Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 ...antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with "fatal" COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.
The outbreak of the novel coronavirus infection in Wuhan City, Hubei Province, China, in December 2019, has spread rapidly around the world, and the number of cases with no apparent route of ...transmission (cases of community transmission) is increasing in Japan. We have encountered 45 cases of COVID-19 infection, including 33 male and 12 female patients. The average age of the patients was 50.6 years. The symptoms were fever in 39 (86.7%) cases, cough in 33 (73.3%) cases, malaise in 24 (53.3%) cases, and diarrhea in 5 (11.1%) cases. In addition, according to the Kanagawa-model severity classification constructed by Kanagawa Prefecture to avoid collapse of the medical infrastructure caused by a sudden increase in patients, 30 cases were classified as having mild disease, 14 as having moderately severe disease, and 1 as having severe disease. Of the 30 patients with mild disease, 1 (3.3%) showed deterioration to moderately severe disease during the clinical course, and of the 14 patients with moderately severe disease, 6 (42.9%) showed deterioration to severe disease. The findings in respect of the subsequent clinical course of the patients suggest that the Kanagawa-model severity classification is a reasonable classification for satisfactory triage of patients.
Inhaled molecular hydrogen gas (H2) has been shown to improve outcomes in animal models of cardiac arrest (CA). H2 inhalation is safe and feasible in patients after CA. We investigated whether ...inhaled H2 would improve outcomes after out-of-hospital CA (OHCA).
HYBRID II is a prospective, multicentre, randomised, double-blind, placebo-controlled trial performed at 15 hospitals in Japan, between February 1, 2017, and September 30, 2021. Patients aged 20–80 years with coma following cardiogenic OHCA were randomly assigned (1:1) using blinded gas cylinders to receive supplementary oxygen with 2% H2 or oxygen (control) for 18 h. The primary outcome was the proportion of patients with a 90-day Cerebral Performance Category (CPC) of 1 or 2 assessed in a full-analysis set. Secondary outcomes included the 90-day score on a modified Rankin scale (mRS) and survival. HYBRID II was registered with the University Hospital Medical Information Network (registration number: UMIN000019820) and re-registered with the Japan Registry for Clinical Trials (registration number: jRCTs031180352).
The trial was terminated prematurely because of the restrictions imposed on enrolment during the COVID-19 pandemic. Between February 1, 2017, and September 30, 2021, 429 patients were screened for eligibility, of whom 73 were randomly assigned to H2 (n = 39) or control (n = 34) groups. The primary outcome, i.e., a CPC of 1 or 2 at 90 days, was achieved in 22 (56%) and 13 (39%) patients in the H2 and control groups (relative risk compared with the control group, 0.72; 95% CI, 0.46–1.13; P = 0.15), respectively. Regarding the secondary outcomes, median mRS was 1 (IQR: 0–5) and 5 (1–6) in the H2 and control groups, respectively (P = 0.01). An mRS score of 0 was achieved in 18 (46%) and 7 (21%) patients in the H2 and control groups, respectively (P = 0.03). The 90-day survival rate was 85% (33/39) and 61% (20/33) in the H2 and control groups, respectively (P = 0.02).
The increase in participants with good neurological outcomes following post-OHCA H2 inhalation in a selected population of patients was not statistically significant. However, the secondary outcomes suggest that H2 inhalation may increase 90-day survival without neurological deficits.
Taiyo Nippon Sanso Corporation.
For the Japanese translation of the abstract see Supplementary Materials section.
Background: Inhaled molecular hydrogen gas (H2) has been shown to improve outcomes in animal models of cardiac arrest (CA). H2 inhalation is safe and feasible in patients after CA. We investigated ...whether inhaled H2 would improve outcomes after out-of-hospital CA (OHCA). Methods: HYBRID II is a prospective, multicentre, randomised, double-blind, placebo-controlled trial performed at 15 hospitals in Japan, between February 1, 2017, and September 30, 2021. Patients aged 20–80 years with coma following cardiogenic OHCA were randomly assigned (1:1) using blinded gas cylinders to receive supplementary oxygen with 2% H2 or oxygen (control) for 18 h. The primary outcome was the proportion of patients with a 90-day Cerebral Performance Category (CPC) of 1 or 2 assessed in a full-analysis set. Secondary outcomes included the 90-day score on a modified Rankin scale (mRS) and survival. HYBRID II was registered with the University Hospital Medical Information Network (registration number: UMIN000019820) and re-registered with the Japan Registry for Clinical Trials (registration number: jRCTs031180352). Findings: The trial was terminated prematurely because of the restrictions imposed on enrolment during the COVID-19 pandemic. Between February 1, 2017, and September 30, 2021, 429 patients were screened for eligibility, of whom 73 were randomly assigned to H2 (n = 39) or control (n = 34) groups. The primary outcome, i.e., a CPC of 1 or 2 at 90 days, was achieved in 22 (56%) and 13 (39%) patients in the H2 and control groups (relative risk compared with the control group, 0.72; 95% CI, 0.46–1.13; P = 0.15), respectively. Regarding the secondary outcomes, median mRS was 1 (IQR: 0–5) and 5 (1–6) in the H2 and control groups, respectively (P = 0.01). An mRS score of 0 was achieved in 18 (46%) and 7 (21%) patients in the H2 and control groups, respectively (P = 0.03). The 90-day survival rate was 85% (33/39) and 61% (20/33) in the H2 and control groups, respectively (P = 0.02). Interpretation: The increase in participants with good neurological outcomes following post-OHCA H2 inhalation in a selected population of patients was not statistically significant. However, the secondary outcomes suggest that H2 inhalation may increase 90-day survival without neurological deficits. Funding: Taiyo Nippon Sanso Corporation. Translation: For the Japanese translation of the abstract see Supplementary Materials section.
要旨
Veno–arterial extracorporeal membrane oxygenation（V–A ECMO）症例においてカニューラ関連の合併症の頻度は少なくない。我々はV–A ...ECMOを装着中にカニューラ関連の出血性合併症により心静止に至ったが救命できた2症例を経験したので報告する。症例1は難治性心室細動の47歳男性で，症例2は心原性および敗血症性ショックに伴う循環不全が進行した感染性心内膜炎の38歳女性。2症例ともV–A ECMOを装着中に送血管刺入部の腫脹と出血を生じた後，急速にV–A ECMOが維持できなくなり波形上心静止となった。送血管の血管内からの逸脱と考え，別ルートによるV–A ECMOの再確立後に腫脹側の動脈修復術を施行した。症例1は外腸骨動脈修復術のみで出血制御できたが，症例2は子宮動脈仮性瘤からの出血を伴っており，同部の経カテーテル的塞栓術を要した。送血管刺入部位の出血，腫脹を伴う出血性合併症は致死的になる可能性があり，その早期認知と対応は重要である。
ABSTRACT
It is not uncommon to encounter cannula problems during veno–arterial extracorporeal membrane oxygenation (V–A ECMO) support. We herein report two survival cases wherein cannula–related bleeding complications occurred during V–A ECMO followed by cardiac arrest. Case 1 was a 47–year–old man admitted for ventricular fibrillation, and Case 2 was a 38–year–old woman diagnosed with infective endocarditis who developed cardiogenic and septic shock. Both cases underwent V–A ECMO, but an unstable ECMO circuit flow occurred with an acute hematoma around the cannulation site, followed by cardiac arrest. After ECMO initiation via the contralateral femoral artery, surgical repair of the arterial injuries was performed in both cases. Bleeding was controlled in Case 1 by surgical repair of the external iliac arterial injuries, while Case 2 needed transcatheter arterial embolization of the right uterine artery using N–butyl–2–cyanoacrylate (NBCA) and coils. We considered the both cases to be the accidental removal of an arterial cannula caused by a hematoma around the cannulation site. A hematoma around the cannulation site can lead to a fatal situation, so the diagnosis and treatment strategy should be determined early.
The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an ...immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.
要旨
...【目的】病着時の静脈血ガス分析におけるPvCO2がECPR導入の指標となりうるかを検討した。【対象】2015年1月から2018年12月の期間で，当院救命救急センターに搬送されECPRを施行された成人院外心肺停止症例を対象とした。病着時に静脈血ガス分析が測定された58例について後方視的に解析した。解析結果からECPR導入の指標となりうる最適なPvCO2のカットオフ値を検討した。最適なカットオフ値の評価のため20～140まで10mmHgごとのPvCO2値を使用し，感度，特異度を計算した。【結果】PvCO2 80mmHgをカットオフ値とした場合，神経学的予後良好に対する感度100%，生存に対する感度88%であり最適なカットオフ値であると考えた。さらに，PvCO2 80mmHgで対象を高PvCO2群（19例），低PvCO2群（39例）の2群に分けてECPRの予後に関わる臨床情報を比較検討した。目撃あり（63% vs. 90%，P=0.022），bystander CPRあり（37% vs. 77%，P=0.004）で有意差を認め，高PvCO2群で有意に低かった。臨床情報から高PvCO2群では心停止時間が有意に長かったことが示唆され，カットオフ値が適切であることを裏付ける結果であった。【結語】PvCO2 80mmHgはECPR導入の指標となる可能性がある。
ABSTRACT
Aims: We sought to determine the value of PvCO2 to predict prognosis after extracorporeal cardiopulmonary resuscitation (ECPR).
Methods: We examined a retrospective cohort of out–of–hospital cardiopulmonary arrest (OHCA) patients who were transported with ongoing CPR to our emergency department and had ECPR initiated between January 1, 2015 and December 31, 2018. We calculated the sensitivity and specificity of favorable neurologic outcomes and survival in each cut–off level of PvCO2.
Results: Of a total of 61 patients, venous blood gas at arrival was obtained in 58. The optimal cut–off value of PvCO2 was 80mmHg with 100% sensitivity and 38% specificity for favorable neurologic outcomes. With this cut–off value, the sensitivity and the specificity of survival was 88% and 41% respectively. In addition, we compared the clinical characteristics of high (>80mmHg, 19 patients) and low (≤80mmHg, 39 patients) PvCO2 groups. Patients who showed high PvCO2 at arrival had fewer cases of arrest witnessed (63% vs. 90%, P=0.022) and a lower rate of bystander CPR (37% vs. 77%, P=0.004). This suggests that the high PvCO2 group had longer intervals before CPR was started.
Conclusion: The use of PvCO2 level may help clinicians decide whether to initiate ECPR in OHCA patients who are transported with ongoing CPR.
要旨
【目的】
病着時の静脈血ガス分析におけるPvCO
2
がECPR導入の指標となりうるかを検討した。
【対象】
2015年1月から2018年12月の期間で，当院救命救急センターに搬送されECPRを施行された成人院外心肺停止症例を対象とした。病着時に静脈血ガス分析が測定された58例について後方視的に解析した。解析結果からECPR導入の指標となりうる最適なPvCO
2
...のカットオフ値を検討した。最適なカットオフ値の評価のため20～140まで10mmHgごとのPvCO
2
値を使用し，感度，特異度を計算した。
【結果】
PvCO
2
80mmHgをカットオフ値とした場合，神経学的予後良好に対する感度100%，生存に対する感度88%であり最適なカットオフ値であると考えた。さらに，PvCO
2
80mmHgで対象を高PvCO
2
群（19例），低PvCO
2
群（39例）の2群に分けてECPRの予後に関わる臨床情報を比較検討した。目撃あり（63% vs. 90%，P=0.022），bystander CPRあり（37% vs. 77%，P=0.004）で有意差を認め，高PvCO
2
群で有意に低かった。臨床情報から高PvCO
2
群では心停止時間が有意に長かったことが示唆され，カットオフ値が適切であることを裏付ける結果であった。
【結語】
PvCO
2
80mmHgはECPR導入の指標となる可能性がある。
ABSTRACT
Aims
: We sought to determine the value of PvCO
2
to predict prognosis after extracorporeal cardiopulmonary resuscitation (ECPR).
Methods
: We examined a retrospective cohort of out–of–hospital cardiopulmonary arrest (OHCA) patients who were transported with ongoing CPR to our emergency department and had ECPR initiated between January 1, 2015 and December 31, 2018. We calculated the sensitivity and specificity of favorable neurologic outcomes and survival in each cut–off level of PvCO
2
.
Results
: Of a total of 61 patients, venous blood gas at arrival was obtained in 58. The optimal cut–off value of PvCO
2
was 80mmHg with 100% sensitivity and 38% specificity for favorable neurologic outcomes. With this cut–off value, the sensitivity and the specificity of survival was 88% and 41% respectively. In addition, we compared the clinical characteristics of high (>80mmHg, 19 patients) and low (≤80mmHg, 39 patients) PvCO
2
groups. Patients who showed high PvCO
2
at arrival had fewer cases of arrest witnessed (63% vs. 90%, P=0.022) and a lower rate of bystander CPR (37% vs. 77%, P=0.004). This suggests that the high PvCO
2
group had longer intervals before CPR was started.
Conclusion
: The use of PvCO
2
level may help clinicians decide whether to initiate ECPR in OHCA patients who are transported with ongoing CPR.
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