Protective effectiveness of prior SARS-CoV-2 infection and hybrid immunity against Omicron infection and severe disease: a systematic review and meta-regression

BackgroundWe aimed to systematically review the magnitude and duration of the protective effectiveness of prior infection (PE) and hybrid immunity (HE) against Omicron infection and severe disease. MethodsWe searched pre-print and peer-reviewed electronic databases for controlled studies from January 1, 2020, to June 1, 2022. Risk of bias (RoB) was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I)-Tool. We used random-effects meta-regression to estimate the magnitude of protection at 1-month intervals and the average change in protection since the last vaccine dose or infection from 3 months to 6 or 12 months. We compared our estimates of PE and HE to previously published estimates of the magnitude and durability of vaccine effectiveness (VE) against Omicron. FindingsEleven studies of prior infection and 15 studies of hybrid immunity were included. For prior infection, there were 97 estimates (27 at moderate RoB and 70 at serious RoB), with the longest follow up at 15 months. PE against hospitalization or severe disease was 82{middle dot}5% [71{middle dot}8-89{middle dot}7%] at 3 months, and 74{middle dot}6% [63{middle dot}1-83{middle dot}5%] at 12 months. PE against reinfection was 65{middle dot}2% [52{middle dot}9-75{middle dot}9%] at 3 months, and 24{middle dot}7% [16{middle dot}4-35{middle dot}5%] at 12 months. For HE, there were 153 estimates (78 at moderate RoB and 75 at serious RoB), with the longest follow up at 11 months for primary series vaccination and 4 months for first booster vaccination. Against hospitalization or severe disease, HE involving either primary series vaccination or first booster vaccination was consistently >95% for the available follow up. Against reinfection, HE involving primary series vaccination was 69{middle dot}0% [58{middle dot}9-77{middle dot}5%] at 3 months after the most recent infection or vaccination, and 41{middle dot}8% [31{middle dot}5-52{middle dot}8%] at 12 months, while HE involving first booster vaccination was 68{middle dot}6% [58{middle dot}8-76{middle dot}9%] at 3 months, and 46{middle dot}5% [36{middle dot}0-57{middle dot}3%] at 6 months. Against hospitalization or severe disease at 6 months, hybrid immunity with first booster vaccination (effectiveness 95{middle dot}3% [81{middle dot}9-98{middle dot}9%]) or with primary series alone (96{middle dot}5% [90{middle dot}2-98{middle dot}8%]) provided significantly greater protection than prior infection alone (80{middle dot}1% [70{middle dot}3-87{middle dot}2%]), first booster vaccination alone (76{middle dot}7% [72{middle dot}5-80{middle dot}4%]), or primary series alone (64{middle dot}6% [54{middle dot}5-73{middle dot}6%]). Results for protection against reinfection were similar. InterpretationPrior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. All protection estimates waned quickly against infection but remained high for hospitalisation or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection against all outcomes, reinforcing the global imperative for vaccination. FundingWHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe global emergence and rapid spread of Omicron (B.1.1.529) variant of concern, characterized by their ability to escape immunity, has required scientists and policymakers to reassess the population protection against Omicron infection and severe disease. So far, few systematic reviews have incorporated data on Omicron, and none have examined the protection against Omicron conferred by hybrid immunity (i.e. the immunity gained from the combination of vaccination and prior infection) which is now widespread globally. While one preprint has recently reported protection from prior infection over time, no systematic review has systematically compared the magnitude and duration of vaccination, prior infection, and hybrid immunity. A large single-country study has reported that protection from either infection or hybrid immunity against Omicron infection wanes to low levels at 15 months, but is relatively stable against severe disease. Added value of this studyPrior infection and hybrid immunity both provided greater and more sustained protection against Omicron than vaccination alone. Individuals with hybrid immunity had the highest magnitude and durability of protection against all outcomes; protection against severe disease remained above 95% until the end of available follow-up at 11 months after hybrid immunity with primary series and 4 months after hybrid immunity with booster vaccination, and was sustained at these high levels of protection in projections to 12 months and 6 months, respectively. Implications of all the available evidenceThese results may serve to tailor guidance on the optimal number and timing of vaccinations. At the public health level, these findings can be combined with data on local infection prevalence, vaccination rates, and their timing. In settings with high seroprevalence, limited resources, and competing health priorities, it may be reasonable to focus on achieving high coverage rates with primary series among individuals who are at higher risk of poor outcome, as this will provide a high level of protection against severe disease for at least one year among those with prior infection. Furthermore, given the waning protection for both infection-and vaccine induced immunity against infection or reinfection, mass vaccination could be timed for roll-out prior to periods of expected increased incidence, such as the winter season. At the individual level, these results can be combined with knowledge of a persons infection and vaccination history. A six-month delay in booster may be justified after the last infection or vaccination for individuals with a known prior infection and full primary series vaccination. Further follow-up of the protective effectiveness of hybrid immunity against hospitalization or severe disease for all vaccines is needed to clarify how much waning of protection might occur with longer duration since the last infection or vaccination. Producing estimates of protection for new variant-containing vaccines will be crucial for COVID-19 vaccine policy and decision-making bodies. Policy makers considering the use and timing of vaccinations should include the local extent of past infection, the protection conferred by prior infection or hybrid immunity, and the duration of this protection as key considerations to inform their decision-making.

Modelling the Test, Trace and Quarantine Strategy to Control the COVID-19 Epidemic in the State of Sao Paulo, Brazil

Testing for detecting the infection by SARS-CoV-2 is the bridge between the lockdown and the opening of society. In this paper we modelled and simulated a test-trace-and-quarantine strategy to control the COVID-19 outbreak in the State of Sao Paulo, Brasil. The State of Sao Paulo failed to adopt an effective social distancing strategy, reaching at most 59% in late March and started to relax the measures in late June, dropping to 41% in 08 August. Therefore, Sao Paulo relies heavily on a massive testing strategy in the attempt to control the epidemic. Two alternative strategies combined with economic evaluations were simulated. One strategy included indiscriminately testing the entire population of the State, reaching more than 40 million people at a maximum cost of 2.25 billion USD, that would reduce the total number of cases by the end of 2020 by 90%. The second strategy investigated testing only symptomatic cases and their immediate contacts - this strategy reached a maximum cost of 150 million USD but also reduced the number of cases by 90%. The conclusion is that if the State of Sao Paulo had decided to adopt the simulated strategy on April the 1st, it would have been possible to reduce the total number of cases by 90% at a cost of 2.25 billion US dollars for the indiscriminate strategy but at a much smaller cost of 125 million US dollars for the selective testing of symptomatic cases and their contacts.

The potential for a controlled human infection platform in Singapore

For over 100 years, controlled human infection (CHI) studies have been performed to advance the understanding of the pathogenesis, treatment and prevention of infectious diseases. This methodology has seen a resurgence, as it offers an efficient model for selecting the most promising agents for further development from available candidates. CHI studies are utilised to bridge safety and immunogenicity testing and phase II/III efficacy studies. However, as this platform is not currently utilised in Asia, opportunities to study therapeutics and vaccines for infections that are important in Asia are missed. This review examines the regulatory differences for CHI studies between countries and summarises other regulatory differences in clinical trials as a whole. We found that the regulations that would apply to CHI studies in Singapore closely mirror those in the United Kingdom, and conclude that the regulatory and ethical guidelines in Singapore are compatible with the conduct of CHI studies.

Trends in importation of communicable diseases into Singapore

<p><b>INTRODUCTION</b>Singapore is a transition country in Southeast Asia that is both vulnerable and receptive to the introduction and re-introduction of imported communicable diseases.</p><p><b>MATERIALS AND METHODS</b>For a 10-year period between 1998 and 2007 we studied the trend, epidemiological characteristics, proportion of imported versus local transmission of malaria, viral hepatitis (hepatitis A and E), enteric fevers (typhoid and paratyphoid), cholera, chikungunya and SARS.</p><p><b>RESULTS</b>Of a total of 4617 cases of the above selected diseases notified in Singapore, 3599 (78.0%) were imported. The majority of the imported cases originated from Southeast Asia and the Indian subcontinent. Malaria constituted the largest bulk (of which 95.9% of the 2126 reported cases were imported), followed by hepatitis A (57.1% of 1053 cases imported), typhoid (87.6% of 596 cases imported), paratyphoid (87.6% of 241 cases imported), and hepatitis E (68.8% of 231 cases imported). Furthermore, there were 14 cases of imported cholera, 6 cases of imported severe acute respiratory syndrome (SARS) and 13 cases of imported chikungunya.</p><p><b>CONCLUSION</b>This study underlines that diseases such as malaria, viral hepatitis and enteric fever occur in Singapore mainly because of importation. The main origin of importation was South and Southeast Asia. The proportion of imported diseases in relation to overall passenger traffic has decreased over the past 10 years.</p>

Graduate public health education--Singapore's contribution to strengthening capacity in the region and beyond

The year 2008 marks the 55th anniversary of the graduate public health programme in Singapore. This article traces the evolution of the programme-from the Diploma in Public Health in 1953 to the Master of Public Health in 2007--in response to changing challenges and needs. It also discusses the role Singapore can continue to play in addressing global inequities in access to public health education and in strengthening public health capacity in the region and beyond.

Travel characteristics and health practices among travellers at the travellers' health and vaccination clinic in Singapore

<p><b>INTRODUCTION</b>Singapore has a fast-growing travel industry, but few studies have been done on travel characteristics and travel health practices. This study describes the profile and healthseeking behaviour of travellers attending a travel health clinic in Singapore.</p><p><b>MATERIALS AND METHODS</b>A cross-sectional survey was conducted on travellers attending the Traveller's Health and Vaccination Centre (THVC) between September and November 2002 using a standardised questionnaire. Information obtained included individual demographic and medical information, travel patterns, vaccination status and travel health practices.</p><p><b>RESULTS</b>Four hundred and ninetyfive (74%) eligible travellers seen at THVC responded to the questionnaire. Their mean age was 36 years; 77% were professionals, managers, executives, and businessmen, students, and white collar workers. Asia was the main travel destination, and most travelled for leisure and resided in hotels or hostels. The median duration of travel was 16 days. Although >90% had previously travelled overseas, only 20% had previously sought pre-travel advice. Malays were significantly underrepresented (P < 0.01); and Caucasians and Eurasians were significantly more likely (P < 0.01) to have previously sought pre-travel advice compared with Chinese, Indians and Malays. Factors associated with seeking pre-travel advice included travel outside of Asia, especially Africa and South America.</p><p><b>CONCLUSION</b>Singaporean travellers travel more often to cities rather than rural areas, compared with non-Asian travellers. Asia is the preferred destination, and travel outside of Asia is perceived as more risky and is associated with seeking pre-travel advice and vaccinations. Travel patterns and behaviours need to be taken into account when developing evidence-based travel medicine in Asia.</p>