Rapid pulmonary calcification within 10 days in a COVID-19 patient: a case report

Abstract

Background

Pulmonary calcification typically occurs months to years after chronic infections or metabolic disorders. In contrast, it is exceedingly rare in acute viral pneumonias. We report the first case of rapid intrapulmonary calcification within 10 days of SARS-CoV-2 infection.

Case presentation

An 82-year-old male was admitted with fever and cough. Chest CT revealed scattered calcified foci with a density of 250 HU. Following antiviral therapy (simnotrelvir/ritonavir) and corticosteroids, the calcified lesions exhibited dynamic changes correlating with the inflammatory status. Specifically, partial resolution in early stages, followed by an increase during clinical deterioration, and persistence at discharge. Laboratory tests excluded metabolic causes of calcification (serum calcium, alkaline phosphatase, and parathyroid hormone were within normal limits).

Conclusion

COVID-19 may be associated with rapid pulmonary calcification, with serial CT imaging providing a means to track dynamic lesion changes. The underlying mechanisms and long-term clinical significance remain uncertain and warrant further investigation.

Introduction

Pulmonary parenchymal calcification typically arises secondary to chronic inflammation (e.g., tuberculosis), neoplastic processes, or disorders of calcium-phosphate metabolism, usually developing over several months to years [1, 2]. Viral pneumonia rarely leads to calcification, with only isolated case reports documenting cytomegalovirus-associated pulmonary calcifications [3]. SARS-CoV-2 infection primarily causes acute alveolar injury. However, recent studies suggest it may also trigger cell death and aberrant mineralization through mitochondrial dysfunction [4]. Here, we present a unique case of rapidly progressive pulmonary calcification occurring within 10 days of SARS-CoV-2 infection. To our knowledge, this is the first such case reported worldwide. We explore its underlying mechanisms and clinical implications, offering new insights into the pathophysiology of viral pneumonias.

Case presentation

An 82-year-old male patient was admitted to the hospital on April 9, 2025, due to fever. Ten days prior to admission, he developed a fever without an obvious trigger, with a peak temperature of 38.6 °C, without chills. The fever was accompanied by cough and scant white sputum, but no wheezing or dyspnea. He also experienced generalized body aches. He had a 20-year history of hypertension. There was no history of tuberculosis, viral hepatitis, surgery, trauma, allergies, or endocrine disorders. There was no history of smoking or exposure to occupational inhalational hazards.

On admission, his vital signs were as follows: temperature 37.0 °C, pulse 86 bpm, respiratory rate 20 breaths/min, and blood pressure 115/65 mmHg. Chest auscultation was unremarkable. Chest computed tomography (CT) revealed bilateral peripheral patchy ground-glass opacities, predominantly in the mid and lower lung zones. Scattered punctate calcifications were observed in the areas of pneumonia on mediastinal window (Fig. 1A). Laboratory tests showed white blood cell count 4.26 × 10⁹/L, neutrophils 3.58 × 10⁹/L, lymphocytes 0.49 × 10⁹/L, C-reactive protein 92.73 mg/L, and normal procalcitonin levels. Urinalysis revealed proteinuria (1+) and trace glycosuria. Blood glucose was 6.15 mmol/L, D-dimer was 0.83 mg/L, with normal electrolytes, renal and liver function, and alkaline phosphatase. Arterial blood gas showed pH 7.48, PaCO₂ 29.4 mmHg, PaO₂ 75 mmHg, HCO₃⁻ 23.8 mmol/L, and BE 1.6 mmol/L, indicating mild respiratory alkalosis. The blood oxygen saturation (SpO₂ 88%) was recorded by the nurse immediately after starting low-flow nasal cannula oxygen. Reverse transcription polymerase chain reaction (RT-PCR) testing was positive for SARS-CoV-2 ORF1ab and N genes, with Ct values of 28.48 for both. Other respiratory pathogen panels including RSV-RNA, influenza A and B, parainfluenza types I and III, adenovirus DNA, Mycoplasma pneumoniae DNA, and Bordetella pertussis DNA were all negative. Sputum cultures revealed no pathogenic organisms. The patient was diagnosed with moderate COVID-19 infection.

Fig. 1.

CT Imaging Findings. A1–A2: Mediastinal and lung window images on admission show patchy ground-glass opacities with high attenuation in the peripheral zones of both lungs, more pronounced in the middle and lower lobes. Scattered punctate calcifications are visible within the pneumonic regions on the mediastinal window. B1–B2: CT images on hospital day 5 demonstrate a reduction in the patchy high-density opacities in both lungs. Small bilateral pleural effusions are noted, and pulmonary calcifications appear decreased. C1–C2: CT images on hospital day 11 reveal progression with increased and consolidated high-density opacities in both lungs, accompanied by enlarged and more numerous calcified foci. Bilateral pleural effusions have increased compared to the prior scan. D1–D4: Additional CT images on hospital day 23 show a reduction in the patchy infiltrates and ground-glass opacities in both lungs. Calcifications are more prominent. E1–E2: Chest CT images obtained on February 28, 2024, prior to symptom onset, showing no evidence of pulmonary calcifications

The patient received 3 L/min nasal oxygen supplementation, which improved oxygen saturation to 96%. Antiviral therapy with simnotrelvir/ritonavir (3 tablets, q12h) was initiated. Methylprednisolone 40 mg IV daily and low-molecular-weight heparin calcium 4000 IU subcutaneously daily were administered for thromboprophylaxis. A 24-hour Holter ECG revealed sinus rhythm with frequent atrial premature contractions (APCs), including bigeminy, trigeminy, paired APCs, non-conducted beats, short runs of atrial tachycardia, occasional ventricular premature contractions, paroxysmal bradycardia, and ST-T segment depression suggestive of coronary artery disease and arrhythmia. The patient was prescribed Shen-Song-Yang-Xin capsules (2 capsules, TID).

On hospital day 5, the patient’s symptoms improved, and methylprednisolone was discontinued. Repeat chest CT showed partial resolution of patchy high-density opacities in both lungs, with minimal bilateral pleural effusion and reduction in calcified lesions (Fig. 1B). Sputum culture remained negative; SARS-CoV-2 PCR remained positive. Serum total protein was 48.8 g/L and albumin (bromocresol green method) 27.5 g/L. Thymalfasin 1.6 mg was administered subcutaneously every other day.

On hospital day 11, the patient had recurrent fever, yellow sputum, and desaturation (88%). Repeat CT showed increased and consolidated bilateral pulmonary opacities, with increased number and size of calcifications and worsened bilateral pleural effusions (Fig. 1C). WBC count rose to 7.18 × 10⁹/L, neutrophils 6.43 × 10⁹/L, lymphocytes 0.28 × 10⁹/L, CRP remained elevated at 92.73 mg/L, and procalcitonin was normal. Sputum culture remained negative. The pneumonia had worsened, likely due to mixed infection. Antibiotics were escalated to meropenem, intravenous albumin was given for hypoproteinemia, and methylprednisolone 40 mg IV daily was re-initiated. By hospital day 15, the patient showed clinical improvement, with only occasional cough and sputum production and no wheezing. Repeat chest CT revealed reduction in patchy ground-glass opacities and consolidation, with no change in pulmonary calcifications. On hospital day 23, SARS-CoV-2 PCR turned negative and simnotrelvir/ritonavir was discontinued. Chest CT showed decreased density of bilateral patchy opacities and ground-glass shadows, but further enlargement and increased number of calcified lesions (Fig. 1D).

Due to the rapid development of extensive pulmonary calcifications, endocrinologic evaluation was performed: serum TSH 1.539 uIU/mL, total T3 0.59 nmol/L, total T4 74.7 nmol/L, free T3 2.58 pmol/L, free T4 20.1 pmol/L — all within normal range. Serum phosphorus was 0.76 mmol/L, intact parathyroid hormone 41.73 pg/mL, cortisol 0.35 µg/dL, ACTH 0.01 pg/mL. Electrolytes and alkaline phosphatase were normal. Endocrinology consultation attributed transient cortisol and ACTH suppression to corticosteroid use. The patient showed clinical improvement and was discharged on hospital day 27 with instructions for regular follow-up.

Discussion

In this case, the patient experienced a first-time SARS-CoV-2 infection, presenting with fever and respiratory symptoms. Chest CT revealed peripheral patchy ground-glass opacities bilaterally, and the SARS-CoV-2 antigen test was positive. Inflammatory markers showed an elevated CRP level (92 mg/L), whereas other inflammatory markers remained within normal ranges, supporting a diagnosis of COVID-19 pneumonia. Notably, a routine chest CT scan performed on February 28, 2024 (Fig. 1E), prior to symptom onset, showed no evidence of calcification. However, within 10 days of symptom onset, chest CT already showed scattered punctate calcifications in areas affected by pneumonia, with HU values reaching approximately 250, indicating unusually early calcification after SARS-CoV-2 infection. The patient initially showed improvement with treatment, as indicated by a partial resolution of inflammation and a temporary decrease in calcified lesions. This was followed by clinical deterioration, along with increased calcification that remained at the time of discharge. This dynamic radiological evolution suggests a temporal relationship between inflammatory activity and the appearance of calcified lesions, although a causal relationship cannot be established based on a single case.

Common causes of pulmonary calcification include infectious diseases such as tuberculosis and histoplasmosis, neoplasms like hamartoma or metastatic osteosarcoma, metabolic disorders such as hyperparathyroidism or chronic renal disease, and rare idiopathic conditions like pulmonary alveolar microlithiasis [5, 6]. In the present case, the patient had normal serum calcium, alkaline phosphatase, and parathyroid hormone levels, and there was no history of malignancy, metabolic disease, or chronic infection, making these established causes unlikely. Pulmonary calcification is rarely reported in viral pneumonias and is traditionally considered a process that develops over months. In contrast, calcification in this case appeared within approximately 10 days. Although the exact mechanism remains unclear, several hypotheses may explain this phenomenon. One possibility is mitochondrial injury associated with SARS-CoV-2 infection. Experimental studies have shown that SARS-CoV-2 may disrupt mitochondrial function in type II alveolar epithelial cells, which could lead to the release of phosphate-rich mitochondrial DNA (mtDNA) [7]. Another proposed mechanism involves virus-induced inflammatory cell death (pyroptosis). Activation of the NLRP3 inflammasome and Gasdermin D has been reported in SARS-CoV-2 infection and may result in cellular membrane rupture and calcium efflux, potentially creating a microenvironment favorable for calcium salt deposition [8, 9]. However, these mechanisms remain hypothetical and were not directly demonstrated in this patient.

The temporal association between inflammatory progression and changes in calcified lesions in this case raises the possibility that pulmonary calcification may be related to acute lung injury and subsequent repair processes during COVID-19 pneumonia. In addition, hypoalbuminemia observed during hospitalization may have increased the proportion of ionized calcium, which could theoretically facilitate local calcium deposition in damaged lung tissue [10]. Nevertheless, these interpretations should be considered exploratory. Importantly, histopathological confirmation was not available in this case, and therefore the precise nature and mechanism of the calcified lesions cannot be definitively determined. Additionally, although clinical deterioration occurred during hospitalization, procalcitonin levels remained normal and sputum cultures were negative, making bacterial coinfection uncertain.

Relevant studies have reported pulmonary calcification or ossification as a potential late complication of COVID-19 pneumonia. García Moreno et al. [11] described accelerated pulmonary ossification as a sequela of SARS-CoV-2 infection, suggesting that severe inflammatory lung injury and subsequent fibrotic remodeling may promote ectopic bone formation in lung tissue. Similarly, Torres Pptes et al. [12] reported pulmonary structural abnormalities following COVID-19 infection. These findings support the possibility that persistent inflammation and tissue repair processes after SARS-CoV-2 infection may contribute to abnormal mineral deposition within the lung parenchyma. Our case further highlights this rare but clinically significant manifestation. Notably, reports describing such rapid pulmonary calcification during the acute phase of COVID-19 pneumonia remain extremely limited. It remains unclear whether these calcifications reflect severe inflammatory injury, represent a transient reparative response, or have long-term clinical implications. Further studies with larger cohorts and histopathological evaluation are warranted to better characterize this phenomenon.

Conclusion

In conclusion, this case suggests a possible association between COVID-19 pneumonia and the rapid appearance of pulmonary calcification, occurring within a relatively short time frame compared with traditionally described calcification processes. The dynamic changes observed on serial CT imaging indicate that calcified lesions may evolve alongside inflammatory activity during the disease course. However, due to the absence of histopathological confirmation, the underlying mechanisms remain uncertain. Additional studies are needed to determine the prevalence, pathogenesis, and potential clinical significance of early pulmonary calcification in patients with COVID-19.

Author contributions

J.L. and P.L. drafted the main manuscript. T.W. contributed to clinical data collection and manuscript revision. Y.Z. and M.L. critically reviewed the manuscript, provided valuable comments, and approved the final version. All authors participated in the study design and implementation, and approved the manuscript for submission.

Funding

None.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study protocol was reviewed and approved by Cangzhou Fifth Hospital (People’s Hospital of Qingxian), approval number [20250804].

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Competing interests

The authors declare no competing interests.