Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial | Global Health | JAMA | JAMA Network
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    3 Comments for this article
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    Placebo
    Aasim Ahmad, MBBS, MHSc (Bioethics) | The Kidney Center Post Graduate Institute, Karachi Pakistan
    It interesting to note that the word placebo is only used once in this whole article. It is a randomized, double-blind placebo-controlled clinical trial; let us call it that. It would also be interesting to know how the Research Ethics Review Committees justified using placebo when effective vaccines are already in use in United Arab Emirates.
    CONFLICT OF INTEREST: None Reported
    Placebo
    Humaid Obaid Al-Shamsi, MD, FRCPC, FACP | Burjeel Cancer Institute, Abu Dhabi
    Regarding the previous comment about how the IRB approved the study while there is an approved vaccine, the trial was registered at the Chinese clinical trial registry CCTR on 2020-07-18. At the time of approval of the trial no vaccine was approved. Hope that clarifies the matter.
    CONFLICT OF INTEREST: None Reported
    Efficacy Trials Need Potential Asymptomatic Carrier Controls
    Samer Singh, MSc (Microbiology), PhD | Institute of Medical Sciences, Banaras Hindu University
    The interim results shared by Kaabi et al about the evaluation of two inactivated SARS-CoV-2 in clinical trials for Symptomatic COVID-19 Infections in adults seem promising. The authors' recognized lacunae of their inability to ascertain the efficacy of inactivated vaccines to prevent asymptomatic infection due to the requirements of ‘formal study-wide surveillance via virologic and serologic tests’ is the most pertinent for all ongoing vaccine trials. Without knowing the actual decrease in population proportion harboring and shedding the virus at any point of an outbreak (i.e., the carriers) we are proceeding blindly – not knowing how much we are increasing the asymptomatic cases. Any increase in the percentage of potential asymptomatic individuals in a population translates into an increased probability of infection for the vulnerable (aged, comorbid, immunocompromised; who are currently not part of trials; not included) and possible deaths due to changes in preventive measures and practices (out of sight, out of mind). In other words, the increase in population proportions who can only become asymptomatic cases (which are already variously estimated upwards of 85%) would increase the probability of the actual vulnerable population component contracting the disease during any outbreak due to expected change in population dynamics in the absence of apparent infections in the majority non-vulnerable. It would be highly desirable that authors make an attempt to ascertain the number of infected asymptomatic participants in the equally exposed control and vaccinated population to realize the potential of the vaccines. To effectively contain epidemic a vaccine that can also decrease the potential number of infected asymptomatic people in a population is needed, not just one that decreases people who are infected and symptomatic. The assessment of change in virologic and serologic parameters is an important endpoint and authors may attempt to include them in the final results to correctly identify vaccines that may be better in terms of decreasing both symptomatic as well as asymptomatic cases in any population to make their trial results relevant and applicable to current crises. All ongoing vaccine trials may actively consider including virologic and serologic parameters to arrive at more meaningful, dependable, and applicable conclusions.
    CONFLICT OF INTEREST: None Reported
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    Original Investigation
    May 26, 2021

    Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial

    Author Affiliations
    • 1Sheikh Khalifa Medical City, Abu Dhabi Health Services Company (SEHA), Abu Dhabi, United Arab Emirates
    • 2China National Biotec Group Company Limited, Beijing, China
    • 3Henan Province Center for Disease Control and Prevention, Zhengzhou, Henan, China
    • 4Bahrain Defence Force Royal Medical Services, Military Hospital, Kingdom of Bahrain
    • 5Ministry of Health and Prevention, Abu Dhabi, United Arab Emirates
    • 6Prince Hamza Hospital, Amman, Jordan
    • 7Ministry of Health, Cairo, Egypt
    • 8Ministry of Health, Kingdom of Bahrain
    • 9National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co, Ltd, Wuhan, Hubei, China
    • 10Beijing Institute of Biological Products Co, Ltd, Beijing, China
    • 11Beijing Key-Tech Statistical Consulting Co, Ltd, Beijing, China
    • 12Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health (incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    • 13G42 Healthcare, Abu Dhabi, United Arab Emirates
    JAMA. Published online May 26, 2021. doi:10.1001/jama.2021.8565
    Key Points

    Question  What is the efficacy of 2 inactivated SARS-CoV-2 vaccines for prevention of symptomatic COVID-19?

    Findings  This prespecified interim analysis of a randomized clinical trial included 40 382 participants who received at least 1 dose of a 2-dose inactivated vaccine series developed from either SARS-CoV-2 WIV04 (5 µg/dose) or HB02 (4 µg/dose) strains or an aluminum hydroxide–only control, with a primary end point of the incidence of symptomatic COVID-19 at least 14 days after the second injection. The efficacy for the 2 vaccines, compared with an aluminum hydroxide–only control, was 72.8% in the WIV04 group and 78.1% in the HB02 group; both comparisons were statistically significant.

    Meaning  Two inactivated SARS-CoV-2 vaccines demonstrated efficacy against symptomatic COVID-19 compared with an aluminum hydroxide–only control.

    Abstract

    Importance  Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed.

    Objective  To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines.

    Design, Setting, and Participants  Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively.

    Interventions  Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)–only control (n = 13 458); they received 2 intramuscular injections 21 days apart.

    Main Outcomes and Measures  The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose.

    Results  Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase–polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]).

    Conclusions and Relevance  In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending.

    Trial Registration  ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780

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