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ORIGINAL ARTICLE
Year : 2021  |  Volume : 38  |  Issue : 7  |  Page : 22-26  

Retrospective review analysis of COVID-19 patients co-infected with Mycoplasma pneumoniae


1 Department of Respiratory Medicine, Doncaster Royal Infirmary, UK
2 Department of Critical Care, Doncaster Royal Infirmary, Sheffield Teaching Hospitals, UK

Date of Submission25-Jul-2020
Date of Acceptance25-Oct-2020
Date of Web Publication06-Mar-2021

Correspondence Address:
Dr. Abhinav Choubey
Department of Respiratory Medicine at Doncaster Royal Infirmary
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/lungindia.lungindia_607_20

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   Abstract 


Introduction: Coronavirus disease 2019 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak of this virus has resulted in significant morbidity and mortality throughout the world. We have seen an unprecedented spread of this virus, leading to extreme pressure on health-care services. Mycoplasma pneumoniae causes atypical bacterial pneumonia and is known to co-infect patients with viral pneumonias. Methods: In this retrospective study, patients' data of 580 inpatients with confirmed SARS-CoV-2 infection were reviewed retrospectively over a 3-month period which included the the first peak of COVID-19 infections in the UK. Results: Eight patients with COVID-19 and M. pneumoniae coinfection were identified – four males and four females. All patients were Caucasian, with an age range of 44–89 years. 37.5% of patients were hypertensive, whereas 25% had Type 2 diabetes mellitus. Dyspnea, cough, and pyrexia were found to be very common in these patients. Majority of the patients had abnormal C-reactive protein, lymphopenia, neutrophilia along with bilateral consolidation, and ground-glass opacities. Two patients required admission to intensive care, both of whom unfortunately died along with one patient receiving ward based care. Conclusion: Our confirmed the presence of co-infection with M. pneumoniae and describes the clinical features, investigation results, clinical course, and outcomes for these patients. Further research is needed to review the role of procalcitonin in excluding bacterial co-infection and to assess the impact of co-infection of patients with COVID-19 on morbidity and mortality.

Keywords: Co-infection, coronavirus disease 2019, Mycoplasma pneumoniae, severe acute respiratory syndrome coronavirus 2


How to cite this article:
Choubey A, Sagar D, Cawley P, Miller K. Retrospective review analysis of COVID-19 patients co-infected with Mycoplasma pneumoniae. Lung India 2021;38, Suppl S1:22-6

How to cite this URL:
Choubey A, Sagar D, Cawley P, Miller K. Retrospective review analysis of COVID-19 patients co-infected with Mycoplasma pneumoniae. Lung India [serial online] 2021 [cited 2021 Apr 13];38, Suppl S1:22-6. Available from: https://www.lungindia.com/text.asp?2021/38/7/22/310905




   Introduction Top


At the end of 2019, a novel coronavirus was identified in Wuhan, China, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has since spread around the world. The illness caused by this virus, coronavirus disease 2019 (COVID-19) has demonstrated huge variability in severity, from an asymptomatic or very mild respiratory illness to acute respiratory distress syndrome and muti-organ failure, with the severe form being more common in older patients and those with underlying comorbidities.[1] To date, it has infected more than 8 million people and resulted in more than 450 thousand deaths around the world according to the World Health Organization statistics.[2] Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes and is a well-recognized cause of atypical pneumonia and known to co-infect patients with viral pneumonia. We aim to review the clinical presentation, investigation results, management, and outcomes of COVID-19 inpatients coinfected with M. pneumoniae.


   Methods Top


Patients admitted to a National Health Service Trust based in Northern England with suspected COVID-19 and concerning clinical features were screened for atypical respiratory infections including M. pneumoniae using an antibody test. We have reviewed the mycoplasma titer all results of inpatients with confirmed SARS-CoV-2 over a 3-month period between March 1, 2020 and May 31, 2020.

Using a cutoff point of 100, particle agglutination test was used to confirm M. pneumoniae infection. Out of 580 patients with confirmed SARS CoV-2, 8 were found to be coinfected with M. pneumoniae.

We then retrospectively collected the data about these patients' presentation, demographic details, investigation results, inpatient management, and outcome from the paper medical notes and electronic records.


   Results Top


A database with all patients admitted with the polymerase chain reaction (PCR) confirmed SARS-CoV-2 was screened for positive Mycoplasma antibody titers. We found eight patients with high IgG titers (defined as >100 in this study) along with a clinical suspicion of superadded bacterial infection. A total of 580 patients were admitted and treated in the hospital with confirmed COVID during this period. Out of these patients, an atypical respiratory screen was performed in 209 patients based on clinical suspicion, as demonstrated in [Figure 1].
Figure 1: Flowchart showing the number of hospital inpatients with confirmed coronavirus disease 2019, those tested for Mycoplasma pneumoniae and those found to have serological evidence of co-infection

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All eight patients were from the local area covered by the hospital and were white Caucasian (100%). The age range for these patients was from 44 to 89 years old. We had an equal male-to-female ratio, i.e., four male and four female patients. Although the mean age for females was 76.75 years old, it was significantly lower at 58.25 years old for male patients.

In terms of underlying comorbidities, 37.5% of the patients had hypertension while 25% had Type 2 diabetes. Twenty-five percent had underlying lung conditions such as chronic obstructive pulmonary disease, bronchiectasis, asthma, or lung nodules.

12.5% had chronic kidney disease. Twenty-five percent of the patients were current smokers, whereas 62.5% were nonsmokers. One patient (12.5%) was an ex-smoker.

Seventy-five percent of the patients presented with worsening dyspnea, whereas 37.5% had a cough. Twenty-five percent reported chest pain as a presenting complaint as well. Other symptoms such as myalgia and headache were reported in 25% of the patients. One patient had haemoptysis on presentation.

The mean systolic blood pressure on presentation was 139.6 mmHg. All of these patients were pyrexic (defined as temperature >38C for this study). 87.5% of the patients were found to be tachycardic on admission with a mean heart rate of 91.6 bpm. 62.5% of patients required oxygen while 75% had tachypnea at the time of admission.

All except one patient had normal hemoglobin while all the patients were lymphopenic on presentation (defined as count <1.5 for this study). Two patients had neutrophilia while high C-reactive protein (CRP) was seen in all patients with the mean being 140.5. Procalcitonin (PCT) was performed in five patients. Of these, 2 had high PCT on admission (defined as >0.5 in this study), whilst three patients had initial normal results followed by an increase in PCT value on repeat testing. Full admission blood results are shown in [Table 1]. Fifty percent of the patients were found to have acute kidney injury with one of them needing continuous venovenous hemofiltration.
Table 1: Blood test results on admission for eight patients with confirmed coronavirus disease 19 and Mycoplasma pneumoniae co-infection

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62.5% of patients had bilateral consolidation while 25% had bilateral ground-glass opacities on chest X-ray. One patient (12.5%) had only atelectasis on presentation. One patient was found to have bilateral pleural effusion and severe biventricular impairment on echocardiogram, in conjunction with a significantly raised troponin I.

Two (25%) of these patients required admission to intensive care where one of them was intubated and ventilated, the other requiring continuous positive airways pressure (CPAP) ventilation. One of these patients also received renal replacement therapy in intensive care for acute renal failure. One patient received CPAP therapy on the ward, whereas others (62.5%) were managed with oxygen therapy alone.

The mean duration of hospital stay was 13.7 days. Five patients survived and were subsequently discharged. Unfortunately, both patients requiring intensive care admission along with one patient receiving oxygen therapy on the medical ward died.


   Discussion Top


COVID-19 caused by SARS-CoV-2 usually presents with symptoms of fever, cough, shortness of breath, and myalgia.[3] Other respiratory pathogens causing respiratory infections share the same symptoms and signs seen in patients with COVID-19 and differentiation between COVID-19 and other types of chest infections based on clinical findings alone is usually challenging.

In the early days of COVID-19 pandemic, the limited capacity for viral testing made some health institutions adopt a strategy of testing patients for common viral and bacterial pathogens and not to proceed with SARS-CoV-2 PCR testing if the results of other pathogens turn to be positive.[4]

This strategy did not last long as growing evidence of coinfection with SARS-CoV-2, and other pathogens were evolving.[4],[5],[6],[7] It is well-known that bacterial co-infection can happen with other viral infections. Moreover, there is a signal toward increased mortality and morbidity in this patients subgroup.[8] Hence, the American thoracic society recommends antibacterial treatment for patients with chest infections who test positive for Influenza because the risk of bacterial coinfection is high.

In light of this and because of the difficulty excluding bacterial co-infection in patients admitted with suspected COVID-19, it has been common practice to treat these patients empirically with antibiotics and test for other respiratory pathogens in addition to SARS-CoV-2 PCR.

M. pneumoniae is a known cause of community-acquired pneumonia. The prevalence of M. pneumoniae in patients diagnosed with chest infection varies between 1.9% and more than 30% depending on the population and diagnostic tests used.[9]

Coinfection of M. pneumoniae with other viral respiratory pathogens is not uncommon. A retrospective analysis revealed that M. pneumoniae is the most common bacteria to co-infect patients with influenza A (H1N1) infection.[10]

SARS-CoV-2 coinfection with M. pneumoniae has been reported in a few case reports in China and Singapore.[11],[12] In addition, the rate and clinical characteristics of co-infection were reviewed in two retrospective cohort studies. A review of 350 patients with confirmed COVID-19 admitted to a community teaching hospital in the USA revealed six cases of coinfection with M. pneumoniae.[13] This is significantly lower than the rate reported in a Chinese review by Quansheng et al., in which the reported prevalence of M. pneumoniae coinfection was 23% out of 68 cases diagnosed with SARS-CoV-2 infection.[14] Both of these observational studies used serological evidence to confirm M. pneumoniae infection and did not rely on PCR of respiratory samples. The notable difference in the rate of M. pneumoniae co-infection between the American and Chinese studies could be related to the demographic variations across both populations.

In our study, patients who were discharged from the Accident and Emergency department were not included. All patients in our intensive care unit with COVID-19 were screened for M. pneumoniae; however, screening for atypical pathogens in patients with suspected and confirmed COVID-19 in the medical wards was based on the clinical suspicion of the treating physician. Therefore, the prevalence of coinfection we reported is subjected to a selection bias. Taking this into account, the prevalence of M. pneumoniae co-infection in our study was very similar to the American review. However, despite the similarities, the majority of patients co-infected in the American study were African American in contrast to white Caucasian in our review.[13] This is possibly related to the difference in the population examined in both reviews.

The patients in our study were equally divided between males and females. All tested positive for SARS-CoV-2 PCR and M. pneumoniae serology. All of them had high CRP and were lymphopenic. D dimer, ferritin, troponin, and lactate dehydrogenase were not tested in all patients which makes it difficult to draw any conclusions. Chest X-ray was abnormal in all patients; main findings noted were bilateral ground-glass opacities and consolidation which have been described as common findings in COVID-19 patients.[15]

Most patients were treated with clarithromycin for 14 days in accordance with hospital policy for M. pneumoniae treatment. One patient received azithromycin instead of Clarithromycin because of drug-drug interaction and two patients received levofloxacin in addition to clarithromycin as shown in [Figure 2].
Figure 2: Graph showing choice of antimicrobial therapy in eight patients with confirmed coronavirus disease 2019 and Mycoplasma pneumoniae co-infection

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The results of PCT in patients co-infected with M. pneumoniae were interesting. Three patients in our review had a PCT below the reference range despite having positive M. pneumoniae titer. This replicates the findings noted by Vijay in their cohort study.[13] These findings may question the efficacy of using PCT to help rule out bacterial coinfection in COVID-19 patients and trigger further research.

Half of the patients developed acute kidney injury; however, only one patient required renal replacement therapy. Unfortunately, two patients required admission to the intensive care unit and passed away.

Our study shed light on the presenting features, investigations results and outcomes of patients coinfected with M. pneumoniae and SARS-CoV-2. M. pneumoniae can cause severe community-acquired chest infections with a mortality of up to 30% reported in the literature. Antibiotics are available and required to treat the infection as it will presumptively improve the outcomes.[16] Therefore, screening for atypical pathogens including M. pneumoniae is still justified despite the low co-infection rate reported in our study.


   Conclusion Top


The COVID-19 pandemic has taken the medical fraternity by surprise and the response to this has been unprecedented. This is largely due to the highly infective and insidious ways that the virus spreads as well as the incidence of severe respiratory failure requiring intensive care support. Our review confirmed the presence of co-infection with M. pneumoniae and describes the clinical features, investigation results, clinical course, and outcomes for these patients. Further research is needed to review the role of PCT in excluding bacterial co-infection and to assess the impact of co-infection of patients with COVID-19 on morbidity and mortality. Future guideline development is warranted to clarify which patient populations with COVID-19 should be screened for M. pneumoniae.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 1
    
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World Health Organisation. Coronavirus Disease (COVID 2019) Situation Reports. UK: World Health Organisation; 2020. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. [Last accessed on 2020 Jun 22].  Back to cited text no. 2
    
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Lai CC, Wang CY, Hsueh PR. Co-infections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents? J Microbiol Immunol Infect 2020;53:505-12.  Back to cited text no. 7
    
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Lim YK, Kweon OJ, Kim HR, Kim TH, Lee MK. Impact of bacterial and viral coinfection in community-acquired pneumonia in adults. Diagn Microbiol Infect Dis 2019;94:50-4.  Back to cited text no. 8
    
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Hammerschlag MR. Mycoplasma pneumoniae infections. Curr Opin Infect Dis 2001;14:181-6.  Back to cited text no. 9
    
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Dhanoa A, Fang NC, Hassan SS, Kaniappan P, Rajasekaram G. Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: The effects of bacterial coinfection. Virol J 2011;8:501.  Back to cited text no. 10
    
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Gao Z, Gao L, Chen X, Xu Y. A 49-year-old Woman Co-infected with SARS-COV-2 and Mycoplasma – A Case Report. Research Square; 2020. Available from DOI: 10.21203/rs.3.rs-16376/v1.(last accessed 17/12/2020)  Back to cited text no. 11
    
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Fan BE, Lim KG, Chong VC, Chan SS, Ong KH, Kuperan P. COVID-19 and Mycoplasma pneumoniae coinfection. Am J Hematol 2020;95:723-4.  Back to cited text no. 12
    
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Gayam V, Konala VM, Naramala S, Garlapati PR, Merghani MA, Regmi N, et al. Presenting characteristics, comorbidities, and outcomes of patients coinfected with COVID-19 and Mycoplasma pneumoniae in the USA. J Med Virol. 2020;92:2181-2187.  Back to cited text no. 13
    
14.
Quansheng X, Guo-Ju L, Yu-Han X, Ting C, Wen-Jie L, Wei N, et al. Precautions Are Needed for COVID-19 Patients with Coinfection of Common Respiratory Pathogens (3/2/2020). Available at SSRN: https://ssrn.com/abstract=3550013 or http://dx.doi.org/10.2139/ssrn.3550013 (Last accessed 17/12/2020).  Back to cited text no. 14
    
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Wang Y, Wang Y, Chen Y, Qin Q. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020;92:568-76.  Back to cited text no. 15
    
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Bajantri B, Venkatram S, Diaz-Fuentes G. Mycoplasma pneumoniae: A potentially severe infection. J Clin Med Res 2018;10:535-44.  Back to cited text no. 16
    


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