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).

Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine.

OBJECTIVES: To examine the differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination. METHODS: Throughout the pandemic, we evaluated the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients over time among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants. RESULTS: A total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (percentage per 30 days [95% CI]) was slower after 3 doses (25% [23-26]) than 2 doses (36% [35-37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9-22]); 3-dose plus infection (21% [17-25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3 doses, except for sex (lower in female participants) and immunosuppressant use. Antibody waned slightly faster in older participants, females, and alcohol drinkers after 2 doses, whereas it did not differ after 3 doses across except sex. DISCUSSION: The 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection modestly enhanced its durability. The antibody levels at a given time point and waning speed after 2 doses differed across background factors; however, these differences mostly diminished after 3 doses.

Omicron BA.1 neutralizing antibody response following Delta breakthrough infection compared with booster vaccination of BNT162b2.

BACKGROUND: Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron. METHODS: Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups. RESULTS: Breakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. CONCLUSIONS: Symptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

Association between SARS-CoV-2 anti-spike antibody titers and the development of post-COVID conditions: A retrospective observational study

Summary The symptoms that persist after an acute coronavirus disease 2019 (COVID-19) are referred to as post- COVID conditions. Although the cause of post-COVID conditions remains unclear, the host immune response to SARS-CoV-2 may be involved. Hence, we aimed to investigate the effect of serum antibody titers against SARS-CoV-2 on the development of post-COVID conditions. We conducted a retrospective observational study of COVID-19-recovered individuals who attended the clinic at the National Center for Global Health and Medicine between January 2020 and April 2021. Serum SARS-CoV-2 anti-spike antibody titers were measured and a questionnaire survey was used to collect information on the presence of post-COVID conditions and demographic characteristics of the participants. Participants were then divided into two groups: high peak antibody titer group [≥ 0.759 OD450 value], and low peak antibody titer group [< 0.759 OD450 value] and compared their frequency of post-COVID conditions. Of 526 individuals attending the clinic, 457 (86.9%) responded to the questionnaire. We analyzed the data of 227 (49.7%) participants with measurements of serum antibody titers during the peak period. The incidence of depressed mood was significantly higher in the group with higher antibody titers (odds ratio: 2.34, 95% CI: 1.17-4.67, p = 0.016). There was no significant difference in the frequency of the remaining symptoms between the two groups. Among post-COVID conditions, the depressed mood was more frequent in the group with high serum antibody titers which suggests a difference in pathogenesis between depressive mood and other post-COVID conditions that requires further investigation.

Remdesivir for the Treatment of Covid-19 - Final Report.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Social implications of a change in the legal classification of COVID-19: The need for pandemic prevention, preparedness, and healthcare system strengthening.

In Japan, there has been a discussion of the potential reclassification of the novel coronavirus infectious disease 2019 (COVID-19) as an infectious disease under the Act on the Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases (the Infectious Diseases Control Law), beginning in late 2022. To make an informed decision, the societal impact of COVID-19 needs to be carefully considered to ensure that any reclassification does not negatively impact healthcare or society as a whole. The disease burden of COVID-19 remains considerable and is likely to persist for an extended period of time. Consequently, numerous special measures have been taken in the healthcare system to cope with COVID-19. Several of these measures must be implemented. Thus, the healthcare system needs to be strengthened in the future. This will result in adequate prevention, preparation, and a response to future pandemics.

Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study.

BACKGROUND: This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. METHODS: Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. RESULTS: A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5-64.9%; mean age: 35.3-37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. CONCLUSIONS: Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. CLINICAL TRIALS REGISTRATION: Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350).

Immunogenicity and safety of single booster dose of KD-414 inactivated COVID-19 vaccine in adults: An open-label, single-center, non-randomized, controlled study in Japan.

Although vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) induce effective immune responses, vaccination with booster doses is necessary because of waning immunity. We conducted an open-label, non-randomized, single-arm study in adults in Japan to assess the immunogenicity and safety of a single booster dose of the KD-414 purified whole-SARS-CoV-2-virion inactivated vaccine candidate after vaccination with a primary series of BNT162b2. The primary endpoint was serum neutralizing activity at 7 days after booster injection compared with the primary series of BNT162b2. The SARS-CoV-2-structural protein-binding antibody level and T cell response against SARS-CoV-2-Spike (S) peptides were also examined as secondary endpoints, and safety profile assessments were conducted. Twenty subjects who participated in a previous study declined an injection of KD-414 (non-KD-414 group) and received a booster dose of BNT162b2 instead. The non-KD-414 group was compared to the KD-414 group as a secondary outcome. A single dose of KD-414 induced lower serum neutralizing activity against the wild-type virus within 7 days compared to after the primary series of BNT162b2 but significantly induced anti-SARS-CoV-2-S1-receptor-binding domain-binding immunoglobulin G (IgG) antibodies and SARS-CoV-2-S peptide-specific CD4+ and CD8+ T cell responses. Local or systemic symptoms were significantly lower in the participants who received KD-414 than in those who received BNT162b2 as the third COVID-19 vaccine dose. The present data indicate that a single booster dose of KD-414 induces a substantial immune response in BNT162b2-primed individuals and has a good safety profile, thereby supporting further clinical trials to identify rational targets.

Exacerbations of Idiopathic Systemic Capillary Leak Syndrome following BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech).

A Japanese man experienced three episodes of hypovolemic shock and was diagnosed with systemic capillary leak syndrome (SCLS). He developed SCLS exacerbation 2 days after receiving a second dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, 1 year after the third episode. After fluid therapy and albumin administration, we initiated terbutaline and theophylline prophylaxis for SCLS. A literature review revealed that SCLS attacks often occur 1-2 days after the second COVID-19 vaccination. Patients with a history of SCLS should avoid COVID-19 vaccination and be carefully monitored for 1-2 days if they receive the vaccine.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases

IMPORTANCE: Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part).

BACKGROUND: Limited treatment options exist for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), irrespective of vaccination history or risk status. Ensitrelvir is a novel oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like (3CL) protease inhibitor. While phase 2 studies of ensitrelvir have demonstrated promising results in treating mild-to-moderate COVID-19, evaluation of its clinical efficacy due to shifting vaccination status and emergence of the Omicron variant represents significant challenges. Here, we describe the protocol for a phase 3 study designed to evaluate the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19, regardless of risk status or vaccination history. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. Patients with mild-to-moderate COVID-19 within 120 hours from onset will be randomized in a 1:1:1 ratio into 3 treatment arms-ensitrelvir 125 mg (375 mg loading dose on Day 1), ensitrelvir 250 mg (750 mg loading dose on Day 1), and placebo. The study interventions will be administered orally, once-daily, for 5 days. The primary endpoint will be the time to resolution of 5 symptoms of COVID-19 (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and the key secondary endpoints will include the change from baseline on Day 4 in the amount of SARS-CoV-2 viral ribonucleic acid (RNA) and the time to first negative SARS-CoV-2 viral titer. The primary population for the primary and key secondary endpoints will be patients with <72 hours from COVID-19 onset to randomization and, subsequently, patients in entire patient population (<120 hours) in the ensitrelvir 125 mg group. Closed testing procedure will be used for the primary and key secondary endpoints in both the primary and entire patient populations. All safety assessments and adverse events (AE) will be reported. DISCUSSION: In a post hoc analysis of the phase 2b study, compared with placebo, ensitrelvir demonstrated a reduced time to resolution of 5 symptoms in patients with mild-to-moderate COVID-19. Through this study, we intend to validate and establish the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19.

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Analysis of Previous Infection, Vaccinations, and Anti-SARS-CoV-2 Antibody Titers and Protection Against Infection With the SARS-CoV-2 Omicron BA.5 Variant.

This cohort study examines whether preinfection anti­SARS-CoV-2 spike antibody titer is associated with protection against Omicron BA.5 infection among staff members of a medical and research center in Tokyo, Japan.

Validation of the severe COVID-19 prognostic value of serum IL-6, IFN-λ3, CCL17, and calprotectin considering the timing of clinical need for prediction.

Although biomarkers to predict coronavirus disease 2019 (COVID-19) severity have been studied since the early pandemic, no clear guidelines on using them in clinical practice are available. Here, we examined the ability of four biomarkers to predict disease severity using conserved sera from COVID-19 patients who received inpatient care between January 1, 2020 and September 21, 2021 at the National Center for Global Health and Medicine, collected at the appropriate time for prediction. We predicted illness severity in two situations: 1) prediction of future oxygen administration for patients without oxygen support within 8 days of onset (Study 1) and 2) prediction of future mechanical ventilation support (excluding non-invasive positive pressure ventilation) or death of patients within 4 days of the start of oxygen administration (Study 2). Interleukin-6, IFN-λ3, thymus and activation-regulated chemokine, and calprotectin were measured retrospectively. Other laboratory and clinical information were collected from medical records. AUCs were calculated from ROC curves and compared for the predictive ability of the four biomarkers. Study 1 included 18 patients, five of whom had developed oxygen needs. Study 2 included 45 patients, 13 of whom required ventilator management or died. In Study 1, IFN-λ3 showed a good predictive ability with an AUC of 0.92 (95% CI 0.76-1.00). In Study 2, the AUC of each biomarker was 0.70-0.74. The number of biomarkers above the cutoff showed the possibility of good prediction with an AUC of 0.86 (95% CI 0.75-0.97). When two or more biomarkers were positive, sensitivity and specificity were 0.92 and 0.63, respectively. In terms of biomarker testing at times when prognostication may be clinically useful, IFN-λ3 was predictive of oxygenation demand and a combination of the four biomarkers was predictive of mechanical ventilator requirement.

Underlying medical conditions and anti-SARS-CoV-2 spike IgG antibody titers after two doses of BNT162b2 vaccination: A cross-sectional study.

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30-50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76-0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42-0.95) and 0.77 (0.63-0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates.

The prevalence of the Omicron subvariant BA.2.75 rapidly increased in India and Nepal during the summer of 2022, and spread globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs is higher than that of BA.2 and BA.5. Of note, BA.2.75 causes focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which is not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicates better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 in a hamster model and should be closely monitored.