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Section 1: Epidemiology, Virology, Clinical Presentation, Diagnostics

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COVID-19 Updatefor Patients with HIV
Section 1:
Epidemiology, Virology, Clinical Presentation, Diagnostics

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V_04032020
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Slide Set Contributors
Avenue 360, Houston: C.Mark Nichols, DDS
Baylor College of Medicine: Shital Patel, MD; Melanie Goebel, MD
Gallup IHS: Jonathan Iralu, MD, FACP
LSUHSC: Paula Seal, MD MPH
PHNT: Deborah Morris-Harris, MD, EMBA
UNMHSC: Carly Floyd, Pharm D PhC AAHIVM; Nestor Sosa, MD; Meghan Brett, MD; Michelle Iandiorio, MD
Valley AIDS Council: Pedro Coronado

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Learning Objectives
Recognize the current pandemic and how it is effecting the nation and region.

Recognize the risk factors for severe COVID-19.

Identify strategies to reduce risk of COVID-19.

Identify strategies to stay healthy during COVID-19 pandemic that People with HIV (PWH) should consider.

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PLWH now PWH per HRSA guidance
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COVID-19
Viral upper respiratory syndrome caused by novel coronavirus, SARS CoV-2

Most people have mild illness (influenza-like, URI, gastroenteritis; or asymptomatic

Some may develop pneumonia

Some have severe symptoms and develop ARDS, septic shock
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80% mild or asymptomatic
Asymptomatic 18-25% (18% on cruise ship, now appears as many as 25% may be asymptomatic concern for asymptomatic shed)
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Transmission
Droplet exposure when infected person coughs or sneezes

Possible asymptomatic shedding

Contact from droplet on hand then exposure to eyes, nose, mouth

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Huang, Ch et al. The Lancet. 2020; Vol 395
Transmissibility reproductive number 1.4-3.28. Same or higher than prior influenza pandemics (Liu, Y et al. Journal of Travel Medicine, 2020 . Biggerstaf, M et al. BMC Infect Dis 2014;12:480.)
[less transmissible than measles or smallpox]
Virus has been found in feces but not clear if this is a potential risk exposure
No perinatal transmission reported

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COVID-19 from SARS CoV-2
COVID-19 disease emerged in December 2019 in Wuhan, Hubei Province in China
Initial cases associated with Huanan Seafood market
Later extensive person-to-person transmission
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Photo: DailyMail.com

COVID-19 Cases in the U.S.
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https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html Updated 4/2/20
As of 4/2/20, total US cases: 213,144; total deaths: 4513
Travel-related: 1144; close contact: 3245; under investigation: 209,755
>1million confirmed cases in the world
NY has the countrie's highes number of cases
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Reported COVID-19 Cases in Region
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https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html#st...
State
Cases
Cases per 100,000
Deaths
Deaths per 100,000
NM
403
19.3
7
0.3
TX
4875
17.5
78
0.3
OK
879
22.4
34
0.9
AR
683
22.8
12
0.4
LA
9150
196.2
310
6.6
As of 4/2/20
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COVID-19 Cases in the U.S.
Cumulative total cases through 4/1/20

Community transmission cases a rising concern in many areas
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https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html
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4/2 WHO director in Europe said 95% coronavirus deaths in >60yo
10-15% of cases in <50yos are moderate-severe.
4/1 Currently 3rd leading cause of death in US
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COVID-19 VIROLOGY
Nestor Sosa, MD
Chief, UNMHSC DOIM Division of Infectious Diseases
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V033020

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Coronavirus
Size: 80-160 nm
Genome: 27-32kb RNA
Genes at 5' end specify for RNA replication proteins (error prone=mutations)
Genes at 3' end specify structural proteins (S, N, M, E)
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Receptor for SARS-CoV-2 is ACE-2: in alveolar epithelial cells, oral and nasal mucosa, nasopharynx, GI tract (Hamming, I et al. Journal of Pathology. 2004; 203:631-637.

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Origin of SARS CoV-2
Highest homology to a bat coronavirus
BetaCoV/bat/Yunnan/RaTG13/13
Intermediate mammal host is still unclear
Li et al analyzed 70 genomes from SARS CoV-2 and concluded that the Time to Most Common Ancestor (TMRCA) between 22-24 Nov 2019, and discarded Pangolins as likely intermediate host
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JMedVirology onlinelibrary.wiley.com

Phylogenetic
Coronaviridae subfamily has two main genera:-Alphacoronavirus: -229E and NL63-Betacoronavirus 3 Lineages Lineage A: -OC43 and HKU1 Linage B: SARSCoV and SARS-CoV-2 Linage C: MERS-CoV
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Forni, D et al. Trends in Microbiology. Jan 2017; Vo 25, No 1.

Genetic Types of SARS-CoV-2
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Xiaolu Tang et al. Microbiology (accepted for publication).
L-type (70%)
S-type (30%)

SPECTRUM OF CLINICAL PRESENTATION IN SARS-COV-2
Paula Seal, MD MPH
Associate Professor, LSUHSC School of Medicine
Clinical Director, LSUHSC AETC
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COVID-19 Clinical Manifestations
Time Course:
Incubation Period 5.1 days [2-14d]
Illness onset to discharge22 days
Illness onset to death18.5 days
Illness onset to intubation14.5 days
Viral Shedding 22 days [8-37d]
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Huang, Ch et al. The Lancet. 2020; Vol 395 Lauer et al, Ann Intern Med, 3/10/20, Zhou et al, Lancet, 2/13/20
95th percentile: 12.5 days

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Clinical Syndrome
Asymptomatic

Mild Illness
Influenza Like Illness, Upper Respiratory Tract Infection, Gastroenteritis

Pneumonia:
Mild to Severe

Severe symptoms with the development of ARDS

Sepsis

Septic Shock

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WHO. "Clinical management of severe acute respiratory infection when 2019-CoVinfection is suspected: Interim guidance.
January 2020. https://www.who.int/docs/default-source/coronaviruse/clinical-management....
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Clinical Syndromes in the Critically Ill
State of Washington, 21 patients in Intensive Care
At presentation:
Cough 48%
Fever 52%
Abnormal radiologic imaging 95%
Hospitalization:
15/21 Ventilated, 71% with ARDS
Cardiomyopathy 33% (7/21) -> 52% progressed to death

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Arentz et al. JAMA 12 March 2020

COVID-19 Symptoms
Hospitalized Patients
Fever at admission
45%
Fever during hospitalization
83- 99%
Cough
59-82%
Fatigue
38-70%
Sputum
34%
SOB
19-31%
Myalgias
11-15%
Sore Throat
5-14%
Nausea and Vomiting
1-5%
Diarrhea
2-4%
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Guan NEJM DOI: 10.1056/NEJMoa2002032. Chen Lancet 2020; 395:507-13
No particular set of signs of symptoms can reliably discriminate COVID-19 from other respiratory viral illnesses
Pre-admission: non-specific viral syndrome, often with poor po intake and/or n/v
Some report reduced sense of taste (nonspecific finding seen in URI and allergic rhinitis)
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Clinical Syndromes in the Critically Ill
State of Washington, 21 patients in Intensive Care
At presentation:
Cough 48%
Fever 52%
Abnormal radiologic imaging 95%
Hospitalization:
15/21 Ventilated, 71% with ARDS
Cardiomyopathy 33% (7/21) -> 52% progressed to death

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Arentz et al. JAMA 12 March 2020
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COVID-19 Gastrointestinal Symptoms
Retrospective analysis
1141 patients

Multicenter cross-sectional analysis
204 patients

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GI symptom as the initial presentation in 16% of patients.1
Nausea
73%
Vomiting
65%
Diarrhea
37%
Abdominal Pain
25%
GI symptom as the initial presentation in 3% of patients. Digestive symptoms at presentation 50. 5%.2
Lack of Appetite
79%
Diarrhea
34%
Vomiting
3.9%
Abdominal Pain
1.9%
1 Lou DOI: 10.1016/j.cgh.2020.03.043. 2 Pan AJG 10.14309/ajg.0000000000000620
As the pandemic has progressive, gastrointestinal symptoms at presentation have been recognized.

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Radiologic Abnormalities

Guan NEJM
Abnormal CT 86%
Ground glass 56%, Bilateral patchy shadowing 52%
Abnormal CXR 59%
Ground glass changes 20%, Bilateral patchy shadowing 37%

Chen Lancet
Abnormal CXR and CT
Bilateral patchy Pneumonia: 75%
Multiple Mottling and Ground glass: 14%
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Guan NEJM DOI: 10.1056/NEJMoa2002032
Chen Lancet 2020; 395:507-13.
Abnormal Chest Imaging often precedes symptoms
Ground Glass->consolidation approx. week 2-> resolving imaging week 3
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COVID-19 Progression of Respiratory Syndrome
Moderate
Mild SOB but requiring O2 supplementation ("silent hypoxia")
Difficulty mobilizing thick secretions
CXR: diffuse infiltrates

Severe
Some progress to requiring high levels of O2
Increased secretions
CXR: progressive consolidation, infiltrates, edema

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Original slide: M. Caridi-Scheible, MD; Emory
From presentation given by Dr. Mark Caridi-Scheible at Emory via ECHO update 3/24/20
Recommend moving to ICU if >10L NC O2 requirement
Guafenisin and aggressive pulmonary hygiene, frequent suctioning, mucolytics, percussive therapy if needed
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COVID-19 Severe Respiratory Syndrome
Some progress to respiratory collapse and may require intubation
Pulmonary edema and effusions
Thick, copious secretions
Waxing/waning fevers
Acute kidney injury
Rapidly rising CRP
Cytokine storm
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Original slide: M. Caridi-Scheible, MD; Emory
From presentation given by Dr. Mark Caridi-Scheible at Emory via Project ECHO
COVID-19 Clinical Rounds 3/24/20
Relatively normal compliance, even when needing high PEEP
Mod-severe V/Q mismatch
Early ATN, then AIN on microscopy
Need diuresis
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COVID-19 Laboratory Abnormalities
Laboratory Values at Presentation
Lymphopenia
70-83%
Thrombocytopenia
36%
Leukopenia
34%
Elevated CRP
61%
Elevated LDH
40-41%
Elevated ALT/AST
21-22%
Elevated D-Dimer
46%
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Guan NEJM DOI: 10.1056/NEJMoa2002032. Wang JAMA 2020; 323(11):1-61-1069.
Recommended surveillance labs: daily ABC, CBC with dif, CMP, CRP, d-dimer, LDH, PT
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Risk Factors for Severe COVID-19
Age >55yo
Cardiovascular disease
Chronic respiratory disease
Diabetes mellitus
Hypertension
Cancer
Immunosuppression
Biologics, transplant
HIV: CD4<200, uncontrolled viremia
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Wu. JAMA. DOI: 10.1001/jama.2020.2648, Guan NEJM DOI: 10.1056/NEJMoa2002032. Huang. Lancet. 2020; 395(10223):497-506., Wang JAMA 2020; 323(11):1-61-1069. CDC. COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/
PLWH have high rates of CVD, lung disease, and high prevalence of smoking prioritize for diagnostic testing
in regards to risk in PLWH - consider the intersection of age; and comormidities that place pts at higher risk of complications from COVID-19

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COVID-19 DIAGNOSTICS
Deborah Morris-Harris, MD, EMBA
Chief Medical Officer, Prism Health North Texas
Clinical Director, PHNTX AETC
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COVID-19 Testing
The gold standard for diagnosing COVID-19 disease is an RT-PCR from a nasopharyngeal specimen for SARS-CoV-2
The NP test had a 63% sensitivity when used on hospitalized patients in Wuhan, China (Oral pharyngeal swabs had a sensitivity of 32%)

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Wang, Wenling et al. JAMA March 11, 2020 . doi: 10.1001/jama.2020.3786.
Two target genes ORFlab and nucleocapsid protein are amplified using probe primers and an RNA template.
Preferred test is now the nasopharygeal swab PCR assay
Nasal swab with viral transport medium
Labcorp and Quest both offer this test
63% NP swabs positive in COVID-19 patients (93% for BAL) Wang,JAMA, 3/11/20
Cepheid Xpert nucleic acid amplification assay approved by FDA
Available as early as 3/30/2020
Many IHS sites have the Gene Xpert machine for GC/CT and TB testing
Assays take 45 min for this test
Remember that staff should be trained on how swabs are done to increase the yield of true positives and reduce false negative results

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Antibody Tests
SD Biosensor has introduced COVID-19 IgM/IgG Duo
The Nucleocapsid protein of the core is relatively conserved among coronaviruses. This antigen is used as a tool for diagnosis of SARS-CoV-2.2
In case of negative PCR results due to a drop in titer of antigen, antibody tests can be useful to determine where patients are in the disease course.
Antibody tests are less sensitive than PCR tests early in the disease course.
Package Insert- available through Henry Schein
Li et. al. Development and Clinical Application of Rapid IgM-IgG Combined Antibody Test for
SARS-CoV-2 Infection Diagnosis. Journal of Medical Virology (2020).
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COVID-19 IN PEOPLE WITH HIV
Melanie Goebel, MD; Infectious Disease Fellow, BCM
Shital M. Patel, MD;
Assistant Professor, Infectious Disease; Clinical Director BCM AETC
Baylor College of Medicine
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Risk in Persons with HIV (PWH)
Incidence of COVID-19 in PLWH is unknown

As of March 24, 2020, one case report of patient in China with co-infection of SARS-CoV-2 and HIV-1 who recovered from viral pneumonia*

During prior SARS epidemic in 2002-2003, there were few case reports of SARS infection in PLWH

Other respiratory viruses (non-SARS coronavirus, rhinovirus, parainfluenza, influenza, human metapneumovirus) can cause pneumonia in PLWH
*Zhu F, et al. J Med Virol 2020.
*Zhu F, Cao Y, Xu S, Zhou M. Co-infection of SARS-CoV-2 and HIV in a patient in Wuhan city, China. J Med Virol 2020.

Make sure HIV Service case managers know the different Ryan White programs to take advantage of support services

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Children with HIV
Children are less likely to have severe COVID-19

Unknown if children with HIV have higher risk for severe disease

Keep immunizations up to date

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Guidance for all PWH
Maintain adequate (> 30-day, ideally > 90-day) supply of ART and other chronic medications
Mail order delivery if possible
Delay switching ART regimens if feasible

Keep vaccinations (influenza, pneumococcal) up to date

Follow CDC recommendations for travel recommendations, social distancing and hand hygiene

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Hospitalized patients with HIV and COVID-19
Continue ART
Avoid drug substitutions
For critically ill patients requiring tube feeding
Consult HIV specialist or pharmacist for ART options that can be crushed
Off-label or investigational treatment of COVID-19
Assess drug interactions between COVID-19 therapy and ART
PWH should be included in clinical trials for treatment of COVID-19 (https://clinicaltrials.gov/)
Gilead is allowing compassionate use again https://www.gilead.com/news-and-press/company-statements/gilead-sciences...
https://www.gilead.com/science-and-medicine/research/compassionate-use
Clinical trials of remdesivir for COVID-19
https://www.clinicaltrials.gov/ct2/results?cond=covid-19&term=remdesivir...

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Resources
Clinical Consultation Center http://nccc.ucsf.edu/
HIV Management
Perinatal HIV
HIV PrEP
HIV PEP line
HCV Management
Substance Use Management

Present case on ECHO http://echo.unm.edu [email protected]
AETC National HIV Curriculum https://aidsetc.org/nhc

AETC National Coordinating Resource Center https://targethiv.org/library/aetc-national-coordinating-resource-center-0

Additional trainings [email protected]
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Find an HIV TeleECHO clinic in your area: https://echo.unm.edu/locations-2/echo-hubs-superhubs-united-states/
Additional Local Trainings in NM: includes preceptorships, telephone/email consultation, on-site trainings, HIV TeleECHO; [email protected]
AETC National HIV Curriculum: 6 core modules for self study; regularly updated; CME, CNE

Clinical Consultation Center HIV PrEP line: 888-448-7737 (9am-8pm ET M-F); https://nccc.ucsf.edu/clinician-consultation/prep-pre-exposure-prophylaxis/
AETC National HIV Curriculum, module on PrEP. https://www.hiv.uw.edu/go/prevention/preexposure-prophylaxis-prep
Clinical Consultation Center HIV PEP line: 888-448-4911 (9am-8pm ET M_F, 11am-8pm ET weekends & holidays); PEP Quick Guide: nccc.ucsf.edu/clinical-resources/pep-resources/pep-quick-guide-for-occupational-exposures/
AETC National HIV Curriculum, module on Non-occupational PEP. https://www.hiv.uw.edu/go/prevention/nonoccupational-postexposure-prophy...

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References
AAHIVM:https://aahivm.org/hiv-care-covid-19/
CDC:https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/hiv.htm...
DHHS:https://aidsinfo.nih.gov/guidelines/html/8/covid-19-and-persons-with-hiv...
IDSA, HIVMA COVID-19: Special Considerations for People with HIV https://www.hivma.org/globalassets/covid-19-special-considerations_v5.pdf
WHO:https://www.who.int/news-room/q-a-detail/q-a-on-covid-19-hiv-and-antiret...
AETC NCRC COVID-19 Resources for HIV providers https://aidsetc.org/resource/covid-19-resources-hiv-providers
HRSA COVID-19 Frequently Asked Questions https://bphc.hrsa.gov/emergency-response/coronavirus-frequently-asked-qu...

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References
Cao B, et al. 2020. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med doi:10.1056/NEJMoa2001282.
Zhu F, Cao Y, Xu S, Zhou M. Co-infection of SARS-CoV-2 and HIV in a patient in Wuhan city, China. J Med Virol 2020.
www.hiv-druginteractions.org
COVID-19 drug interactions website: www.covid19-druginteractions.org
Natural Medicines Interaction Checker at www.naturalmedicines.therapeuticresearch.com
https://www.healthline.com/nutrition/immune-boosting-supplements
https://www.discovermagazine.com/health/can-natural-remedies-really-help...
https://www.pharmacytimes.com/news/what-are-drug-prevention-and-treatmen...

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References
Harm Reduction Coalition. Syringe Services and Harm Reduction Provider Operations During the COVID-19 Outbreak.
https://harmreduction.org/miscellaneous/covid-19-guidance-for-people-who...
Sex and COVID-19 https://www1.nyc.gov/assets/doh/downloads/pdf/imm/covid-sex-guidance.pdf
CDC: Coronavirus Disease 2019: Information for Healthcare Professionals https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html
POZ:https://www.poz.com/article/people-hiv-need-know-new-coronavirus
https://www.nytimes.com/2020/03/28/nyregion/coronavirus-larry-kramer-aid...

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