RESUMO
To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
RESUMO
We report three cases of meningeal carcinomatosis that metastasized from lung cancer. The patients were men of 73, 65 and 77 years old. The histological type was adenocarcinoma in all cases. At the time of emergence of neurological symptoms such as nausea, headache and cataplexy, enhanced CT of the brain did not disclose brain metastasis. Although brain MRI failed to detect abnormal meningeal findings in cases 1 and 2, meningeal carcinomatosis was diagnosed by cerebrospinal fluid cytology in all three cases. As for treatment, in case 1, methotrexate and prednisolone were administered intrathecally, while the optimum supportive care was given in cases 2 and 3. Because it is difficult to detect meningeal carcinomatosis by brain CT and MRI alone, careful neurological observation and cerebrospinal fluid cytology are necessary for its diagnosis.