Reconstructing COVID-19 incidences from positive RT-PCR tests by deconvolution.

BACKGROUND: The emergency of new COVID-19 variants over the past three years posed a serious challenge to the public health. Cities in China implemented mass daily RT-PCR tests by pooling strategies. However, a random delay exists between an infection and its first positive RT-PCR test. It is valuable for disease control to know the delay pattern and daily infection incidences reconstructed from RT-PCR test observations. METHODS: We formulated the convolution model between daily incidences and positive RT-PCR test counts as a linear inverse problem with positivity restrictions. Consequently, the Richard-Lucy deconvolution algorithm was used to reconstruct COVID-19 incidences from daily PCR tests. A real-time deconvolution was further developed based on the same mathematical principle. The method was applied to an Omicron epidemic data set of a bar outbreak in Beijing and another in Wuxi in June 2022. We estimated the delay function by maximizing likelihood via an E-M algorithm. RESULTS: The delay function of the bar-outbreak in 2022 differs from that reported in 2020. Its mode was shortened to 4 days by one day. A 95% confidence interval of the mean delay is [4.43,5.55] as evaluated by bootstrap. In addition, the deconvolved infection incidences successfully detected two associated infection events after the bar was closed. The application of the real-time deconvolution to the Wuxi data identified all explosive incidence increases. The results revealed the progression of the two COVID-19 outbreaks and provided new insights for prevention and control strategies, especially for the role of mass daily RT-PCR testing. CONCLUSIONS: The proposed deconvolution method is generally applicable to other infectious diseases if the delay model can be assumed to be approximately valid. To ensure a fair reconstruction of daily infection incidences, the delay function should be estimated in a similar context in terms of virus variant and test protocol. Both the delay estimate from the E-M algorithm and the incidences resulted from deconvolution are valuable for epidemic prevention and control. The real-time feedback is particularly useful during the epidemic's acute phase because it can help the local disease control authorities modify the control measures more promptly and precisely.

Oral lesions with immunohistochemical evidence of Sars-CoV-2 in swab-negative post-COVID syndrome.

OBJECTIVES: Growing evidence exists about post-COVID condition/syndrome as sequelae of Sars-CoV-2 infection in healed patients, possibly involving the lungs, brain, kidney, cardiovascular and neuromuscular system, as well the persistency of taste dysfunction. Such symptoms develop during or after infection and continue for more than 12 weeks with pathogenesis related to virus persistency but variable by organs or systems. MATERIALS AND METHODS: We recently observed six patients recovered from COVID-19 and with negative RT-PCR testing, showing oral mucosa lesions (mainly ulcers) overlapping those occurring in the acute phase, persisting up to 20 days and thus needing a biopsy with histological investigation and spike protein evaluation by immunohistochemistry. RESULTS: We found epithelial ulceration, inflammatory infiltrate, vessels with increased diameter and flattened endothelium but no thrombi formation; also, we found a weak epithelial SARS-CoV-2 positivity limited to the basal/spinosum layers, progressively decreasing toward the periphery, and the intraepithelial lymphomonocytes, endothelium, and perivascular pericytes too. CONCLUSIONS: Our findings provide evidence that SARS-CoV-2 can persist, as for other organs/systems, also in the oral epithelium/mucosa after the acute phase and can be responsible for lesions, although by a pathogenetic mechanism that should be better defined but certainly referable as the oral mucosa counterpart of post-COVID syndrome.

Optimal diagnostic test allocation strategy during the COVID-19 pandemic and beyond.

Timely diagnostic testing for active SARS-CoV-2 viral infections is key to controlling the spread of the virus and preventing severe disease. A central public health challenge is defining test allocation strategies with limited resources. In this paper, we provide a mathematical framework for defining an optimal strategy for allocating viral diagnostic tests. The framework accounts for imperfect test results, selective testing in certain high-risk patient populations, practical constraints in terms of budget and/or total number of available tests, and the purpose of testing. Our method is not only useful for detecting infections, but can also be used for long-time surveillance to detect new outbreaks. In our proposed approach, tests can be allocated across population strata defined by symptom severity and other patient characteristics, allowing the test allocation plan to prioritize higher risk patient populations. We illustrate our framework using historical data from the initial wave of the COVID-19 outbreak in New York City. We extend our proposed method to address the challenge of allocating two different types of diagnostic tests with different costs and accuracy, for example, the RT-PCR and the rapid antigen test (RAT), under budget constraints. We show how this latter framework can be useful to reopening of college campuses where university administrators are challenged with finite resources for community surveillance. We provide a R Shiny web application allowing users to explore test allocation strategies across a variety of pandemic scenarios. This work can serve as a useful tool for guiding public health decision-making at a community level and adapting testing plans to different stages of an epidemic. The conceptual framework has broader relevance beyond the current COVID-19 pandemic.

Comparing two sample pooling strategies for SARS-CoV-2 RNA detection for efficient screening of COVID-19.

The emerging pandemic of coronavirus disease 2019 (COVID-19) has affected over 200 countries and resulted in a shortage of diagnostic resources globally. Rapid diagnosis of COVID-19 is vital to control the spreading of the disease, which, however, is challenged by limited detection capacity and low detection efficiency in many parts of the world. The pooling test may offer an economical and effective approach to increase the virus testing capacity of medical laboratories without requiring more laboratory resources such as laboratory workers, testing reagents, and equipment. In this study, the sample pools of 6 and 10 were detected by a real-time reverse transcription-polymerase chain reaction assay targeting ORF1ab and N genes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Each pool consisted of five or nine negative SARS-CoV-2 samples and one positive counterpart with varying viral loads. Two different strategies of sample pooling were investigated and the results were compared comprehensively. One approach was to pool the viral transport medium of the samples in the laboratory, and the other was to pool swab samples during the collection process. For swab pooling strategy, qualitative results of SARS-CoV-2 RNA, specific tests of ORF1ab and N genes, remained stable over the different pool sizes. Together, this study demonstrates that the swab pooling strategy may serve as an effective and economical approach for screening SARS-CoV-2 infections in large populations, especially in countries and regions where medical resources are limited during the pandemic and may thus be potential for clinical laboratory applications.

Clinical characteristics, cause analysis and infectivity of COVID-19 nucleic acid repositive patients: A literature review.

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and lives. The virus is still spreading throughout the world, and the cumulative number of confirmed cases is increasing. After patients with COVID-19 are treated and discharged, some have repeated clinical symptoms and become positive for nucleic acid tests a second time. Through analysis and review of the existing literature, the proportion of repositive patients in the discharged patient population and their clinical characteristics were systematically described for the first time. Furthermore, an in-depth analysis of the causes of repositive nucleic acid tests and the potential transmission of the disease provides the basis for the management and protection of discharged patients with COVID-19.

Detection of COVID-19 Infection from Routine Blood Exams with Machine Learning: A Feasibility Study.

The COVID-19 pandemia due to the SARS-CoV-2 coronavirus, in its first 4 months since its outbreak, has to date reached more than 200 countries worldwide with more than 2 million confirmed cases (probably a much higher number of infected), and almost 200,000 deaths. Amplification of viral RNA by (real time) reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard test for confirmation of infection, although it presents known shortcomings: long turnaround times (3-4 hours to generate results), potential shortage of reagents, false-negative rates as large as 15-20%, the need for certified laboratories, expensive equipment and trained personnel. Thus there is a need for alternative, faster, less expensive and more accessible tests. We developed two machine learning classification models using hematochemical values from routine blood exams (namely: white blood cells counts, and the platelets, CRP, AST, ALT, GGT, ALP, LDH plasma levels) drawn from 279 patients who, after being admitted to the San Raffaele Hospital (Milan, Italy) emergency-room with COVID-19 symptoms, were screened with the rRT-PCR test performed on respiratory tract specimens. Of these patients, 177 resulted positive, whereas 102 received a negative response. We have developed two machine learning models, to discriminate between patients who are either positive or negative to the SARS-CoV-2: their accuracy ranges between 82% and 86%, and sensitivity between 92% e 95%, so comparably well with respect to the gold standard. We also developed an interpretable Decision Tree model as a simple decision aid for clinician interpreting blood tests (even off-line) for COVID-19 suspect cases. This study demonstrated the feasibility and clinical soundness of using blood tests analysis and machine learning as an alternative to rRT-PCR for identifying COVID-19 positive patients. This is especially useful in those countries, like developing ones, suffering from shortages of rRT-PCR reagents and specialized laboratories. We made available a Web-based tool for clinical reference and evaluation (This tool is available at https://covid19-blood-ml.herokuapp.com/ ).

Erratum: Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial.

[This corrects the article DOI: 10.3389/fmed.2023.1139046.].

Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial.

Background: To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. Methods: CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020-October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility. A single oral dose of ivermectin (200 µg/kg) or placebo was administered under fasting. The primary outcome was time to a negative COVID-19 RT-PCR test result for SARS-CoV-2 nucleic acid, assessed using stratified log-rank test and Cox regression models. Results: Overall, 112 and 109 patients were randomized to ivermectin and placebo, respectively; 106 patients from each group were included in the full analysis set (male [%], mean age: 68.9%, 47.9 years [ivermectin]; 62.3%, 47.5 years [placebo]). No significant difference was observed in the occurrence of negative RT-PCR tests between the groups (hazard ratio, 0.96; 95% confidence interval [CI] 0.70-1.32; p = 0.785). Median (95% CI) time to a negative RT-PCR test was 14.0 (13.0-16.0) and 14.0 (12.0-16.0) days for ivermectin and placebo, respectively; 82.1% and 84% of patients achieved negative RT-PCR tests, respectively. Conclusion: In patients with COVID-19, single-dose ivermectin was ineffective in decreasing the time to a negative RT-PCR test. Clinical Trial Registration: ClinicalTrials.gov, NCT04703205.

Psychological status of medical staff dedicated to nucleic acid collection in COVID-19 epidemic during closed-loop management: A cross-sectional study.

Background: To investigate the depression, anxiety and somnipathy situation occurred in the nucleic acid collection staff during the closed-loop management period of COVID-19. And try to understand the influencing factors of related psychological status. Methods: A cross-sectional study of 1,014 nucleic acid collection staff from seven Chinese hospitals was conducted. Various investigation methods were involved in the questionnaires to collect data, including 12-items self-made questionnaire survey of basic demographic information, 9-items patient health questionnaire depression scale (PHQ-9), 7-items generalized anxiety disorder scale (GAD-7) and Pittsburgh sleep quality index (PSQI). Data analysis was performed using SPSS version 26.0 and Excel software. Mann-Whitney U-test, Chi-square test, correlation analysis, mono-factor analysis and binary logistic regression were applied accordingly for further analysis. Results: The positive rate of depression, anxiety and sleep disorder of 1,014 nucleic acid collectors under closed-loop management were 33.5, 27.2, and 50.1%, respectively. Depression was significantly positively correlated with anxiety and sleep (P < 0.05). The scores of depression scale were positively correlated with the age and the fear for infection (r = 0.106, 0.218, both P < 0.05); The scores of anxiety scale were also positively correlated with the age and the fear for infection (r = 0.124, 0.225, both P < 0.05); The length of service, collection time and the degree of worry about infection and was positively correlated with the score of sleep scale (r = 0.077, 0.074, 0.195, both P < 0.05); Education level had a significant negative association with PHQ-9, GAD-7 and PSQI (r = -0.167,-0.172, both P < 0.05). Binary logistic regression analysis showed that age, technical title, education level, collection time, collection frequency, collection location, fear for infection and external environment were important influencing factors of depression, anxiety and sleep disorders. Conclusion: The results of this study suggested that when carrying out nucleic acid collection mission, managers should intervene to optimize the collection location, control the duration of each collection mission, replace the collection staff in time and pay close attention to the psychological state of the collection staff.

A Young Adult With Multisystem Inflammatory Syndrome Following Weeks of Initial COVID-19 Respiratory Infection, With No Prior COVID-19 Vaccination: A Case Report.

Multisystem inflammatory syndrome (MIS) following COVID-19, a condition primarily diagnosed in children, has also been observed less frequently in adults. It usually presents with a multitude of symptoms, mimicking a shock-like state characterized by multiple organ failure. Diagnosis often involves ruling out other conditions and timely management to mitigate morbidity and mortality. In this case, a 39-year-old unvaccinated Caucasian male patient reported symptoms of fever, chills, night sweats, diarrhea, headache, nasal congestion, and facial pain. Despite treatment with antipyretics, the fever persisted. The patient had tested positive for COVID-19 via polymerase chain reaction (PCR) six weeks prior. Clinical findings included low oxygen saturation, sinus tachycardia, abnormal liver function, elevated inflammatory markers, a negative respiratory viral panel, a negative immunologic workup, and a positive Clostridium difficile (C. difficile) PCR. Following complaints of chest pain which quickly escalated to cardiac arrest, he was diagnosed with myopericarditis. These manifestations met the multisystem inflammatory syndrome in adults (MIS-A) diagnostic criteria as stipulated by the Centers for Disease Control and Prevention. The diagnosis of MIS-A was reached through exclusion. Notably, the patient responded well to symptomatic management. Given the infrequent occurrence of MIS-A cases, even in 2023, it remains a challenging diagnosis. Despite existing guidelines for management, the recovery of this patient solely through symptomatic treatment prior to the consideration of conventional treatment is striking. The patient had concurrent infections, including a C. difficile infection, but these did not account for the overall clinical presentation, particularly the myopericarditis and positive laboratory findings.

Trend of SARS-Cov-2-Specific IgG Antibody Titers Among COVID-19 Pneumonia Patients: A Nine-Month Follow-Up.

Introduction Understanding the dynamics of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) spike antibody titers after natural infection is important for understanding immunological memory. This longitudinal study was conducted to assess the trend in serum SARS-CoV-2 IgG spike antibody titers in a cohort of recovered cases up to nine months after SARS infection. Materials and methods We examined the neutralizing antibody response (IgG spike) in serum samples from a cohort of 86 SARS-CoV-2 quantitative polymerase chain reaction (qPCR)-confirmed infection, comprising cases having minor COVID-19 pneumonia and severity, which was determined by CT severity scores. Patients were enrolled in August/September 2020 and serum samples have been processed at one, three, six, and nine months. CT severity scores were rated between 1-25 and antibody titers≥ 1.4 were considered positive. Results The mean anti-SARS-CoV-2-specific IgG antibody titers at one month, three months, six months, and nine months were 22.02 ± 18.36, 14.62 ± 12.61, 8.93 ± 8.10, and 3.86 ± 5.70, respectively. The difference was statistically significant. The seropositivity rates (titer ≥1.4 IU) were 93.02%, 82.56%, 76.74%, and 58.14% at one, three, six, and nine months after infection, respectively. Cases with severe CT severity scores showed significantly higher mean antibody levels at all follow-up visits.

Clinical Characteristics of Patients Returning to Emergency Department With Initial False-Negative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Based COVID-19 Test.

Background: The coronavirus disease 2019 (COVID-19) outbreak is an international public health emergency. Early identification of COVID-19 patients with false-negative RT-PCR tests is paramount in the ED to prevent both nosocomial and community transmission. This study aimed to compare clinical characteristics of repeat emergency department (ED) visits among coronavirus disease 2019 (COVID-19) patients with initial false-negative reverse transcriptase-polymerase chain reaction (RT-PCR)-based COVID-19 test. Methods: This is a retrospective, multi-center, cohort study conducted at 12 hospitals affiliated with Baylor Scott & White Health system. Patients visiting the EDs of these hospitals between June and August 2020 were screened. Patients tested negative for viral RNA by quantitative RT-PCR in the first ED visit and positive in the second ED visit were included. The primary outcome was the comparison of clinical characteristics between two consecutive ED visits including the clinical symptoms, triage vital signs, laboratory, and chest X-ray (CXR) results. Results: A total of 88 confirmed COVID-19 patients with initial false-negative RT-PCR COVID-19 test in the ED were included in the final analyses. The mean duration of symptoms in the second ED visit was significantly higher (3.6 ± 0.4 vs. 2.6 ± 0.3 days, p = 0.020). In the first ED visit, lymphocytopenia (35.2%), fever (32.6%), nausea (29.5%), and dyspnea (27.9%) are the most common signs of COVID-19 infection during the window period. There were significant increases in the rate of hypoxia (13.6% vs. 4.6%, p = 0.005), abnormal infiltrate on CXR (59.7% vs. 25.9%, p < 0.001), and aspartate aminotransferase (AST) elevation (26.1% vs. 9.1%, p < 0.001) in the second ED visit. Conclusions: Early COVID-19 testing (less than 3 days of symptom duration) could be associated with a false-negative result. In this window period, lymphocytopenia, fever, nausea, and dyspnea are the most common early signs that can potentially be clinical hints for COVID-19 diagnosis.

Evaluation of Cost-Benefit and Measures During the COVID-19 Pandemic for Incoming Travelers Through Tests in Origin in Spain.

Background: The World Health Organization has promoted preventive measures for reducing the impact of the pandemic. One of these measures was tests in origin for travelers. Testing strategies for COVID-19 facilitate the overall public health response to the pandemic and contributes to minimize the infection among the population COVID-19. Goal: In this work, we assess the efficiency of diagnostic testing of incoming travelers in the Canary Islands, Spain, during a period of 4 months, with a focus on the economic impact for the regional government. We study the cost-benefit of this measure as well as the potential influence on the number of positive cases in the population. Methods: We processed the real data in the Canary Islands of pre-flight PCR and antigen tests that were required to the residents when traveling back to the Canaries from anywhere in Spain in a period of 4 months, from 14 December, 2020 to 4 April, 2021. As a result, we calculated the economic impact of doing those tests and compare them with the estimated costs of passengers under the hypothesis of entering the islands without testing. The cost-benefit was obtained for different scenarios, where the incoming passengers generated hospitalization and intensive care unit (ICU) costs directly and via transmissions. Results: The incoming testing funded by the government, if applied during the bad evolution of the pandemic with 1.2 ratio of transmission, clearly saved money to the public health system. In addition to the economic impact of this measure, we estimated the potential influence on the number of positive cases in the population according to different scenarios of the propagation of the pandemic. At the beginning of February 2021, the savings were about €130.551,47, with a 95% confidence interval (CI) of €24.677,94-236.425,00. By the end of April 2021, the savings were above €2,000,000 (€2.284.788,50 on average and 95% CI of €2.092.914,84-2.476.662,16) and the savings increased as the pandemic evolved. At the end of the period, the savings were twice the expenses. Conclusions: Testing in origin has proved to be a good measure that helped to mitigate COVID-19 spread among regions. Our results confirm that the free PCR or rapid antigen tests produce relevant savings to the public budget. We studied 61.990 reported data during 2020 and 2021 from the travelers from national flights, against 346.449 of total incoming travelers to the Canary Islands in this period. The measure pursued by the Government of the Canary Islands of providing free tests for residents showed a clear benefit for both, limiting the propagation of COVID-19 and reducing the costs of the hospitalizations and ICU admissions. It should be noted that the free testing measure in this period was before starting the vaccination campaigns. As measure of public health in the airports, testing helped to control and make the mobility of travelers secure.

Comparison of chest computed tomography findings of RT-PCR negative and RT-PCR positive cases in COVID-19 patients.

OBJECTIVE: The purpose was to compare the results of the RT-PCR test, with the findings of Chest CT and to determine the features of CT for the diagnosis of COVID-19 and how to approach RT-PCR negative patients. MATERIAL METHOD: Chest CT findings of 569 COVID-19 diagnosed patients, followed up at the pandemic wards between March and June 2020 were retrospectively examined. Patients were grouped according to RT-PCR results, gender, and age. RESULTS: 284 (49%) were RT-PCR(+), 285 (50.8%) were RT-PCR(-) of total 569 patients. 11 (1.9%) of RT-PCR(+) had no involvement in Chest CT while all the RT-PCR(-) patients were CT(+). The distribution of lesions in CT were; 544 (95.6%) bilateral, 553 (97.2%) multilobar, 557(98%) peripherally 151 (26.5%) posteriorly localized. The most common findings were; 539 (94.7%) ground-glass opacity (GGO), 365 (64.1%) consolidation, 160 (28.1%) crazy paving interlobular septal thickening. CO-RADS mean value was 5.4 ± 0.7. GGO and reticulation in RT-PCR(-) patients were 280 (98.2%) and 24 (8.4%); while they were 259 (91.2%) and 12 (4.2%) in RT-PCR(+) patients, were significantly higher (p < 0.05). No significant difference was observed, in CT findings for gender. Only the findings of crazy paving interlobular septal thickening and reticulation in 18-64 age group were significantly higher than that in 65-94 age group, 105 (24.8%)-55 (37.9%), 19 (4.5%)-17 (11.7%) respectively (p < 0.05). CONCLUSION: The typical findings of COVID-19 pneumonia in Chest CT are: GGO, consolidation and crazy paving in bilateral, peripheral, posterior localization. CT plays an essential role for diagnosis, isolation and treatment in cases of COVID-19 and RT-PCR negative test should be verified by CT.

Rapid detection of the widely circulating B.1.617.2 (Delta) SARS-CoV-2 variant.

The emergence of the B.1.617.2 (Delta) variant of the severe acute syndrome coronavirus (SARS-CoV-2) that emerged in 2019 (COVID-19), resulted in a surge of cases in India and has expanded and been detected across the world, including in the United States. The B.1.617.2 (Delta) variant has been seen to be twice more transmissible coupled with potential increases in disease severity and immune escape. As a result, case numbers and hospitalisations are once again on the rise in the USA. On 16 July 2021, the Centers for Disease Control and Prevention (CDC) reported a 7-day average 69.3% increase in new cases and a 35% increase in hospitalisations. Although the gold standard for SARS-CoV-2 variants identification remains genomic sequencing, this approach is not accessible to many clinical laboratories. The main goal of this study was to validate and implement the detection of the B.1.617.2 (Delta) variant utilising an open reverse transcription polymerase chain reaction (RT-PCR) platform by explicitly detecting the S-gene target failure (SGTF) corresponding to the deletion of two amino acids (ΔE156/ΔF157) characteristic of B.1.617.2 (Delta) variant. This approach was conceived as a rapid screening of B.1.617.2 (Delta) variant in conjunction with CDC's recommended N1 (nucleocapsid gene), N2, and RP (human RNase P) genes, as a pre-screening tool prior to viral genomic sequencing. We assessed 4,937 samples from 5 July to 5 September 2021. We identified the B.1.617.2 (Delta) variant in 435 of 495 positive samples (87.8%); the additional positive samples (7 samples, 1.4%) were found to belong to the B.1.1.7 (Alpha, UK) lineage and the remaining 53 samples (10.7%) were reported as 'other' lineages. Whole genome sequencing of 46 randomly selected samples validated the strains identified as positive and negative for the B.1.617.2 (Delta) variant and confirmed the S gene deletion in addition to B.1.617.2 characteristic mutations including L452R, T478K, P681R and D950N located in the spike protein. This modality has been used as routine testing at the Riverside University System Health (RUHS) Medical Center as a method for detection of B.1.617.2 (Delta) to pre-screen samples before genome sequencing. The assay can be easily implemented in clinical laboratories, most notably those with limited economic resources and access to genomic platforms.

Effectiveness of COVID-19 Vaccines against SARS-CoV-2 Infection among Persons Attending the RT-PCR center at a Medical College Hospital in Telangana: A Case- Control Study.

Background: In January 2021, India's drug regulator issued restricted emergency approval for COVISHIELD and COVAXIN, which were manufactured in India. In mid-January 2021, in India, there were 10.5 million confirmed cases and 0.15 million deaths. The objectives were to evaluate vaccine effectiveness (VE) of coronavirus disease 2019 (COVID-19) vaccines made in India against severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection. Materials and Methods: A test-negative case-control study was conducted from May 2021 to December 2021 for a duration of 8 months among people attending a reverse transcriptase polymerase chain reaction (RT-PCR) center at a medical college hospital for RT-PCR test for SARS-CoV-2. The baseline characteristics and RT-PCR report were collected from the RT-PCR center. The exposure to COVID-19 vaccines was enquired via phone call or was checked with data available with the health authorities. Results: After applying inclusion and exclusion criteria and case and control definitions, a total of 380 participants (95 cases and 285 controls) were included. The adjusted VE of two doses of COVISHIED vaccine against symptomatic SARS-CoV-2 infection was 52.2% (41.7 to 62.1), and that of a single dose was 40.88% (31.26 to 51.29). The adjusted VE of two doses of COVAXIN vaccine against SARS-CoV-2 infection was 39% (29.40 to 49.27). The overall VE was 48.20% (37.90 to 58.22) for two doses of any vaccines. Conclusions: Vaccines made in India were nearly 50% effective. Further new studies should be conducted as new variants of SARS-CoV-2 are emerging. We do not know the VE against the variants, and whether booster doses are required or not is not yet established.

Evaluation of SARS-CoV-2 transmission in COVID-19 isolation wards: On-site sampling and numerical analysis.

Although airborne transmission has been considered as a possible route for the spread of SARS-CoV-2, the role that aerosols play in SARS-CoV-2 transmission is still controversial. This study evaluated the airborne transmission of SARS-CoV-2 in COVID-19 isolation wards at Prince of Wales Hospital in Hong Kong by both on-site sampling and numerical analysis. A total of 838 air samples and 1176 surface samples were collected, and SARS-CoV-2 RNA was detected using the RT-PCR method. Testing revealed that 2.3% of the air samples and 9.3% of the surface samples were positive, indicating that the isolation wards were contaminated with the virus. The dispersion and deposition of exhaled particles in the wards were calculated by computational fluid dynamics (CFD) simulations. The calculated accumulated number of particles collected at the air sampling points was closely correlated with the SARS-CoV-2 positive rates from the field sampling, which confirmed the possibility of airborne transmission. Furthermore, three potential intervention strategies, i.e., the use of curtains, ceiling-mounted air cleaners, and periodic ventilation, were numerically investigated to explore effective control measures in isolation wards. According to the results, the use of ceiling-mounted air cleaners is effective in reducing the airborne transmission of SARS-CoV-2 in such wards.

Healthcare use and RT-PCR testing during the first wave of the COVID-19 pandemic in Japan.

BACKGROUND: Rapid testing, tracing, and isolation among symptomatic patients are the standard for controlling the COVID-19. However, during spring 2020, Japan employed a RT-PCR test policy by using a guideline, which was used for the public to visit hospitals or clinics when they had mild symptoms for 4 days or longer ("4-day rule") among low-risk patients. It is unknown of patients' experience of healthcare use and testing during the period under the guideline. Thus, we investigated the healthcare visiting and testing among patients who developed cold-like symptoms during the period. METHODS: Our survey was conducted online in September 2020 to a nationally representative sample of adults throughout Japan. We investigated the public's understanding of the guideline. In addition, we asked their experience with healthcare use and testing if they had noticed new-onset cold-like symptoms. RESULTS: Of 2,137 people surveyed, 1,698 (79.5%) recognized the guidelines, but 422 people (19.7%) misunderstood. There were 144 (6.7% of 2,137 people) who developed cold-like symptoms, and many of them experienced difficulties in getting through telephone calls to a public health center, and 25 (17% of 144 people) visited healthcare institutions. Of these 25 symptomatic patients, 15 (60%) could not receive testing because of decisions by physicians (14 patients) or a local public health center (1 patient). CONCLUSION: There was a low use of healthcare and testing among symptomatic patients during the first wave of the pandemic in Japan. Testing capacity should be increased to provide effective care for patients with suspected COVID-19 in Japan.

COVID-19 screening in a Portuguese pediatric population.

OBJECTIVE: To assess the characteristics of suspected coronavirus disease 19 (COVID-19) and the rate of confirmed COVID-19 in a pediatric population at the beginning of the pandemic in Portugal. STUDY DESIGN: Suspected COVID-19 pediatric cases that were tested in a Portuguese hospital between March 17 and April 2 2020 were included in this descriptive retrospective study. The analyzed data included socio-demographic parameters, characteristics of the household, underlying medical conditions and symptoms. RESULTS: Ninety-four patients were included and all of them were symptomatic and treated without hospitalization. The most common symptoms were cough (80%;n=75), rhinorrhea (72%;n=68) and fever (60%;n=56). There was only one positive for SARS-CoV-2 in a five-year-old child with mild illness without epidemiologic linkage. CONCLUSION: This study showed a low rate of confirmed COVID-19 in children. The causes for this low rate can be multifactorial and illustrates how differently this virus spreads in the pediatric population.

Quarantine and testing strategies to ameliorate transmission due to travel during the COVID-19 pandemic: a modelling study.

BACKGROUND: Numerous countries have imposed strict travel restrictions during the COVID-19 pandemic, contributing to a large socioeconomic burden. The long quarantines that have been applied to contacts of cases may be excessive for travel policy. METHODS: We developed an approach to evaluate imminent countrywide COVID-19 infections after 0-14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as "sufficient." FINDINGS: We present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases. INTERPRETATION: For nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts. FUNDING: EasyJet (JPT and APG), the Elihu endowment (JPT), the Burnett and Stender families' endowment (APG), the Notsew Orm Sands Foundation (JPT and APG), the National Institutes of Health (MCF), Canadian Institutes of Health Research (SMM) and Natural Sciences and Engineering Research Council of Canada EIDM-MfPH (SMM).