Background When a new infectious disease emerges, appropriate case definitions are important for clinical diagnosis and for public health surveillance. Tracking case numbers over time is important to establish the speed of spread and the effectiveness of interventions. We aimed to assess whether changes in case definitions affected inferences on the transmission dynamics of coronavirus disease 2019 (COVID-19) in China.Methods We examined changes in the case definition for COVID-19 in mainland China during the first epidemic wave. We used exponential growth models to estimate how changes in the case definitions affected the number 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.Findings From Jan 15 to March 3, 2020, seven versions of the case definition for COVID-19 were issued by the National Health Commission in China. We estimated that when the case definitions were changed, the proportion of infections being detected as cases increased by 7•1 times (95% credible interval [CrI] 4•8-10•9) from version 1 to 2, 2•8 times (1•9-4•2) from version 2 to 4, and 4•2 times (2•6-7•3) from version 4 to 5. If the fifth version of the case definition had been applied throughout the outbreak with sufficient testing capacity, we estimated that by Feb 20, 2020, there would have been 232 000 (95% CrI 161 000-359 000) confirmed cases in China as opposed to the 55 508 confirmed cases reported.Interpretation The case definition was initially narrow and was gradually broadened to allow detection of more cases as knowledge increased, particularly milder cases and those without epidemiological links to Wuhan, China, or other known cases. These changes should be taken into account when making inferences on epidemic growth rates and doubling times, and therefore on the reproductive number, to avoid bias.

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Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 ± 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.

Our analysis of data collected from multiple epidemics in Hong Kong indicated a shorter serial interval and generation time of infections with the SARS-CoV-2 Omicron variant. The age-specific case-fatality risk for Omicron BA.2.2 case-patients without complete primary vaccination was comparable to that of persons infected with ancestral strains in earlier waves.