Our ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by the dependence of their effects on the genetic background and environment. Even when molecular interactions between genes are known, it is unclear how these translate to organism-level interactions between alleles. We therefore characterized the interplay of genetic and environmental dependencies in determining fitness by quantifying ~4000 fitness interactions between expression variants of two metabolic genes, starting from various environmentally modulated expression levels. We detect a remarkable variety of interactions dependent on initial expression levels and demonstrate that they can be quantitatively explained by a mechanistic model accounting for catabolic flux, metabolite toxicity, and expression costs. Complex fitness interactions between mutations can therefore be predicted simply from their simultaneous impact on a few connected molecular phenotypes.

In the first trimester 2020, a significant number of countries implemented general lockdowns of their populations to contain the quickly expanding SARS-CoV-2 epidemic and avoid major saturation of health care capacity. Understanding how these unprecedented measures impacted population behaviour and contact patterns is key to predict more accurately the health, social and economic impacts of such extreme actions if they were to be applied to future outbreaks. We set up an online survey to measure how the lockdown affected social contact patterns in France, and collected information from 42,036 participants aged 18 years and over between April 10 and April 28, 2020. Among the participants who normally worked outside home prior to the lockdown (72% of the survey population), 68% reported that they had moved to working from home and 17% reported being unemployed during the lockdown. Only 2% of participants used public transport during lockdown, as opposed to 37% before it. Participants reported increased frequency of washing hands, switch in greeting behaviour, but generally limited use of masks outside home. 138,934 contacts were reported, with an average 3.3 contacts per individual per day (1.7 for individuals aged >65 years old compared to 3.6 for younger age-groups). This represented a 70% reduction compared with previous surveys, consistent with reductions in transmission rates measured during the lockdown. Contacts in workplaces, shops, and transports on the previous day were respectively reported in only 11%, 31% and 0.5% of the participants. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%. This study shows that the lockdown dramatically affected population's behavior, work, risk perception and contact patterns. Both frequency and heterogeneity of contacts were affected, impacting potential important features of virus dissemination. Such surveys are essential to evaluate more accurately the impact of past or future lockdowns and anticipate epidemic dynamics in these conditions.

Introduction SARS-CoV-2, the virus that causes COVID-19, has spread rapidly worldwide. In January 2020, a surveillance system was implemented in France for early detection of cases and their contacts to help limit secondary transmissions. Aim To use contact-tracing data collected during the initial phase of the COVID-19 pandemic to better characterise SARS-CoV-2 transmission. Methods We analysed data collected during contact tracing and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate and characterised the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread. Results During the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95% confidence interval (CI): 3.6–4.6), increasing with age of index case and contact. Compared with co-workers/friends, family contacts were at higher risk of becoming cases (adjusted odds ratio (AOR): 2.1, 95% CI: 1.4–3.0) and nosocomial contacts were at lower risk (AOR: 0.3, 95% CI: 0.1–0.7). Of 328 infector/infectee pairs, 49% were family members. The distribution of secondary cases was highly over-dispersed: 80% of secondary cases were caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range (IQR): 2–8 days) in contact tracing pairs, where late transmission events may be censored, and 6.8 (3–8) days in pairs investigated retrospectively. Conclusion This study increases knowledge of SARS-CoV-2 transmission, including the importance of superspreading events during the onset of the pandemic.