Long COVID Mimicking Interstitial Lung Disease: A Case Series.

Interstitial lung diseases (ILD) can occur due to various known or unknown causes. They usually present with dry cough and exertional dyspnea. On radiology usual findings are ground glass opacities (GGO's), reticular shadows, nodules etc. Some patients after acute COVID-19 (coronavirus disease 2019) suffer from persistent symptoms/manifestations. These have been called 'Long COVID'. Long COVID also has radiological features like GGO's, nodules and reticulations. Further, patients even without history of acute COVID-19, can also present with 'Long COVID'. In the present case series, we describe three such cases with no history of having suffered from COVID-19, presenting with ILD like features and diagnosed as Long COVID. We infer from these cases that 'Long COVID' can both clinically and radiologically mimic ILD's. Hence, emphasizing the fact that in the present COVID-19 pandemic situation, 'Long COVID should be a differential diagnosis to be considered while making a new diagnosis of ILD.

Introduction

Pulmonary interstitium, referred to as supportive tissue around the alveoli, is commonly involved in interstitial lung diseases (ILDs) [1].

Involvement of pulmonary interstitium can occur due to some known and other unknown aetiologies [2].

Organic and inorganic dust, various drugs and infections can cause one or the other form of ILD [3].

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has emerged as a potentially hazardous infection in the recent times [4].

Lungs are among the most commonly involved organs [5].

The severity of the disease can range from mild symptoms to a life-threatening infection [6,7].

COVID-19 (Coronavirus Disease 2019) infection of the lungs shows various CT (Computed Tomography) manifestations mimicking ILD including ground glass opacities, septal thickening and/or reticulations, crazy paving pattern and nodules [8].

Although these findings are more common in severe COVID 19, cases with mild disease can also have such features [9].

In this case series we describe three patients without any history suggestive of acute COVID and presentation similar to interstitial lung diseases, but were subsequently confirmed as cases of ‘Long COVID’ [10].

The present work was part of project approved by the Institute Human Ethics Committee (IHEC).

Cases

We had three patients presenting to us with history of dry cough and insidious onset exertional breathlessness.

The duration of symptoms varied from 6-10 weeks.

None of them had any history of prior respiratory ailments. Clinical-radiological findings were suggestive of ILD (Table 1).

Table 1

Comparison of various parameters among three cases

Parameters	Case 1	Case 2	Case 3
Age (Years)	56	65	53
Gender	Male	Male	Male
Diabetes Mellitus (Duration)	No	Yes (15 years)	Yes (16 years)
Hypertension (Duration)	No	No	Yes (2 years)
Symptoms	Cough and exertional dyspnea for 6 weeks	Cough, exertional dyspnea and chest pain for 8 weeks	Cough and exertional dyspnea for 10 weeks
Auscultatory findings	Bilateral infrascapular inspiratory fine crepts	Bilateral infrascapular inspiratory fine crepts	Bilateral infrascapular inspiratory fine crepts
Baseline Chest X-ray	Bilateral diffuse reticulations (Figure 1a)	Bilateral lower zone reticulations	Bilateral lower zone reticulations
Baseline CT Chest	Diffuse patches of ground glass opacities (GGOs) (Figure 2a)	Bilateral peripheral GGOs in lower lobes (Figure 3a)	Bilateral lower lobe reticulations (Figure 4a)
COVID Antibody level (in OD ratio)	2.10	4.0	5.4
Treatment given	Oral corticosteroids in tapering doses for 4 weeks	Oral corticosteroids in tapering doses for 2 weeks	Oral corticosteroids in tapering doses for 2 weeks
Post treatment Radiology	Clearing of reticulations & GGOs (Figures 1b & 2b)	Clearing of GGOs (Figure 3b)	Clearing of reticulations (Figure 4b)

RT-PCR for COVID-19 was negative in all three patients.

All serological investigations for ruling out various ILD were negative.

In view of the current COVID-19 pandemic status, the patients were subjected to IgG antibodies test against SARS-COV-2, which was found to be positive in all three of them.

Based on above findings, these patients were diagnosed as ‘Long COVID’.

They were started on short course of systemic corticosteroids.

Post-treatment clinical and radiological profile of all three patients showed improvement.

Also, a written informed consent was obtained from all the patients before publication of their data.

Figure 1

(a), Case 1 Chest X-ray (posteroanterior view) showing bilateral diffuse reticulations; (b), Case 1 showing clearing of reticulations after 7 weeks

Figure 2

(a), Case 1 CT scan of chest showing patchy areas of ground glass opacities. (b), Case 1 showing clearing of ground glass opacities after 7 weeks

Figure 3

(a), Case 2 CT scan of chest showing diffuse ground glass opacities with interstitial thickening; (b), Case 2 showing clearing of ground glass opacities after 10 weeks

Figure 4

(a), Case 3 CT scan of chest showing bilateral lower lobe reticulations; (b), Case 3 showing clearing of reticulations after 12 weeks

Discussion

Corona Virus Disease 2019 (COVID 19) has emerged as a public health emergency [11].

The disease severity can range from mild infection to a severe one [12].

Patients suffering from severe disease are more at risk of developing complications including lung fibrosis.

But in the literature, cases have been reported of patient with mild diseases having severe cardiorespiratory complications including sudden death [9].

Patients with mild infection have minimal symptoms or are often asymptomatic.

And the infection can go unrecognized until some complications develop.

Our case series highlights the importance of this fact.

We described 3 cases, who presented to the hospital with a short history of respiratory symptoms and evidence of lung fibrosis.

All of them had tested negative for the SARS-CoV-2 by RT-PCR.

On presentation these patients had dry cough, exertional dyspnea, bibasilar crepitations on auscultation, bilateral reticulations on chest radiography and ground glass opacities in CT scan of the chest. Hence, ILD was the probable diagnosis in these cases.

But considering the current COVID pandemic situation the possibility of COVID 19 infection as a differential diagnosis was also kept.

IgG antibodies against SARS-CoV-2 were found to be positive in all the cases, confirming a diagnosis of past COVID-19 infection with residual disease i.e., ‘Long COVID’.

ILD are an important differential diagnosis of patients with exertional dyspnea, dry cough and bilateral reticular/ground glass shadows on radiology, when infections/malignancy have been ruled out.

Interstitial lung involvement in sarcoidosis, acute hypersensitivity pneumonitis, eosinophilic pneumonias and idiopathic interstitial pneumonias can show ground glass opacities [13].

The common radiographic patterns observed in Long COVID includes diffuse reticulations, diffuse nodular shadows and diffuse ground glass opacities [14].

These radiologic patterns hence, mimic those seen in ILDs.

Whereas the treatment guidelines are defined in the literature for most of the ILDs, not much literature evidence is available for the pharmacological management of ‘Long COVID’.

So, it is very important to diagnose long COVID patient before labelling it as some idiopathic form of ILD based on the radiology. Idiopathic form of ILD is termed when no underlying cause or association is found.

In the present pandemic, many patients are recovering from the COVID and are suffering from manifestations of Long COVID.

All the three patients in the present case series did not have any symptoms/history suggestive of acute COVID.

Despite this they had manifestations of ‘Long COVID’ as confirmed by suggestive radiology and positive serology for SARS-CoV-2.

This case series highlights the importance of considering ‘Long COVID’ disease as a differential to the diseases with interstitial involvement with short history at presentation.

After making a diagnosis of long COVID, these patients were treated with tapering doses of systemic corticosteroids which helped in clinical and radiological recovery.

Other studies have also found similar outcomes on usage of systemic corticosteroids in long COVID patients [15,16,17].

There were limitations in the present study, Firstly, owing to the COVID pandemic situation bronchoscopy and pulmonary function tests could not be performed in these patients.

Secondly, this is a small sample observation and would benefit from large scale studies.

Further, a longer duration follow up would add to the observations.

Conclusions

The clinical and radiological presentation of ‘Long COVID’ resembles that of ILD’s. Further asymptomatic COVID infection can also manifest signs and symptoms of ‘Long COVID’.

Therefore, in the current COVID-19 pandemic situation, patients with short history of respiratory symptoms and radiological features suggestive of ILD’s-‘Long COVID’ should also be ruled out, before making a diagnosis of ILD.

Conflict of interest

None to declare.