Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

Background: Understanding the extent of virus transmission that can occur before symptom onset is vital for targeting control measures against the global pandemic of COVID-19.Objective: Estimation of (1) the proportion of pre-symptomatic transmission of COVID-19 that can occur and (2) timing of transmission relative to symptom onset. Design: Secondary analysis of published dataData sources: Meta-analysis of COVID-19 incubation period and a rapid systematic review of serial interval and generation time, which are published separately.Methods: Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset were calculated and the proportion of pre-symptomatic transmission was estimated. Results:A total of 23 estimates of serial interval and five estimates of generation time from 17 publications were included. These came from nine different data source categories (presented here in descending order of the proportion of pre-symptomatic transmission):Hong Kong, Tianjin, pooled data from Hong Kong and Shenzhen, Singapore, Mainland China excluding Hubei, mixed sources, Shenzhen, northern Italy and Wuhan. Transmission time relative to symptom onset ranged from a mean of 2.05 days before symptom onset for Hong Kong to 1.72 days after symptom onset for Wuhan. Proportion of pre-symptomatic transmission ranged from 33.7% in Wuhan to 72.7% in Hong Kong. Based on individual estimates, transmission time relative to symptom onset ranged from mean of 2.95 days before symptom onset to 1.72 days after symptom onset and proportion of pre-symptomatic transmission ranged from 33.7% to 79.9%. Simple unweighted pooling of estimates based on serial intervals resulted in a mean time of transmission of 0.67 days before symptoms, and an estimated 56.1% of transmission occurring in the pre-symptomatic period. Conclusions:Contact rates between symptomatic infectious and susceptible people are likely to influence the proportion of pre-symptomatic transmission. There is substantial potential for pre-symptomatic transmission of COVID-19 in a range of different contexts. Our work suggests that transmission of SARS-CoV-2 is most likely in the day before symptom onset whereas estimates suggesting most pre-symptomatic transmission highlighted a mean transmission times almost 3 days before symptom onset. These findings highlight the urgent need for extremely rapid and effective case detection, contact tracing and quarantine measures if strict social distancing measures are to be eased.

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Objectives: The aim of this study was to conduct a scoping review of estimates of the relative infectiousness of asymptomatic persons infected with SARS-CoV-2 compared with symptomatic individuals. Design: Rapid scoping review of literature available until 8th April 2020. Setting: International studies on the infectiousness of individuals infected with SARS-CoV-2 Participants: Studies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from pre-symptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics. Primary outcome measures: The relative number of secondary cases produced by an average primary case, the relative probability of transmitting infection upon contact, and the degree of viral shedding. Results: Very few studies reported estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. Significant differences exist in the definition of infectiousness. Viral shedding studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals but are likely to be impacted by insufficient statistical power. Two contact tracing studies provided estimates of 0.7 and 1.0, but differences in approach and definition preclude comparison across the two studies. Finally, two modelling studies suggest a relative infectiousness of around 0.5 but one of these was more reflective of the infectiousness of undocumented rather than asymptomatic cases. Importantly, one contact tracing study showing a very low level of infectiousness of asymptomatic was not included in the analysis at this point due difficulties interpreting the reported findings. Conclusions: The present study highlights the need for additional studies in this area as a matter of urgency. For the purpose of epidemiological modelling, we cautiously suggest that at present, asymptomatics could be considered to have a degree of infectiousness which is about 0.40-0.70 that of symptomatics. However, it must be stressed that this suggestion comes from a very low evidence base and that estimates exist that are close to zero and close to 1.

Background: The serial interval is the time between symptom onsets in an infector-infectee pair. The generation time, also known as the generation interval, is the time between infection events in an infector-infectee pair. The serial interval and the generation time are key parameters for assessing the dynamics of a disease. A number of scientific papers reported information pertaining to the serial interval and/or generation time for COVID-19.

ObjectiveTo estimate the proportion of presymptomatic transmission of SARS-CoV-2 infection that can occur, and the timing of transmission relative to symptom onset.Setting/designSecondary analysis of international published data.Data sourcesMeta-analysis of COVID-19 incubation period and a rapid review of serial interval and generation time, which are published separately.ParticipantsData from China, the Islamic Republic of Iran, Italy, Republic of Korea, Singapore and Vietnam from December 2019 to May 2020.MethodsSimulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset, and the proportion of presymptomatic transmission, were estimated.Outcome measuresTransmission time of SARS-CoV-2 relative to symptom onset and proportion of presymptomatic transmission.ResultsBased on 18 serial interval/generation time estimates from 15 papers, mean transmission time relative to symptom onset ranged from −2.6 (95% CI −3.0 to –2.1) days before infector symptom onset to 1.4 (95% CI 1.0 to 1.8) days after symptom onset. The proportion of presymptomatic transmission ranged from 45.9% (95% CI 42.9% to 49.0%) to 69.1% (95% CI 66.2% to 71.9%).ConclusionsThere is substantial potential for presymptomatic transmission of SARS-CoV-2 across a range of different contexts. This highlights the need for rapid case detection, contact tracing and quarantine. The transmission patterns that we report reflect the combination of biological infectiousness and transmission opportunities which vary according to context.

ObjectivesThe aim of this study was to determine the relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals based on a scoping review of available literature.DesignRapid scoping review of peer-reviewed literature from 1 January to 5 December 2020 using the LitCovid database and the Cochrane library.SettingInternational studies on the infectiousness of individuals infected with SARS-CoV-2.ParticipantsStudies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from presymptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics.Primary outcome measuresPCR result (PCR studies), the rate of infection (mathematical modelling studies) and secondary attack rate (contact tracing studies) - in each case from asymptomatic in comparison with symptomatic individuals.ResultsThere are only a limited number of published studies that report estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. 12 studies were included after the screening process. Significant differences exist in the definition of infectiousness. PCR studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals; however, the number of study subjects is generally limited. Two modelling studies estimate relative infectiousness to be 0.43 and 0.57, but both of these were more reflective of the infectiousness of undocumented rather than asymptomatic cases. The results from contact tracing studies include estimates of relative infectiousness of 0, but with insufficient evidence to conclude that it is significantly different from 1.ConclusionsThere is considerable heterogeneity in estimates of relative infectiousness highlighting the need for further investigation of this important parameter. It is not possible to provide any conclusive estimate of relative infectiousness, as the estimates from the reviewed studies varied between 0 and 1.

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