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Covid-19: Airborne transmission is being underestimated, warn experts

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2720 (Published 07 July 2020) Cite this as: BMJ 2020;370:m2720

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Re: Covid-19: Airborne transmission is being underestimated, and Covid-19 in Liquid Nitrogen is a potential threat

Dear Editor
We read with interest the appeal to the medical community and to the relevant national and international bodies made by Morawska and Milton to recognize the potential for airborne spread of COVID-19 and their plea for the use of preventive measures to mitigate airborne transmission [1]. We would like to warn also about the risks related with the use of Liquid Nitrogen which, we truly believe, is still disregarded.
Liquid Nitrogen (LN2) and its gaseous form Nitrogen Vapor (NV) are key cryogenic agents for cooling and freezing in healthcare and the food industry. They can, however, become contaminated by viruses, bacteria, and fungi [2, 3]. In 1995, a hepatitis B virus contamination of a cryostorage tank used for bone-marrow stem cells caused acute icteric hepatitis B in six patients following transplantation [2].
Human assisted reproductive technology (ART) is the only medical discipline where human gametes and embryos with potential to produce live births are routinely stored in LN2/NV. Many embryo/oocyte cryopreservation techniques utilize “open” cryo-devices with direct contact with LN2/NV during cooling. Even with “closed” systems, accidental contact with LN2/NV may occur during storage and warming of material. The fact that infections traceable to cryostorage have not been reported after millions of embryo transfers may be due to innate immunity in the female reproductive tract and reduced dosage of infective agents during laboratory procedures. However, the risk of infection is real, especially when new, highly infective agents arise.
Airborne contaminants come in contact with LN2/NV and remain cryopreserved [3]. Although some industrial sectors (drug manufacturing, food and beverage sterile packaging) carry out raw filtration of LN2 before use, this does not guarantee sterility, and it is not effective against smaller microorganisms.
However, LN2/NV can be efficiently sterilized by UV-C radiation, an adequate dose proving effective against even the smallest microorganisms, such as viruses (HIV, Hepatitis, Coronavirus, Ebolavirus, etc.) [4]. Unfortunately, UV-C LN2/VN sterilization is not yet a mainstream practice, although it is increasingly used in human ART.
In this Covid-19 pandemic, manufacturers of drugs/disposables/culture media are trying to mitigate risk by sourcing raw materials to low-risk regions, but this is not applicable to LN2/NV, which can thus become potential vectors of contamination. Aerosol and surface stability of Covid-19 has been investigated [5] but the risk of this virus being accidentally cryopreserved in LN2/NV has not yet been studied. The use of contaminated LN2/NV risks virus awakening and the contamination of thawing cells, environment and operators.
ART practices worldwide have been provided with recommendations that aim to safeguard the health and safety of patients and staff by cancellation of all fresh embryo transfers and freezing for later embryo transfer [6].
Our plea to ART practitioners is to not underestimate the potential risk of LN2/NV mediated Covid-19 infection and to put in place strategies to prevent this eventuality.

References

1. Morawska L, Milton DK. It is Time to Address Airborne Transmission of COVID-19. Clinical Infectious Diseases 06 July 2020

2. Tedder RS, Zukerman MA, Goldstone AH, Hawkins AE, Fielding A, Briggs EM et al. Hepatitis B transmission from contaminated cryopreservation tank. Lancet 1995; 346: 137-140.
3. Morris GJ. The origin, ultrastructure, and microbiology of the sediment accumulating in liquid nitrogen storage vessels. Cryobiology 2005; 50:231–8.
4. Parmegiani L, Accorsi A, Cognigni GE, Bernardi S, Troilo E, Filicori M. Sterilization of liquid nitrogen with ultraviolet irradiation for safe vitrification of human oocytes or embryos. Fertil Steril 2010; 94:1525—1528.
5. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17 [Epub ahead of print].
6. ASRM COVID-19 Task Force Issues Recommendations. Patient Management and Clinical Recommendations During The Coronavirus (COVID-19) Pandemic. 2020, Mar 17 (https://www.asrm.org/news-and-publications/patient-management-and-clinic...).

Competing interests: Dr Parmegiani reports fees from Origio-Coopersurgical, Merck, and Irvine-Fujifilm and is shareholder of Nterilizer Srl . Prof Vajta reported receiving personal fees and being a founder, shareholder and consultant to VitaVitro Shenzhen Pty Ltd. Dr Alikani is on the Scientific Advisory Board of TMRW.

16 July 2020
Lodovico Parmegiani
Head of Embryology
Gabor Vajta, RVT Australia, Brinsmead , Australia; Mina Alikani, Northwell Health Fertility Laboratories, New York, NY, USA
GynePro Medical Centers- NextClinics International
GynePro Medical Centers Via T. Cremona,8 40137 Bologna-Italy