Predictive factors and clinical impact of ICU-acquired weakness on functional disability in mechanically ventilated patients with COVID-19

Background Patients with critical COVID-19 often require invasive mechanical ventilation (IMV) and admission to the intensive care unit (ICU), resulting in a higher incidence of ICU-acquired weakness (ICU-AW) and functional decline. Objective This study aimed to examine the causes of ICU-AW and functional outcomes in critically ill patients with COVID-19 who required IMV. Methods This prospective, single-center, observational study included COVID-19 patients who required IMV for ≥48 hours in the ICU between July 2020 and July 2021. ICU-AW was defined as a Medical Research Council sum score <48 points. The primary outcome was functional independence during hospitalization, defined as an ICU mobility score ≥9 points. Results A total of 157 patients (age: 68 [59-73] years, men: 72.6%) were divided into two groups (ICU-AW group;n=80 versus non-ICU-AW;n=77). Older age (adjusted odds ratio [95% confidence interval]: 1.05 [1.01–1.11], p = 0.036), administration of neuromuscular blocking agents (7.79 [2.87–23.3], p <0.001), pulse steroid therapy (3.78 [1.49–10.1], p = 0.006), and sepsis (7.79 [2.87–24.0], p <0.001) were significantly associated with ICU-AW development. In addition, patients with ICU-AW had significantly longer time to functional independence than those without ICU-AW (41 [30-54] vs 19 [17-23] days, p<0.001). The development of ICU-AW was associated with delayed time to functional independence (adjusted hazard ratio: 6.08;95% CI: 3.05–12.1;p <0.001). Conclusions Approximately half of the patients with COVID-19 requiring IMV developed ICU-AW, which was associated with delayed functional independence during hospitalization.

Predictive factors and clinical impact of ICU-acquired weakness on functional disability in mechanically ventilated patients with COVID-19.

BACKGROUND: Patients with critical COVID-19 often require invasive mechanical ventilation (IMV) and admission to the intensive care unit (ICU), resulting in a higher incidence of ICU-acquired weakness (ICU-AW) and functional decline. OBJECTIVE: This study aimed to examine the causes of ICU-AW and functional outcomes in critically ill patients with COVID-19 who required IMV. METHODS: This prospective, single-center, observational study included COVID-19 patients who required IMV for ≥48 h in the ICU between July 2020 and July 2021. ICU-AW was defined as a Medical Research Council sum score <48 points. The primary outcome was functional independence during hospitalization, defined as an ICU mobility score ≥9 points. RESULTS: A total of 157 patients (age: 68 [59-73] years, men: 72.6%) were divided into two groups (ICU-AW group; n = 80 versus non-ICU-AW; n = 77). Older age (adjusted odds ratio [95% confidence interval]: 1.05 [1.01-1.11], p = 0.036), administration of neuromuscular blocking agents (7.79 [2.87-23.3], p < 0.001), pulse steroid therapy (3.78 [1.49-10.1], p = 0.006), and sepsis (7.79 [2.87-24.0], p < 0.001) were significantly associated with ICU-AW development. In addition, patients with ICU-AW had significantly longer time to functional independence than those without ICU-AW (41 [30-54] vs 19 [17-23] days, p < 0.001). The development of ICU-AW was associated with delayed time to functional independence (adjusted hazard ratio: 6.08; 95% CI: 3.05-12.1; p < 0.001). CONCLUSIONS: Approximately half of the patients with COVID-19 requiring IMV developed ICU-AW, which was associated with delayed functional independence during hospitalization.

Longitudinal changes in mental health outcomes after COVID-19 hospitalization: A prospective study.

BACKGROUND: The long-term trends of COVID-19 mental sequelae remain unknown. Thus, this study aimed to survey the one-year temporal trends of PTSD and health-related quality of life of COVID-19 survivors. METHODS: Patients hospitalized with COVID-19 were followed up at three, six, and 12 months after discharge. Patients with COVID-19 who were able to communicate and complete the questionnaires were included in the study. All participants were asked to complete the Medical Outcomes Study 36-Item Short-Form Health (SF-36) survey and the Impact of Event Scale-Revised (IES-R). The cutoff point of 24/25 of IES-R was defined as preliminary PTSD. Patients exhibiting PTSD symptoms at six months or later were regarded as "delayed patients," while those exhibiting PTSD symptoms at all the time points were "persistent patients." RESULTS: Of the 98 patients screened between June and November 2020, 72 participated in the study. A total of 11 (15.3%) had preliminary PTSD at three months, 10 (13.9%) at six months, and 10 (13.9%) at 12 months; delayed and persistent patients were four patients (7.54%) each. Patients with preliminary PTSD had lower mental summary scores in SF-36; 47 (IQR 45, 53) for patients with preliminary PTSD and 60 (49, 64) without preliminary PTSD at three months, 50 (45, 51) and 58 (52, 64) at six months, and 46 (38, 52) and 59 (52, 64) at 12 months. CONCLUSION: Healthcare providers should care about the courses of PTSD in COVID-19 survivors and be aware that patients with PTSD symptoms may have a lower health-related quality of life.

Clinical outcomes of COVID-19 caused by the Alpha variant compared with one by wild type in Kobe, Japan. A multi-center nested case-control study.

OBJECTIVES: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. METHODS: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. RESULTS: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. CONCLUSION: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality.

Detection of outlier prefectures on the mortality due to COVID-19 in Japan.

Japan has suffered from COVID-19 with significant mortality, but its prefectural differences are not well investigated. Since the mortality due to COVID-19 was likely to be associated with the number of infected cases, the population density, and the proportion of the elderly population, we tried to detect the outlier prefectures by multiple linear regression analyses. With the use of the Hampel identifier, we found that Hokkaido and Hyogo were the outlier prefectures with higher mortality after adjusting the variables above. Further studies should delineate the causes of these differences.

Patient-centered outcomes at hospital discharge in mechanically ventilated COVID-19 patients in Kobe, Japan: A single-center retrospective cohort study.

BACKGROUND: Apart from saving the lives of coronavirus disease (COVID-19) patients on mechanical ventilation (MV), recovery from the sequelae of prolonged MV (PMV) is an emerging issue.c METHODS: We conducted a retrospective study among consecutive adult COVID-19 patients admitted to an intensive care unit (ICU) in Kobe, Japan, between March 3, 2020, and January 31, 2021, and received invasive MV. Clinical outcomes included in-hospital mortality and recovery from COVID-19 in survivors regarding organ dysfunction, respiratory symptoms, and functional status at discharge. We compared survivors' outcomes with MV durations of >14 days and ≤14 days. RESULTS: We included 85 patients with a median age of 69 years (interquartile range, 64-75 years); 76 (89%) patients had at least 1 comorbidity, 72 (85%) were non-frail, and 79 (93%) were functionally independent before COVID-19 infection. Eighteen patients (21%) died during hospitalization. At discharge, 59/67 survivors (88%) no longer required respiratory support, 50 (75%) complained of dyspnea, and 40 (60%) were functionally independent. Of the survivors, 23 patients receiving MV for >14 days had a worse recovery from COVID-19 at discharge compared with those on MV for ≤14 days, as observed using the Barthel index (median: 35 [5-65] vs. 100 [85-100]), ICU mobility scale (8 [5-9] vs. 10 [10-10]), and functional oral intake scale (3 [1-7] vs. 7 [7-7]) (P < 0.0001). CONCLUSION: Although four-fifths of the patients survived and >50% of survivors demonstrated clinically important recovery in organ function and functional status during hospitalization, PMV was related to poor recovery from COVID-19 at discharge.

Is COVID-19 mortality associated with test number?

Introduction: With the ongoing pandemic of coronavirus disease 2019 (COVID-19), there is an argument on whether we should increase the number of testing for the coronavirus (SARS-CoV-2) to mitigate the epidemic in a given country. Therefore, we investigated the correlation between testing number and mortality to evaluate the hypothesis. Methods: Data on an open-access database of COVID-19 was retrieved. Member countries of the Organization for Economic Co-operation and Development (OECD), BRICs nations (Brazil, Russia, India, and China), and Taiwan were included in the analysis, but 2 countries were removed as outliers. Results: There was a weak, positive correlation between mortality and testing (r = 0.34, P = 0.03). On regression analysis, there was a positive slope but the coefficient was very small (0.00064). Conclusions: We found a very small positive correlation between testing number and mortality for COVID-19.

The Vicissitude of Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) Order During COVID-19 Pandemic in Japan - A Retrospective Cohort Study.

Introduction: Japan went through five surges of coronavirus disease 2019 (COVID-19) or "waves". However, their impacts on the do not attempt cardiopulmonary resuscitation (DNACPR) of the patients are not known. Methods: A retrospective single-center cohort study was conducted for all hospitalized patients with COVID-19 from March 1, 2020, to September 30, 2021. Their code status was retrieved, and its association with the waves and other parameters, such as in-hospital mortality, was investigated. The relationship between DNACPR status and each wave was examined, as well as the effect on in-hospital mortality. Results: A total of 1153 patients were hospitalized with the diagnosis of COVID-19 during the study period. On admission, 117 patients (10.1%) had DNACPR orders, 373 patients (32.4%) were on full code, 45 patients (3.9%) stated that they cannot decide code status. DNACPR rate appeared to increase at the summit of each wave. Subsequently, 160 patients (13.9%) became DNACPR status, 385 patients (33.4%) became full code, and 12 patients (1.0%) stated that they remained unable to decide code status. There was no association between DNACPR status and each wave, and DNACPR status was not associated with higher mortality (P = 0.87), both by logistic regression analysis. Conclusion: DNACPR status among hospitalized COVID-19 patients appeared to have changed over multiple waves in Japan, but it is more likely due to the change of the patients' demographics, particularly their age. DNACPR was common among the elderly, but it was not independently associated with higher mortality.

Clinical Effectiveness of REGN-COV2 in Patients with COVID-19 in Japan: A Retrospective Cohort Study with a Bayesian Inference.

BACKGROUND: Neutralizing antibody cocktail therapy, REGN-COV2, is promising in preventing a severe form of coronavirus disease 2019 (COVID-19), but its effectiveness in Japan has not been fully investigated. MATERIALS AND METHODS: To evaluate the effectiveness of REGN-COV2, clinical data of 20 patients with COVID-19 who received REGN-COV2 was compared with the control by matching age and sex. The primary outcome was the time from the onset to defervescence, the duration of hospitalization, and oxygen requirement. A sensitivity analysis using Bayesian analysis was also conducted. RESULTS: The time to defervescence was significantly shorter in the treatment group (5.25 vs. 7.95 days, P = 0.02), and so was the duration of hospitalization (7.115 vs. 11.45, P = 0.0009). However, the oxygen therapy requirement did not differ between the two groups (15% vs. 35%, P = 0.27). For Bayesian analysis, the median posterior probability of the time to defervescence since the symptom onset on the REGN-COV2 group was 5.28 days [95% credible interval (CrI): 4.28 - 6.31 days], compared with the control of 7.99 days (95% CrI: 6.81 - 9.24 days). The posterior probability of the duration of the hospitalization on the REGN-COV2 group was 7.17 days (95% CrI: 5.99 - 8.24 days), compared with the control of 11.54 days (95% CrI: 10.28 - 13.14 days). The posterior probability of the oxygen requirement on the REGN-COV2 group was 18% (95% CrI: 3 - 33%), compared with the control of 36% (95% CrI: 16 - 54%). CONCLUSION: REGN-COV2 may be effective in early defervescence and shorter hospitalization. Its effectiveness for preventing a severe form of infection needs to be evaluated by further studies.

A cross-sectional follow up study to estimate seroprevalence of coronavirus disease 2019 in Kobe, Japan.

ABSTRACT: We conducted a study to estimate the seroprevalence of coronavirus disease 2019 (COVID-19) in Kobe, Japan with positive immunoglobulin G (IgG) rate of 3.3% (95% confidence interval [CI] 2.3%-4.6%) in April 2020. Because there were large concerns about the spread of COVID-19 among citizens thereafter, we conduct a follow-up cross-sectional study to estimate the seroprevalence, and we also added a validation study using a different assay.We conducted cross-sectional serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody using 1000 samples from patients at outpatient settings who visited the clinic from May 26 to June 7, 2020, stratified by the decade of age and sex. We used both Kurabo and Abbott serology assays to identify IgG against SARS-CoV-2.There were 18 and 2 positive IgG among 1000 serum samples using Kurabo and Abbott serology assays, respectively (1.8%, 95% CI 1.1%-2.8%, and 0.2%, 95% CI 0.02%-0.7% respectively). By applying the latter figure to the census of Kobe City (population: 1,518,870), it is estimated that the number of people with positive IgG is 3038 (95% CI: 304-10,632) while a total of 285 patients were identified by polymerase chain reaction (PCR) testing at the end of the study period. Assuming Abbott assay as the reference, Kurabo assay had calculated sensitivity and specificity of 100% and 98.4% respectively. Age and sex adjusted prevalence of positivity was calculated to be 0.17%.We found a lower seroprevalence than 2 months before in Kobe city although the figures were still higher than those detected by PCR. Kurabo assay showed more false positives than true positives despite reasonable sensitivity and specificity, due to low prevalence in Kobe.

PK/PD in the treatment of infectious diseases

Current status of the novel coronavirus : an urgent discussion / Kentaro Iwata, Naoki Kishida, Kutsuna Kenshi, Fumie Sakamoto[ speaker] ・Novel coronavirus infection : extra edition / Kutsuna Kenshi [author] ・Infectious Diseases and the Infectious Disease Consultant : Dr. Kishida's Challenge / Kishida Naoki [author]

Increase of blood culture contamination during COVID-19 pandemic. A retrospective descriptive study.

BACKGROUND: Secondary bacterial infection during the care of coronavirus disease 2019 (COVID-19) patients poses risks to the patients, but there are concerns of an increase in blood culture contamination. METHODS: A retrospective comparative study was conducted from April 1 to December 31, 2020, when the patients with COVID-19 were taken care of (pandemic period, PP), and it was compared with the same period in 2019 (pre-pandemic period, pre-PP). RESULTS: A total of 346 patients with COVID-19 were hospitalized during the study period in 2020. A total of 1,040 and 918 blood cultures were taken during PPP and PP respectively. 38 and 56 contaminations occurred during pre-PP and PP respectively (3.7% [95% CI 2.6%-5.0%], vs 6.1% [95% CI 4.6%-7.8%], P = .015). For the ICU, 10 and 32 contaminations occurred during the same periods (5.0% [95% CI 2.4%-9.0%], vs 12.5% [95% CI 8.7%-17.1%], P = .0097). True bacteremia in the ICU per patient-day also increased during the PP. CONCLUSIONS: We found a significant increase in blood culture contamination during the COVID-19 pandemic in the ICU setting, while true bacteremia also increased. A safe and effective way to obtain blood cultures from patients with COVID-19 should be sought.

Massive surge of mRNA expression of clonal B-cell receptor in patients with COVID-19.

BACKGROUND: Antibody production is one of the primary mechanisms for recovery from coronavirus disease 2019 (COVID-19). It is speculated that massive clonal expansion of B cells, which can produce clinically meaningful neutralizing antibodies, occurs in patients who recover on the timing of acquiring adaptive immunity. METHODS: To evaluate fluctuations in clonal B cells and the size of the clones, we chronologically assessed the B-cell receptor (BCR) repertoire in three patients with COVID-19 who recovered around 10 days after symptom onset. RESULTS: We focused on the three dominant clonotypes (top 3) in each individual. The percentage frequencies of the top 3 clonotypes increased rapidly and accounted for 27.8 % on day 9 in patient 1, 10.4 % on day 12 in patient 2, and 10.8 % on day 11 in patient 3, respectively. The frequencies of these top 3 clonotypes rapidly decreased as the patients' clinical symptoms improved. Furthermore, BCR network analysis revealed that accumulation of clusters composed of similar complementarity-determining region 3 (CDR3) sequences were rapidly formed, grew, and reached their maximum size around 10 days after symptom onset. CONCLUSIONS: BCR repertoire analysis revealed that a massive surge of some unique BCRs occurs during the acquisition of adaptive immunity and recovery. The peaks were more prominent than expected. These results provide insight into the important role of BCRs in the recovery from COVID-19 and raise the possibility of developing neutralizing antibodies as COVID-19 immunotherapy.

Estimation of seroprevalence of novel coronavirus disease (COVID-19) using preserved serum at an outpatient setting in Kobe, Japan: A cross-sectional study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been affecting many people on earth and our society. Japan is known to have relatively smaller number of its infections as well as deaths among developed nations. However, accurate prevalence of COVID-19 in Japan remains unknown. Therefore, we conducted a cross-sectional study to estimate seroprevalence of SARS-CoV-2 infection. METHODS: We conducted a cross-sectional serologic testing for SARS-CoV-2 antibody using 1000 samples from patients at outpatient settings who visited the clinic from March 31 to April 7, 2020, stratified by the decade of age and sex. RESULTS: There were 33 positive IgG among 1000 serum samples (3.3%, 95%CI: 2.3-4.6%). By applying this figure to the census of Kobe City (population: 1,518,870), it is estimated that the number of people with positive IgG be 50,123 (95%CI: 34,934-69,868). Age and sex adjusted prevalence of positivity was calculated 2.7% (95%CI: 1.8-3.9%), and the estimated number of people with positive IgG was 40,999 (95%CI: 27,333-59,221). These numbers were 396 to 858-fold more than confirmed cases with PCR testing in Kobe City. CONCLUSIONS: Our cross-sectional serological study suggests that the number of people with seropositive for SARS-CoV-2 infection in Kobe, Japan is far more than the confirmed cases by PCR testing.

Was school closure effective in mitigating coronavirus disease 2019 (COVID-19)? Time series analysis using Bayesian inference.

OBJECTIVES: The Coronavirus disease 2019 (COVID-19) pandemic is causing significant damage to many nations. For mitigating its risk, Japan called on all elementary, junior high, and high schools nationwide to close beginning March 1, 2020. However, its effectiveness in decreasing the disease burden has not been investigated. METHODS: We used daily data of the COVID-19 and coronavirus infection incidence in Japan until March 31, 2020. Time-series analyses were conducted using the Bayesian method. Local linear trend models with interventional effects were constructed for the number of newly reported cases of COVID-19, including asymptomatic infections. We considered that the effects of the intervention started to appear nine days after the school closure. RESULTS: The intervention of school closure did not appear to decrease the incidence of coronavirus infection. If the effectiveness of school closure began on March 9, the mean coefficient α for the effectiveness of the measure was calculated to be 0.08 (95% confidence interval -0.36 to 0.65), and the actual reported cases were more than predicted, yet with a rather wide confidence interval. Sensitivity analyses using different dates also did not demonstrate the effectiveness of the school closure. DISCUSSION: School closure carried out in Japan did not show any mitigating effect on the transmission of novel coronavirus infection.

[A Physical Therapist's Challenge to COVID-19 - Could you save one and save ten? From acute to community collaboration]

What was going on at the scene of the confrontation with the novel coronavirus infection? What can be done to prepare for the second wave?