Background. Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no ...comparable quantitative data to our knowledge on naturally acquired infections. Methods. In a community-based study in Hong Kong in 2008, we followed up initially healthy individuals to quantify trends in viral shedding on the basis of cultures and reverse-transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. Results. Trends in symptom scores more closely matched changes in molecular viral loads measured with RT-PCR for influenza A than for influenza B. For influenza A virus infections, the replicating viral loads determined with cultures decreased to undetectable levels earlier after illness onset than did molecular viral loads. Most viral shedding occurred during the first 2–3 days after illness onset, and we estimated that 1%–8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding at RT-PCR were asymptomatic, and viral shedding was low in these cases. Conclusions. Our results suggest that “silent spreaders” (ie, individuals who are infectious while asymptomatic or presymptomatic) may be less important in the spread of influenza epidemics than previously thought.
We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles 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% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.
Superspreading events (SSEs) have characterized previous epidemics of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections
. ...For SARS-CoV-2, the degree to which SSEs are involved in transmission remains unclear, but there is growing evidence that SSEs might be a typical feature of COVID-19
. Using contact tracing data from 1,038 SARS-CoV-2 cases confirmed between 23 January and 28 April 2020 in Hong Kong, we identified and characterized all local clusters of infection. We identified 4-7 SSEs across 51 clusters (n = 309 cases) and estimated that 19% (95% confidence interval, 15-24%) of cases seeded 80% of all local transmission. Transmission in social settings was associated with more secondary cases than households when controlling for age (P = 0.002). Decreasing the delay between symptom onset and case confirmation did not result in fewer secondary cases (P = 0.98), although the odds that an individual being quarantined as a contact interrupted transmission was 14.4 (95% CI, 1.9-107.2). Public health authorities should focus on rapidly tracing and quarantining contacts, along with implementing restrictions targeting social settings to reduce the risk of SSEs and suppress SARS-CoV-2 transmission.
The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, ...robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January-July 2022. We estimated that Omicron infected 45% (41-48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34-64%) and 69% (46-98%) for three and four doses of BNT162b2, respectively; VE of 30% (1-66%) and 56% (6-97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7-41%) and 35% (10-71%) for three and four doses of BNT162b2, and to 6% (0-29%) and 11% (0-54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.
The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody ...responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT
) and 50% (PRNT
) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT
titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT
antibody titres to decrease by half (T
) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT
and PRNT
antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.
Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals' ability to detect disease outbreaks faster than ...traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health?Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes?Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n = 15), Infectious Diseases (n = 6), Non-infectious Diseases (n = 4), Medication and Vaccines (n = 3), and Other (n = 5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n = 10), Infectious Diseases (n = 3), Non-infectious Diseases (n = 9), and Other (n = 10).
The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.
Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs ...among community-dwelling COVID-19 outpatients in Hong Kong.
In this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30–59 mL/min per 1·73 m2). Outpatient oral antiviral users were matched with controls using propensity score (1:10) according to age, sex, date of SARS-CoV-2 infection diagnosis, Charlson Comorbidity Index score, and vaccination status. Study outcomes were death, COVID-19-related hospitalisation, and in-hospital disease progression (in-hospital death, invasive mechanical ventilation, or intensive care unit admission). Hazard ratios (HRs) were estimated by Cox regression for the primary analysis, and odds ratios in oral antiviral users compared with non-users by logistic regression for the sensitivity analysis.
Among 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 85·9% vs 4418 88.7% aged >60 years) and less likely to have been fully vaccinated (1850 33·4% vs 800 16·1%). Molnupiravir use was associated with lower risks of death (HR 0·76 95% CI 0·61–0·95) and in-hospital disease progression (0·57 0·43–0·76) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 0·89–1·06). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 0·22–0·52), hospitalisation (0·76 0·67–0·86), and in-hospital disease progression (0·57 0·38–0·87) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis.
During Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation.
Health and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China.
For the Chinese translation of the abstract see Supplementary Materials section.
Data on the effectiveness of oral antivirals in patients with mild-to-moderate COVID-19 are urgently needed. This retrospective cohort study aimed to evaluate the clinical and virological outcomes ...associated with molnupiravir or nirmatrelvir–ritonavir use in hospitalised patients with mild-to-moderate COVID-19 during a pandemic wave dominated by the omicron BA.2 subvariant.
We analysed data from a territory-wide retrospective cohort of patients in Hong Kong who were hospitalised with a confirmed diagnosis of SARS-CoV-2 infection between Feb 26 and April 26, 2022. Data were extracted from the Hospital Authority, the Department of Health, and the Hong Kong Death Registry. Patients were eligible for inclusion if their admission date was within 3 days before or after confirmation of their COVID-19 diagnosis. Those who were admitted to hospital more than 5 days after symptom onset, were younger than 18 years, had a history of oral antiviral use before admission, required supplemental oxygen on admission, had drug-related contraindications to nirmatrelvir–ritonavir use, or had severe renal or severe liver impairment were excluded. Patients who received the oral antivirals molnupiravir or nirmatrelvir–ritonavir were matched with controls using propensity-score matching in a ratio of 1:1. The primary outcome was all-cause mortality and secondary outcomes included a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation IMV, intensive care unit ICU admission, or the need for oxygen therapy) and each of these individual disease progression outcomes, and time to reaching a low viral burden (RT-PCR cycle threshold value ≥30). For each event outcome, crude incidence rates were calculated and hazard ratios (HRs) estimated using Cox regression models.
We identified 40 776 patients hospitalised with SARS-CoV-2 infection during the study period, with a mean follow-up of 41·3 days (total 925 713 person-days). After exclusions and propensity-score matching, we included 1856 molnupiravir recipients and 1856 matched controls, and 890 nirmatrelvir-ritonavir recipients and 890 matched controls. A lower risk of all-cause mortality was observed in molnupiravir recipients (crude incidence rate per 10 000 person-days 19·98 events 95% CI 16·91–23·45) versus matched controls (38·07 events 33·85–42·67; HR 0·48 95% CI 0·40–0·59, p<0·0001) and in nirmatrelvir–ritonavir recipients (10·28 events 7·03–14·51) versus matched controls (26·47 events 21·34–32·46; HR 0·34 0·23–0·50, p<0·0001). Oral antiviral recipients also had lower risks of the composite disease progression outcome (molnupiravir HR 0·60 95% CI 0·52–0·69, p<0·0001; nirmatrelvir–ritonavir 0·57 0·45–0·72, p<0·0001) and need for oxygen therapy (molnupiravir 0·69 0·57–0·83, p=0·0001; nirmatrelvir–ritonavir 0·73 0·54–0·97, p=0·032) compared with controls. Time to achieving a low viral burden was significantly shorter among oral antiviral recipients than matched controls (molnupiravir HR 1·38 95% CI 1·15–1·64, p=0·0005; nirmatrelvir–ritonavir 1·38 1·07–1·79, p=0·013). Significant differences in initiation of IMV and ICU admission were not found.
During a wave of SARS-CoV-2 omicron BA.2, initiation of novel oral antiviral treatments in hospitalised patients not requiring oxygen therapy on admission showed substantial clinical benefit. Our findings support the early use of oral antivirals in this population of patients.
Health and Medical Research Fund (Health Bureau, Government of the Hong Kong Special Administrative Region).
For the Chinese translation of the abstract see Supplementary Materials section.
Abstract
SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults are unclear. Here, we report SARS-CoV-2 specific T cell responses in infected adults ...and children and find that the acute and memory CD4
+
T cell responses to structural SARS-CoV-2 proteins increase with age, whereas CD8
+
T cell responses increase with time post-infection. Infected children have lower CD4
+
and CD8
+
T cell responses to SARS-CoV-2 structural and ORF1ab proteins when compared with infected adults, comparable T cell polyfunctionality and reduced CD4
+
T cell effector memory. Compared with adults, children have lower levels of antibodies to β-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses are increased, whilst monocyte numbers are reduced, indicating rapid adaptive co-ordination of the T and B cell responses and differing levels of inflammation. Therefore, reduced prior β-coronavirus immunity and reduced T cell activation in children might drive milder COVID-19 pathogenesis.
PDF
