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 Table of Contents  
Year : 2021  |  Volume : 65  |  Issue : 3  |  Page : 307-310  

COVID-19 vaccine and the cold chain implications for global adoption

Director Projects, The INCLEN Trust International, New Delhi, India

Date of Submission19-Nov-2020
Date of Decision17-Jul-2021
Date of Acceptance13-Aug-2021
Date of Web Publication22-Sep-2021

Correspondence Address:
Manoja Kumar Das
The INCLEN Trust International, F1/5, Okhla Industrial Area, Phase 1, New Delhi - 110 020
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijph.IJPH_1353_20

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The COVID-19 pandemic has spread globally with 190.8 million infected cases and 4.1 million deaths as of July 18, 2021. In absence of any definite antiviral agent availability and therapeutic armamentarium, vaccines are considered critical. While 20 vaccines are in use, about 295 vaccines are underdevelopment globally using eleven technological platforms. While the vaccines have >80% efficacy, the ultracold (−70°C and −20°C) storage and logistics requirements for some raise concerns for implementation, especially in developing countries. The Ebola vaccination in African countries, which required an ultracold chain provided lessons for these COVID-19 vaccines. The existing vaccine cold chain system suffers from temperature excursions at cold chain stores and during transportations in different countries suggests careful assessment and addressing the gaps for effective vaccine introduction. Appropriate attention for cold chain storage, logistics (especially the last mile), and vaccine management and upgradation is needed to achieve optimal vaccine effectiveness for curtailing the pandemic.

Keywords: Cold chain storage, COVID-19, vaccine, vaccine logistics

How to cite this article:
Das MK. COVID-19 vaccine and the cold chain implications for global adoption. Indian J Public Health 2021;65:307-10

How to cite this URL:
Das MK. COVID-19 vaccine and the cold chain implications for global adoption. Indian J Public Health [serial online] 2021 [cited 2023 Apr 2];65:307-10. Available from:

   Introduction Top

The novel coronavirus infection (COVID-19), since its emergence in China's Wuhan province in December 2019, has spread worldwide with 190.8 million infected people and 4.1 million deaths as of July 18, 2021 ( The United States, India, and Brazil are the three top countries with the highest case burden. The pandemic has severely dampened the economic activities across all sectors along with the social and academic activities apart from the routine health services. To curb the infection spread, lockdown, and restrictions on travel, social and business activities of varying degrees have been adopted by countries. After few months of unlocking, several countries had to declare a second lockdown due to re-emergence of COVID-19 cases.

No specific antiviral agent is available for COVID-19. Several repurposed medications, antimalarial, antivirals, antibiotics, and antiparasites (chloroquine, hydroxychloroquine, remdesivir, lopinavir, ritonavir, azithromycin, and ivermectin) are being used, either singly or in combination apart from the convalescent plasma, plasma therapy, and immunoglobulins, with variable success. Some drugs (hydroxychloroquine, azithromycin, and ivermectin) and vaccines (bacillus Calmette–Guérin and measles) are being used as preventive measures with variable effects. In addition, steroids are prescribed to tackle immune-mediated systemic pathologies. With suboptimal clinical successes of the therapeutic armamentarium, the whole globe is banking on the vaccines for pandemic control.

   Vaccine Development Top

The COVID vaccine development efforts are progressing at an unprecedented pace and scale. The efforts against SARS, MERS, and Ebola along with the evolving technology platforms have been leveraged for potential vaccine candidate identification and development. As of July 18, 2021, about 20 vaccines are authorized for use and 295 candidate vaccines using eleven platforms are underdevelopment [Table 1].[1] Out of these, 111 candidate vaccines are in clinical phases including 19 in Phase-3, 9 in Phase-2/3, 10 in Phase-2, 28 in Phase-1/2, and 38 in Phase-1. There are 184 vaccines in preclinical phase of development. Several of the technologies and platforms are new for vaccines. With encouraging Phase-3 results for the vaccines, about 20 vaccines have been authorized for use across various countries.[2],[3],[4],[5],[6] While these results have raised hopes, the cold chain blues are also anticipated for some. The Pfizer vaccines (mRNA) require storage at −70°C and once the vials are thawed, they can be refrigerated and used within 5 days. The Moderna vaccine (mRNA) storage norm has been revised from −70°C to −20°C and can be stored at +2°C–8°C for 30 days. The Gamaleya Research Institute's vaccine, Sputnik-V (rAD26/rAD5), requires storage at −18°C or lesser. Janssen vaccine (AD26) can be stored at +2°C–8°C for 3 months. The AstraZeneca–Oxford/Covishield (ChAdOx1), Covaxin (inactivated whole virus), and two Chinese (CoronaVac and BBIBP-CorV, both inactivated) vaccines require storage +2°C–8°C throughout. Several other vaccines in Phase-3 clinical trial require the standard cold chain storage conditions (+2°C–8°C), as applicable for the routine immunization program globally.
Table 1: The pipeline of COVID-19 candidate vaccines by technology type and development stages (as of July 16, 2021, World Health Organization)

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Preparation for induction of the COVID vaccine is very critical, in view of the target populations and the speed, although subject to the vaccine availability. A minimum vaccine coverage of 60%–80% is proposed for curtailing the COVID pandemic. Two primary doses are needed for most of the COVID-19 vaccines. The volume of the population vaccinated and proportionately required doses appear humongous. The immunization program in most of the countries targets children and pregnant women. In many developing countries, most of the immunization services are delivered by the public sector. The currently used vaccines are stored and transported primarily at +2°C–8°C and to a lesser extent at −20°C. Thus, any vaccine storage requirement outside the +2°C–8°C range is a challenge not only for bulk storage but also for last-mile storage and transportation.

While majority of the vaccine packaging are multidose vials, some of the COVID-19 vaccine packaging specifications are yet to be finalized: single-dose vial, prefilled syringe or multidose vial, and number of doses, which shall decide the cold chain footprint. Furthermore, the duration of protection with the COVID-19 vaccines and the need for booster or periodic vaccination such as influenza are being studied. Despite several uncertainties, the cold chain is critical for the COVID-19 vaccine handling and vaccination globally, more important for developing countries. In 2014, no cold chain storage facility was available at 20% of the health facilities in low- and middle-income countries (LMICs). Out of the facilities with cold chain devices, 2% had devices with optimal technology, 23% had functional devices with outdated technologies, 41% had poorly performing devices, and 14% had nonfunctional devices. Only 14% of the LMICs met the WHO cold chain temperature control criteria. The vaccine storage capacity was adequate in 43% of countries. The vaccine supply chain management policies and effective distribution criteria were met by 33% and 15% of the countries, respectively.[7] Since 2014, several countries have added newer childhood vaccines into the routine immunization program, which would have further filled up the cold chain spaces. According to WHO, up to 50% of the lyophilized and 25% of liquid vaccine doses are wasted either before or after a vial is opened, mostly attributed to the supply chain and logistics issues.[8] Studies from both developing and developed countries have reported frequent excursions, to both extremes, lower and higher temperature ranges at stores and during transportations.[9],[10],[11],[12],[13] Vaccine vial monitors (VVMs) on the vials indicate the usability status. In absence of the temperature stability information, the COVID-19 vaccines have been authorized for use without any VVM, which further challenge tracking the temperature excursions. This poses an operational challenge for the immunization system in LMICs without a continuous temperature monitoring mechanism.

   Experiences from Past Top

The Ebola vaccine (rVSV△G-ZEBOV-GP) use in some African countries that required ultra-cold chain storage (−60°C or lesser) and logistics raised several concerns. Due to nonavailability of the ultracold freezers, the devices were procured and shipped from Europe and Asia. For ensuring smooth function of these ultracold freezers, temperature-controlled environments (range, -20°C to -25°C ) were created and electrical grid supply was upgraded. Despite multiple power sources and backup plans and freezers, frequent power interruptions and freezer failures were observed. The repair and maintenance of the freezers was also a challenge. Shipping of the vaccines was done in polyurethane-insulated containers with pelletized dry ice and replenishment of dry ice was required during the 3–10 days transportation period. The vaccines from stores were transported to the districts in customized Arktek-DF containers. Additional human resources were also engaged for the cold chain management and monitoring. The temperature remained below −60°C for 6.5 days. An overall vaccine wastage of 28% was observed with 32% (range: 23%–52%) and 22% (range: 12%–41%) at immediate and deferred vaccination, respectively. These challenges were tackled in project mode and required additional investments.[14] However, such investment at a large scale and in multiple countries would be really resource intensive and may not be feasible for the LMICs to meet without donors' support. Arranging the cold chain devices, monitoring tools, trained human resources, and funding over a short period appears to be a humongous task.

   COVID-19 Vaccine Cold Chain Blues Top

An effective COVID-19 vaccine compatible with the existing cold chain storage norm (+2°C–8°C) would be attractive globally. Assuming a two-dose schedule, prefilled syringe formulation would be inefficient for many LMICs with already challenged immunization cold chain infrastructure. A multidose vaccine vial (5–10 doses) would be useful and cold chain efficient. Assuming a minimum of 5 doses per vial COVID-19 vaccine packaging and target coverage of 60%–80% of the population, the anticipated cold chain space projection is about 10–20 times of the current need for routine immunization. This cold chain space expansion over a short period is not easy for several LMICs. Thus, apart from the cold chain space available in public sector, additional space must be arranged from private sector facilities and/or hired. The global vaccine manufacturing capacity and availability pipeline are still under evolution. Several countries are negotiating with the manufacturers for ensuring availability. Under the COVAX program, the COVID-19 vaccines shall be available in phases to the countries. The political and financial negotiations are ongoing in this context. From the H1N1 influenza pandemic vaccine utilization experience, the effective and efficient COVID-19 vaccine induction shall depend on the population priority, system preparedness, economics, and political scenario of the countries.[15],[16]

While everyone globally is eagerly waiting for the COVID-19 vaccine, the success of candidate vaccines has raised hopes, cold chain blues for vaccine storage, handling, and logistics are anticipated, especially for the LMICs. Many developing countries shall face challenges related to cold chain space, stringent temperature monitoring, in-country logistics, and last-mile transportation to maintain the vaccine integrity. In view of these immunization infrastructures, logistics and managerial capacity challenges, and budgetary need to revamp, it appears that the use of the vaccine in several developing countries may be delayed. While the globe was unprepared for the COVID pandemic, ill-prepared cold chain and immunization logistics system cannot be an excuse. While the research and development must target at immunization system compatible vaccine candidates, the immunization system requires urgent assessment and investments for upgradation to adopt them quickly and vaccine delivery to the remotest places.

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Conflicts of interest

There are no conflicts of interest.

   References Top

World Health Organisation. COVID-19 Vaccine Tracker and Landscape (July 16, 2021). World Heal Organisation, Geneva; 2020. Available from: [Last accessed on 2021 Jul 18].  Back to cited text no. 1
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020;383:2603-15.  Back to cited text no. 2
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-16.  Back to cited text no. 3
Voysey M, Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99-111.  Back to cited text no. 4
Logunov DY, Dolzhikova IV, Shcheblyakov DV, Tukhvatulin AI, Zubkova OV, Dzharullaeva AS, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled Phase 3 trial in Russia. Lancet 2021;397:671-81.  Back to cited text no. 5
Tanriover MD, Doğanay HL, Akova M, Güner HR, Azap A, Akhan S, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): Interim results of a double-blind, randomised, placebo-controlled, Phase 3 trial in Turkey. Lancet 2021;398:213-22.  Back to cited text no. 6
WHO, UNICEF. Achieving Immunization Targets with the Comprehensive Effective Vaccine Management (EVM) Framework: WHO/UNICEF Joint Statement. World Heal Organisation, Geneva; 2016. Available from: [Last accessed on 2020 Oct 20].  Back to cited text no. 7
World Health Organisation. Monitoring Vaccine Wastage at Country Level. Guidelines for Program Managers. World Heal Organisation, Geneva; 2005. Available from: 1_eng.pdf?sequence=1&isAllowed=y. [Last accessed on 2020 Oct 20].  Back to cited text no. 8
Matthias DM, Robertson J, Garrison MM, Newland S, Nelson C. Freezing temperatures in the vaccine cold chain: A systematic literature review. Vaccine 2007;25:3980-6.  Back to cited text no. 9
Hanson CM, George AM, Sawadogo A, Schreiber B. Is freezing in the vaccine cold chain an ongoing issue? A literature review. Vaccine 2017;35:2127-33.  Back to cited text no. 10
Murhekar MV, Dutta S, Kapoor AN, Bitragunta S, Dodum R, Ghosh P, et al. Frequent exposure to suboptimal temperatures in vaccine cold-chain system in India: Results of temperature monitoring in 10 states. Bull World Health Organ 2013;91:906-13.  Back to cited text no. 11
Das MK, Arora NK, Mathew T, Vyas B, Sindhu M, Yadav A. Temperature integrity and exposure to freezing temperature during vaccine transfer under the universal immunization program in three states of India. Indian J Public Health 2019;63:139-42.  Back to cited text no. 12
[PUBMED]  [Full text]  
Das MK, Arora NK, Mathew T, Vyas B, Devi SK, Yadav A. Temperature integrity and exposure of vaccines to suboptimal temperatures in cold chain devices at different levels in three states of India. Trop Dis Travel Med Vaccines 2020;6:8.  Back to cited text no. 13
Jusu MO, Glauser G, Seward JF, Bawoh M, Tempel J, Friend M, et al. Rapid Establishment of a cold chain capacity of -60°C or colder for the STRIVE Ebola vaccine trial during the Ebola outbreak in sierra Leone. J Infect Dis 2018;217:S48-55.  Back to cited text no. 14
Porter RM, Goldin S, Lafond KE, Hedman L, Ungkuldee M, Kurzum J, et al. Does having a seasonal influenza program facilitate pandemic preparedness? An analysis of vaccine deployment during the 2009 pandemic. Vaccine 2020;38:1152-9.  Back to cited text no. 15
World Health Organisation. Main Operational Lessons Learnt from the WHO Pandemic Influenza A(H1N1) Vaccine Deployment Initiative. Geneva: World Heal Organisation; 2011.  Back to cited text no. 16


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