Estimating the transmission dynamics of Omicron in Beijing, November to December 2022

We tracked the effective reproduction number Rt of Omicron BF.7 in Beijing in November - December 2022 by fitting a transmission dynamic model parameterized with real-time mobility data to (i) the daily number of new symptomatic cases on November 1-11 (when the zero-covid interventions were still strictly enforced) and (ii) the proportion of individuals who participated in online polls on December 10-14 and self-reported to have been previously test-positive. After the announcement of "20 measures", we estimated that Rt increased to 3.42 (95% CrI: 2.79 - 4.17) on November 18. Infection incidence peaked on December 10, and the cumulative infection attack rate was 42.5% (95% CrI: 20.3 - 63.9) on December 14. Surveillance programmes should be rapidly set up to monitor the evolving epidemiology and evolution of SARS-CoV-2 across China.

Modelling the adjustment of COVID-19 response and exit from dynamic zero-COVID in China

BackgroundSince the initial Wuhan outbreak, China has been containing COVID-19 outbreaks through its "dynamic zero-COVID" policy. Striking a balance between sustainability and cost-benefit, China has recently begun to adjust its COVID-19 response strategies, e.g. by announcing the "20 measures" on 11 November and further the "10 measures" on 7 December 2022. Strategies for safely exiting from dynamic zero-COVID (i.e. without catastrophically overburdening health systems and/or incurring unacceptably excessive morbidity and mortality) are urgently needed. MethodsWe use simulations to assess the respective and combined effectiveness of fourth-dose heterologous boosting, large-scale antiviral treatment and public health and social measures (PHSMs) that might allow China to further adjust COVID-19 response and exit from zero-COVID safely after 7 December 2022. We also assess whether local health systems can cope with the surge of COVID-19 cases posed by reopening, given that chunyun, a 40-day period with extremely high mobility across China associated with Spring Festival, will begin on 7 January 2023. FindingsReopening against Omicron transmission should be supported by the following interventions: 1) fourth-dose heterologous boosting 30-60 days before reopening by vaccinating 4-8% of the population per week with [≥]85% uptake across all ages; 2) timely antiviral treatment with [≥]60% coverage; 3) moderate PHSMs to reduce transmissibility by 47-69%. With fourth-dose vaccination coverage of 85% and antiviral coverage of 60%, the cumulative mortality burden would be reduced by 26-35% to 448-503 per million, compared with reopening without any of these interventions. Simultaneously reopening all provinces under current PHSMs would still lead to hospitalisation demand that are 1.5-2.5 times of surge hospital capacity (2.2 per 10,000 population per day). InterpretationAlthough the surge of disease burden posed by reopening in December 2022 - January 2023 would likely overload many local health systems across the country, the combined effect of vaccination, antiviral treatment and PHSMs could substantially reduce COVID-19 morbidity and mortality as China transits from dynamic-zero to normality. Planning for such a nationwide, coordinated reopening should be an urgent priority as part of the global exit from the acute phase of the COVID-19 pandemic. FundingCOVID-19 Vaccines Evaluation Program, Chinese Center for Disease Control and Prevention; Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong SAR; General Research Fund, Research Grants Council, Hong Kong Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and preprint archives for articles published up to 7 December 2021, that contained information about exit strategies of zero-COVID or reopening in China after the emergence of Omicron using the terms "China", "Omicron", "B.1.1.529", "COVID-19", "SARS-CoV-2", "vaccin*", "vaccine", "antiviral", "control measures", "non-pharmaceutical intervention", "public health and social measure", "zero-COVID", "exit strategy" and "reopen*". We only found one study by Wang et al (doi: 10.1101/2022.05.07.22274792) but they assessed the feasibility of sustaining SARS-CoV-2 containment with zero-COVID strategy in China. To our knowledge, there is no discussion of exit strategies of the zero-COVID strategy or assessment of feasibility of reopening in China. Added value of this studyReopening against Omicron transmission should be supported by the following interventions: 1) fourth-dose heterologous boosting 30-60 days before reopening by vaccinating 4-8% of the population per week with [≥]85% uptake across all ages; 2) timely antiviral treatment with [≥]60% coverage; 3) moderate PHSMs to reduce transmissibility by 47-69%. With fourth-dose vaccination coverage of 85% and antiviral coverage of 60%, the cumulative mortality burden would be reduced by 26-35% to 448-503 per million, compared with reopening without any of these interventions. Simultaneously reopening all provinces under current PHSMs would still lead to hospitalisation demand that are 1.5-2.5 times of surge hospital capacity (2.2 per 10,000 population per day). Implications of all the available evidenceAlthough the surge of disease burden posed by reopening in December 2022 - January 2023 would likely overload many local health systems across the country, the combined effect of vaccination, antiviral treatment and PHSMs could substantially reduce COVID-19 morbidity and mortality as China transits from dynamic-zero to normality. Planning for such a nationwide, coordinated reopening should be an urgent priority as part of the global exit from the acute phase of the COVID-19 pandemic.

Population-based sero-epidemiological estimates of real-world vaccine effectiveness against Omicron infection in an infection-naive population, Hong Kong, January to July 2022

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. While current vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections (i.e. irrespective of symptoms) remains sparse. We addressed this knowledge-gap using a community-wide serosurvey with 5,310 subjects by estimating how vaccination histories modulated risk of infection in Hong Kong (which was largely infection naive) during a large wave of Omicron epidemic during January-July 2022. We estimated that Omicron infected 45% (41-48%) of the Hong Kong population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection (VE of 47% (95% credible interval 34-68%) and 70% (43-99%) for three and four doses of BNT162b2 respectively; VE of 31% (1-73%) and 59% (10-99%) for three and four doses of CoronaVac respectively) seven days after vaccination, but protection waned with half-lives of 15 (3-47) weeks for BNT162b2 and 5 (1-37) weeks for CoronaVac. Our findings suggest that booster vaccination can temporarily enhance population immunity ahead of anticipated waves of infections.

Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong

The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number "Rt", a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of Rt, and provided additional insights into the impact of public health measures on transmission of infections. One-Sentence SummaryReal-time estimates of serial interval distributions can improve assessment of COVID-19 transmission dynamics and control.

Homologous and heterologous boosting with CoronaVac and BNT162b2: a randomized trial (the Cobovax study)

BackgroundThere are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. MethodsWe conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. ResultsWe enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac ("CC-C", n=101) or BNT162b2 ("CC-B", n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac ("BB-C", n=118) or BNT162b2 ("BB-B", n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Antibody responses against the ancestral virus, Omicron BA.1 and BA.2 subvariant by surrogate neutralization and PRNT50 were stronger for the recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. CD4+ T cells boost only occurred in CoronaVac-primed arms. We did not identify differences in CD4+ and CD8+ T cell responses between arms. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). ConclusionsSimilar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.

Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine

IntroductionThird doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses. MethodsWe administered BNT162b2 as a third dose to adults aged [≥]30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2. ResultsWe administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity. ConclusionsWhile antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.

Within-hotel transmission of SARS-CoV-2 during on-arrival quarantine in Hong Kong

BackgroundOn-arrival quarantine has been one of the primary measures used to prevent the introduction of COVID-19 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine varying throughout the pandemic for various reasons. However, hotels are not necessarily designed with infection control in mind. We aimed to study the potential risk of transmission between persons in on-arrival quarantine. MethodsWe examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the full genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. A combination of epidemiological information and sequence information was then used to identify probable transmission events. FindingsAmong 221 imported cases that overlapped with other quarantined cases, phylogenetic analysis identified eight suspected clusters comprising 20 cases in total. Only three of these clusters had been recognised as hotel transmission events. InterpretationWe have identified potential occurrences of COVID-19 transmission within hotel quarantine in Hong Kong demonstrating the underlying low but non-zero risk associated with sequestering arrivals within hotels. In future pandemics, on-arrival quarantine in hotels could be used to delay the introduction of infection, but the construction of purpose-built facilities for on-arrival quarantine might be necessary to minimize importation risk. FundingHealth and Medical Research Fund, Hong Kong

Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir among COVID-19 inpatients during Hong Kong's Omicron BA.2 wave: an observational study

BackgroundReal-world evidence on the effectiveness of oral antivirals in mild-to-moderate COVID-19 patients is urgently needed. This retrospective cohort study aims to evaluate the clinical and virologic outcomes associated with molnupiravir and nirmatrelvir/ritonavir use in COVID-19 patients during a pandemic wave dominated by the Omicron BA.2 variant. MethodsWe analyzed data from a territory-wide retrospective cohort of hospitalized patients with confirmed diagnosis of SARS-CoV-2 infection from 26th February 2022 to 26th April 2022 in Hong Kong. Oral antiviral users were matched with controls using propensity-score matching in a ratio of 1:4. Study outcomes were a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], or intensive care unit admission) and their individual outcomes, and lower viral load of cycle threshold (Ct) value [≥]30 cycles. Hazard ratios (HR) of event outcomes were estimated using Cox regression models. ResultsAmong 40,776 hospitalized patients with SARS-CoV-2 infection over a mean follow-up of 41.3 days with 925,713 person-days, 2,359 and 1,000 patients not initially requiring oxygen therapy were initiated with molnupiravir and nirmatrelvir/ritonavir, respectively. The crude incidence rates of all-cause mortality and IMV were 22.24 and 1.06 events per 10,000 person-days among molnupiravir users, 11.04 and 1.75 events per 10,000 person-days among nirmatrelvir/ritonavir users. Oral antiviral use was associated with a significantly lower risk of the composite outcome of disease progression (molnupiravir: HR=0.53, 95%CI=0.46-0.62, p<0.001; nirmatrelvir/ritonavir: HR=0.33, 95%CI=0.24-0.46, p<0.001) than non-use, which was consistently observed for all-cause mortality (molnupiravir: HR=0.55, 95%CI=0.47-0.63, p<0.001; nirmatrelvir/ritonavir: HR=0.32, 95%CI=0.23-0.45, p<0.001). Molnupiravir users had lower risks of IMV (HR=0.31, 95%CI=0.16-0.61, p<0.001). Time to achieving lower viral load was significantly shorter among oral antiviral users than matched controls (molnupiravir: HR=1.21, 95%CI=1.07-1.37, p=0.002; nirmatrelvir/ritonavir: HR=1.25, 95%CI=1.04-1.50, p=0.015). Amongst survivors, nirmatrelvir/ritonavir had shorter length of hospital stay (-0.70 days, 95%CI=-1.37 to -0.04, p=0.039) than matched controls. Head-to-head comparison of molnupiravir and nirmatrelvir/ritonavir reported higher risk of mortality (HR=1.53 95%CI=1.01-2.31, p=0.047) and longer length of hospital stay (0.83 days, 95%CI=0.07-1.58, p=0.032) for molnupiravir users. ConclusionsAgainst Omicron BA.2, initiation of novel oral antiviral treatment in hospitalized patients not requiring any oxygen therapy was associated with lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster. FundingHealth and Medical Research Fund, Food and Health Bureau Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe medical and research community are actively exploring the use of oral antivirals in COVID-19 patients to lower their risks of hospitalization and death, and to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 13 May 2022 using the search terms "SARS-CoV-2 OR COVID-19" AND "molnupiravir OR Lagevrio OR EIDD-2801" OR "nirmatrelvir OR Paxlovid OR PF-07321332". Major studies examining the safety and efficacy of molnupiravir include MOVe-IN and MOVe-OUT trials conducted in hospitalized and non-hospitalized COVID-19 patients, respectively. Clinical evidence for the use of ritonavir-boosted nirmatrelvir came from the EPIC-HR trial conducted among non-hospitalized adults with COVID-19. While no clinical benefits have been observed with molnupiravir use in the inpatient setting among patients with moderate-to-severe COVID-19, early initiation of molnupiravir or nirmatrelvir/ritonavir within 5 days of symptom onset in non-hospitalized patients with mild-to-moderate COVID-19 and risk factors for progression to severe disease has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Notably, these clinical trials were conducted prior to the prevalence of Omicron variant, and the efficacy of oral antivirals against this current variant of concern can only be inferred from experimental evidence to date. Real-world evidence of oral antiviral use in patients with SARS-CoV-2 infection of Omicron variant is lacking. Added value of this studyTo the best of our knowledge, this is the first real-world study exploring the clinical use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. We conducted a territory-wide, retrospective cohort study to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in COVID-19 patients who did not require supplemental oxygen on admission in Hong Kong. Early initiation of oral antivirals within 2 days of admission was associated with significantly lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster than their respective matched controls. Molnupiravir use was also associated with a significantly lower risk of requiring invasive mechanical ventilation than non-use. Furthermore, our head-to-head comparison suggested a relatively larger reduction in mortality risk with nirmatrelvir/ritonavir than molnupiravir use. Implications of all the available evidenceCurrent guidelines are now prioritizing the distribution of oral antivirals to those who do not require supplemental oxygen, but who are at the highest risk of disease progression. Our study cohort reflected such prescription pattern in real-world clinical practice. The antiviral effect and mortality benefit observed in this patient cohort support the use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission during a pandemic wave of Omicron variant. Our findings also support the prioritization of nirmatrelvir/ritonavir over molnupiravir use in COVID-19 patients whenever accessible and clinically appropriate, in view of the formers substantial mortality benefit. Ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations (by vaccination status and viral variants), drug combinations, and different healthcare settings.

Vaccine effectiveness of two and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong

BackgroundHong Kong maintained extremely low circulation of SARS-CoV-2 until a major community epidemic of Omicron BA.2 starting in January 2022. Both mRNA BNT162b2 (BioNTech/Fosun Pharma) and inactivated CoronaVac (Sinovac) vaccines are widely available, however coverage has remained low in older adults. Vaccine effectiveness in this predominantly infection-naive population is unknown. MethodsWe used individual-level case data on mild/moderate, severe/fatal and fatal hospitalized COVID-19 from December 31, 2021 to March 8, 2022, along with census information and coverage data of BNT162b2 and CoronaVac. We used a negative binomial model, adjusting for age and calendar day to estimate vaccine effectiveness of one, two and three dose schedules of both vaccines, and relative effectiveness by number of doses and vaccine type. FindingsA total of 12.7 million vaccine doses were administered in Hong Kongs 7.3 million population, and we analyzed data from confirmed cases with mild/moderate (N=5,474), severe/fatal (N=5,294) and fatal (N=4,093) COVID-19. Two doses of either vaccine protected against severe disease and death, with higher effectiveness among adults [≥]60 years with BNT162b2 (VE: 88.2%, 95% confidence interval, CI: 84.4%, 91.1%) compared to CoronaVac (VE: 74.1%, 95% CI: 67.8%, 79.2%). Three doses of either vaccine offered very high levels of protection against severe outcomes (VE: 98.1%, 95% CI: 97.1%, 98.8%). InterpretationThird doses of either BNT162b2 or CoronaVac provide substantial additional protection against severe COVID-19 and should be prioritized, particularly in older adults who received CoronaVac primary schedules. Longer follow-up is needed to assess persistence of different vaccine platforms and schedules. FundingCOVID-19 Vaccines Evaluation Program, Chinese Center for Disease Control and Prevention

Strength and durability of antibody responses to BNT162b2 and CoronaVac

We studied 2780 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine ("Comirnaty", BioNTech/Fosun Pharma). We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women.

BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults who previously received two doses of inactivated vaccine

BackgroundLimited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. MethodsWe conducted an open label trial of a third vaccine dose of an mRNA vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged [≥]30 years who had previously received two doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. ResultsIn 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.2 (p<0. 001), and mean sVNT levels increased from an inhibition of 17% to 96% (p<0.001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by at least 24 fold from Day 0 to Day 28 against the ancestral virus (p<0.001) and rose by at least 11 fold against the Omicron variant (p<0.001). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. ConclusionsA third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier. SummaryIn this open label trial of Chinese adults aged [≥]30 years who received two doses of inactivated COVID-19 vaccine 6 months earlier, third-dose mRNA vaccine substantially improved antibody levels against the ancestral virus and Omicron variant with well-tolerated safety profile.

Comparative effectiveness of allocation strategies of COVID-19 vaccines and antivirals against emerging SARS-CoV-2 variants of concern in East Asia and Pacific region

BackgroundWe aimed to evaluate the impact of various allocation strategies of COVID-19 vaccines and antiviral such that the pandemic exit strategy could be tailored to risks and preferences of jurisdictions in the East Asia and Pacific region (EAP) to improve its efficiency and effectiveness. MethodsVaccine efficacies were estimated from the titre distributions of 50% plaque reduction neutralization test (PRNT50), assuming that PRNT50 titres of primary vaccination decreased by 2-10 folds due to antibody waning and emergence of VOCs, and an additional dose of vaccine would increase PRNT50 titres by 3- or 9-fold. We then used an existing SARS-CoV-2 transmission model to assess the outcomes of vaccine allocation strategies with and without the use of antivirals for symptomatic patients in Japan, Hong Kong and Vietnam. FindingsIncreasing primary vaccination coverage was the most important contributing factor in reducing the total and peak number of COVID-19 hospitalizations, especially when population vaccine coverage or vaccine uptake among older adults was low. Providing antivirals to 50% of symptomatic infections only further reduced total and peak hospitalizations by 10-13%. The effectiveness of an additional dose of vaccine was highly dependent on the immune escape potential of VOCs and antibody waning, but less dependent on the boosting efficacy of the additional dose. InterpretationIncreasing primary vaccination coverage should be prioritised in the design of allocation strategies of COVID-19 vaccines and antivirals in the EAP region. Heterologous vaccination with any available vaccine as the additional dose could be considered when planning pandemic exit strategies tailored to the circumstances of EAP jurisdictions. FundingHealth and Medical Research Fund, General Research Fund, AIR@InnoHK

SARS-CoV-2 under an elimination strategy in Hong Kong

Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity. One sentence summaryOut of the 170 detected introductions of SARS-CoV-2 in Hong Kong during 2020, three introductions caused 90% of community cases.

Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor binding domain of the spike protein have rapidly become prevalent in the UK. We estimated that the earlier 501Y lineage without amino acid deletion {Delta}69/{Delta}70 circulating mainly between early September to mid-November was 10% (6-13%) more transmissible than the 501N lineage, and the currently dominant 501Y lineage with amino acid deletion {Delta}69/{Delta}70 circulating since late September was 75% (70-80%) more transmissible than the 501N lineage.

Real-time tracking and prediction of COVID-19 infection using digital proxies of population mobility and mixing

Digital proxies of human mobility and physical mixing have been used to monitor viral transmissibility and effectiveness of social distancing interventions in the ongoing COVID-19 pandemic. We developed a new framework that parameterizes disease transmission models with age-specific digital mobility data. By fitting the model to case data in Hong Kong, we were able to accurately track the local effective reproduction number of COVID-19 in near real time (i.e. no longer constrained by the delay of around 9 days between infection and reporting of cases) which is essential for quick assessment of the effectiveness of interventions on reducing transmissibility. Our findings showed that accurate nowcast and forecast of COVID-19 epidemics can be obtained by integrating valid digital proxies of physical mixing into conventional epidemic models.

Empirical transmission advantage of the D614G mutant strain of SARS-CoV-2

The SARS-CoV-2 lineage carrying the amino acid change D614G has become the dominant variant in the global COVID-19 pandemic. The rapid spread of the G614 mutant suggests that it may have a transmission advantage over the D614 wildtype. Using our previous epidemiological framework to analyze COVID-19 surveillance and sequence data, we estimated that the G614 mutant is 31% (28-34%) more transmissible than the D614 wildtype. As such, interventions that were previously effective in containing or mitigating the D614 wildtype (e.g. in China, Vietnam, Thailand, etc.) might be less effective against the G614 mutant. Our framework can be readily integrated into current COVID-19 surveillance to monitor the emergence and fitness of mutant strains, such that pandemic surveillance, disease control and development of treatment and vaccines can be adjusted dynamically.

Impact of changing case definitions for COVID-19 on the epidemic curve and transmission parameters in mainland China

BackgroundWhen a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and also for public health surveillance. Tracking case numbers over time allows us to determine speed of spread and the effectiveness of interventions. Changing case definitions during an epidemic can affect these inferences. MethodsWe examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used simple models assuming exponential growth and then exponential decay to estimate how changes in the case definitions affected the numbers of cases reported each day. We then inferred how the epidemic curve would have appeared if the same case definition had been used throughout the epidemic. FindingsFrom January through to early March 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. As of February 20, there were 55,508 confirmed cases reported in mainland China. We estimated that when the case definitions were changed from version 1 to 2, version 2 to 4 and version 4 to 5, the proportion of infections being detected as cases were increased by 7.1-fold (95% credible interval (CI): 4.8, 10.9), 2.8-fold (95% CI: 1.9, 4.2) and 4.2-fold (95% CI: 2.6, 7.3) respectively. If the fifth version of the case definition had been applied throughout the outbreak, we estimated that by February 20 there would have been 232,000 (95% CI: 161,000, 359,000) confirmed cases. InterpretationThe case definition was initially narrow, but was gradually broadened to allow detection of more cases as knowledge increased, particularly milder cases and those without epidemiological links to Wuhan or other known cases. This should be taken into account when making inferences on epidemic growth rates and doubling times, and therefore on the reproductive number, to avoid bias. FundingCommissioned grant from the Health and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong Special Administrative Region.

Temporal dynamics in viral shedding and transmissibility of COVID-19

We report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.

Impact assessment of non-pharmaceutical interventions against COVID-19 and influenza in Hong Kong: an observational study

BackgroundA range of public health measures have been implemented to delay and reduce local transmission of COVID-19 in Hong Kong, and there have been major changes in behaviours of the general public. We examined the effect of these interventions and behavioral changes on the incidence of COVID-19 as well as on influenza virus infections which may share some aspects of transmission dynamics with COVID-19. MethodsWe reviewed policy interventions and measured changes in population behaviours through two telephone surveys, on January 20-23 and February 11-14. We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (Rt), for COVID-19 and influenza A(H1N1). FindingsCOVID-19 transmissibility has remained at or below 1, indicating successful containment to date. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% confidence interval, CI: 34% to 53%) reduction in transmissibility in the community, and a 33% (95% CI: 24% to 43%) reduction in transmissibility based on paediatric hospitalization rates. In the two surveys we estimated that 74.5% and 97.5% of the general adult population wore masks when going out, and 61.3% and 90.2% avoided going to crowded places, respectively. ImplicationsContainment measures, social distancing measures and changes in population behaviour have successfully prevented spread of COVID-19. The social distancing measures and behavioural changes led to a substantial reduction in influenza transmission in early February 2020. However, it may be challenging to avoid fatigue and sustain these measures and population behaviours as COVID-19 continues to spread globally. FundingHealth and Medical Research Fund, Hong Kong

Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China

The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.