Here, we report that COVID-19 hospitalization rates follow an exponential relationship with age, doubling for every 16 years of age or equivalently increasing by 4.5% per year of life (R² = 0.98). This mirrors the well-studied exponential decline of both thymus volume and T-cell production, which halve every 16 years. COVID-19 can therefore be added to the list of other diseases with this property, including those caused by methicillin-resistant Staphylococcus aureus, MERS-CoV, West Nile virus, Streptococcus pneumoniae and certain cancers, such as chronic myeloid leukaemia and brain cancers. In addition, the incidence of severe disease and mortality due to COVID-19 are both higher in men, consistent with the degree to which thymic involution (and the decrease in T-cell production with age) is more severe in men compared to women. Since these properties are shared with some non-contagious diseases, we hypothesized that the age dependence does not come from social-mixing patterns, i.e. that the probability of hospitalization given infection rises exponentially, doubling every 16 years. A Bayesian analysis of daily hospitalizations, incorporating contact matrices, found that this relationship holds for every age group except for the under 20s. While older adults have fewer contacts than young adults, our analysis suggests that there is an approximate cancellation between the effects of fewer contacts for the elderly and higher infectiousness due to a higher probability of developing severe disease. Our model fitting suggests under 20s have 49–75% additional immune protection beyond that predicted by strong thymus function alone, consistent with increased juvenile cross-immunity from other viruses. We found no evidence for differences between age groups in susceptibility to infection or infectiousness to others (given disease state), i.e. the only important factor in the age dependence of hospitalization rates is the probability of hospitalization given infection. These findings suggest the existence of a T-cell exhaustion threshold, proportional to thymic output and that clonal expansion of peripheral T-cells does not affect disease risk. The strikingly simple inverse relationship between risk and thymic T-cell output adds to the evidence that thymic involution is an important factor in the decline of the immune system with age and may also be an important clue in understanding disease progression, not just for COVID-19 but other diseases as well.

在这里，我们报告说，COVID-19 住院率与年龄呈指数关系，每 16 岁就翻一番，或相当于每年增加 4.5% ( R ² = 0.98)。这反映了经过充分研究的胸腺体积和 T 细胞产量的指数下降，每 16 年减半。因此，COVID-19 可以添加到具有此特性的其他疾病列表中，包括由耐甲氧西林金黄色葡萄球菌、中东呼吸综合征冠状病毒、西尼罗河病毒、肺炎链球菌和某些癌症（例如慢性粒细胞白血病和脑癌）引起的疾病。此外，男性因 COVID-19 导致的严重疾病的发生率和死亡率均较高，这与男性胸腺复旧（以及 T 细胞产量随年龄增长而减少）比女性更严重的程度一致。由于这些特性与一些非传染性疾病相同，我们假设年龄依赖性并非来自社会混合模式，即感染后住院的概率呈指数增长，每 16 年翻一番。对每日住院治疗进行贝叶斯分析，结合接触矩阵，发现这种关系适用于除 20 岁以下以外的每个年龄组。虽然老年人的接触次数比年轻人少，但我们的分析表明，老年人接触次数较少与由于患严重疾病的可能性较高而导致的较高传染性之间存在近似抵消。我们的模型拟合表明，20 岁以下的人具有 49-75% 的额外免疫保护，超出了单独强大的胸腺功能所预测的水平，这与青少年对其他病毒的交叉免疫增强一致。 我们没有发现任何证据表明年龄组之间对感染或对他人的传染性（给定疾病状态）的易感性存在差异，即住院率年龄依赖性的唯一重要因素是感染后住院的概率。这些发现表明存在 T 细胞耗竭阈值，与胸腺输出成正比，并且外周 T 细胞的克隆扩增不会影响疾病风险。风险与胸腺 T 细胞输出之间极其简单的反比关系进一步证明，胸腺退化是免疫系统随年龄下降的一个重要因素，也可能是了解疾病进展的重要线索，而不仅仅是针对新冠病毒19 但还有其他疾病。