We have hypothesized that genetic predisposition influences the progression of SARS. Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases. This time, the polymorphism was genotyped in 44 Vietnamese SARS cases, with 103 healthy controls who had had a contact with the SARS patients and 50 controls without any contact history. SARS cases were divided into either non-hypoxemic or hypoxemic groups. Despite the small sample size, the frequency of the D allele was significantly higher in the hypoxemic group than in the non-hypoxemic group (p=0.013), whereas there was no significant difference between the SARS cases and controls, irrespective of a contact history. ACE1 might be one of the candidate genes that influence the progression of pneumonia in SARS.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

with symptoms of acute respiratory tract infection, a history of high-risk exposure or chest radiographic fi ndings such as pneumonia, and positive fi ndings for A/H5 viral RNA by reverse transcription-PCR. We investigated data from 29 patients (mean age 35.1 years) of whom 7 (24.1%) had died. Mortality rates were 20% (5/25) and 50% (2/4) among patients treated with or without oseltamivir (p = 0.24), respectively, and were 33.3% (5/15) and 14.2% (2/14) among patients treated with and without methylprednisolone (p = 0.39), respectively. After exact logistic regression analysis was adjusted for variation in severity, no signifi cant effectiveness for survival was observed among patients treated with oseltamivir or methylprednisolone.

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For the purpose of nationwide surveillance of antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, the Japanese Society of Chemotherapy (JSC) started a survey in 2006. From 2009, JSC continued the survey in collaboration with the Japanese Association for Infectious Diseases and the Japanese Society for Clinical Microbiology. The fourth-year survey was conducted during the period from January and April 2009 by the three societies. A total of 684 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 635 strains (130 Staphylococcus aureus, 127 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 123 Haemophilus influenzae, 70 Moraxella catarrhalis, 78 Klebsiella pneumoniae, and 103 Pseudomonas aeruginosa). A maximum of 45 antibacterial agents including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), four aminoglycosides, four macrolides (including ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). Incidence of methicillin-resistant S. aureus (MRSA) was as high as 58.5 %, and that of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) was 6.3 % and 0.0 %, respectively. Among H. influenzae, 21.1 % of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 18.7 % to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.7 % to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5 %) of β-lactamase-producing strains has been suspected in Moraxella catarrhalis isolates. Four (3.2 %) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5 %) of P. aeruginosa were found to be metallo-β-lactamase-producing strains, including three (1.9 %) suspected multi-drug resistant strains showing resistance against imipenem, amikacin, and ciprofloxacin. Continuous national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.