Abstract A new concept of multisystem disease has emerged as a long-term condition following mild-severe COVID-19 infection. The main symptoms of this affection are breathlessness, chest pain, and fatigue. We present here the clinical case of four COVID-19 patients during hospitalization and 60 days after hospital discharge. Physiological impairment of all patients was assessed by spirometry, dyspnea score, arterial blood gas, and 6-minute walk test 60 days after hospital discharge, and computed tomographic scan 90 days after discharge. All patients had fatigue, which was not related to hypoxemia or impaired spirometry values, and interstitial lung alterations, which occurred in both mechanically ventilated and non-mechanically ventilated patients. In conclusion, identifying the prevalence and patterns of permanent lung damage is paramount in preventing and treating COVID-19-induced fibrotic lung disease. Additionally, and based on our preliminary results, it will be also relevant to establish long-term outpatient programs for these individuals.