Medical Corner: Covid-19 Vaccine: A Game Changer?

The novel Coronavirus (COVID-19) pandemic has been wreaking havoc on people, institutions and infrastructures around the globe since 2020. It still remains as a huge challenge in 2021 causing uncertainty to the future of the public health system.

Despite intensive research and experimental drugs tested in human trials, there is still a lack of robust data to improve clinical outcomes of sick COVID-19 patients. Corticosteroids and possibly remdisivir are possible exceptions to this. With a present second wave due to the resurgence of the highly infectious virus and emerging new variants from the UK, South Africa and Brazil spreading across different continents, the scientific community is urging the speedy roll-out of a vaccine to reduce COVID-19’s clinical burden and community transmission and stop this public health crisis.

What are the leading COVID-19 vaccines available?
1. Traditional (inactivated virus vaccine)
  • Sinovac
  • Sinopharm (China)
2. Novel mRNA vaccine:
  • BNT162b2 COVID-19 vaccine from Pfizer-BioNtech, (Germany)
  • mRNA-1273 SARS-CoV-2 vaccine from Moderna (USA)
3. Vector vaccine (“modified adenovirus vaccine”)
  • ChAdOx1 nCOV-19 Vaccine (AZD1222) from Oxford-Astra Zeneca (Oxford-AZ, UK)
  • Ad26.COV.S Covid-19 vaccine from Johnson and Johnson
  • rAd26, rAd5 Gam-COVID-Vac (Sputnik V) from Russia

4. SARS-CoV-2 recombinant spike protein nanoparticle (NVX-CoV2373) vaccine from Novovax Company

What is the current evidence available to support the available vaccines?


  • Lipid nanoparticle-formulated, nucleoside mRNA vaccine
  • Age >16 y/o, 30ug per dose IM, 2-dose regimen 21 days apart
  • 43,448 participants injected (21,720 BNT162b2, 21,728 placebo) with 95% efficacy (95% CI, 90.3 to 97.6)
  • Low short-term serious adverse events (SAE), transient minor events (e.g. headache, fatigue, pain at injection site)
  • Temperature storage -70 Cº
(NEJM C4591001 Phase 3 Clinical Trial Group Dec 10 2020)


  • Lipid nanoparticle-encapsulated mRNA vaccine
  • Age >18 y/o, 100ug IM, 2-dose regimen 28 days apart
  • 30,420 participants injected IM (15,210 each group of mRNA-1273 vaccine and placebo) with 94.1% efficacy (95% CI 89.3 to 96.8% p is less than 0.001)
  • Rare SAE, short-term and transient mild reactogenicity resolved within 72 hours
  • Temperature storage -20 Cº
(NEJM The COVE study group Phase 3 trial Dec 30 2020)


  • Replication-deficient chimpanzee adenoviral vector ChAdOx1
  • Age >18 yo (small number of participants above 65 yo), 2 cohorts with 2 doses each with 4 to 12 weeks interval
  • 11,636 participants from UK (7,548 subjects), Brazil (4,088 subjects) and rest from South Africa
    • 2 standard doses cohort (SD:SD) with 62.1% efficacy (95% CI 41-75.7)
    • Low dose first then standard dose second cohort (LD:SD) with 90% efficacy (67.4- 97 P interaction 0.010)
    • Overall vaccine efficacy in both groups of 70.4% (95% CI 54.8-80.6) and reported higher efficacy rate if booster dose interval is longer
  • 84 SAEs in trial vaccine and 91 in control group in 74,341 persons-months safety follow-up (median 3.4 months, IQR 1.3-4.8) - mostly short-term, transient reactogenicity
  • Temperature storage 2-8 Cº
(LANCET The Oxford COVID Vaccine Trial Group Interim analysis of Phase 3 trial Dec 08 2020)

Johnson and Johnson:

  • Recombinant vector Adenovirus vaccine (Ad.26.COV2.S or JNJ-78436725)
  • Age >18 y/o (34% above 60 yo)
  • Placebo-controlled double-blind RCT with 43,783 participants
  • Single dose, multi-country (USA, Peru, Mexico, Argentina, Brazil, Colombia, South Africa)
  • Vaccine efficacy in preventing moderate to severe disease varied in each region:
    • 72% in USA
    • 66% in Latin America
    • 57% in South Africa after 28 days post-vaccination
    • 85% in preventing severe / critical COVID-19 disease across all regions
  • Temperature storage 2-8 Cº
(Preliminary results of ENSEMBLE Phase 3 study)
(Awaiting publication in major scientific journals)


  • Recombinant nanoparticle vaccine (NVX-CoV2373) using baculovirus as a virus carrier to infect moth cells to produce copies of spike protein that are harvested and purified into vaccine.
  • Preliminary analysis of small subjects resulted in 89% efficacy
  • Phase 3 trial is underway recruiting 15,000 participants from UK

Moths: an unlikely ally in COVID-19 vaccine development (David Havel/ Shutterstock)

Sputnik V:

  • Recombinant adenovirus (rAd)-based vaccine, 2 vector components (rAd26-S, rAd5-S)
  • 0.5 mL IM, 21 days interval
  • 21,977 participants (16,501 vaccine, 5476 placebo) with 91.6% efficacy (95% CI 85.6-95.2)
  • Mostly mild and transient adverse events - 0.4% SAE and less than 0.1% death non-related to vaccine
  • Temperature storage 2-8 Cº
(LANCET The Gam-COVID Vac Vaccine Trial group Feb 02 2021)


  • Inactivated virus vaccine (CoronaVac)
  • Brazilian clinical trials with 12,000 participants had overall 50.4% efficacy
  • Indonesian and Turkish trials had efficacy between 65% to 91% (small, nonconclusive studies)
  • Temperature storage 2-8 Cº
(Awaiting publication in major scientific journals)

Vaccine is a game-changer BUT “not a magic bullet”!

Based on current evidence available, vaccines are generally safe and effective in preventing COVID-19 illness (“symptomatic infection”) and may reduce serious illness, hospitalisation and death. However, it remains unclear whether the vaccine will prevent asymptomatic infection and suppress community transmission. People who have had a previous COVID-19 infection may defer for up to 6 months before getting a jab.

The vaccine may offer immediate protection within 2 weeks of the first dose (“priming dose”) and higher immunoprotection after the second dose (“booster dose”) but it is still unclear how long this immunity will last. The vaccine is recommended in adults including the elderly with stable medical conditions (e.g. hypertension, diabetes mellitus, asthma, liver or kidney disease). There is limited evidence in immunocompromised people including HIV patients and people on immunosupressive drugs – this will require separate data analysis.

Based on the current data, the vaccine is NOT recommended in the following:

  • People with a history of severe allergic reaction to any component of vaccine - the second dose is withheld if severe anaphylactic reaction occurs from the first dose.
  • Pregnant women and lactating women.
  • Children aged less than 16 y/o.

Currently, the WHO Emergency Use Listing (EUL) has only approved vaccines from Pfizer-BioNtech and Oxford-AZ for emergency use, and COVAX roll-out globally will be based on data reviewed and submitted by pharmaceutical industry. A joint statement from WHO and UNICEF cited that 130 countries with 2.5 billion people have not received a single dose whereas most of the 128 million doses were administered so far in only 10 countries (“vaccine inequity”). Australia’s COVID vaccine roll-out will begin on February 22, 2021, with first doses from the Pfizer-BioNtech vaccine followed by the Oxford-AZ vaccine to be manufactured locally and possibly additional doses from the Novovax vaccine if proven safe and effective.

Vaccines and COVID-19 Variants
There are 3 new variants of COVID-19 circulating in a few countries today:
  • UK Variant (B.1.1.7) with 23 mutations in the spikelike S protein.
  • South African Variant (B.1.351) with 23 mutations in the S protein.
  • Brazil variant (P.1) with 17 mutations.

According to scientists, the virus developed variant strains through “jumping species”, random genetic mutations or new strains escaping from sick immunocompromised individuals harbouring the virus for a longer period of time after infection. There are small data and laboratory modelling that show mRNA vaccines will provide protection against variants identified from UK and South Africa. It is reported that new COVID-19 variants from South Africa and Brazil (“polymorphism e484K” not seen in UK variant) can reduce antibody binding and potentially reduce the efficacy of current vaccines, making reinfection possible. It remains uncertain how the emerging variant strains will affect long-term vaccine efficacy, establishments of herd immunity and tailored-epidemiologic modelling, genomic surveillance and vaccine roll-out plan.

In the meantime, we must continue the social preventative measures and proven public health measures including hand hygiene, face masks, cough etiquette, avoidance of crowded places without proper ventilation, high-level of testing / contact tracing / isolation and quarantine of positive and suspected cases and international border restrictions and biosecurity. Yes, we need vaccines to get the pandemic under control – the more options we have, the faster we can move forward and contain this evolving global pandemic.

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