COVID-19 Pneumonia Followed by Anti-signal Recognition Particle Antibody-positive Fibrosing Interstitial Lung Disease.

Coronavirus disease 2019 (COVID-19) pneumonia is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently accompanied by various sequelae. Interstitial lung diseases (ILDs) are observed in COVID-19 pneumonia patients after recovery, probably due to persistent inflammation in the lungs. We herein report a case of ILD with anti-signal recognition particle antibodies following severe COVID-19 pneumonia. The patient was diagnosed with ILD three months after COVID-19 pneumonia. Although the exact mechanism is unknown, the autoantibody-induced immune response might have been the pulmonary fibrosis trigger in this patient.

Association of SARS-CoV-2 RNA Copy Number with the COVID-19 Mortality Rate and Its Effect on the Predictive Performance of Mortality in Severe Cases.

Factors associated with mortality are important in the treatment of coronavirus disease 2019 (COVID-19). Polymerase chain reaction (PCR) is the gold standard for diagnosing COVID-19, which reflects the viral load in the upper respiratory tract. In total, 523 patients were enrolled in this study; of them, 441 and 75 patients underwent PCR testing of nasopharyngeal swabs and sputum samples, respectively, within 20 days from onset of COVID-19. We investigated the association between RNA copy number and the COVID-19 severity and mortality rate and its effect on the predictive performance for severity and mortality. RNA copy numbers in nasopharyngeal swabs were higher in the non-survivor group than in the survivor group. Multivariate logistic regression analysis identified that the high RNA copy number (≥9 log10 /swab) in nasopharyngeal swabs was a factor associated with mortality (odds ratio, 4.50; 95% confidence interval, 1.510-13.100; P = 0.008). Furthermore, adding RNA copy number (≥9 log10 /swab) in severe cases, adjusted by duration from onset to PCR, improved mortality predictive performance based on known factors. The RNA copy number is a factor associated with the mortality of patients with COVID-19 and can improve the predictive performance of mortality in severe cases.

Arterial and Venous Thrombosis Complicated in COVID-19: A Retrospective Single Center Analysis in Japan.

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

Predictors associated with clinical improvement of SARS-CoV-2 pneumonia.

BACKGROUND: There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. OBJECTIVES: This study aimed to investigate the factors associated with the clinical improvement of COVID-19. METHODS: Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. RESULTS: Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002-1.114), no hypertension (HR, 2.077; 95% CI, 1.006-4.287), and low D-dimer levels (<1 µg/ml) (HR, 2.372; 95% CI, 1.229-4.576) were confirmed to be significant predictive factors for time to clinical improvement. Furthermore, a lower SARS-CoV-2 RNA copy number was also a predictive factor for clinical improvement. CONCLUSIONS: Several predictors for the clinical improvement of COVID-19 pneumonia were identified. These results may be important for the management of COVID-19 pneumonia.

MuLBSTA score is a useful tool for predicting COVID-19 disease behavior.

BACKGROUND: The prediction of COVID-19 disease behavior in the early phase of infection is challenging but urgently needed. MuLBSTA score is a scoring system that predicts the mortality of viral pneumonia induced by a variety of viruses, including coronavirus, but the scoring system has not been verified in novel coronavirus pneumonia. The aim of this study was to validate this scoring system for estimating the risk of disease worsening in patients with COVID-19. METHODS: This study included the patients who were treated between April 1 st and March 13 th , 2020. The patients were classified into mild, moderate, and severe groups according to the extent of respiratory failure. MuLBSTA score was applied to estimate the risk of disease worsening in each severity group and we validated the utility of the scoring system. RESULTS: A total of 72 patients were analyzed. Among the 46 patients with mild disease, 17 showed disease progression to moderate or severe disease after admission. The model showed a sensitivity of 100% and a specificity of only 34.5% with a cut-off value of 5 points. Among the 55 patients with mild or moderate disease, 6 deteriorated to severe disease, and the model showed a sensitivity of 83.3% and a specificity of 71.4% with a cut-off value of 11 points. CONCLUSIONS: This study showed that MuLBSTA score is a potentially useful tool for predicting COVID-19 disease behavior. This scoring system may be used as one of the criteria to identify high-risk patients worsening to life-threatening status.

COVID-19 pneumonia complicated by bilateral pneumothorax: A case report.

BACKGROUND: Pneumothorax is a rare but life-threatening complication associated with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CASE PRESENTATION: Informed consent was obtained from the patient himself.A 50-year-old man presented with a 9-day history of fever, cough, and dyspnoea. He was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia and was admitted to the Medical Hospital, Tokyo Medical and Dental University. Chest CT showed diffuse patchy ground-glass opacities (GGOs). His state of oxygenation deteriorated, and mechanical ventilation was initiated on day 4 after admission (12th day from onset). He improved gradually and was weaned from ventilation on day 15. Sudden onset of bilateral pneumothorax occurred on day 21 with severe respiratory failure, and chest CT revealed pneumatocele formation on both lower lobes. CONCLUSIONS: Pneumothorax is a notable complication in cases of severe COVID-19 pneumonia, especially in those who require positive-pressure ventilation.