Three-month follow-up after severe COVID-19 infection: are chest CT results associated with respiratory outcomes and respiratory recovery in COVID-19 patients?

BACKGROUND: CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its correlation with respiratory parameters remains unknown. This study aims to assess the association between CT-SS and respiratory outcomes, both in hospital and at three months after hospitalization. METHODS: Patients from the COVID-19 High-intensity Immunosuppression in Cytokine storm Syndrome (CHIC) study surviving hospitalization due to COVID-19 associated hyperinflammation were invited for follow-up assessment at three months after hospitalization. Results of CT-SS three months after hospitalization were compared with CT-SS at hospital admission. CT-SS at admission and at 3-months were correlated with respiratory status during hospitalization and with patient reported outcomes as well as pulmonary- and exercise function tests at 3-months after hospitalization. RESULTS: A total of 113 patients were included. Mean CT-SS decreased by 40.4% (SD 27.6) in three months (P < 0.001). CT-SS during hospitalization was higher in patients requiring more oxygen (P < 0.001). CT-SS at 3-months was higher in patients with more dyspnoea (CT-SS 8.31 (3.98) in patients with modified Medical Council Dyspnoea scale (mMRC) 0-2 vs. 11.03 (4.47) in those with mMRC 3-4). CT-SS at 3-months was also higher in patients with a more impaired pulmonary function (7.4 (3.6) in patients with diffusing capacity for carbon monoxide (DLCO) > 80%pred vs. 14.3 (3.2) in those with DLCO < 40%pred, P = 0.002). CONCLUSION: Patients surviving hospitalization for COVID-19-associated hyperinflammation with higher CT-SS have worse respiratory outcome, both in-hospital and at 3-months after hospitalization. Strict monitoring of patients with high CT-SS is therefore warranted.

Invasive Pulmonary Aspergillosis with Marked Eosinophilia as a Unique Presentation of Chronic Granulomatous Disease.

Background: Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder resulting in phagocytic cell dysfunction. It is characterized by deficient cellular immunity against bacteria and fungi, and an excessive inflammatory response resulting in granuloma formation. It manifests, usually in early childhood, with recurrent bacterial and fungal infections or inflammatory complications. The infections, such as invasive pulmonary aspergillosis, can be life-threatening. Case description: Our patient was a 40-year-old man with no pulmonary history who presented with bilateral pulmonary nodules and pronounced eosinophilia in peripheral blood and bronchoalveolar lavage fluid, mimicking eosinophilic pneumonia. During treatment with corticosteroids, the patient deteriorated clinically and radiographically. Extensive investigations failed to provide a diagnosis. A lung biopsy demonstrated the presence of granulomas and Aspergillus fumigatus hyphae. Advanced screening to detect underlying immunodeficiency revealed CGD. Discussion: This case report describes a unique first presentation of CGD. It reminds physicians of the possibility of CGD as an underlying immune disorder in invasive aspergillosis and highlights the challenges of diagnosing invasive pulmonary aspergillosis. We discuss the diagnostic pitfalls of this case and propose a diagnostic work-up for eosinophilic lung disease. LEARNING POINTS: Pulmonary aspergillosis can present as eosinophilic pneumonia and should be included in the differential diagnosis of eosinophilic lung disease.In case of invasive pulmonary aspergillosis, investigation for chronic granulomatous disease should be considered.Chronic granulomatous disease in adults is probably underdiagnosed because of its variable clinical presentations.

Three-month and six-month outcomes of patients with COVID-19 associated hyperinflammation treated with short-term immunosuppressive therapy: follow-up of the CHIC study.

OBJECTIVES: To prospectively investigate differences in medium-term patient-reported outcome measures and objective functional outcome measures, between patients receiving and those not receiving intensive short-term immunosuppressive therapy for coronavirus disease 19 (COVID-19)-associated hyperinflammation. METHODS: Patients previously included in the COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome (CHIC) study who received immunosuppressive treatment versus standard of care for COVID-19-associated hyperinflammation were invited for follow-up at 3 and 6 months after hospitalisation. At both visits, patients were assessed by a pulmonologist, completed quality of life (QoL) questionnaires and performed pulmonary and exercise function tests. At 3 months, patients additionally completed questionnaires on dyspnoea, anxiety, depression and trauma. Outcomes were compared between patients receiving and those not receiving intensive short-term immunosuppressive therapy for COVID-19-associated hyperinflammation. RESULTS: 131 (66.5%) patients survived hospitalisation due to COVID-19-associated hyperinflammation and 118 (90.1%) were included. QoL questionnaires, pulmonary- and exercise function tests showed improvement between 3 and 6 months after discharge, which was similar in both groups. Assessed patients reached levels that were close to levels predicted from the normal population. In contrast, diffusing capacity of the lung for carbon monoxide was disturbed in both groups: 69.6% predicted (SD 16.2) and 73.5% predicted (SD 16.5) in control group and treated group, respectively. CONCLUSIONS: No differences in medium-term outcomes are demonstrated in survivors of COVID-19-associated hyperinflammation treated or not treated with methylprednisolone with or without tocilizumab during the acute phase. Short-term benefits of this therapy, as showed in the baseline CHIC study analysis, are thus not hampered by medium-term adverse events.

Outcomes of persons with coronavirus disease 2019 in hospitals with and without standard treatment with (hydroxy)chloroquine.

OBJECTIVE: To compare survival of individuals with coronavirus disease 2019 (COVID-19) treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine. METHODS: We analysed data of COVID-19 patients treated in nine hospitals in the Netherlands. Inclusion dates ranged from 27 February to 15 May 2020, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated patients with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox regression with adjustment for age, sex and covariates based on premorbid health, disease severity and the use of steroids for adult respiratory distress syndrome, including dexamethasone. RESULTS: Among 1949 individuals, 21-day mortality was 21.5% in 1596 patients treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 15.0% in 353 patients treated in hospitals that did not. In the adjusted Cox regression models this difference disappeared, with an adjusted hazard ratio of 1.09 (95% CI 0.81-1.47). When stratified by treatment actually received in individual patients, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95% CI 1.24-2.02) in the full model. CONCLUSIONS: After adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in hospitalised patients with COVID-19.

Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia.

COVID-19 is a novel viral disease caused by SARS-CoV-2. The mid- and long-term outcomes have not yet been determined. COVID-19 infection is increasingly being associated with systemic and multi-organ involvement, encompassing cytokine release syndrome and thromboembolic, vascular and cardiac events. The patient described experienced unusually rapid development of pulmonary hypertension (PH) and right ventricular failure after recent severe COVID-19 pneumonia with cytokine release syndrome, which initially was successfully treated with methylprednisolone and tocilizumab. The development of pulmonary hypertension and right ventricular failure - in the absence of emboli on multiple CT angiograms - was most likely caused by progressive pulmonary parenchymal abnormalities combined with microvascular damage of the pulmonary arteries (group III and IV pulmonary hypertension, respectively). To the best of our knowledge, these complications have not previously been described and therefore awareness of PH as a complication of COVID-19 is warranted. LEARNING POINTS: COVID-19 increasingly presents with systemic and multi-organ involvement with vascular, thromboembolic and cardiac events.Patients with severe COVID-19 pneumonia and concomitant cytokine release syndrome may be particularly at risk for the development of secondary pulmonary hypertension and right ventricular failure.Pulmonary hypertension can develop unusually rapidly following COVID-19 pneumonia and probably results from progressive pulmonary interstitial and microvascular abnormalities due to COVID-19.

Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome.

Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening. There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS. We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ). The rapid clinical and biochemical improvement following TCZ administration suggests that treatment with immunotherapy can be life-saving in selected patients with COVID-19-induced CRS. LEARNING POINTS: Cytokine release syndrome may cause sudden and potentially life-threatening clinical deterioration in COVID-19 pneumonia, particularly in younger patients.Immunosuppressive therapy may provide important additional therapeutic benefit in these patients.Tocilizumab, a specific IL-6 inhibitor, led to dramatic clinical improvement in a young patient with severe COVID-19-associated cytokine release syndrome.