Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study
Authors: Nakagawara Kensuke , Kamata Hirofumi , Chubachi Shotaro , Namkoong Ho , Tanaka Hiromu , Lee Ho , Otake Shiro , Fukushima Takahiro , Kusumoto Tatsuya , Morita Atsuho , Azekawa Shuhei , Watase Mayuko , Asakura Takanori , Masaki Katsunori , Ishii Makoto , Endo Akifumi , Koike Ryuji , Ishikura Hiroyasu , Takata Tohru , Matsushita Yasushi , Harada Norihiro , Kokutou Hiroyuki , Yoshiyama Takashi , Kataoka Kensuke , Mutoh Yoshikazu , Miyawaki Masayoshi , Ueda Soichiro , Ono Hiroshi , Ono Takuya , Shoko Tomohisa , Muranaka Hiroyuki , Kawamura Kodai , Mori Nobuaki , Mochimaru Takao , Fukui Mototaka , Chihara Yusuke , Nagasaki Yoji , Okamoto Masaki , Amishima Masaru , Odani Toshio , Tani Mayuko , Nishi Koichi , Shirai Yuya , Edahiro Ryuya , Ando Akira , Hashimoto Naozumi , Ogura Shinji , Kitagawa Yuichiro , Kita Toshiyuki , Kagaya Takashi , Kimura Yasuhiro , Miyazawa Naoki , Tsuchida Tomoya , Fujitani Shigeki , Murakami Koji , Sano Hirohito , Sato Yuki , Tanino Yoshinori , Otsuki Ryo , Mashimo Shuko , Kuramochi Mizuki , Hosoda Yasuo , Hasegawa Yoshinori , Ueda Tetsuya , Takaku Yotaro , Ishiguro Takashi , Fujiwara Akiko , Kuwahara Naota , Kitamura Hideya , Hagiwara Eri , Nakamori Yasushi , Saito Fukuki , Kono Yuta , Abe Shinji , Ishii Tomoo , Ohba Takehiko , Kusaka Yu , Watanabe Hiroko , Masuda Makoto , Watanabe Hiroki , Kimizuka Yoshifumi , Kawana Akihiko , Kasamatsu Yu , Hashimoto Satoru , Okada Yukinori , Takano Tomomi , Katayama Kazuhiko , Ai Masumi , Kumanogoh Atsushi , Sato Toshiro , Tokunaga Katsushi , Imoto Seiya , Kitagawa Yuko , Kimura Akinori , Miyano Satoru , Hasegawa Naoki , Ogawa Seishi , Kanai Takanori , Fukunaga Koichi ,   The Japan COVID-19 Task Force
Published: April 2023

Abstract
Background
Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19.

Methods
We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections.

Results
Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil–lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality.

Conclusions
Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.