Lithium, widely used in treating bipolar disorder, also exhibits antiviral activity.¹ Lithium's antiviral effects may extend to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19).² Experimental data show that SARS‐CoV‐2 inhibition starts at very high lithium levels (>5 mEq/L).² This preliminary study investigates whether trace lithium, such as that in drinking water, may be associated with a low COVID‐19 mortality.

In addition to the lithium data in drinking water from our recent study,³ COVID‐19‐associated mortality data of all 47 prefectures in Japan as on August 22, 2020 were obtained from the Ministry of Health, Labour and Welfare in Japan. We calculated the mean lithium levels of all cities in the prefecture and the COVID‐19‐associated standardized mortality ratios (SMRs) of each prefecture. The population sizes across the 47 prefectures being very different and multiple regression analyses adjusted for each population size were performed to predict COVID‐19 SMRs from the lithium levels and relevant factors of the prefectures, including the proportion of elderly people, the proportion of one‐person households, the number of general hospitals per 100,000 people, and the number of deaths associated with diabetes mellitus, hypertension, and heart disease per 100,000 people.

The mean lithium level of the 47 prefectures was 2.37 μg/L (range: 0.4‐11 μg/L). There was no significant association between the lithium levels and the COVID‐19 SMRs in the crude model (β=−0.08, p = 0.593). After adjusting for the relevant factors using a stepwise method, the model could predict COVID‐19 SMRs with statistical significance (F = 42.1, p < 0.001). However, the lithium level was not a significant contributor to the COVID‐19 SMR (β = 0.073, p = 0.367). Among the relevant factors, only the proportion of elderly people (β = 0.629, p < 0.001) and the proportion of one‐person households (β = −0.334, p = 0.002) were significant contributors.

Unlike the significant inverse association between the lithium levels in drinking water and suicide SMRs,³ our findings suggest that trace lithium is not associated with a low mortality ratio in COVID‐19. The lack of significance might be due to the narrow range of lithium levels as we calculated the mean lithium levels of the cities of each prefecture to arrive at the lithium level of each prefecture. This was done because the number of COVID‐19‐associated deaths could not be obtained per city but per prefecture. A wider range of lithium levels might show a significant association. In any case, further studies are required to investigate the therapeutic effects of lithium for COVID‐19.

广泛用于治疗躁郁症的锂也具有抗病毒活性。¹锂的抗病毒作用可能扩展到严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2），这会导致2019年冠状病毒病（COVID-19）。²实验数据表明，SARS-CoV-2抑制作用始于非常高的锂含量（> 5 mEq / L）。²这项初步研究调查了痕量锂（例如饮用水中的痕量锂）是否可能与低COVID-19死亡率相关。

除了我们最近的研究中饮用水中的锂数据外，³截至2020年8月22日，日本所有47个县的COVID-19相关死亡率数据均来自日本厚生劳动省。我们计算了县内所有城市的平均锂水平以及每个县的COVID-19相关的标准化死亡率（SMR）。47个州的人口规模差异很大，并针对每种人口规模进行了多元回归分析，以便根据锂含量和相关因素（包括老年人比例，单人比例）来预测COVID-19 SMR。住户数，每100,000人的综合医院数量以及每100,000人与糖尿病，高血压和心脏病相关的死亡人数。

47个州的平均锂水平为2.37μg/ L（范围：0.4-11μg/ L）。粗模型中锂含量与COVID-19 SMR之间无显着关联（β= -0.08，p  = 0.593）。使用逐步方法调整相关因素后，该模型可以预测具有统计学意义的COVID-19 SMR（F = 42.1，p  <0.001）。但是，锂含量对COVID-19 SMR的贡献不大（β= 0.073，p  = 0.367）。在相关因素中，只有老年人的比例（β= 0.629，p  <0.001）和一人家庭的比例（β= -0.334，p  = 0.002）是重要的贡献者。

与饮用水中的锂含量和自杀性SMR之间显着的逆相关性不同，³我们的发现表明，痕量锂与COVID-19中的低死亡率无关。重要性不足的原因可能是锂含量范围狭窄，因为我们计算了每个县市的平均锂含量以得出每个县的锂含量。之所以这样做，是因为无法获得每个城市而是每个州的与COVID-19相关的死亡人数。更大范围的锂含量可能显示出显着的关联。无论如何，需要进一步的研究来研究锂对COVID-19的治疗作用。