Vaccination with two doses (at least 4 weeks apart) of the CoronaVac inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (from the Chinese Sinovac company) prevented 65 percent of COVID-19 infections and nearly 90 percent of COVID-19-related hospitalizations, ICU admissions, and deaths related to COVID-19 in an observational "real-world" study with 10.2 million Chileans, reported in the New England Journal of Medicine (2021; doi: 10.1056/NEJMoa2107715). A single dose was less effective, but still gave some protection.
"Our results suggest that the inactivated SARS-CoV-2 vaccine effectively prevented COVID-19 [infection]-including severe disease and death," wrote the investigators led by Rafael Araos, MD, of the Instituto de Ciencias e Innovacion en Medicina, Universidad del Desarrollo in Las Condes, Chile. "Overall, our results underscore the potential of this vaccine to save lives and substantially reduce demands on the health care system."
CoronaVac also had a practical advantage, the researchers explained. It did not need to be frozen and could be stored at standard refrigerator temperatures for up to 3 years without losing activity.
Trial Method
The analysis was based on findings from a prospective national cohort of Chilean residents who were at least 16 years old during the study period from February 2 to May 1, 2021, and were receiving health care from the public national health care system. The subjects were classified into three groups: 1) those who remained unvaccinated, 2) those who were partially immunized-having had at least one dose of CoronaVac, and 3) those who were fully immunized (having had two doses).
The researchers assessed the effectiveness of the vaccine for preventing COVID-19 infection, hospitalization related to COVID-19, admission to the ICU, and death. They estimated the change in the "hazard ratio" associated with partial immunization (at least 14 days after a single dose of vaccine) and with full immunization (after receiving the second dose) as compared with unvaccinated study participants.
Altogether, 10,187,720 Chileans were included in the final study population (after those infected with COVID-19 and those receiving the BNT162b2 [Pfizer/BioNTech] vaccine were excluded). Of these, 5,471,728 were not vaccinated during the study period, 542,418 study subjects had received only one dose of the vaccine, and 4,173,574 had both doses (separated by the required period of at least 4 weeks).
Research Findings
The study identified 218,784 cases of COVID-19 infection. Of these, 22,866 patients needed hospitalization, 7,873 were admitted to the ICU, and 4,042 died. Among study subjects who were fully immunized (double-vaccinated), the vaccine effectiveness was 65.9 percent (with a high level of statistical significance) for the prevention of COVID-19 symptomatic infection. For prevention of hospitalization, the effectiveness was higher at 87.5 percent. COVID-19-related death was prevented in 90.3 percent of fully vaccinated subjects, and there was an 86.3 percent reduction of the risk of entering the ICU due to COVID-19.
In participants who had only received a single vaccination, CoronaVac provided a modest 15 percent reduction in the risk of COVID-19 infection, 45 percent protection against coronavirus-related ICU admission or death, and 37 percent protection against hospitalization.
Older Populations
The Chilean study included enough participants to make it possible to do a statistically sound subgroup analysis of participants over 60. The vaccine effectiveness in the fully immunized group of persons 60 years of age or older was found to be very similar to the overall cohort: 66.6 percent protection against COVID-19 infection, 85.3 percent against hospitalization, 89.2 percent against ICU admission, and 86.5 percent against COVID-19-related death.
A strength of the Chilean real-world study findings was derived from the sheer quantity of data coming from such a large cohort of participants. Although Phase III randomized controlled studies of CoronaVac from Brazil, Indonesia, and Turkey had already reported promising efficacy, their results-based on datasets orders of magnitude smaller-varied from one study to the next and did not include enough data to assess the vaccine in older patients.
Writing in an editorial section of the New England Journal of Medicine, Annelies Wilder-Smith, MD, PhD, of the World Health Organization, and Kim Mulholland, MBBS, MD, Professor of Child Health and Vaccinology at the London School of Hygiene and Tropical Medicine and Chairholder at the Murdoch Children's Research Institute in Melbourne, Australia, noted that the world needed more vaccines against SARS-CoV-2 and that even vaccines with lower effectiveness could have substantial effects on public health.
Multiple Vaccines Needed
Rather than scoring vaccines for their effectiveness as a way of choosing one rather than another, Wilder-Smith and Mulholland urged the need to look at the specific roles that various vaccines could play in the global battle against the coronavirus.
"Each vaccine has different attributes, advantages, and disadvantages, and multiple factors must be considered in guiding policy decisions," they noted.
Chile is widely praised for having espoused vaccination nationally. And the Chilean government has invested in a diverse portfolio of SARS-CoV-2 vaccines, including-most recently-CoronaVac.
"Despite the effectiveness of the vaccine against symptomatic illness being lower than that observed with the messenger RNA (mRNA) vaccines, the effectiveness of the CoronaVac vaccine against hospitalizations and deaths may still be substantial, wrote Wilder-Smith and Mulholland. "These findings are encouraging. Reducing deaths and protecting health care systems are the primary public health goals during the acute phase of the pandemic."
But the reviewers pointed out that the Chilean study did not throw light on whether vaccination reduced transmission of SARS-CoV-2. They also feared that the low level of protection against infection among subjects receiving only one dose of CoronaVac was unlikely to inhibit the spread of the virus sufficiently to promote long-term herd immunity to reduce the risk of further "variants of concern" emerging. And the vaccine's effect against the recently arrived gamma variant of SARS-CoV-2 had yet to be tested.
Wilder-Smith and Mulholland stated: "The national cohort study from Chile should serve as a useful model for other countries to follow, but longer follow-up time is needed to monitor vaccine effectiveness over time, against variants, and in various subpopulations and settings. The global health community needs to work together to resolve remaining knowledge gaps regarding COVID-19 vaccine effectiveness in order to support prompt policy decisions."
Peter M. Goodwin is a contributing writer.