A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo,Japan: A case report

IntroductionAn ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings.CaseA 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24.ConclusionsStrict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care.     

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study

IntroductionThe severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020.MethodsAll patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients’ records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software.ResultsData from 61 patients (16 Pt–CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt–CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt–CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt–CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt–CSI than in Pt-MMI (P = 0.013). Among the 16 Pt–CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died.ConclusionsThe illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.     

Clinical Characteristics,Treatment, and Outcomes of Critically Ill Patients With COVID-19: A Scoping Review

A growing number of studies on coronavirus disease 2019 (COVID-19) are becoming available, but a synthesis of available data focusing on the critically ill population has not been conducted. We performed a scoping review to synthesize clinical characteristics, treatment, and clinical outcomes among critically ill patients with COVID-19. Between January 1, 2020, and May 15, 2020, we identified high-quality clinical studies describing critically ill patients with a sample size of greater than 20 patients by performing daily searches of the World Health Organization and LitCovid databases on COVID-19. Two reviewers independently reviewed all abstracts (2785 unique articles), full text (218 articles), and abstracted data (92 studies). The 92 studies included 61 from Asia, 16 from Europe, 10 from North and South America, and 5 multinational studies. Notable similarities among critically ill populations across all regions included a higher proportion of older males infected and with severe illness, high frequency of comorbidities (hypertension, diabetes, and cardiovascular disease), abnormal chest imaging findings, and death secondary to respiratory failure. Differences in regions included newly identified complications (eg, pulmonary embolism) and epidemiological risk factors (eg, obesity), less chest computed tomography performed, and increased use of invasive mechanical ventilation (70% to 100% vs 15% to 47% of intensive care unit patients) in Europe and the United States compared with Asia. Future research directions should include proof-of-mechanism studies to better understand organ injuries and large-scale collaborative clinical studies to evaluate the efficacy and safety of antivirals, antibiotics, interleukin 6 receptor blockers, and interferon. The current established predictive models require further verification in other regions outside China.     

COVID-19-associated pulmonary aspergillosis in a Japanese man: A case report

CAPA (COVID-19 associated pulmonary aspergillosis) is an important complication of COVID-19. It has been reported that the incidence of CAPA is as high as 19%–33% worldwide. However, its onset has not been reported in Japan. A 72-year-old Japanese man was diagnosed with COVID-19 and was transferred to our hospital due to deterioration of respiratory condition. Treatment with remdesivir, dexamethasone (DEXA), and antibiotics was performed under mechanical ventilation. Although the condition improved temporarily, a new shadow appeared in the lung, and Aspergillus fumigatus was cultured from sputum. The patient was clinically diagnosed with CAPA and treated with voriconazole. However, his progress deteriorated and he died. High-risk COVID-19 patients should be tested for Aspergillus to ensure early diagnosis of CAPA.     

Clinical characteristics and prognosis of immunosuppressed inpatients with COVID-19 in Japan

IntroductionWe aimed to analyze the clinical characteristics and outcomes of immunosuppressed inpatients with coronavirus disease 2019 (COVID-19).MethodsIn this observational study, we utilized a large nationwide registry of hospitalized patients with COVID-19 in Japan. Patients’ baseline characteristics and outcomes were compared according to the immunosuppressed states of the patients. The impact of different therapeutic agents on the clinical courses of the patients was evaluated.ResultsData of 14,760 patients were included, and 887 (5.9%) were immunosuppressed. The immunosuppressed state of the patient resulted from solid tumor (43.3%, n = 384), chemotherapy within 3 months (15.6%, n = 138), collagen disease (16.9%, n = 150), use of immunosuppressive agents (16.0%, n = 142), and metastatic solid tumor (13.5%, n = 120). Immunosuppressed patients were older and had a higher severity of illness at admission and during hospitalization than non-immunosuppressed patients. The mortality rates for major diseases causing immunosuppression were as follows: solid tumor, 12.5% (48/384; P < 0.001; relative risk [RR], 3.41); metastatic solid tumor, 31.7% (38/120; P < 0.001; RR, 8.43); leukemia, 23.1% (9/39; P < 0.001; RR, 5.87); lymphoma, 33.3% (20/60; P < 0.001; RR, 8.63); and collagen disease, 15.3% (23/150; P < 0.001; RR 3.97). Underlying diseases with high mortality rates were not necessarily associated with high rates of invasive supportive care.ConclusionsThe prognosis of immunosuppressed COVID-19 inpatients varied according to the different immunosuppressed states. Multiple factors, including the severity of the underlying diseases, might have affected their invasive supportive care indications.     

Intensive care burden of COVID-19 in tertiary care hospitals during the first year of outbreak in Kawasaki City,Japan: A retrospective cohort study

IntroductionThis study aimed to describe the changes in the intensive care burden of coronavirus disease 2019 (COVID-19) during the first year of outbreak in Japan.MethodsThis retrospective cohort study included COVID-19 patients who received mechanical ventilation (MV) support in two designated hospitals for critical patients in Kawasaki City. We compared the lengths of MV and stay in the intensive care unit (ICU) or high care unit (HCU) according to the three epidemic waves. We calculated in-hospital mortality rates in patients with or without MV.ResultsThe median age of the sample was 65.0 years, and 22.7% were women. There were 37, 29, and 62 patients in the first (W1), second (W2), and third waves (W3), respectively. Systemic steroids, remdesivir, and prone positioning were more frequent in W2 and W3. The median length of MV decreased from 18.0 days in W1 to 13.0 days in W3 (P = 0.019), and that of ICU/HCU stay decreased from 22.0 days in W1 to 15.5 days in W3 (P = 0.027). The peak daily number of patients receiving MV support was higher at 18 patients in W1, compared to 8 and 15 patients in W2 and W3, respectively. The mortality rate was 23.4%, which did not significantly change (P = 0.467).ConclusionsThe lengths of MV and ICU/HCU stay per patient decreased over time. Despite an increase in the number of COVID-19 patients who received MV in W3, this study may indicate that the intensive care burden during the study period did not substantially increase.     

Viral Endothelial Dysfunction: A Unifying Mechanism for COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus with significant global impact, morbidity, and mortality. The SARS-CoV-2 virus may result in widespread organ manifestations including acute respiratory distress syndrome, acute renal failure, thromboembolism, and myocarditis. Virus-induced endothelial injury may cause endothelial activation, increased permeability, inflammation, and immune response and cytokine storm. Endothelial dysfunction is a systemic disorder that is a precursor of atherosclerotic vascular disease that is associated with cardiovascular risk factors and is highly prevalent in patients with atherosclerotic cardiovascular and peripheral disease. Several studies have associated various viral infections including SARS-CoV-2 infection with inflammation, endothelial dysfunction, and subsequent innate immune response and cytokine storm. Noninvasive monitoring of endothelial function and identification of high-risk patients who may require specific therapies may have the potential to improve morbidity and mortality associated with subsequent inflammation, cytokine storm, and multiorgan involvement.     

Risk factors associated with hospitalization in patients with asymptomatic or mild COVID-19 in public accommodation facilities in Tokyo

IntroductionIn Japan, patients with coronavirus disease 2019 (COVID-19) who do not require medical intervention are provided care in recovery accommodation facilities (RAFs). However, some patients may require hospitalization if their symptoms become more severe during their stay. We conducted an observational study using epidemiological data of patients with COVID-19 admitted to RAFs in Tokyo.MethodsThis was an observational cohort study using data from COVID-19 patients admitted to one of the RAFs in Tokyo from December 2020 to November 2021. Admissions to the facilities were limited to patients with asymptomatic or mild COVID-19 with no underlying disease or at least stable underlying disease at the time of admission. Patients were hospitalized when they required oxygen administration or when they had, or persistent fever, or severe respiratory symptoms. We evaluated the association between hospitalization and the risk factors for hospitalization using a Cox regression model.ResultsThe number of patients with COVID-19 admitted to the RAF was 6176. The number of hospitalized patients was 393 (6.4%), and the median length of stay was 5.50 days (IQR: 4.50, 6.50). In the Cox regression analysis, the hazard ratio increased with age and was significantly higher among patients aged >60 years (HR = 10.23, 95% CI: 6.72–15.57) than those in other age groups. This trend is similar to that observed in the sensitivity analysis.ConclusionPatients with diabetes, the elderly, obesity, and medications for gout and psychiatric diseases may be at a high risk of hospitalization. In particular, an age over 60 years was strongly associated with hospitalization.     

Prevalence of thromboembolic events and status of prophylactic anticoagulant therapy in hospitalized patients with COVID-19 in Japan

IntroductionOne of the most prominent and concerning complications associated with coronavirus disease 2019 (COVID-19) is venous and arterial thromboembolisms. The aim of the present study was to delineate the prevalence of thromboembolic events and the current status of prophylactic anticoagulation therapy in patients with COVID-19 in Japan.MethodsBetween February 1 and August 31, 2020, we performed a dual-center, retrospective cohort study based on data obtained from the medical charts of COVID-19 patients admitted to healthcare facilities in Japan. The primary outcome was any thromboembolic event including pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction, ischemic stroke and other systemic thromboemboli.ResultsDuring the study period, we extracted 628 consecutive patients admitted for COVID-19. Prophylactic anticoagulant therapy was administered in 63 (10%) patients of whom 20 (31.7%) were admitted to the intensive care unit (ICU). Thromboembolic events occurred in 18 (2.9%) patients (14.3% of patients in ICU and 2.2% of patients in the general wards). DVT were detected in 13 (2.1%) patients, PE in 11 (1.8%), and both DVT and PE in 6 (0.96%) patients. An increasing prevalence in thromboembolic events was noted with progressive clinical severity. Overall in-hospital mortality was 4.8%.ConclusionsProphylactic anticoagulation therapy was administered in only 10% of all hospitalized COVID-19 patients. The prevalence of any thromboembolic events was 2.9% in COVID-19 patients with most events occurring in severe and critical patients. Therefore, prophylactic anticoagulation therapy may be warranted in severe and critical patients but in asymptomatic to moderate patients the practice remains controversial.     

Acute cerebellar ataxia during acute COVID-19: A case series and review of the literature

Acute coronavirus disease 2019 (COVID-19)-associated cerebellar ataxia without multisystem inflammatory syndrome in children (MIS-C) or encephalopathy in children has been rarely reported. We reviewed medical records of hospitalized children who had developed cerebellar ataxia during the acute phase of COVID-19 infection, without MIS-C or encephalopathy, in our center. We also conducted a literature review and summarized the clinical characteristics, treatment, and outcomes. We found three cases in our center and additional three cases in the literature. All patients were male and five were preschool children. The cerebellar symptoms started between day 2 and day 10 during the acute phase of the COVID-19 infection. Two cases were complicated by mutism. One patient received therapy for acute cerebellar ataxia with corticosteroids, and others did not receive any specific therapy for acute cerebellar ataxia. The symptoms improved completely in all patients, with the recovery interval ranging from one week to two months. Further studies are warranted to elucidate the pathogenesis of acute cerebellar ataxia during acute COVID-19 in children.     

Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking iguratimod treated with ciclesonide

We report a coronavirus disease 2019 (COVID-19) case with rheumatoid arthritis taking iguratimod. The patient who continued iguratimod therapy without dose reduction was treated with ciclesonide had an uneventful clinical course, but prolonged detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed after resolution of symptoms. The effects of disease-modifying antirheumatic drugs (DMARDs) and ciclesonide on clinical course and viral shedding remain unknown and warrant further investigation.     

Evidence-Based Strategies for Clinical Organizations to Address COVID-19 Vaccine Hesitancy

The success of vaccination programs is contingent upon irrefutable scientific safety data combined with high rates of public acceptance and population coverage. Vaccine hesitancy, characterized by lack of confidence in vaccination and/or complacency about vaccination that may lead to delay or refusal of vaccination despite the availability of services, threatens to undermine the success of coronavirus disease 2019 (COVID-19) vaccination programs. The rapid pace of vaccine development, misinformation in popular and social media, the polarized sociopolitical environment, and the inherent complexities of large-scale vaccination efforts may undermine vaccination confidence and increase complacency about COVID-19 vaccination. Although the experience of recent lethal surges of COVID-19 infections has underscored the value of COVID-19 vaccines, ensuring population uptake of COVID-19 vaccination will require application of multilevel, evidence-based strategies to influence behavior change and address vaccine hesitancy. Recent survey research evaluating public attitudes in the United States toward the COVID-19 vaccine reveals substantial vaccine hesitancy. Building upon efforts at the policy and community level to ensure population access to COVID-19 vaccination, a strong health care system response is critical to address vaccine hesitancy. Drawing on the evidence base in social, behavioral, communication, and implementation science, we review, summarize, and encourage use of interpersonal, individual-level, and organizational interventions within clinical organizations to address this critical gap and improve population adoption of COVID-19 vaccination.     

Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: Report of three cases

No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.     

Immunochromatography and chemiluminescent enzyme immunoassay for COVID-19 diagnosis

IntroductionThe rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required to prevent the spread of COVID-19. This study evaluated the utility of two SARS-CoV-2 antigen detection methods.MethodsWe evaluated two types of antigen detection methods using immunochromatography (Espline) and quantitative chemiluminescent enzyme immunoassay (Lumipulse). RT-PCR was performed as a standard procedure for COVID-19 diagnosis. Lumipulse and RT-PCR were performed for all 486 nasopharyngeal swabs and 136 saliva samples, and the Espline test was performed for 271 nasopharyngeal swabs and 93 saliva samples.ResultsThe sensitivity and specificity of the Espline test were 10/11 and 260/260 (100%), respectively for the nasopharyngeal swabs and 3/9 and 84/84 (100%), respectively for the saliva samples. High sensitivities for both saliva (8/9) and nasopharyngeal swabs (22/24) were observed in the Lumipulse test. The specificities of the Lumipulse test for nasopharyngeal swabs and saliva samples were 460/462 (99.6%) and 123/127 (96.9%), respectively.ConclusionThe Espline test is not effective for saliva samples but is useful for simple and rapid COVID-19 tests using nasopharyngeal swabs because it does not require special devices. The Lumipulse test is a powerful high-throughput tool for COVID-19 diagnosis because it has high detection performance for nasopharyngeal swabs and saliva samples.     

Outcome of COVID-19 in interstitial lung disease patients treated with anti-inflammatory drugs and antiviral drugs

A recent study reported that patients with interstitial lung disease (ILD) are at increased risk of death from coronavirus disease 2019 (COVID-19). However, there are no studies on the outcome of COVID-19 patients with preexisting ILD treated with corticosteroids or antiviral drugs. We extracted 26 patients with preexisting ILD by medical records and HRCT pattern. Of 503 patients with COVID-19, we selected 52 patients as control matched for age and sex. Twenty out of the 26 ILD patients (76.9%) received corticosteroid therapy, and 23 patients (88.5%) also received antiviral treatment with remdesivir or favipiravir. Although no statistical difference was found, the proportion of severe patients in ILD group tended to be higher than in non-ILD group (23.1% vs. 42.3%; p = 0.114). Also, mortality rate in ILD group tended to be higher than in non-ILD patients (11.5% vs. 3.8%; p = 0.326). In univariate analysis to evaluate risk factors for severe condition, diagnosis of idiopathic pulmonary fibrosis, usual interstitial pneumonia pattern, and honeycomb lung were not risk factors of severe disease. Treatment with corticosteroids, antiviral drugs, and immunosuppressive agents may affect the outcome of COVID-19 patients with ILD.     

Clinical characteristics of COVID-19 in hospitalized children during the Omicron variant predominant period

IntroductionInformation regarding the clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in children under the Omicron variant predominant period is still limited.MethodsA nationwide retrospective cohort study was conducted. Pediatric COVID-19 patients (<18 years of age) hospitalized between August 1, 2021 and March 31, 2022 were enrolled. Epidemiological and clinical characteristics between the Delta variant predominant period (August 1 to December 31, 2021) and the Omicron variant predominant period (January 1 to March 31, 2022) were compared.ResultsDuring the study period, 458 cases in the Delta predominant period and 389 cases in the Omicron predominant period were identified. Median age was younger (6.0 vs. 8.0 years, P = 0.004) and underlying diseases were more common (n = 65, 16.7% vs. n = 53, 11.6%) in the Omicron predominant period than those in the Delta variant predominant era. For clinical manifestations, fever ≥38.0 °C at 2 to <13 years old, sore throat at ≥ 13 years, and seizures at 2 to <13 years old were more commonly observed, and dysgeusia and olfactory dysfunction at ≥ 6 years old were less commonly observed in the Omicron variant predominant period. The number of patients requiring noninvasive oxygen support was higher in the Omicron predominant period than that in the Delta predominant period; however, intensive care unit admission rates were similar and no patients died in both periods.ConclusionsIn the Omicron variant predominant period, more pediatric COVID-19 patients experienced fever and seizures, although the overall outcomes were still favorable.     

CT screening for COVID-19 in asymptomatic patients before hospital admission

IntroductionIn the novel coronavirus disease (COVID-19) pandemic era, it is essential to rule out COVID-19 effectively to prevent transmission in both communities and medical facilities. According to previous reports in high prevalence areas, CT screening may be useful in the diagnosis of COVID-19. However, the value of CT screening in low prevalence areas has scarcely been reported.MethodsThis report examines the diagnostic efficacy of CT screening before admission to a hospital in Tokyo. We conducted a retrospective analysis at Keio University Hospital from April 6, 2020, through May 29, 2020. We set up an outpatient screening clinic on April 6 for COVID-19, administering both PCR with nasopharyngeal swabs and chest CT for all patients scheduled for surgery under general anesthesia.ResultsA total of 292 asymptomatic patients were included in this study. There were three PCR-positive patients, and they all had negative CT findings, which revealed that both the sensitivity and positive predictive value of CT (PPV) were 0%. There were nine CT-positive patients; the specificity and the negative predictive value (NPV) were 96.9% and 98.9%, respectively.ConclusionCT screening was not useful in low prevalence areas at this time in Tokyo, even with the inclusion of the most prevalent phase. Given that the utility of CT screening depends on disease prevalence, the criteria for performing CT screening based on the prevalence of COVID-19 should be established.     

Clinical efficacy of remdesivir for COVID-19 in children: A propensity-score-matched analysis

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333).     

Year 3 of COVID-19: Harsh Truths,Brutal Realities,and Glimmers of Hope

Severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease 2019 (COVID-19), has now killed 1 of every 303 Americans. Whereas 4 vaccines are approved in the United States and masks are widely available, too few are fully immunized and most of the population has stopped wearing protective masks. The ongoing consequences of this include continued excess morbidity and mortality and the generation of immune-evading variants and subvariants, which in toto are injurious and ultimately self-defeating. Herein we briefly update and review COVID-19 vaccines, waning immunity, and new variants.