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Co-infection in COVID-19, a cohort study

Published:October 08, 2020DOI:https://doi.org/10.1016/j.jinf.2020.10.006
      Dear editor,
      Co-infection in COVID-19 patients may inflence the outcome of the disease and needs more attention and investigations. In this journal, Lansbury and colleges reported a meta-analysis of co-infections in COVID-19 patients.
      • Lansbury L.
      • Lim B.
      • Baskaran V.
      • Lim W.S.
      Co-infections in people with COVID-19: a systematic review and meta-analysis.
      In this study, we investigated a COVID-19 cohort in Shanghai, China. We screened viruses include Human parainfluenza virus 1, Human parainfluenza virus 2, Human parainfluenza virus 3, Human parainfluenza virus4, Influenza A virus, Influenza B virus, Human rhinovirus, Human metapneumovirus, Human respiratory syncytial virus, Human Bocavirus, Human adenovirus, Human Coronavirus 229E, Human Coronavirus NL63, Human Coronavirus HKU1, Human Coronavirus OC43; bacteria include Pseudomonas aeruginosa, Moraxella catarrhalis, Mycobacterium tuberculosis, Legionella pneumophila, Group A Streptococcus, Haemophilus influenza, Staphylococcus aureus, Acinetobacter baumannii, Streptococcus pneumonia, Klebsiella.peneumoniae, Escherichia coli and Mycoplasma pneumonia, Chlamydia pneumonia by a taqman-based real time PCR methods.
      Eighty-nine patients were enrolled with disease outcomes include mild, moderate, severe and critical (Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th edition) published by China National Health Commission on March 4, 2020. http://www.gov.cn/zhengce/zhengceku/2020–03/04/content_5486705.htm). Nine patients showed severe or critical symptoms. As reported, age is a risk factor for severe symptoms (Table 1).
      • Mei X.
      • Zhang Y.
      • Zhu H.
      • Ling Y.
      • Zou Y.
      • Zhang Z.
      • et al.
      Observations about symptomatic and asymptomatic infections of 494 patients with COVID-19 in Shanghai, China.
      ,
      • Zhang Xiaonan
      • Tan Yun
      • Ling Yun
      • Lu Gang
      • et al.
      Viral and host factors related to the clinical outcome of COVID-19.
      Nucleic acids from the throat swab samples of the COVID-19 patients were used as template for Real-time PCR. Real-time PCR was performed by using One Step PrimeScript RT-PCR kit (Takara) in a 25µl reaction mixture as following: 2.5µl of nucleic acid was added in the mixture of 12.5µl of 2 × one step RT-PCR buffer, 0.5µl of EX Taq HS, 0.5μl of RT Enzyme, 1.6µl of primer mix (10µM each), 0.4µl of probe (10µM) and H2O up to 25µl. The R-PCR program was run with incubation at 42 °C for 10 min, followed by 40 cycles of a program (95 °C, 10 s; 95 °C 10 s, 60 °C, 1 min). The primers and probes for Influenza A virus were as following: sense (5′-CTT CTA ACC GAG GTC GAA ACG TA-3′), antisense: (5′-GGT GAC AGG ATT GGT CTT GTC TTT A-3′) and probe: (5′-FAM-TCA GGC CCC CTC AAA GCC GAG −3′-BHQ1); For E. coli were as flowing: sense (5′-GGA TAT CGT CTG GGA CTT CCG-3′), antisense (5′-GCG GAG CCA GAC CGA ATT T-3′) and probe (5′-FAM-GTG AAA TCG ATC AGT GCT TCA GGC CA −3′-BHQ1). Screening for other pathogens were performed by using real-time PCR detection kits from BioGerm (Shanghai, China) as following: human parainfluenza virus 1/human parainfluenza virus 3(PIV1/PIV3) (BioGerm, SJ-HX-215–2), human parainfluenza virus 2/human parainfluenza virus 4 (PIV2/PIV4)(BioGerm, SJ-HX-216–2), Influenza B virus (FLUB)(BioGerm, SJ-LG-006–2), human rhinovirus/human metapneumovirus/Human respiratory syncytial virus (HRV/HMPV/RSV)(BioGerm, SJ-HX-303–2), human Bocavirus/human adenovirus (HBOV/RADV)(BioGerm, SJ-HX-207–2), human Coronavirus 229E/human Coronavirus NL63 (BioGerm, SJ-HX-204–2), human Coronavirus HKU1/ human Coronavirus OC43 (BioGerm, SJ-HX-205–2), Pseudomonas aeruginosa (PA)(BioGerm, SJ-HX-039–2), Moraxella catarrhalis (MC)(BioGerm, SJ-HX-027–2), Mycobacterium tuberculosis (MTB)(BioGerm, SJ-HX-040–2), Mycoplasma pneumonia/Chlamydia pneumonia/Legionella pneumophila (MP/CP/LP)(BioGerm, SJ-HX-302–2), Group A Streptococcus/Haemophilus influenzae/Staphylococcus aureus (GA/HI/SA)(BioGerm, SJ-HX-319–2), Acinetobacter baumannii/Streptococcus pneumoniae/Klebsiella peneumoniae (AB/SP/KP)(BioGerm, SJ-HX-309–2).
      Table 1Patients in this study.
      AgePatients (Total number)Patients (Severe or critical symptom)
      15–60661
      61–75205
      >7533
      As shown in the Table 2, we detected co-infections in 18 patients. We detected co-infection with Kp (Klebsiella.peneumoniae) in 6 patients, co-infection with EC (E. coli) in 5 patients, co-infection with Mcat (Moraxella catarrhalis) in 4 patients, co-infection with Hi (Haemophilus influenzae) in 4 patients, co-infection with Ab (Acinetobacter baumannii) in 2 patients, co-infection with Sa (Staphylococcus aureus) in 2 patients, co-infection with PA (Pseudomonas aeruginosa) in 1 patient, and co-infection with GAS (Group A Streptococcus) in 1 patients. Notably, 6 patients got coinfection with more than two bacteria. One patient with a moderate to severe disease and one patient with severe disease got co-infection with Mcat (Moraxella catarrhalis). One patient with a critical disease got co-infection with Ab (Acinetobacter baumannii). We didn't detect co-infection with any virus in these patients.
      Table 2Co-infection in the COVID-19 patients.
      PatientsPathogenAgeCt ValueDisease Severity
      277#PA, Pseudomonas aeruginosa1535.47Mild
      726#Mcat, Moraxella catarrhalis7635.14Moderate to Severe
      144#Kp, Klebsiella.peneumoniae3232.87Mild
      973#Hi, Haemophilus influenzae5730.52Moderate
      994#Mcat, Moraxella catarrhalis3524.16Mild
      GAS, Group A Streptococcus32.46
      903#Hi, Haemophilus influenza2126.55Mild
      Kp, Klebsiella.peneumoniae35.82
      830#Ab, Acinetobacter baumannii6530.17Critical
      14#Mcat, Moraxella catarrhalis3734.49Mild
      Hi, Haemophilus influenza34.01
      Kp, Klebsiella.peneumoniae26.19
      743#Hi, Haemophilus influenza3635.13Mild
      Ab, Acinetobacter baumannii32.11
      952#Sa, Staphylococcus aureus3331.94Moderate
      EC, E. coli35.77
      976#Kp, Klebsiella.peneumoniae3235.42Mild
      75#EC, E. coli4526.40Mild
      1002#Sa, Staphylococcus aureus1934.68Moderate
      225#Mcat, Moraxella catarrhalis6728.62Severe
      63#Kp, Klebsiella.peneumoniae3432.02Mild
      EC, E. coli27.38
      67#EC, E. coli2723.01Mild
      74#EC, E. coli6628.43Mild
      327#Kp, Klebsiella.peneumoniae6433.97Mild
      M. catarrhalis typically infect adults with a weakened immune system.
      • catarrhalis Moraxella
      • J.C.Verhaegh Suzanne
      • Schaar Viveka
      • ChingSu Yu
      • Riesbeck Kristian
      John P.Hays Molecular Medical Microbiology.
      Elderly COVID-19 patients have impaired Cytotoxic CD8+ T Cell Responses, which may make them highly risk for infection.
      • Westmeier Jaana
      • Paniskaki Krystallenia
      • Karaköse Zehra
      • Werner Tanja
      • et al.
      Impaired cytotoxic CD8 1 + T cell response in elderly COVID-19 patients.
      A. baumannii is a common pathogen in Intensive Care Units (ICU) and evolves rapidly to be resistant to many antibiotics and should be seriously considered for critical COVID-19 patients.
      • Nhu N.T.K.
      • Lan N.P.H.
      • Campbell J.I.
      • Parry C.M.
      • Thompson C.
      • Tuyen H.T.
      • et al.
      Emergence of carbapenem-resistant Acinetobacter baumannii as the major cause of ventilator-associated pneumonia in intensive care unit patients at an infectious disease hospital in southern Vietnam.
      In summary, we carried out an extensive pathogen screening in a COVID-19 cohort. We didn't detect co-infection of SARS-CoV-2 with other viruses. Co-infection with bacteria was detected in 18 of the 89 patients. M. catarrhalis was detected in two patients with severe symptoms and A. baumannii was detected in one patient with critical symptoms. These bacterial co-infections should be taken care in managing the COVID-19 patients.

      Ethics statements

      This study was approved by the ethics committee of Shanghai public health clinical center under the study number YJ-2020-S077-02, and the procedures were carried out in accordance with approved guidelines. Informed consent was obtained from the subjects.

      Authors’ contributions

      YZ conceived the manuscript; SW and JX performed experiments; ZX, LY collected samples; YZ all authors performed litera- ture search; YZ wrote the first draft of the manuscript; all authors reviewed it. SW and JX contributed equally.

      Declaration of Competing Interest

      The authors declare no conflicts of interest.

      Acknowledgments

      This work was supported in part by the National Science and Technology Major Project of China (2017ZX10103009), Key Emergency Project of Shanghai Science and Technology Committee (20411950103).

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