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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.
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BackgroundHong Kong has enforced stringent travel restrictions particularly for inbound travellers since the emergence of SARS-CoV-2. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. MethodsWe conducted a retrospective cohort study to summarise the characteristics of cases classified as imported cases that were detected on or soon after arrival into Hong Kong from 13 November 2020 through to 31 January 2022, when all arriving persons were required to quarantine in a hotel or a designated quarantine facility. We analysed individual demographics, and clinical information including symptoms and disease severity, virus variants, and Ct values. ResultsThere were 2269 imported COVID-19 cases aged 0-85 years identified in Hong Kong. Almost half (48.6%) of the imported cases were detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than cases infected with the ancestral strain and other variants (12 days; p<0.001) while lower Ct values at isolation were observed in cases infected with Omicron than the ancestral strain or other variants. No Omicron cases were detected beyond 14 days after arrival, and the cases (n=58, 2.6%) detected after 14 days of quarantine more frequently presented without symptoms at isolation and had a higher RT-PCR Ct-value during isolation. At least some of these cases were post-arrival infections. ConclusionsTesting inbound travellers at arrival and during on-arrival quarantine can detect imported cases early although it may not be sufficient to prevent all introductions of COVID-19 into the community. Public health measures should be adjusted in responses to the emergence of new variants of SARS-CoV-2 based on the epidemiologic evidence from continuous surveillance.
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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.
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Hong Kong reported 12,631 confirmed COVID-19 cases and 213 deaths in the first two years of the pandemic but experienced a major wave predominantly of Omicron BA.2.2 in early 2022 with over 1.1 million reported SARS-CoV-2 infections and more than 7900 deaths. Our data indicated a shorter incubation period, serial interval, and generation time of infections with Omicron than other SARS-CoV-2 variants. Omicron BA.2.2 cases without a complete primary vaccination series appeared to face a similar fatality risk to those infected in earlier waves with the ancestral strain.
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Superspreading in transmission is a feature of SARS-CoV-2 transmission. We conducted a systematic review and meta-analysis on globally reported dispersion parameters of SARS-CoV-2. The pooled estimate was 0.55 (95% CI: 0.30, 0.79). The study location and method were found to be important drivers for its diversity.
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Omicron, a fast-spreading SARS-CoV-2 variant of concern reported to the World Health Organization on November 24, 2021, has raised international alarm. We estimated there is at least 50% chance that Omicron had been introduced by travelers from South Africa into all of the 30 countries studied by November 27, 2021.
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BackgroundThe Delta variant of SARS-CoV-2 has become predominant globally. We evaluated the transmission dynamics and epidemiological characteristics of the Delta variant in an outbreak in southern China. MethodsData on confirmed cases and their close contacts were retrospectively collected from the outbreak that occurred in Guangdong, China in May-June 2021. Key epidemiological parameters, temporal trend of viral loads and secondary attack rates were estimated and compared between the Delta variant and the wild-type SARS-CoV-2 virus. We also evaluated the association of vaccination with viral load and transmission. ResultsWe identified 167 patients infected with the Delta variant in the Guangdong outbreak. The mean estimates of the latent period and the incubation period were 4.0 days and 5.8 days, respectively. A relatively higher viral load was observed in Delta cases than in wild-type infections. The secondary attack rate among close contacts of Delta cases was 1.4%, and 73.9% (95% confidence interval: 67.2%, 81.3%) of the transmissions occurred before onset. Index cases without vaccination (OR: 2.84, 95% confidence interval: 1.19, 8.45) or with one dose of vaccination (OR: 6.02, 95% confidence interval: 2.45, 18.16) were more likely to transmit infection to their contacts than those who had received 2 doses of vaccination. DiscussionPatients infected with the Delta variant had more rapid symptom onset. The shorter and time-varying serial interval should be accounted in estimation of reproductive numbers. The higher viral load and higher risk of pre-symptomatic transmission indicated the challenges in control of infections with the Delta variant.
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A fast-spreading SARS-CoV-2 variant identified in the United Kingdom in December 2020 has raised international alarm. We estimate that, in all 15 countries analyzed, there is at least a 50% chance the variant was imported by travelers from the United Kingdom by December 7th.
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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.
