B cell receptor repertoire analysis from autopsy samples of COVID-19 patients

Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being developed world over. We investigated the possibility of producing artificial antibodies from the formalin fixation and paraffin-embedding (FFPE) lung lobes of a patient who died by coronavirus disease 2019 (COVID-19). The B-cell receptors repertoire in the lung tissue where SARS-CoV-2 was detected were considered to have highly sensitive virus-neutralizing activity, and artificial antibodies were produced by combining the most frequently detected heavy and light chains. Some neutralizing effects against the SARS-CoV-2 were observed, and mixing two different artificial antibodies had a higher tendency to suppress the virus. The neutralizing effects were similar to the immunoglobulin G obtained from healthy donors who had received a COVID-19 mRNA vaccine. Therefore, the use of FFPE lung tissue, which preserves the condition of direct virus sensitization, to generate artificial antibodies may be useful against future unknown infectious diseases.

B cell receptor repertoire analysis from autopsy samples of COVID-19 patients.

Neutralizing antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being developed world over. We investigated the possibility of producing artificial antibodies from the formalin fixation and paraffin-embedding (FFPE) lung lobes of a patient who died by coronavirus disease 2019 (COVID-19). The B-cell receptors repertoire in the lung tissue where SARS-CoV-2 was detected were considered to have highly sensitive virus-neutralizing activity, and artificial antibodies were produced by combining the most frequently detected heavy and light chains. Some neutralizing effects against the SARS-CoV-2 were observed, and mixing two different artificial antibodies had a higher tendency to suppress the virus. The neutralizing effects were similar to the immunoglobulin G obtained from healthy donors who had received a COVID-19 mRNA vaccine. Therefore, the use of FFPE lung tissue, which preserves the condition of direct virus sensitization, to generate artificial antibodies may be useful against future unknown infectious diseases.

Immune Cells Profiles in the Different Sites of COVID-19-Affected Lung Lobes in a Single Patient.

Whereas the COVID-19 disease pathophysiology is under investigation, it is important to identify the pathways of viral transmission and inflammation from the pre-illness to the disease-onset stages. We analyzed five lung lobes from a patient with COVID-19 who finally died after prolonged lung protective ventilation. Pathological examination revealed moderate inflammation in upper lung lobes and uneven yet severe inflammation and diffuse alveolar damage in lower lung lobes. SARS-CoV-2 was detected at higher levels not in severely, but rather moderately inflamed middle lung lobes, and immunohistochemistry and bulk RNA-sequencing results showed that immune cells were detected at higher levels in lower lung lobes. The mRNA expression of cytokine families varied. We found an increase in keratin 5- or aquaporin 3-expressing basal cells in the severely inflamed lower lung lobes, and the alveolar stromal tissues were filled with them. Thus, this analysis of lung samples from a patient helps to determine the COVID-19 pathophysiology at a specific time point, and the virus localization and inflammatory responses at each site of the lungs provide various important indications.

Multisystem inflammatory syndrome in adults after acute coronavirus disease 2019 in a Japanese woman: A case report.

Multisystem inflammatory syndrome in adults (MIS-A) is a rare and emerging syndrome after coronavirus disease 2019 (COVID-19). To the best of our knowledge, Japanese cases of MIS-A are rarely reported. Here, we describe a case of MIS-A in a 44-year-old Japanese woman presenting with multiorgan dysfunction (i.e., cardiovascular and mucocutaneous involvement) and markedly elevated inflammatory markers 2 weeks after recovery from COVID-19. Treatment with intravenous immunoglobulins and corticosteroids resolved her symptoms. On the 13th day, she was discharged from the hospital with no recurrences on follow-up. This study highlights the importance of recognizing this emerging syndrome when treating patients with multiorgan dysfunction after COVID-19.

Case Report: A Rehabilitation Practice Report During ICU Management for a Patient With Multiple Disabilities Due to COVID-19 Pneumonia and COPD.

Patients with severe coronavirus disease (COVID-19) and admitted to the intensive care unit (ICU) are at high risk of developing ICU-acquired weakness and disuse syndrome. Although their medical management may include prolonged deep sedation for pulmonary protection and ventilator management, we aim for early mobilization of these patients with COVID-19. We present the case of a 71-year-old man with chronic obstructive pulmonary disease (COPD) and COVID-19 pneumonia. Passive range of motion training and sitting on the edge of the bed were started in the ICU while the patient was under deep sedation. His activities of daily living eventually improved to where he could independently walk to the toilet without respiratory distress. Patients with severe COVID-19 who require mechanical ventilation are at risk of muscle weakness and exercise intolerance. These patients require rehabilitation therapy, beginning in the acute phase of illness, to recover their physical function. Although validation with a larger cohort is necessary, our results suggest that patients with COPD and COVID-19 pneumonia should undergo rehabilitation concurrently with status-driven changes in respiratory management.

Feasibility of sit training for patients with severe COVID-19 pneumonia during deep sedation: A case report.

RATIONALE: There have been a few reports on the early rehabilitation of patients with coronavirus disease (COVID-19), and none on the effectiveness and adverse events of early mobilization for mechanical ventilation patients (other than COVID-19) during deep sedation. This report indicates that sitting without adverse events is possible in patients with severe COVID-19 pneumonia during deep sedation with muscle relaxation. PATIENT CONCERNS: A 65-year-old man with a history of diabetes mellitus, lacunar infarction, and Parkinson's disease was admitted to a local hospital for pneumonia due to COVID-19. After admission, the patient was managed on a ventilator under deep sedation with muscle relaxants and sedatives. Twelve days after admission, the patient was transferred to our hospital due to his worsening respiratory status. DIAGNOSIS: Pneumonia due to COVID-19 was diagnosed using a polymerase chain reaction-dependent method. INTERVENTIONS: The day following transfer, a physical therapist started passive range of motion training and sitting. OUTCOMES: The period spanning his initial rehabilitation to muscle relaxant medication interruption was 9 days, and he underwent 7 rehabilitation sessions. The patient was unable to sit during only one of the 7 sessions due to pre-rehabilitation hypoxemia. In 5 of the 6 sitting sessions, PaO2/FiO2 transiently decreased but recovered by the time of subsequent blood sampling. The patient's PaCO2 decreased during all sessions. His blood pressure did not drastically decrease in any sitting session, except the first. Sputum excretion via sputum suction increased during sitting, and peak inspiratory pressure did not change. LESSONS: The patient eventually died of pneumonia due to COVID-19. However, sitting during deep sedation with muscle relaxants did not cause any serious adverse events nor did it appear to cause obvious negative respiratory effects.

Protracted course of coronavirus disease with severe acute respiratory distress syndrome: a case report.

BACKGROUND: Coronavirus disease (COVID-19) is a growing concern worldwide. Approximately 5% of COVID-19 cases require intensive care. However, the optimal treatment for respiratory failure in COVID-19 patients is yet to be determined. CASE PRESENTATION: A 79-year-old man with severe acute respiratory distress syndrome due to COVID-19 was admitted to our intensive care unit. Prone ventilation was effective in treating the patient's hypoxemia. Furthermore, the patient received lung protective ventilation with a tidal volume of 6-8 mg/kg (predicted body weight). However, the patient's respiratory failure did not improve and he died 16 days after admission because of multiple organ failure. Serial chest computed tomography revealed a change from ground-glass opacity to consolidation pattern in both lungs. CONCLUSIONS: We report a protracted case of COVID-19 in a critically ill patient in Japan. Although prone ventilation could contribute to treating hypoxemia, its efficacy in preventing mortality from COVID-19 is unknown.