Pneumonia: Diagnosis, Treatment, and Challenges in the Context of COVID-19

Introduction

Community-acquired pneumonia significantly affects global health, resulting in high mortality, morbidity, and treatment costs [1]. The COVID-19 pandemic and advancements in diagnostic technologies have increased the identification of atypical pathogens, although the diagnostic process remains lengthy [2]. Among acute primary cases caused by Chlamydia psittaci, 10% pose a life-threatening risk [3]. The clinical features of Chlamydia psittaci infection are generally nonspecific. However, there have been reports of yellow-white sputum production in a minority of cases of Chlamydia psittaci pneumonia [3–5]. Research has demonstrated that the color of sputum can serve as a significant predictor of potentially pathogenic microorganisms. While sputum color is utilized in the diagnostic assessment of various pathogens, its sensitivity and specificity are currently limited, necessitating reliance on laboratory diagnosis for accurate identification [6–8]. Conventional testing methods for zoonotic diseases often present interpretative challenges, due to the diverse clinical manifestations, emphasizing the need for swift diagnosis and appropriate treatment. Currently, there is no sensitive, straightforward, and easily executable diagnostic approach available. Culturing atypical pathogens, in particular, is laborious and time-intensive. With advancements in molecular biology, several molecular diagnostic techniques have been developed. Among these, metagenomic next-generation sequencing (mNGS) is gaining prominence in clinical settings for its ability to perform shotgun sequencing of DNA or RNA from clinical samples (mNGS technology detects nucleic acid, which cannot be simply equated with pathogenic microorganisms) [9]. A wide range of pathogenic microorganisms (including viruses, bacteria, fungi, and parasites) can be unbiasedly detected, typed, and assessed for drug resistance. The detection process typically takes 48 to 72 h. Given factors such as cost-effectiveness and practical feasibility, mNGS has the potential to emerge as a primary method for screening unconventional pathogens associated with severe infectious diseases in the foreseeable future.

Case Report

A 58-year-old man from rural Chongqing in southwest China, who kept poultry but had no significant travel history, tick bites, exposure to live bird markets, or contact with pet birds, presented with dizziness, fatigue, and fever starting 6 days prior. His symptoms included a high fever reaching 40 °C and cough with golden purulent sputum production. The diagnosis of community-acquired pneumonia was considered based on blood gas analysis and computed tomography (CT) examination. Initial antibiotic treatment with cefoperazone-sulbactam sodium failed to alleviate symptoms, resulting in disease progression. Consequently, the patient was transferred to the Intensive Care Unit (ICU) of Daping Hospital, affiliated with the Army Medical University.

On admission (day 1), the patient was conscious, with a normal body temperature and blood pressure, pulse rate of 115 beats/min, respiratory rate of 39 breaths/min, and extensive rales in both lungs. Laboratory test results revealed an inflammatory response, with a neutrophil ratio of 92.2%, C-reactive protein level of 205.41 mg/L, total lymphocyte count of 0.22×109/L, lymphocyte percentage of 2.3%, and procalcitonin level of 45.32 ng/mL. Given the likelihood of a bacterial infection, imipenem-cilastatin antibiotics were administered. However, the patient’s respiratory function worsened on day 2, with an oxygenation index remaining below 100 mm Hg. Meanwhile, multiple organ dysfunction, such as hemodynamic disturbance, acute kidney injury, and acute hepatic insufficiency, was observed. After obtaining consent from the patient’s family, teicoplanin was added to the treatment regimen, and the patient was placed in a prone position (>18 h/ day). Venovenous extracorporeal membrane oxygenation (VVECMO) support was initiated, along with continuous renal replacement therapy and plasma exchange. Bronchoscopy was performed to obtain alveolar lavage fluid, along with mNGS.

On the day 4 of hospitalization, mNGS identified Chlamydia psittaci, with a high pathogen load, with nearly complete genome coverage of the sample microorganisms (Figure 1). mNGS performs high-throughput sequencing of nucleic acids directly from clinical samples, which is then compared and analyzed with databases to determine the types of pathogenic micro-organisms contained, based on the sequence information obtained from the comparison. Subsequently, the antibiotic regimen was modified to azithromycin, leading to a progressive improvement in the patient’s condition. The patient was gradually weaned off ECMO and ventilator support, and was eventually discharged on day 45 of hospitalization.

One month after discharge, a CT scan indicated the presence of interstitial fibrosis in both lungs. The patient experienced asthma-like symptoms and fatigue after extended periods of walking, but no other complications or neurological deficits were reported. The final diagnosis included community-acquired Chlamydia psittaci pneumonia, type I respiratory failure, multiple organ failure, and ICU-acquired weakness.

Discussion

This case highlights the medical community’s limited awareness of atypical pathogen infections during the epidemic era. While emphasis has been placed on history taking and screening for COVID-19, infections caused by atypical pathogens and the need for specialized history taking have been overlooked, resulting in the progression to severe pneumonia. There is evidence suggesting that psittacosis can spread not only from animal to animal but also within families [10], introducing new challenges in diagnosis and treatment. The absence of specific epidemiological history and the lack of sensitive diagnostic methods complicate the management of severe cases [11].

Currently, there is no laboratory test available for evaluating lung function during ECMO in conjunction with ventilator support. This gap in assessment methods has led to the exploration of alternatives such as bedside ultrasound, electrical impedance tomography, and chest CT. The advancement of imaging technologies plays a crucial role in enhancing our understanding of pulmonary infections. These technologies allow for functional evaluations and morphological monitoring from the initial occurrence to the progression of the disease, guiding targeted treatments. In diagnostic processes, imaging abnormalities, such as the distribution range of lesions, amount and quality of thoracic exudation, and pathophysio-logical structure of lesions, serve as vital tools to elucidate the underlying pathophysiological mechanisms for identifying the specific pathogens [12].

Severe community-acquired pneumonia poses a significant challenge to public health worldwide. In southern China, Chlamydia psittaci, an uncommon pathogen, remains a prevalent cause of severe community-acquired pneumonia, warranting increased vigilance toward pneumonia induced by this rare pathogen [13,14]. Although cases of severe pneumonia caused by Chlamydia psittaci are infrequent, they are associated with a high mortality rate. Clinicians should maintain a high index of suspicion for this condition in patients who present with a history of avian contact, production of yellow-white sputum, signs of pulmonary inter-stitial disease, or progressive disease despite the use of broad-spectrum antibiotics that cover common pathogens.

mNGS serves as an effective diagnostic adjunct when conventional laboratory tests are inconclusive, particularly when mechanical ventilation support is necessary during the wait for results [10,15]. Its ability to accurately identify pathogens, including those causing atypical community-acquired severe pneumonia, supports a “support first, target later” approach to treatment (Figure 2). The diagnostic and therapeutic approach in this case study can be applied to, but not limited to, patients with severe pneumonias caused by uncommon pathogens such as Chlamydia psittaci. ECMO, an advanced life support technology facilitating basic respiratory and circulatory functions, has been used in clinical settings for nearly 2 decades. The sophistication and acceptance of ECMO have significantly increased, particularly during the 2020 COVID-19 global pandemic, when it earned widespread public endorsement. ECMO becomes the preferred intervention when conventional strategies, such as mechanical ventilation with lung protective strategies and prone positioning, are no longer effective [16]. This approach not only provides healthcare professionals with greater confidence when confronting severe illnesses but also contributes to lowering mortality rates associated with treatable conditions.

The rapid diagnosis of epidemiological history and pathogens is increasingly recognized as critical in the treatment of global disease outbreaks. However, during the COVID-19 pandemic, the significance of rare pathogen infections emerged as a vital consideration. While the focus often remains on common and typical pathogens, managing atypical pathogen pneumonia is essential, especially for critically ill patients. Addressing the underlying cause of a reversible disease to correct the host’s or organ’s unregulated response is a complex, long-term process. During the search for the disease’s root cause, the patient can experience severe multiple-organ dysfunction or even reach a state of exhaustion. Although the disease itself might be reversible, the body’s unregulated response to it may not be, underscoring the need for solutions that rely on supporting multiple organ functions and providing comprehensive care.

This foundational approach not only aims at treating the immediate health issue but also has significant implications for the patient’s quality of life in both the short and long term.

Conclusions

Given the scarcity of reports on human psittacosis in China, this report aims to heighten awareness of this rare infectious disease, acknowledging the significant challenge of diagnosing severe pneumonia caused by atypical pathogens amid the COVID-19 pandemic. The utilization of multi-organ function support in reversible diseases affords clinicians valuable time for pathogen screening and treatment. It also introduces innovative approaches to diagnosing and managing severe pneumonia triggered by atypical pathogens during an epidemic, suggesting a broader framework for addressing similar infectious diseases.