled early
Describe all the knowledge variables, info to be collected, the supply of the knowledge, and the way the knowledge might be operationally measured.
All mission important personnel enrolled to the DiLorenzo Tricare Health Clinic or Pentagon Flight Medicine Clinic unable to telework or appropriately socially distance with entry to the Pentagon throughout the declared public well being disaster.
Known recovered COVID-19 affected person, G6PD poor people, people with vital QT abnormalities, non-compliant sufferers, and sufferers who refuse randomization or consent.
Recruitment by Arms:
1. 2, 3. Individuals might be approached by protocol employees and every other employees added to the protocol after preliminary submission throughout their screening for medical visits or entry screening to important areas. They might be requested 2 questions:
a. Are you conscious of an ongoing research inside the Pentagon making an attempt to find out the efficacy of a medicine to stop or deal with COVID-19 infections?
i. If the particular person solutions sure:
a. Have you already elected or are you curious about collaborating?
i. If sure they’re or are fascinated by collaborating they are going to be referred for enrollment as acceptable.
ii. If not they are going to be thanked for his or her time.
ii. If the particular person solutions no:
a. Would you wish to study extra or are you curious about enrolling?
i. Yes: Referred for enrollment.
ii. No: They might be thanked for his or her time.
4. PIs and AIs who’re seeing sufferers for doable COVID-19 publicity or who’ve examined optimistic as half of their routine medical duties will provide enrollment to arm Four these people. At their first go to.
Informed and appropriately witnessed consent* as required might be obtained by the PI or every other AI added in subsequent modifications to the protocol. Due to telemedicine and social distancing with the ongoing disaster this might be by distance mechanisms together with digital versus moist signature as clinically indicated based mostly on the state of affairs to attenuate affected person and supplier dangers.
Patients might be assigned sequential affected person identifier numbers throughout their consent course of for monitoring functions.
Initial procedures for security monitoring together with CBC, CMP, UA, G6PD testing (if prior information unavailable), and EKG (if prior information unavailable) might be obtained after consent.
The affected person will then current to the DTHC pharmacy with their envelope and duplicate of their enrollment consent to retrieve their medicines. The pharmacist will open their envelope and hand them treatment 1, 2, or Three as acceptable, and document their research quantity and group quantity on a working spreadsheet maintained with out PII in the pharmacy.
Patients will present their research quantity to the pharmacy for any refills throughout the period of the research.
If a person is on pre-exposure prophylaxis and develops COVID-19 they are going to proceed on therapy by means of the post-exposure prophylaxis window of 7 days on the dose they have been assigned at randomization.
Patient information might be queried in 5 methods: 1. At research enrollment 2. During consent affected person’s might be requested to tell research personnel in the event that they develop into sick or uncovered to COVID-19; sufferers will current with issues 3. Monthly information critiques might be carried out to find out if sufferers have develop into optimistic or are displaying indicators of COVID-19 4. When the research personnel are knowledgeable by public well being officers of a optimistic COVID-19 affected person assigned to the Pentagon 5. When the declared public well being emergency is over or the research ends (at its 1 yr anniversary if the public well being emergency has not ended).
Results might be retrieved from AHTLA, CHCS, request to treating civilian suppliers for care exterior the MHS, Essentris, and MHS imaging techniques similar to Impax.
Records assortment will embody as acceptable:
1. Date of publicity – to find out optimum timing of post-exposure prophylaxis throughout knowledge evaluation.
2. Date of optimistic check – to find out optimum timing of post-exposure prophylaxis on knowledge evaluation.
3. Medical comorbidities as they’re identified or develop into identified together with HTN, DM, Male Gender, Age, Pulmonary Disease, Health Care Worker / First Responder, and/or identified cardiac illness. – to manage and check for cofounding circumstances in addition to danger stratify
4. CXR outcomes, Chest CT outcomes, Intracranial Imaging outcomes, cardiac testing, CBCs, CMPs, COVID-19 check outcomes, Infectious Disease notes, Pulmonary notes, Cardiology/Cardiac surgical procedure notes, and Neurology notes. – to manage and check for cofounding circumstances in addition to danger stratify. To decide whether or not a person is protected to enroll and obtain research medicines. To decide if a person underneath remedy has develop into contaminated and guage severity of the an infection. All imaging being carried out is for traditional of care and never research functions.
5. Date of symptom onset – to find out optimum timing of post-exposure prophylaxis throughout knowledge evaluation. To decide time to occasion.
6. Date of decision – to evaluate results of treatment therapy on period and severity of illness.
7. All medicines that the affected person is on or has been on inside the continuing 1 month – to evaluate for doable issues or treatment interactions.
8. Hospitiization information, particulary information close to ICU admission, ICU discharge, want for supplemental oxygen, size of keep, ICU size of keep, and/or want for mechanical air flow – to correctly assess severity, illness period, and course for secondary end result evaluation.
9. Date of therapy begin – to evaluate for optimum timing of initiation of secondary prophylaxis or time to onset of signs after prophylaxis.
10. Date of therapy termination – to evaluate for relapses or worsening timing after cessation of therapy.
“In order to conduct human analysis on this Commonwealth of Virginia, knowledgeable consent have to be obtained if the one who is to be the human topic is as follows:(i) succesful of making an knowledgeable resolution, then it shall be subscribed to in writing by the individual and witnessed; or (ii) incapable of making an knowledgeable resolution at the time consent is required, then it shall be subscribed to in writing by the individual and witnessed. Therefore the “neutral witness” part in the consent kind might be used for all topics consented in the Commonwealth of Virginia.
Responsibilities of the neutral witness embody the following:
– Read the knowledgeable consent and all written supplies given to the topic
– Confirm the topic was offered enough info to guarantee that the topic was really knowledgeable
– Sign and date the knowledgeable consent kind after the knowledgeable consent and every other written info offered to the topic is learn and defined.
A signature from the neutral witness will function documentation of this course of inside the topic’s research file. The topic may also must signal and date or mark the knowledgeable consent displaying acceptable consent for participation.”