Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.

BACKGROUND: The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. METHODS: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. RESULTS: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2'-deoxyguanosine (p = 0.0481, baseline vs. 6 months). CONCLUSION: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.

Evaluation of Statistical Approaches in Developing a Predictive Model of Severe COVID-19 during Early Phase of Pandemic with Limited Data Resources.

As evidence of risk factors for severe cases of coronavirus disease 2019 (COVID-19) was uncertain in early phases of the pandemic, the development of an efficient predictive model for severe cases to triage high-risk individuals represented an urgent yet challenging issue. It is crucial to select appropriate statistical models when available data and evidence are limited. This study was conducted to assess the accuracy of different statistical models in predicting severe cases using demographic data from patients with COVID-19 prior to the emergence of consequential variants. We analyzed data from 929 consecutive patients diagnosed with COVID-19 prior to March 2021, including their age, sex, body mass index, and past medical histories, and compared areas under the receiver operating characteristic curve (ROC AUC) between different statistical models. The random forest (RF) model, deep learning (DL) models with not too many neurons, and naïve Bayes model exhibited AUC measures of > 0.70 with the validation datasets. The naïve Bayes model performed the best with the AUC measures of > 0.80. The accuracies in RF were more robust with narrower distribution of AUC measures compared to those in DL. The benefit of performing feature selection with a training dataset before building models was seen in some models, but not in all models. In summary, the naïve Bayes and RF models exhibited ideal predictive performance even with limited available data. The benefit of performing feature selection before building models with limited data resources depended on machine learning methods and parameters.

Insertion and deletion mutations preserved in SARS-CoV-2 variants.

The insertion/deletion (indel) mutation profiles of SARS-CoV-2 variants, including Omicron, remain unclear. We compared whole-genome sequences from various lineages and used preserved indels to infer the ancestral relationships between different lineages. Thirteen indel patterns from twelve sites were seen in ≥ 2 sequences; six of these sites were located in the N-terminal domain of the viral spike gene. Preserved indels in the coding regions were also identified in the non-structural protein 3 (Nsp3), Nsp6, and nucleocapsid genes. Seven of the thirteen indel patterns were specific to the Omicron variants, four of which were observed in BA.1, making it the most mutated variant. Other preserved indels observed in the Omicron variants were also seen in Alpha and/or Gamma, but not Delta, suggesting that Omicron is phylogenetically more proximal to Alpha. We demonstrated distinct profiles of preserved indels among SARS-CoV-2 variants and sublineages, suggesting the importance of indels in viral evolution.

Recently Added Frameshift Mutation in Human Monkeypox Virus (hMPXV) OPG191 Gene.

Human monkeypox virus (hMPXV) has caused sporadic outbreaks intermittently across countries in recent years, with the largest outbreak in 2022. However, the underlying mechanisms remain unclear. This study searched for recently developed structural variants of the viral genome. A total of 22 hMPXV whole genome sequences were randomly selected from the National Center for Biotechnology Information GenBank sequence database for initial screening. As a result, a recent frameshift mutation based on a 2-base insertion in a coding region was identified at the 3' terminal of the OPG191 gene, which encodes MPXVgp168 (B7R) protein. With this insertion, the protein was prematurely truncated, and the last 11 amino acids were missing, with 3 alternative amino acids added. Among the hMPXV genome sequences registered in the GenBank database as of January 2023, 61 sequences lacked the 2-base insertion and 3,362 sequences were inserted. All 61 sequences without mutations were collected before 2020, whereas 3,358 (99.9%) of the 3,362 sequences with the insertion were collected during or after 2022. These findings imply that a 2-base insertion has recently emerged and has been fixed among the virus population that prevailed in 2022. In summary, a recently emerged frameshift mutation with a 2-base insertion was identified in hMPXV OPG191 gene. Although the structural and functional consequences of this mutation on virulence and infectivity are unknown, research on the possible associations between this mutation and recent hMPXV outbreaks is warranted.

Trinucleotide Substitutions at Two Locations in the SARS-CoV-2 Nucleocapsid (N) Gene.

The genomes of sarbecoviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), incorporate mutations with short sequence exchanges based on unknown processes. Currently, the presence of such short-sequence exchanges among the genomes of different SARS-CoV-2 lineages remains uncertain. In the present study, multiple SARS-CoV-2 genome sequences from different clades or sublineages were collected from an international mass sequence database and compared to identify the presence of short sequence exchanges. Initial screening with multiple sequence alignments identified two locations with trinucleotide substitutions, both in the nucleocapsid (N) gene. The first exchange from 5'-GAT-3' to 5'-CTA-3' at nucleotide positions 28,280-28,282 resulted in a change in the amino acid from aspartic acid (D) to leucine (L), which was predominant in clade GRY (Alpha). The second exchange from 5'-GGG-3' to 5'-AAC-3' at nucleotide positions 28,881-28,883 resulted in an amino acid change from arginine and glycine (RG) to lysine and arginine (KR), which was predominant in GR (Gamma), GRY (Alpha), and GRA (Omicron). Both trinucleotide substitutions occurred before June 2020. The sequence identity rate between these lineages suggests that coincidental succession of single-nucleotide substitutions is unlikely. Basic local alignment search tool sequence search revealed the absence of intermediating mutations based on single-base substitutions or overlapping indels before the emergence of these trinucleotide substitutions. These findings suggest that trinucleotide substitutions could have developed via an en bloc exchange. In summary, trinucleotide substitutions at two locations in the SARS-CoV-2 N gene were identified. This mutation may provide insights into the evolution of SARS-CoV-2.

Acute Adverse Events at a Mass Vaccination Site after the Third and Fourth COVID-19 Vaccinations in Japan.

The third and fourth doses of the vaccine against coronavirus disease 2019 (COVID-19) were widely administered in Japan since December 2021. Currently, however, data are scarce regarding acute adverse events with the third and fourth doses. The present study reports the profiles of acute adverse events after the third and fourth COVID-19 vaccine doses, seen at the site of a mass vaccination center in Japan. Between December 2021 and July 2022, 267,515 individuals received the third, and 32,934 received the fourth COVID-19 vaccine dose at the mass vaccination center, of whom 442 recipients of the third (0.19%), and 22 recipients of the fourth (0.07%) dose reported acute adverse events and were examined by doctors on site. The most common diagnosis was vasovagal syncope/presyncope (incidence: 0.01-0.10%), followed by other miscellaneous complaints, acute allergic reactions (0.05-0.005%), and anaphylaxis (< 0.005%). Vasovagal syncope/presyncope occurred most frequently in recipients in those in their 20s, whereas acute allergic reactions were most frequent in those in their 40s. Both reactions were more frequent in women than men. The peak occurrence of vasovagal syncope/presyncope was earlier than 15 min after the injection, whereas that of acute allergic reaction was later than 15 min after the injection. The incidence of acute allergic reactions appeared to differ between various vaccine manufacturers, whereas that of vasovagal syncope/presyncope did not. These real-world data may benefit the safe and efficient implementation of mass vaccination campaigns for citizens who want to receive COVID-19 vaccines now and in the future.

Time-Dependent Analysis of Sicca Symptoms and Anti-Ro/SSA and Anti-La/SSB Antibodies in Patients with AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Anti-aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and Sjögren syndrome (SS) are likely comorbidities. However, the exact effects of age and disease duration on the positivity rates of serum anti-Ro/SSA and anti-La/SSB (anti-SSA/SSB) antibodies and the presence of sicca symptoms in patients with AQP4-IgG remain unknown. In the present study, we evaluated the data from patients with suspected NMOSD who had neurological episodes and tested for serum AQP4-IgG. Associations between the presence of serum AQP4-IgG and SS-related findings were evaluated. The presence of anti-SSA/SSB antibodies [odds ratio (OR), 7.34; 95% confidence interval (CI), 5.71-9.43; p < 0.0001] and that of sicca symptoms (OR, 2.08; 95% CI, 1.67-2.58; p < 0.0001) were both higher in patients with AQP4-IgG (n = 1,651) than in those without AQP4-IgG (n = 2,796). Meanwhile, neither age nor the elapsed time from neurological onset was linked to the prevalence of anti-SSA/SSB antibodies or sicca symptoms, and the prevalence rates of the SS-related factors were elevated since the onset of neurological episodes in those with AQP4-IgG. The frequency of sicca symptoms among those with anti-SSA/SSB antibodies was irrespective of AQP4-IgG (OR, 1.11; 95% CI, 0.67-1.85; p = 0.6892). The measured AQP4-IgG titers did not differ significantly according to the presence of anti-SSA/SSB antibodies (p = 0.2386; Mann-Whitney U test). In summary, age and duration of NMOSD were not the factors producing an elevated prevalence of anti-SSA/SSB antibodies and sicca symptoms in patients with AQP4-IgG, implying that the occurrence of comorbid SS is likely to temporarily precede or synchronize with the onset of AQP4-IgG-positive NMOSD.

Predictors for the Development of Hypoxia or Prolonged Acute Symptoms among Non-Hospitalized Mild-to-Moderate Patients with Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic remains a global public health concern. The clinical course and risk of developing severe illness among patients with COVID-19 who are at low-risk of severe COVID-19 remain uncertain. This retrospective cohort study from an isolation facility for low-risk COVID-19 patients in Japan evaluated the potential risks for severe disease with hypoxia (SpO2 ≤ 93%) or experiencing prolonged isolation period longer than 14 days with persistent acute symptoms. The study was performed before the spread of the alpha variant in the country and before the start of a nationwide mass vaccination campaign against COVID-19. Among the 929 participants with reliable outcome data regarding the development of hypoxia, 63 (6.8%) developed severe disease with hypoxia during their stays at the facility. Higher age [adjusted odds ratio (aOR), 1.08; 95% confidence interval (CI), 1.06-1.10] and male sex (aOR, 4.70; 95% CI, 2.39-9.22) were associated with this outcome. As for the experience of prolonged isolation period, higher age (aOR, 1.02; 95% CI, 1.01-1.04), atopic diseases (aOR, 1.69, 95% CI, 1.09-2.64), presence of cough at onset (aOR, 1.64; 95% CI, 1.09-2.48), and prescription of oral antibiotics before positive test results for COVID-19 (aOR, 2.37; 95% CI, 1.33-4.22) were associated with this outcome. In summary, 5-10% of low-risk COVID-19 patients later develop hypoxia. Older age and male sex were associated with both the development of hypoxia and prolonged acute symptoms. The unnecessary prescription of antibiotics before COVID-19 diagnosis may prolong COVID-19 symptoms.

Comparison of Insertion, Deletion, and Point Mutations in the Genomes of Human Adenovirus HAdvC-2 and SARS-CoV-2.

Virus genome mutation profiles with insertion, deletion, and point mutations have recently been revealed to differ remarkably between viruses. In RNA viruses like human coronaviruses or influenza viruses, genome samples collected over two to three decades usually show point mutations in 10-20% of the bases, while the rate of insertion and/or deletion mutations (indels) largely depends on the virus. This study evaluates the mutation profiles of DNA viruses by comparing a recently sampled genome of human adenovirus species C type 2 (isolate SG06/HAdvC2/2016) with a genome of the same species sampled in the 1970s. It was found insertions of 23 bases at seven sites and deletions of 22 bases at nine sites. The longest indels were 6-base insertions in E2B and L4. All indels in the coding regions were in-frame mutations with base lengths in multiples of three. In the non-coding regions, the lengths of the indels ranged from 1-4 consecutive bases. Long indels with more than 10 consecutive bases, which comprise nearly half of indels in the SARS-CoV-2 genome, were absent. In other sites, the point mutation rate was approximately 0.3%, which was significantly lower than in RNA viruses. In summary, the estimated point mutation rate in human adenovirus species C type 2 (HAdvC-2) was over 10 times lower than in RNA viruses. Unlike the relatively long indels in the SARS-CoV-2 genome, the indels in HAdvC-2 were short, with 6 or fewer consecutive bases.

Genetic Recombination Sites Away from the Insertion/Deletion Hotspots in SARS-Related Coronaviruses.

The genome sequences of severe acute respiratory syndrome (SARS)-related coronaviruses (sarbecoviruses) have been reported to include many long and complex insertions/deletions (indels) in specific genomic regions, including open reading frame 1a (ORF1a), S1 domain of the spike, and ORF8 genes. These indel hotspots incorporate various non-classical, long, and complex indels with uncertain developmental processes. A possible explanation for these complex and diversified indels at the hotspots is genetic recombination. To determine the possible association between recombination events and development of indel hotspots, this study investigated the genome sequences of many sarbecoviruses from different countries and hosts and compared the distributions of the indel hotspots and recombination sites by performing multiple sequence alignments and recombination analyses. The genomes of 19 SARS-related coronaviruses (15 coronaviruses that infect bats, two that infect humans, one that infects pangolins, and one that infects civets), including human-infecting SARS-CoV and SARS-CoV-2, were evaluated. Hotspots of complex indels with diverse RNA sequences around gaps were clustered in non-structural protein 2 (Nsp2) and Nsp3 of ORF1a, S1, and ORF8. Phylogenetic reconstructions revealed different structures of the inferred phylogenetic trees between genomic regions, and recombination analyses identified multiple recombination sites across ORF1ab and S genes. However, the nucleotide positions of the indel hotspots were not identical with the identified recombination sites in the recombinant viruses, suggesting the involvement of different developmental processes of indel hotspots and genetic recombination. Further research is required to elucidate the developmental mechanisms underpinning clustered complex indels and recombination events in the evolutionary history of sarbecoviruses.

Prolonged Diarrhea Following COVID-19 Vaccination: A Case Report and Literature Review.

Vaccination against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently underway across countries worldwide. However, the prevalence and characteristics of prolonged adverse events lasting for several months after receiving the vaccine remain largely unknown. We herein report a 46-year-old woman with prolonged diarrhea and vomiting after receiving the BNT162b2 mRNA vaccine for COVID-19. She had no notable medical history, including that of gastrointestinal diseases. She developed vomiting several hours after receiving the first vaccine dose and further developed severe diarrhea after 7 days. Several days after the second vaccine dose, her condition deteriorated, unrelieved by symptomatic therapies, including anti-diarrheal drugs. Abdominal computed tomography (CT) revealed inflammatory changes in the entire segment of the small intestine with wall thickening. The upper and lower gastrointestinal and capsule endoscopies were unremarkable. The patient's symptoms persisted for more than 6 months after the second vaccine dose. A Vaccine Adverse Event Reporting System (VAERS) database search suggested that diarrhea is observed in approximately 3% of all vaccine recipients, but a literature review indicated that prolonged gastrointestinal symptoms lasting for several months is very rare. In summary, a case of prolonged unexplained gastrointestinal symptoms, possibly based on inflammatory changes in the small intestine, is described. A literature search revealed that this type of manifestation is very rare, and further evidence is needed to determine the causality between vaccination and gastrointestinal symptoms.

Refractory Chest Pain in Mild to Moderate Coronavirus Disease 2019 Successfully Treated with Saikanto, a Japanese Traditional Medicine.

Coronavirus disease 2019 (COVID-19) causes a variety of pain symptoms in the acute phase. Severe chest pain suddenly occurs even without abnormalities on examination and is sometimes refractory to analgesics. Such pain is a clinical concern in care facilities with limited resources, and this is the first report on the use of saikanto for its treatment. In Miyagi Prefecture, Japan, COVID-19 patients with mild symptoms were admitted to a hotel that operated as an isolation facility, and their symptoms were observed. In this article, we report four cases in which chest pain comorbid with mild to moderate COVID-19 was successfully treated with saikanto, a traditional Japanese (Kampo) medicine. The patients presented with chest pain and underwent medical examination at the facility. Two patients had severe chest pain refractory to acetaminophen. Critical cardiopulmonary diseases were ruled out in all the patients, and three patients had features of pneumonia on chest radiograph. Medications, including saikanto, were administered to the patients. The patients' chest pain and other symptoms improved 1-4 days after the administration of saikanto, and they left the care facility without hospitalization. The cause of the chest pain experienced by these patients is unclear, but we speculate that it could be minimal pleural inflammation or neuropathy. Previous pharmacological studies have suggested anti-inflammatory and analgesic properties of the crude drugs that constitute saikanto. This case report suggests that saikanto could be a treatment option for chest pain refractory to analgesics in patients with mild to moderate COVID-19.

Response to Glucocorticoid Therapy in Patients with Mild to Moderate Coronavirus Disease 2019 at a Japanese Care Facility.

The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic caused by delta variant infection depleted medical resources, and the Japanese government announced glucocorticoid use for outpatients. An appropriate outpatient-glucocorticoid treatment for COVID-19 has not been established; therefore, we created treatment manuals with indications for glucocorticoid administration in a care facility adequately equipped to manage patients with mild to moderate COVID-19. Thirty-eight patients (24 males, 14 females; mean age 40.5 ± 11.8 years) were treated with glucocorticoids from August 1 to October 1, 2021 [COVID-19 staging, mild (n = 1), moderate I (n = 19), and moderate II (n = 18)]. Patients were treated with 6.6 mg/day d.i.v. or 6 mg/day p.o. dexamethasone, or 20-30 mg/day p.o. prednisolone. The median (25th-75th percentile) number of days from the date of onset to glucocorticoid administration was 8.0 days (7.0-11.25 days). While 24 patients were hospitalized, the condition of 14 improved without hospitalization. The median number of days from glucocorticoid administration to hospitalization was 1.0 day (range, 1.0-1.0 day). In the non-hospitalized patients, the median number of days of glucocorticoid administration was 5.0 days (5.0-5.25 days). The mean number of days from glucocorticoid administration to discharge from the care facility for non-hospitalized patients was 8.4 ± 3.3 days. The adverse reactions among non-hospitalized patients included insomnia (n = 1) and mild liver dysfunction (n = 3). The present method of glucocorticoid administration can be safely used for patients with COVID-19 in care facilities.

COVID-19-Related Symptoms during the SARS-CoV-2 Omicron (B.1.1.529) Variant Surge in Japan.

The exact profiles of the clinical symptoms related to the SARS-CoV-2 Omicron variant (B.1.1.529) remain largely uncertain. Therefore, this study aimed to clarify the clinical manifestations of infection with this variant. We enrolled individuals who were tested by quantitative nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test at a large screening center in a city of Japan during the B.1.1.529 Omicron variant wave between January and May 2022, after contact with COVID-19 patients. Swab tests were planned to be performed approximately 4-5 days after contact. The presence of COVID-19-related symptoms was assessed at the swab test site. Among the 2,507 enrolled individuals, 943 (37.6%) were RT-PCR test-positive and 1,564 (62.4%) were test-negative. Among the 943 PCR test-positive participants, the prevalence of the symptoms was as follows: 47.3% with cough, 32.9% with sore throat, 18.4% with fatigability, 12.7% with fever of ≥ 37.5℃, 9.9% with dyspnea, 2.1% with dysosmia, and 1.4% with dysgeusia. The prevalence of cough, sore throat, dyspnea, and fatigability was higher among adults aged ≥ 18 years than among children and adolescents. The prevalence of dysosmia and dysgeusia remarkably decreased during the Omicron wave (1-3%) compared to during the pre-Omicron variant waves (15-25%). In summary, common COVID-19-related symptoms during the Omicron variant wave included cough and sore throat, followed by fatigability, fever, and dyspnea. The prevalence of most of these symptoms was higher in adults than in non-adults. The prevalence of dysosmia and dysgeusia remarkably decreased with the Omicron variant than with pre-Omicron variants.

Effectiveness of mRNA COVID-19 Vaccines in Japan during the Nationwide Pandemic of the Delta Variant.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remained a major global health concern in 2021. To suppress the spread of infection, mass vaccinations have been performed across countries worldwide. In Japan, vaccinations of the first and second doses for most of the nation were performed during the nationwide outbreak of the B.1.617.2 (Delta) variant with the L452R spike protein mutation, and the effectiveness of the vaccinations to suppress the spread of COVID-19 among the people in Japan remains uncertain. In this study, adults aged ≥18 years, who were in contact with patients with COVID-19 and underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) tests during August and September 2021 at a mass screening test center in Japan, were enrolled. In this period, more than 95% of the COVID-19 infections were reportedly caused by the Delta variant. As a result, a total of 784 adults with recent contact history, including 231 (29.5%) RT-PCR test-positive cases, were enrolled. The test positivity rate was lower in individuals who had been vaccinated twice than in unvaccinated individuals (12.5% vs. 39.0%, p < 0.0001), with the risk ratio of 0.32 (95% confidence interval 0.23-0.46). The vaccine effectiveness was the highest between 7-90 days after the second vaccine dose. In conclusion, two doses of mRNA COVID-19 vaccines effectively suppressed transmission in Japan during the nationwide pandemic of the Delta variant, estimated to have prevented 50-80% of the infection.

Retrospective study revealed that Zn relate to improvement of swallowing function in the older adults.

BACKGROUND: Zinc is an essential micronutrient for maintaining biological activity. The level of zinc in the blood is known to decrease with age, especially in those over 75 years of age. In older adults patients with impaired functional status, aspiration pneumonia based on dysphagia often becomes problematic. However, the relationship between zinc deficiency and swallowing function has not been studied before. METHODS: A total of 52 older adults subjects (15 males and 37 females) living in a nursing home were enrolled for this study. At the time of enrollment, data of gender, age, body weight, serum zinc levels, serum albumin levels, and the time in a simple 2-step swallowing provocation test (S-SPT) were collected. In patients with serum zinc levels < 60 µg/dL, we initiated 2 months of oral zinc supplementation therapy with a 34 mg/day zinc load. Those who underwent zinc supplementation were re-evaluated after the treatment period and serum zinc levels and S-SPT time were measured. RESULTS: At the time of enrollment, serum zinc level was significantly correlated with serum albumin levels (Pearson's R = 0.58, p < 0.0001) and time in the S-SPT (Spearman's rho = - 0.32, p = 0.0219). Twenty-five of the 52 patients had zinc deficiency with a serum zinc level < 60 µg/dL. After 2 months of oral zinc supplementation, both serum zinc levels (p < 0.0001) and time in the S-SPT (p = 0.04) significantly improved. Meanwhile, serum albumin level (p = 0.48) or body weight (p = 0.07) did not significantly change following zinc supplementation. Zinc supplementation significantly improved swallowing function, especially in the older adults who had comorbid dysphagia and zinc deficiency. CONCLUSIONS: Zinc deficiency is associated with compromised swallowing function in older adults patients with impaired general functions. Oral zinc supplementation can alleviate dysphagia in older adults patients with zinc deficiency even though this is a retrospective study. Further study will be needed to confirm this positive effect.

Treatment of COVID-19-Related Olfactory Disorder Promoted by Kakkontokasenkyushin'i: A Case Series.

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

Impacts of Natural Environmental Factors and Prevalence of Airway Symptoms on the Local Spread of COVID-19: A Time-Series Analysis in Regional COVID-19 Epidemics.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the world's largest public health concern in 2021. This study evaluated the associations of the prevalence of airway symptoms among the tested individuals and data regarding the natural environmental factors with the weekly number of newly diagnosed COVID-19 patients in Sendai City (Nt). For the derivatives of the screening test results, data from individuals with a contact history who underwent nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) testing between July 2020 and April 2021 (6,156 participants, including 550 test-positive patients) were used. The value of Nt correlated with the weekly RT-PCR test-positive rate after close contact, prevalence of cough symptoms in test-positive individuals or in test-negative individuals, lower air temperature, lower air humidity, and higher wind speed. The weekly test-positive rate correlated with lower air humidity and higher wind speed. In cross-correlation analyses, natural environmental factors correlated with the regional epidemic status on a scale of months, whereas the airway symptoms among non-COVID-19 population affected on a scale of weeks. When applying an autoregression model to the serial data of Nt, large-scale movements of people were suggested to be another factor to influence the local epidemics on a scale of days. In conclusion, the prevalence of cough symptoms in the local population, lower air humidity or higher wind speed, and large-scale movements of people in the locality would jointly influence the local epidemic status of COVID-19.

COVID-19 Transmission at Schools in Japan.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health concern in 2021. However, the risk of attending schools during the pandemic remains unevaluated. This study estimated the secondary transmission rate at schools using the results of a real-time reverse transcription-polymerase chain reaction (RT-PCR) screening test performed between July 2020 and April 2021, before starting the nationwide mass vaccination. A total of 1,924 students (20 RT-PCR-positive; 1.0%) from 52 schools or preschools were evaluated, together with 1,379 non-adults (95 RT-PCR-positive; 6.9%) exposed to SARS-CoV-2 in non-school environments. Assuming that the infectious index cases were asymptomatic and the transmission at schools followed a Bernoulli process, we estimated the probability of transmission after each contact at school as approximately 0.005 (0.5% per contact) with the current infection prevention measures at schools in Japan (i.e., hand hygiene, physical distancing, wearing masks, and effective ventilation). Furthermore, assuming that all children are capable of carrying the infection, then contact between an index case and 20-30 students per day at schools would yield the expected value for secondary cases of ≥ 1.0, during the 10 days of the infectious period. In conclusion, with the current infection prevention measures at schools in Japan, secondary transmission at schools would occur in approximately every 200 contacts. When considering this rate, compliance with the current infection prevention measures at schools and early detection and quarantine of the index cases would be effective in preventing the spread of COVID-19 at schools.

Predictors of SARS-CoV-2 Positivity Based on RT-PCR Swab Tests at a Drive-Through Outpatient Clinic for COVID-19 Screening in Japan.

In response to the COVID-19 pandemic caused by SARS-CoV-2 in 2020, we conducted drive-through nasopharyngeal swab testing for COVID-19 in Sendai city, Japan, since April 2020. All tested individuals were judged in advance by public health centers for the necessity of undergoing the test with possible contact history and/or symptoms suggestive of COVID-19. In this study, to identify the predictors of SARS-CoV-2 test positivity for more efficient and evidenced selection of suspected individuals, we enrolled 3,540 consecutive individuals, tested in the first 7 months of the testing program, with data regarding to the history of close contact with COVID-19 patients, including those involved in cluster outbreaks. This cohort included 284 foreign students (257 males and 27 females) from a vocational school involved in the largest cluster outbreak in the area. Close contact history was present in 952 (26.9%) of the participants. The reverse transcription-polymerase chain reaction (RT-PCR) test results showed that 164 participants (4.6%) were positive and 3,376 participants (95.4%) were negative for the SARS-CoV-2 nucleocapsid gene (N2). In the univariate and multivariate analyses, history of close contact with COVID-19 patients, higher age, cough symptoms, and non-native ethnicity were predictors for SARS-CoV-2 test positivity. However, the significance of age and foreign nationality disappeared or declined upon excluding the foreign students from the aforementioned largest cluster outbreak. In conclusion, a history of close contact with COVID-19 patients and the presence of cough symptoms are significant predictors of SARS-CoV-2 test positivity.