Does coronavirus disease affect cord blood collection?

Dr. Kouzi

Many people have contacted Parent’s Guide to Cord Blood Foundation with questions about the novel coronavirus COVID-19. We have assembled a summary of Frequently Asked Questions for parents and professionals.

Are pregnant women at increased risk for COVID-19?

The professional society of obstetricians in the United States, ACOG, says that the data available at this time does not indicate that pregnant women are at increased risk of catching COVID-19¹. However, when pregnant women do contract respiratory infections, they are known to be at greater risk for experiencing severe symptoms. Hence, pregnant women “should be considered an at-risk population for COVID-19”¹. If you are pregnant during the coronavirus pandemic, you should follow strict precautions to avoid exposure to COVID-19. If you are pregnant and suspect that you have COVID-19, you should tell your doctor immediately.

It is important to point out that the novel coronavirus COVID-19 is not a flu virus². Nonetheless, the symptoms of COVID-19 are similar to flu and the way it spreads is similar to flu, so in this report we base part of our guidance on previous research about pregnancy and flu viruses.

During pregnancy, changes occur in the immune system to prevent the mother’s body from recognizing her baby as foreign and attacking it. But these changes mean that pregnant women have lower immunity to disease³. Pregnant women also have increased loads on their heart and lungs. A healthy woman that is pregnant has an increased risk of being hospitalized with the flu; during the first, second, and third trimester of pregnancy the risk of hospitalization increases by a factor of 1.7, 2.1, and 5.1³. When the pregnant woman has preexisting health conditions, like diabetes or asthma, the increased risk factors are 2.9, 3.4, and 7.9 for the three trimesters³.

Does having the flu during pregnancy influence pregnancy outcomes?

If an expectant mother becomes severely sick with the flu, there is an increased risk of miscarriage or premature labor^3-6.  A small study of 10 births in China found that maternal COVID-19 pneumonia at the time of birth was associated with fetal distress and premature labor⁷.  Again, if you are pregnant and suspect you have COVID-19, you should tell your doctor immediately. 

Can sick mothers transmit COVID-19 to their baby?

While a baby is still in the womb, the placenta works to protect the baby against disease.  The placenta is an amazing organ that allows antibodies to pass from the mother to the baby, but most of the time the placenta blocks diseases from crossing to the baby^8,9.

In the case of ordinary influenza, aka the “flu”, a large hospital study found no evidence for trans-placental transmission of the infection from mother to baby¹⁰.

In the case of COVID-19, initial studies coming out of China suggest that the coronavirus may sometimes be transmitted from mother to baby, but it will take more studies of bigger patient groups to confirm this. The most often quoted study¹¹ from Wuhan China looked at 33 babies born to mothers that were sick with the coronavirus. Three of these babies were diagnosed with COVID-19 as newborns, even though they were delivered via C-section. Despite suffering from fevers and pneumonia shortly after birth, all three babies recovered and tested negative for COVID-19 by age one week.

After giving birth, a mother that is actively sick with COVID-19 can transmit the virus to her newborn through close contact. In that situation it is helpful for the mother pump her milk and have another caregiver feed and handle the baby until mom is recovered.

Does cord blood contain COVID-19?

To the best of our knowledge, the umbilical cord blood will not contain COVID-19, even if the mother is sick at the time of delivery.  It is important to clarify that there is a difference between studies that look for COVID-19 disease transmission between mother and baby, versus studies that test for signs of COVID-19 in the cord blood; these are two separate topics.

When a person is sick with a respiratory virus, it is very rare for the virus to appear in their blood^3,10,12. The patient’s blood will show antibodies to the virus, but not the virus itself. For this reason, the FDA does not recommend¹³ tests to screen asymptomatic blood donors for COVID-19. It is extremely unlikely for COVID-19 to appear in cord blood.

A 2006 study¹² sponsored by the American Red Cross is almost prescient in describing the current COVID-19 pandemic. The paper predicts that during a flu pandemic, donated blood will be safe, but there will be a blood shortage due to disruption of blood center operations. That is exactly what is happening now, and in response the FDA has relaxed their restrictions on blood donors¹⁴.

Further reassurance that COVID-9 does not appear in the umbilical cord blood or birth tissues comes from a study¹⁵ of nine births in Wuhan China. The nine mothers were all suffering from COVID-19 pneumonia, and their babies were delivered via C-section. While the babies were still in the sterile operating room, and before they had contact with their mothers, samples were collected of their amniotic fluid, cord blood, and neonatal throat swabs. Later the mother’s breastmilk was collected. All of these samples tested negative for COVID-19, using both the CDC test and the hospital’s in-house RT-PCR test¹⁵.

Hence, if a mom has COVID-19 during her pregnancy or even during birth, she does not need to worry that the virus will be present in the umbilical cord blood or the tissues of the placenta and umbilical cord.

Virus protection from maternal antibodies

Once again, the placenta is amazing: at the same time that it protects the baby from disease, it allows antibodies from the mother to cross into the baby’s blood^8,9. The baby inherits its mother’s immune system and has resistance to most diseases that mom resists until about age six months.

If the mother has immunity to COVID-19, most likely so will the newborn baby.  Any woman who has had the coronavirus and recovered from the illness is carrying protective antibodies. A small study in Wuhan China confirmed that, when 6 mothers who were sick with COVID-19 pneumonia gave birth, all of their babies had antibodies to COVID-19 in their blood¹⁶.

Hopefully someday there will be a vaccine against COVID-19, and if mom has received the vaccine it should protect her newborn too. Studies have shown that seasonal influenza vaccines given to pregnant women have greatly reduced newborn flu infections, and the vaccine is effective when given at least two weeks before birth^5,6.

Are cord blood banks screening moms for COVID-19?

Yes, cord blood banks have modified their maternal health history forms to ask about possible exposure to COVID-19, even though the virus is not expected to appear in the umbilical cord blood or the tissues of the afterbirth. The philosophy is to collect the information now in case it becomes important later.

Most public banks that collect cord blood donations have had to modify their procedures due to COVID-19, simply to reduce person-to-person contact. For example, maternal consent interviews might be conducted by telephone. If you are planning to donate your baby’s cord blood or placenta, check in advance to find out how the program at your delivery hospital is operating.

Family cord blood banks have not had to change their collection procedures, because the cord blood is collected by the staff that will be in the delivery room anyway.

How have cord blood banks modified their operations due to COVID-19?

Cord blood banks are essential services that continue to operate during shelter in place orders.  Ironically, COVID-19 has not required any changes to the laboratory operations of cord blood banks, but the banks have had to make accommodations to their logistics and personnel management.

Once cord blood or birth tissue arrives in a laboratory for processing, it is managed with standard protections against blood borne pathogens. These include staff wearing personnel protective equipment and handling the blood and tissue samples under a hood that maintains a sterile field. Therefore, it is not necessary to take any additional precautions.

However, the shipping of the collection kit to the laboratory can be fraught with difficulty during this pandemic, especially if the kit needs to travel long distance or cross international borders. Parents should talk to their bank to plan around these logistics. Most hospitals are restricting entry to only allow patients and staff, which means that medical couriers cannot pick up collection kits at the bedside. There have been reports that often someone close to the mother must walk the kit out of the hospital to the courier.

When a collection kit containing cord blood or birth tissue arrives in a laboratory, it is placed in a special receiving zone, away from regular working areas in case the outside of the kit is contaminated with coronavirus. Designated personnel carefully open the kits and transfer the cord blood and tissue samples to the laboratory.

The biggest concern that cord blood banks are struggling with at this time is the possibility that their staff will become sick with COVID-19. A worst case scenario would be a staff member infecting others at work. To guard against this, laboratory technicians have been assigned to teams that do not have contact with each other. Even if an entire team is exposed and has to be quarantined, the other teams can keep working. Common areas at the work place, such as locker rooms or break rooms, are cleaned repeatedly with medical grade disinfectant. Staff members either work remotely or stay socially distant.

Is the coronavirus a reason to bank cord blood?

During the COVID-19 pandemic, many parents are more mindful of ways that they can protect their baby’s health, and as a result we have seen a spike in inquiries about cord blood banking. Nonetheless, the long-term odds of using your child’s cord blood or birth tissues have not been changed by COVID-19.  The basic motivation for banking cord blood is that it can benefit patients in need of donors or it can be a form of health insurance for your family.

Links to Resources:

• AABB: Coronavirus and Blood Donation
• ACOG: American College of Obstetricians and Gynecologists (ACOG) Practice Advisory
• ASH: American Society of Hematology COVID-19 Resources
• ASTCT: American Society for Transplantation and Cellular Therapy COVID-19 Interim Patient Care Guidelines
• Be The Match: Response to COVID-19
• CDC: Coronavirus (COVID-19) | Pregnancy and Breastfeeding
• COVIDplasma.org: How to donate COVID-19 convalescent plasma
• FACT: Foundation for the Accreditation of Cellular Therapy COVID-19 Update
• FDA: Updated Information for HCT/P Establishments Regarding the Coronavirus 2019 Pandemic
• Flourish: COVID-19: free live mobile-friendly visualizations
• MassGen: Massachusetts General Hospital | Coronavirus (COVID-19) During Pregnancy
• JHU-CSSE: Johns Hopkins University COVID-19 global case tracker
• Red Cross: Staying Safe and Helping Others During COVID-19
• WHO: Q&A on COVID-19, pregnancy, childbirth and breastfeeding
• WMDA: World Marrow Donor Association Medical Suitability Recommendations 

References:

1. ACOG Clinical Guidance. Novel Coronavirus 2019 (COVID-19). Practice Advisory. Last updated 2020-03-13
2. Maragakis LL. Coronavirus Disease 2019 vs. the Flu Johns Hopkins website sourced 2020-04-08
3. Rasmussen SA, Jamieson DJ, and Uyeki TM. Effects of influenza on pregnant women and infants. American Journal of Obstetrics and Gynecology 2012; 207(3-Supplement):S3-S8.
4. Harris JW. Influenza occurring in pregnant women. A statistical study of thirteen hundred and fifty cases. JAMA. 1919; 72(14):978-980.
5. Tamma PD, Steinhoff MC, and Omer SB. Influenza infection and vaccination in pregnant women. Expert Rev. Resp. Med. 2010; 4(3):321-328.
6. Blanchard-Rohner G, Meier S, Bel M, Combescure C, Othenin-Girard V, Swali RA, de Tejada BM, and Siegrist CA. Influenza Vaccination Given at Least 2 Weeks Before Delivery to Pregnant Women Facilitates Transmission of Seroprotective Influenza-specific Antibodies to the Newborn. The Pediatric Infectious Disease Journal 2013; 32(12):1374-1380.
7. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, Xia S, and Zhou W. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Translational Pediatrics 2020; 9(1):51-60.
8. Cetrulo CL, and Cetrulo KJ. Placental and pregnancy stem cells: everyone is, or should be, interested in the placenta. Stem Cell Reviews 2006; 2(2):79-80.
9. Simister NE. Placental transport of immunoglobulin G. Vaccine 2003; 21(24):3365-3369.
10. Irving WL, James DK, Stephenson T, Laing P, Jameson C, Oxford JS, Chakraverty P, Brown DWG, Boon ACM, and Zambon MC. Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. British Journal of Obstetrics and Gynecology 2000; 107(10):1282-1289.
11. Zeng L, Xia S, Yuan W, Yan K, Xiao F, Shao J, and Zhou W. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatrics 2020;
12. Zou S. Potential Impact of Pandemic Influenza on Blood Safety and Availability. Transfusion Medicine Reviews 2006; 20(3):181-189.
13. FDA. Updated Information for Human Cell, Tissue, or Cellular or Tissue-based Product (HCT/P) Establishments Regarding the Coronavirus Disease 2019 Pandemic. web page Released 2020-04-01
14. Allyn B. FDA Loosens Restrictions On Gay Blood Donors Amid 'Urgent Need' Caused By Coronavirus. NPR 2020-04-02
15. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, Li J, Zhao D, Xu D, Gong Q, Liao J, Yang H, Hou W, and Zhang Y. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet 2020; 395:809-815.
16. Zeng H, Xu C, Fan J, Tang Y, Deng Q, Zhang W, and Long X. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia JAMA 2020; doi:10.1001/jama.2020.4861

 

 

Cord Tissue mesenchymal Stem cells in the treatment of Covid 19

Dr. Kouzi

Advanced Therapy Medicinal Products under investigation (n=24) (wording taken from the titles of the registered studies)

10  out of 24 products that have been employeed in clinical trials for the treatment of Covid 19 are from perinatal tissues, mostly from cord tissue. 

·     Aerosol inhalation of vMIP: viral macrophage inflammatory protein

·     Ankylosaurus; M1 macrophages target

·     Anti-2019-nCoV inactivated convalescent plasma

·     Anti-SARS-CoV-2 inactivated convalescent plasma

·     Biological preparation of human placenta

·     Convalescent plasma treatment

·     Cord blood mesenchymal stem cells

·     Human menstrual blood-derived stem cells

·     Immunoglobulin from cured patients

·     Inactivated Mycobacterium vaccine

·     Infusion of convalescent plasma

·     Mesenchymal stem cells

·     Mesenchymal stem cells exosomes atomization

·     mRNA-1273

·     NK cells

·     Plasma treatment

·     Recombinant cytokine gene-derived protein injection

·     Regulating intestinal flora

·     Therapeutic antibody from recovered novel coronavirus pneumonia patients

·     Umbilical cord blood mononuclear cells

·     Umbilical cord mesenchymal stem cells (hucMSCs)

·     Umbilical cord Wharton’s Jelly derived mesenchymal stem cells

·     Umbilical Cord(UC)-derived mesenchymal stem cells

·     Washed microbiota transplantation

Carl Heneghan is the Editor in Chief BMJ EBM and Professor of EBM, Centre for Evidence-Based Medicine in the Nuffield Department of Primary Care Health Sciences, University of Oxford Oxford     https://www.cebm.net/covid-19/registered-trials-and-analysis/

 

NK of cord blood in the treatment of coronavirus

Dr. Kouzi

https://www.forbes.com/sites/alexknapp/2020/04/02/fda-gives-green-light-to-test-a-treatment-against-covid-19-coronavirus-that-flattens-the-curve-in-patients/#1909bc544b57

FDA Green-Lights Clinical Trial For COVID-19 Coronavirus Treatment That ‘Flattens The Curve’ In Patients

Celularity founder Robert Hariri

 CELULARITY

Therapeutics startup Celularity announced Thursday morning that it has received FDA clearance to begin a clinical trial of a proposed stem-cell treatment for COVID-19. The approval of the New Jersey-based company’s IND application enables the company to begin a clinical trial with patients who have the disease. The company’s therapy, called CYNK-001 for now, uses “Natural Killer” (NK) cells, a form of white blood cells that wage war against cancer and viral infection, derived from placental stem cells. The company’s been developing similar treatments for several years against cancer and Crohn’s disease, several of which are being tested as well.

The idea behind the therapy is that for patients who are starting to show symptoms, or who may be at risk for a more severe form of the disease, can receive an intravenous infusion of NK cells to bolster their immune response to the virus, says founder and CEO Robert Hariri. That’s because the additional NK cells help slow down the viruses’ ability to replicate within the body. It’s an approach he likens to social distancing—slowing the spread of COVID-19 so hospitals don’t get even more overwhelmed—within patients themselves.‘’By administering our NK cells to patients, we are acting to ‘flatten the viral titer curve,’ so the patient’s adaptive immune system can get in gear and do the job of clearing the virus,” he says.Celularity was cofounded by Hariri and X Prize Foundation chair Peter Diamandis in 2016 as a spinout of pharmaceutical company Celgene. About a decade before, the company had found itself in the business of collecting and storing umbilical cord blood from placentas after birth. The undifferentiated stem cells found in that blood offer a universal way to generate NK cells that potentially reduce risk of rejection or other complications.It’s a strategy that’s earned the company support from investors like Bill Maris at Section 32, Sorrento Therapeutics, and former Apple CEO John Sculley. According to Pitchbook, the company has raised over $327 million in backing to date. The primary thrust of the company’s therapeutic efforts have been to leverage these treatments against forms of cancer such as myelomas and leukemia. But because NK cells are often involved in protecting the body against viruses, Hariri says he’s always looked to the company one day going after infectious disease.According to Hariri, it may take only a matter of days to see results from the first clinical trial of COVID-19 patients. That test will involve use of the treatment in a patient group of up to 86 people. If that’s successful, Hariri hopes those results will mean accelerating to a larger trial, and then, if all goes well, out to market. 

“This is a very easy product to deploy,” says Hariri. “We’re hopeful that if we get compelling enough data, the agency and the CDC and the NIH will work with us to scale up production.”

 

Cord tissue mesenchymal stem cells in the treatment of covid -10 pneumonia

Dr. Kouzi

 

 Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia

Zikuan Leng1,5,#, Rongjia Zhu2,#, Wei Hou3,#, Yingmei Feng3,#, Yanlei Yang4, Qin Han2, Guangliang Shan2, Fanyan Meng1, Dongshu Du1, Shihua Wang2, Junfen Fan2, Wenjing Wang3, Luchan Deng2, Hongbo Shi3, Hongjun Li3, Zhongjie Hu3, Fengchun Zhang4, Jinming Gao4, Hongjian Liu5*, Xiaoxia Li6, Yangyang Zhao2, Kan Yin6, Xijing He7, Zhengchao Gao7, Yibin Wang7, Bo Yang8, Ronghua Jin3*, Ilia Stambler9,10,11, Lee Wei Lim9,10,12, Huanxing Su9,10,13, Alexey Moskalev9,10,14, Antonio Cano9,10,15, Sasanka Chakrabarti16, Kyung-Jin Min9,10,17, Georgina Ellison-Hughes9,10,18, Calogero Caruso9,10,19, Kunlin Jin9,10,20*, Robert Chunhua Zhao1,2,9,10* 1School of Life Sciences, Shanghai University, Shanghai, China. 2Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China. 3Beijing YouAn Hospital, Capital Medical University, Beijing, China. 4Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 5Department of Orthopaedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 6Institute of Stem Cell and Regeneration Medicine, School of Basic Medicine, Qingdao University, Shandong, China. 7Department of Orthopaedics, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China. 8Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 9The Executive Committee on Anti-aging and Disease Prevention in the framework of Science and Technology, Pharmacology and Medicine Themes under an Interactive Atlas along the Silk Roads, UNESCO, Paris, France. 10International Society on Aging and Disease, Fort Worth, Texas, USA. 11The Geriatric Medical Center "Shmuel Harofe", Beer Yaakov, affiliated to Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 12School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. 13Institute of Chinese Medical Science, University of Macau, Taipa, Macau, China. 14Institute of Biology, Komi Science Center of Russian Academy of Sciences, Syktyvkar, Russia. 15Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain. 16Maharishi Markandeshwar Deemed University, Mullana-Ambala, India. 17Department of Biological Sciences, Inha University, Incheon, South Korea. 18Faculty of Life Sciences & Medicine, King's College London, London, UK. 19Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy. 20University of North Texas Health Science Center, Fort Worth, TX76107, USA.

[Received February 25, 2020; Revised February 28, 2020; Accepted February 28, 2020]  Aging and Disease Vol 11,N02; 216-228

ABSTRACT: A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.

 

Key words: COVID-19, ACE2 negative, mesenchymal stem cells, cell transplantation, immunomodulation, function recovery