A histopathological analysis of extrapulmonary lesions in fatal coronavirus disease (COVID-19).

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues. MATERIALS AND METHODS: The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated. RESULTS: In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD. DISCUSSION: The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging. CONCLUSION: Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.

Pathology of COVID-19 Lung Disease.

The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated.

Imaging of the Spectrum of Acute Lung Injury.

Organizing pneumonia, acute fibrinous and organizing pneumonia, and diffuse alveolar damage, represent multi-compartment patterns of lung injury. The initial region of injury in all remains the same and is centered on the fused basement membrane (BM) between the capillary endothelium and type I pneumocyte. Injury leads to cellular death, BM denudation, increased cellular permeability, and BM structural damage, which leads to exudation, organization, and attempts at repair. When acute lung injury does lead to fibrosis, in some instances it can lead to histologic and/or radiologic usual interstitial pneumonia or nonspecific interstital pneumonia patterns suggesting that lung injury is the primary mechanism for the development of fibrosis.

Multidisciplinary Approach to the Diagnosis of Idiopathic Interstitial Pneumonias: Focus on the Pathologist's Key Role.

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome.

Introduction: The acute respiratory distress syndrome (ARDS), secondary to viral pneumonitis, is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019)-ongoing SARS-CoV-2 infection- reached more than 0.7 billion registered cases. Methods: Recently, we elaborated a non-surgical and reproducible method of the unilateral total diffuse alveolar damage (DAD) of the left lung in ICR mice-a publicly available imitation of the ARDS caused by SARS-CoV-2. Our data read that two C-C chemokine receptor 5 (CCR5) ligands, macrophage inflammatory proteins (MIPs) MIP-1α/CCL3 and MIP-1ß/CCL4, are upregulated in this DAD model up to three orders of magnitude compared to the background level. Results: Here, we showed that a nonpeptide compound TAK-779, an antagonist of CCR5/CXCR3, readily prevents DAD in the lung with a single injection of 2.5 mg/kg. Histological analysis revealed reduced peribronchial and perivascular mononuclear infiltration in the lung and mononuclear infiltration of the wall and lumen of the alveoli in the TAK-779-treated animals. Administration of TAK-779 decreased the 3-5-fold level of serum cytokines and chemokines in animals with DAD, including CCR5 ligands MIP-1α/ß, MCP-1, and CCL5. Computed tomography revealed rapid recovery of the density and volume of the affected lung in TAK-779-treated animals. Discussion: Our pre-clinical data suggest that TAK-779 is more effective than the administration of dexamethasone or the anti-IL6R therapeutic antibody tocilizumab, which brings novel therapeutic modality to TAK-779 and other CCR5 inhibitors for the treatment of virus-induced hyperinflammation syndromes, including COVID-19.

An Autopsy Case of COVID-19 with New Diffuse Pulmonary Ossification.

We present the case of a 61-year-old man who developed coronavirus disease 2019 (COVID-19) and died during treatment for relapsing polychondritis. The patient was intubated and treated with steroid pulse therapy, remdecivir, antibacterial agents, baricitinib, and tocilizumab. However, his respiratory condition worsened, and he died 108 days after disease onset. An autopsy revealed diffuse alveolar damage in the fibrotic phase in all lung lobes, diffuse pulmonary ossification, and cytomegalovirus-infected cells in the middle lobe of the right lung. We herein discuss the clinical features and pathological findings of COVID-19 in immunosuppressed patients.

Dissemination of Reactivated Coccidioidomycosis Inducing Diffuse Alveolar Damage: A Rare Autopsy Case Report.

Coccidioidomycosis is a fungal infection prevalent in the Southwestern United States and Northern Mexico. Given its rarity and often asymptomatic nature, disseminated coccidioidomycosis frequently omitted in preliminary differential diagnoses. Our case study presents the postmortem results of an individual who had a reactivated coccidioidomycosis, causing diffuse alveolar damage and resulting in his death. This case study underscores the importance of considering coccidioidomycosis in initial differential diagnoses, particularly in patients with prior exposure to the infection and associated risk factors.

Autopsy of Drug-induced Lung Injury with Atypical Diffuse Alveolar Disorder due to Amiodarone: A Case Report.

Amiodarone, a prominent antiarrhythmic drug, may cause lung injury. We herein report the case of an 87-year-old man who had been taking amiodarone for 5 years and was subsequently referred due to respiratory failure. Chest computed tomography revealed multiple consolidations with air bronchograms in both lungs. Despite administering steroid pulse therapy, his respiratory failure worsened, and he died 3 days later. Autopsy revealed hyaline membrane formation and organic formation with fibrin deposition. Drug-induced lung injury caused by amiodarone was confirmed by autopsy. Caution is therefore required when fibrin deposition in the alveolar spaces is observed in such cases, which are prone to suffer a rapid deterioration.

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19.

BACKGROUND: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. METHODS: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. FINDINGS: Forty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. INTERPRETATION: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. FUNDING: UK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust.

Spatiotemporal single-cell transcriptomic profiling reveals inflammatory cell states in a mouse model of diffuse alveolar damage.

Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single-cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD-induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper-inflammatory state, and the subsequent occurrence of a CXCL1-CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close-knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper-inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression.

Histologic Characteristics and Clinical Courses of Primary Viral Pneumonia Other than COVID-19.

Objective To clarify both the histologic changes in primary viral pneumonia other than COVID-19 and whether patients with severe lung injury (SLI) on biopsy specimens progress to severe respiratory insufficiency. Methods Patients with primary viral pneumonia other than COVID-19, who underwent lung tissue biopsy, were retrospectively studied. Patients Forty-three patients (41 living patients and 2 autopsied cases) were included in the study. Results Nine patients had SLI, whereas most of patients who recovered from primary viral pneumonia showed a nonspecific epithelial injury pattern. One patient underwent a biopsy under mechanical ventilation. Two of 8 (25.0%) patients on ambient air or low-flow oxygen therapy progressed to a severe respiratory condition and then to death, while only 1 (3.1%) of 32 patients without SLI progressed to a severe respiratory condition and death (p=0.096). The proportion of patients who required O2 treatment for ≥2 weeks was higher in patients with SLI than in those without SLI (p=0.033). The 2 autopsy cases showed a typical pattern of diffuse alveolar damage, with both showing hyaline membranes. Non-specific histologic findings were present in 32 patients without SLI. Conclusion Some patients with SLI progressed to severe respiratory insufficiency, whereas those without SLI rarely progressed to severe respiratory insufficiency or death. The frequency of patients progressing to a severe respiratory condition or death did not differ significantly between those with and without SLI. The proportion of patients who required longer O2 treatment was higher in SLI group than in those without SLI.

An Autopsy Case of Post-COVID-19 Interstitial Lung Disease with Acute Exacerbation.

The prognosis of patients with post-coronavirus disease 2019 (COVID-19) interstitial lung disease remains unclear. We herein report an autopsy case in which serial progression after the onset of post-COVID-19 interstitial lung disease resulted in an acute exacerbation, leading to a fatal outcome. Autopsy findings included hyaline membrane formation/interstitial inflammatory cell infiltration, suggestive of acute lesions, and severe regional fibrosis, indicating a preexisting chronic condition. In the present case, we histopathologically confirmed the acute exacerbation of post-COVID-19 interstitial lung disease.

Case report: A case of acute exacerbation of interstitial pneumonia associated with TAFRO syndrome.

Cytokine storm caused by the overproduction of inflammatory interleukin (IL)-6 plays a central role in the development of acute inflammation. The extremely rare disease, TAFRO syndrome, progresses quickly. Renal dysfunction, fever, reticulin fibrosis, anasarca, thrombocytopenia, and organomegaly with pathological findings such as idiopathic multicentric Castleman disease are all characteristics of TAFRO syndrome. Interstitial pneumonia (IP), which is not characteristic of this disease, is probably a complication of the inflammatory process. An 88-year-old man presented with a 3-day history of fever, dry cough, and progressive dyspnea. After he was first treated with antibiotics, he was transferred to our hospital because he showed no improvement. Data showed hemoglobin Hb 90.00 (SI) (9.0 g/dL); leukocyte count WBC 23 × 109/L (SI) [23,000/µL (neutrophils 87.5%, lymphocytes 2.5%, blast cells 0%)]; hemoglobin 90 g/L (9.0 g/dL); platelet count 101.00 × 109/L (10 100/µL); lactate dehydrogenase 4.78 µkat/L (286 U/L); serum albumin 25.00 g/L (2.5 g/dL); blood urea nitrogen 18.17 µmol/L (50.9 mg/dL); creatinine 285.53 µmol/L (3.23 mg/dL); C-reactive protein 161.50 mg/L (16.15 mg/dL); IL-61830 pg/mL; and surfactant protein D level 26.6 ng/mL. Findings from computed tomography indicated increased ground-glass opacities without traction bronchiectasis consistent with acute IP. The diagnosis was leukocytosis and progressive kidney injury. After bone marrow aspiration caused by persistent pancytopenia, mild reticulin fibrosis was identified. Because of the high IL-6 concentration, which revealed small atrophic follicles with regressed germinal centers surrounded by several lymphocytes, right inguinal lymph node biopsy was performed. Two minor and three major criteria led to diagnosis of TAFRO syndrome. Administrations of antibiotic therapy and methylprednisolone pulse therapy were ineffective. After rapid progress of respiratory failure, the patient died on day 30 of hospitalization. Autopsy of lung tissues showed diffuse alveolar damage with hyaline membranes. Based on these findings, we diagnosed acute exacerbation of IP associated with TAFRO syndrome due to IL-6 overproduction-associated cytokine storm.

Minimally invasive autopsies for the investigation of pulmonary pathology of COVID-19-experiences of a longitudinal series of 92 patients.

Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48-98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5-8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit (p=0.026 and p<0.001) and younger age (p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns (p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance.

An autopsy case of anti-MDA5 antibody-positive amyopathic dermatomyositis with an initial manifestation of panniculitis on the left upper arm.

A 53-year-old man was presented with refractory panniculitis on the left upper arm that had persisted for 10 months. The patient was diagnosed with lupus profundus, wherein oral glucocorticoid therapy was initiated. Four months prior, ulceration was observed in the same area. Dapson was administered instead, scarring the ulcer but enlarging the panniculitis. Five weeks earlier, he developed a fever, productive cough, and dyspnoea. Three weeks earlier, a skin rash was observed on the forehead, left auricle posterior to the neck, and extensor aspect of the left elbow. Chest computed tomography showed pneumonia in the right lung, after which the patient's dyspnoea worsened. The patient was admitted and diagnosed with anti-MDA5 antibody-positive amyopathic dermatomyositis (ADM) based on skin findings, hyperferritinaemia, and rapidly progressive diffuse lung shadows. Glucocorticoid pulse therapy, intravenous cyclophosphamide, and tacrolimus were initiated, and later, plasma exchange therapy was combined. However, his condition worsened and required management with extracorporeal membrane oxygenation. The patient expired on day 28 after hospitalisation. An autopsy revealed hyalinising to fibrotic stages of diffuse alveolar damage. Strong expression of myxovirus resistance protein A was observed in three skin biopsy specimens from the time of initial onset, consistent with ADM. Anti-MDA5 antibody-positive ADM not only manifests typical cutaneous symptoms, but also rarely occurs with localised panniculitis, such as in the present case. In patients with panniculitis of unknown aetiology, the possibility of initial symptoms of ADM should be included in the differential diagnosis.

Morphological prediction of lethal outcomes in the evaluation of lung tissue structural changes in patients on respiratory support with СOVID-19: Ukrainian experience.

The impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on lung tissue in patients on respiratory support is of significant scientific interest in predicting mortality. This study aimed to analyze post-mortem histological changes in the lung tissue of COVID-19 patients on respiratory support using vital radiology semiotics. A total of 41 autopsies were performed on patients who died of SARS-CoV-2 and had confirmed COVID-19 by polymerase chain reaction (PCR) and radiological evidence of lung tissue consolidation and ground glass opacity. The results showed that the duration of COVID-19 in patients on respiratory support was significantly associated with the development of all stages of diffuse alveolar damage, acute fibrous organizing pneumonia, pulmonary capillary congestion, fibrin thrombi, perivascular inflammation, alveolar hemorrhage, proliferating interstitial fibroblasts, and pulmonary embolism. The prediction model for lethal outcomes based on the duration of total respiratory support had a sensitivity of 68.3% and a specificity of 87.5%. In conclusion, for COVID-19 patients on long-term respiratory support with radiological signs of ground glass opacity and lung consolidation, post-mortem morphological features included various stages of diffuse alveolar lung damage, pulmonary capillary congestion, fibrin clots, and perivascular inflammation.

Postmortem lung and heart examination of COVID-19 patients in a case series from Jordan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic for more than 2 years. Autopsy examination is an invaluable tool to understand the pathogenesis of emerging infections and their consequent mortalities. The aim of the current study was to present the lung and heart pathological findings of COVID-19-positive autopsies performed in Jordan. METHODS: The study involved medicolegal cases, where the cause of death was unclear and autopsy examination was mandated by law. We included the clinical and pathologic findings of routine gross and microscopic examination of cases that were positive for COVID-19 at time of death. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed through molecular detection by real-time polymerase chain reaction, serologic testing for IgM and electron microscope examination of lung samples. RESULTS: Seventeen autopsies were included, with male predominance (76.5%), Jordanians (70.6%), and 50 years as the mean age at time of death. Nine out of 16 cases (56.3%) had co-morbidities, with one case lacking such data. Histologic examination of lung tissue revealed diffuse alveolar damage in 13/17 cases (76.5%), and pulmonary microthrombi in 8/17 cases (47.1%). Microscopic cardiac findings were scarcely detected. Two patients died as a direct result of acute cardiac disease with limited pulmonary findings. CONCLUSIONS: The detection of SARS-CoV-2 in postmortem examination can be an incidental or contributory finding which highlights the value of autopsy examination to determine the exact cause of death in controversial cases.

Severe COVID-19 pneumonia leads to post-COVID-19 lung abnormalities on follow-up CT scans.

Purpose: To investigate the association of the maximal severity of pneumonia on CT scans obtained within 6-week of diagnosis with the subsequent development of post-COVID-19 lung abnormalities (Co-LA). Methods: COVID-19 patients diagnosed at our hospital between March 2020 and September 2021 were studied retrospectively. The patients were included if they had (1) at least one chest CT scan available within 6-week of diagnosis; and (2) at least one follow-up chest CT scan available ≥ 6 months after diagnosis, which were evaluated by two independent radiologists. Pneumonia Severity Categories were assigned on CT at diagnosis according to the CT patterns of pneumonia and extent as: 1) no pneumonia (Estimated Extent, 0%); 2) non-extensive pneumonia (GGO and OP, <40%); and 3) extensive pneumonia (extensive OP and DAD, >40%). Co-LA on follow-up CT scans, categorized using a 3-point Co-LA Score (0, No Co-LA; 1, Indeterminate Co-LA; and 2, Co-LA). Results: Out of 132 patients, 42 patients (32%) developed Co-LA on their follow-up CT scans 6-24 months post diagnosis. The severity of COVID-19 pneumonia was associated with Co-LA: In 47 patients with extensive pneumonia, 33 patients (70%) developed Co-LA, of whom 18 (55%) developed fibrotic Co-LA. In 52 with non-extensive pneumonia, 9 (17%) developed Co-LA: In 33 with no pneumonia, none (0%) developed Co-LA. Conclusions: Higher severity of pneumonia at diagnosis was associated with the increased risk of development of Co-LA after 6-24 months of SARS-CoV-2 infection.

Bystander CD8 + T cells may be involved in the acute phase of diffuse alveolar damage.

Acute respiratory distress syndrome (ARDS) is a serious complication of systemic inflammatory response syndrome, and diffuse alveolar damage (DAD) is a histological manifestation of ARDS. Endothelial cell injury is mainly responsible for ARDS. Many neutrophils and macrophages/monocytes, which are inflammatory cells that play a role in innate immunity, infiltrate the lung tissue in DAD. In recent years, it has become clear that CD8 plays an important role not only in the acquired immune system, but also in the innate immune system. Non-antigen-activated bystander CD8 + T cells express the unique granzyme B (GrB) + /CD25-/programmed cell death-1 (PD-1)-phenotype. The involvement of bystander CD8 + T cells in lung tissue in DAD is an unexplored field. This study aimed to determine whether bystander CD8 is involved in DAD. Twenty-three consecutive autopsy specimens were retrieved from patients with DAD, and the phenotypes of infiltrating lymphocytes in the DAD lesions were evaluated using immunohistochemistry. In most cases, the number of CD8 + T cells was higher than that of CD4 + T cells, and many GrB + cells were also observed. However, the number of CD25 + and PD-1 + cells was low. We conclude that bystander CD8 + T cells may be involved in cell injury during the development of DAD.

What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant?

Pulmonary damage in SARS-CoV-2 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis. In addition, nosocomial bacterial superinfections and ventilator-induced lung injury (VILI) are likely to occur. The SARS-CoV-2 Omicron variant have manifested itself as a more diffusive virus which mainly affects the upper airways, such as the nose and pharynx. The mechanism leading to a lung injury with a complex clinical course for the Omicron SARS-CoV-2 variant remains unclear. A key question is whether the organ damage is due to direct organ targeting of the virus or downstream effects such as an altered immune response. An immune escape process of Omicron variant is being studied, which could lead to prolonged viral shedding and increase hospitalization times in patients with comorbidities, with an increased risk of pulmonary co-infections/superinfections and organ damage. This brief commentary reports the current knowledge on the Omicron variant and provides some useful suggestions to the scientific community.