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Coronavirus disease 2019 (COVID‐19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID‐19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID‐19 patients that were collected within 24 h of patient admission (baseline, n = 80) and after hospital discharge at day‐90 post‐admission (n = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high‐sensitivity nano flow cytometry. In patients recovered from COVID‐19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day‐90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID‐19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil‐to‐lymphocyte ratio and for granulocyte/macrophage‐released CD66b+/CD68+‐cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID‐19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre‐infection levels at 90 days post‐infection in recovered patients discriminate parental cells affected by disease. [ABSTRACT FROM AUTHOR]

Objective: Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear. Methods: Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed. Results: The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205-24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05). Conclusion: Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID. [ABSTRACT FROM AUTHOR]

Abstract Coronavirus disease 2019 (COVID‐19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID‐19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID‐19 patients that were collected within 24 h of patient admission (baseline, n = 80) and after hospital discharge at day‐90 post‐admission (n = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high‐sensitivity nano flow cytometry. In patients recovered from COVID‐19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day‐90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID‐19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil‐to‐lymphocyte ratio and for granulocyte/macrophage‐released CD66b+/CD68+‐cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID‐19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre‐infection levels at 90 days post‐infection in recovered patients discriminate parental cells affected by disease.

Fumihiro Yamaguchi,1 Ayako Suzuki,2 Miyuki Hashiguchi,3 Emiko Kondo,3 Atsuo Maeda,4 Takuya Yokoe,1 Jun Sasaki,4 Yusuke Shikama,1 Munetaka Hayashi,4 Sei Kobayashi,5 Hiroshi Suzuki6 1Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan; 2Department of Pharmacy, Showa University Fujigaoka Hospital, Yokohama, Japan; 3Department of Infection Control, Showa University Fujigaoka Hospital, Yokohama, Japan; 4Department of Emergency and Critical Care Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan; 5Department of Otolaryngology, Showa University Fujigaoka Hospital, Yokohama, Japan; 6Department of Cardiology, Showa University Fujigaoka Hospital, Yokohama, JapanCorrespondence: Fumihiro Yamaguchi, Department of Respiratory Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501, Japan, Email f_y@med.showa-u.ac.jpBackground: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), immediately became a pandemic. Therefore, nosocomial infection control is necessary to screen for patients with possible COVID-19.Objective: This study aimed to investigate commonly measured clinical variables to predict COVID-19.Methods: This cross-sectional study enrolled 1087 patients in the isolation ward of a university hospital. Conferences were organized to differentiate COVID-19 from non-COVID-19 cases, and multiple nucleic acid tests were mandatory when COVID-19 could not be excluded. Multivariate logistic regression models were employed to determine the clinical factors associated with COVID-19 at the time of hospitalization.Results: Overall, 352 (32.4%) patients were diagnosed with COVID-19. The majority of the non-COVID-19 cases were predominantly caused by bacterial infections. Multivariate analysis indicated that COVID-19 was significantly associated with age, sex, body mass index, lactate dehydrogenase, C-reactive protein, and malignancy.Conclusion: Some clinical factors are useful to predict patients with COVID-19 among those with symptoms similar to COVID-19. This study suggests that at least two real-time reverse-transcription polymerase chain reactions of SARS-CoV-2 are recommended to exclude COVID-19.Keywords: severe acute respiratory syndrome coronavirus-2, coronavirus disease 2019, nosocomial infection control, nucleic acid test, obesity, cross sectional study, Japan

The waves of the Coronavirus Disease 2019 (COVID-19) pandemic have disrupted healthcare systems globally, with a staggering number of confirmed cases reaching 593 million and a death toll of six million. While the primary target organ of COVID-19 is the lungs, the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) also shows a preference for the intestinal epithelium, which expresses Angiotensin Converting Enzyme 2 (ACE2), a receptor necessary for viral entry into host cells. The composition and abundance of beneficial gut microbiota play a critical role in protecting against severe disease and complications, whereas dysbiosis contribute to systemic inflammation and immune imbalances during SARS-CoV-2 infection. Recent insights into the microbiome have emphasised the importance of the gut-lung axis and the microenvironments of the gut and lungs in the context of COVID-19. These findings offer opportunities for the development of new diagnostic and therapeutic strategies. In this review, the significance of the gut-lung axis, as well as the intestinal and pulmonary microbiota, in COVID-19, were explored with a particular focus on their potential applications.

BackgroundIn COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.MethodsAdults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615.FindingsBy day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference -0·5% [95% CI -9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase-quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti-SARS-CoV-2 antibodies at day 60.InterpretationThere was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments.FundingF. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

The waves of the Coronavirus Disease 2019 (COVID-19) pandemic have disrupted healthcare systems globally, with a staggering number of confirmed cases reaching 593 million and a death toll of six million. While the primary target organ of COVID-19 is the lungs, the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) also shows a preference for the intestinal epithelium, which expresses Angiotensin Converting Enzyme 2 (ACE2), a receptor necessary for viral entry into host cells. The composition and abundance of beneficial gut microbiota play a critical role in protecting against severe disease and complications, whereas dysbiosis contribute to systemic inflammation and immune imbalances during SARS-CoV-2 infection. Recent insights into the microbiome have emphasised the importance of the gut-lung axis and the microenvironments of the gut and lungs in the context of COVID-19. These findings offer opportunities for the development of new diagnostic and therapeutic strategies. In this review, the significance of the gut-lung axis, as well as the intestinal and pulmonary microbiota, in COVID-19, were explored with a particular focus on their potential applications. [ABSTRACT FROM AUTHOR]

ObjectiveHuman identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promoted the coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA) via NamiRNA-enhancer network, based on previous experimental research. This study aimed to investigate the predictive value of HA for the severity of SARS-CoV-2 infection in the post-COVID-19 era.MethodsA total of 217 consecutive patients with COVID-19 were enrolled at Beijing Ditan Hospital between July 2023 and October 2023. HA levels were analyzed using biochemical detector. Logistic regression analysis was used to screen independent factors for severe COVID-19. The predictive performance of HA for severe infection was assessed by ROC curve. Furthermore, the relationship between HA levels and COVID-19 severity was investigated using multivariate logistic regression models after adjustment for potential confounders.ResultsAccording to the cut-off value of HA, COVID-19 patients were divided into HA < 90 ng/mL group (80 cases) and HA ≥ 90 ng/mL group (137 cases). High HA levels were positively associated with the severe SARS-CoV-2 infection, including elevated inflammatory indicators, severe lung involvement, prolonged clinical course, and higher incidence of respiratory failure and death (P < 0.05). Logistic regression analysis suggested that HA was an independent predictor of severe COVID-19 (OR = 4.540, 95% CI = 2.105-9.790, P < 0.001). ROC curve analysis showed that the AUC of HA for severe infection was 0.724. HA levels were significantly higher in COVID-19 cases compared to the healthy population (123.9 (82.6, 174.1) vs. 50.5 (37.8, 66.8), P < 0.001), but similar to those with non-SARS-CoV-2 lung infection (121.6 (78.5, 175.6) vs. 106.0 (66.5, 149.7), P = 0.244). We also found that the first COVID-19 infections had higher HA levels (118.8 (79.5, 174.3) vs. 85.0 (61.1, 128.8), P < 0.001) and a higher proportion of severe infection (37.1% vs. 21.3%, P = 0.043) than re-infections. However, HA expression failed to fully return to normal levels with infection recovery (204.7 (152.9, 242.2) vs. 97.0 (69.3, 137.3), P < 0.001).ConclusionHA was associated with severe SARS-CoV-2 infection and could be used as a novel serum biomarker to predict the risk of COVID-19 progression in the post-COVID-19 era.

This review was focused on global data analysis and risk factors associated with morbidity and mortality of coronavirus disease 2019 from different countries, including Bangladesh, Brazil, China, Central Eastern Europe, Egypt, India, Iran, Pakistan, and South Asia, Africa, Turkey and UAE. Male showed higher confirmed and death cases compared to females in most of the countries. In addition, the case fatality ratio (CFR) for males was higher than for females. This gender variation in COVID-19 cases may be due to males cultural activities, but similar variations in the number of COVID-19 affected males and females globally. Variations in the immune system can illustrate this divergent risk comparatively higher in males than females. The female immune system may have an edge to detect pathogens slightly earlier. In addition, women show comparatively higher innate and adaptive immune responses than men, which might be explained by the high density of immune-related genes in the X chromosome. Furthermore, SARS-CoV-2 viruses use angiotensin-converting enzyme 2 (ACE2) to enter the host cell, and men contain higher ACE2 than females. Therefore, males may be more vulnerable to COVID-19 than females. In addition, smoking habit also makes men susceptible to COVID-19. Considering the age-wise distribution, children and older adults were less infected than other age groups and the death rate. On the contrary, more death in the older group may be associated with less immune system function. In addition, most of these group have comorbidities like diabetes, high pressure, low lungs and kidney function, and other chronic diseases. Due to the substantial economic losses and the numerous infected people and deaths, research examining the features of the COVID-19 epidemic is essential to gain insight into mitigating its impact in the future and preparedness for any future epidemics.

Introduction: Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients. Material and methods: All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia. Conclusions: Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients. [ABSTRACT FROM AUTHOR]

This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Part I), alleviating clinical symptoms or severity of disease (Part II), and decreasing the incidence of SARS-CoV-2 infection (Part III). Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) with restrictions were searched up to 3rd March 2023. Twenty-three studies (22 RCTs and one NRCT) met the inclusion criteria for this systematic review. Five RCTs (454 patients and nine interventions) in Part I were eligible for NMA. The NMA results showed that, in comparison with no rinse, sodium chloride (NaCl) was the most effective mouth rinse for reducing the viral load, followed by povidone-iodine (PVP-I), ß-cyclodextrin + citrox (CDCM), hydrogen peroxide (HP), chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), placebo and hypochlorous acid (HClO). However, these results were not significant. Based on surface under the cumulative ranking curve scores, PVP-I was likely to be the most efficacious mouth rinse for reducing SARS-CoV-2 viral load, followed by CDCM, HP, NaCl, CHX, CPC, placebo, no rinse and HClO. Due to heterogeneity of the primary studies, the effectiveness of different mouth rinses to reduce viral infectivity, improve clinical symptoms or prevent SARS-CoV-2 infection remains inconclusive. [ABSTRACT FROM AUTHOR]

Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease. Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report. Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16–0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11–5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07–74.61, p = 0.043) were more likely to prolong the time from infection to recovery. Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: We aimed to characterize the course of COVID-19 in autoimmune inflammatory rheumatic disease (AIIRD) patients in Israel, taking into consideration several remarkable aspects, including the outcomes of the different outbreaks, the effect of vaccination campaigns, and AIIRD activity post-recovery. Methods: We established a national registry of AIIRD patients diagnosed with COVID-19, including demographic data, AIIRD diagnosis, duration and systemic involvement, comorbidities, date of COVID-19 diagnosis, clinical course, and dates of vaccinations. COVID-19 was diagnosed by a positive SARS-CoV-2 polymerase chain reaction. Results: Israel experienced 4 outbreaks of COVID-19 until 30.11.2021. The first three outbreaks (1.3.2020 - 30.4.2021) comprised 298 AIIRD patients. 64.9% had a mild disease and 24.2% had a severe course; 161 (53.3%) patients were hospitalized, 27 (8.9%) died. The 4th outbreak (delta variant), starting 6 months after the beginning of the vaccination campaign comprised 110 patients. Despite similar demographic and clinical characteristics, a smaller proportion of AIIRD patients had negative outcomes as compared to the first 3 outbreaks, with regards to severity (16 patients, 14.5%), hospitalization (29 patients, 26.4%) and death (7 patients, 6.4%). COVID-19 did not seem to influence the AIIRD activity 1-3 months post-recovery. Conclusions: COVID-19 is more severe and has an increased mortality in active AIIRD patients with systemic involvement, older age and comorbidities. Vaccination with 3 doses of the mRNA vaccine against SARS-CoV-2 protected from severe COVID-19, hospitalization and death during the 4th outbreak. The pattern of spread of COVID-19 in AIIRD patients was similar to the general population. [ABSTRACT FROM AUTHOR]

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants associated with the adaptive evolution of the virus is prolonging the global coronavirus disease 2019 (COVID-19) pandemic. The modification of neutralizing antibodies based on structural information is expected to be a useful approach to rapidly combat emerging variants. A dimerized variable domain of heavy chain of heavy chain antibody (VHH) P17 that has highly potent neutralizing activity against SARS-CoV-2 has been reported but the mode of interaction with the epitope remains unclear. Here, we report the X-ray crystal structure of the complex of monomerized P17 bound to the SARS-CoV-2 receptor binding domain (RBD) and investigated the binding activity of P17 toward various variants of concern (VOCs) using kinetics measurements. The structure revealed details of the binding interface and showed that P17 had an appropriate linker length to have an avidity effect and recognize a wide range of RBD orientations. Furthermore, we identified mutations in known VOCs that decrease the binding affinity of P17 and proposed methods for the acquisition of affinity toward the Omicron RBD because Omicron is currently the most predominant VOC. This study provides information for the rational design of effective VHHs for emerging VOCs. [ABSTRACT FROM AUTHOR]

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes.

Introduction Coronavirus disease 2019 (COVID-19), a global public health emergency, has brought life to an unprecedented near-standstill. So many respiratory viruses including the new pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can be attributed to influenza-like illnesses (ILIs). The differentiation of different respiratory viruses based on symptoms and clinical examination is very difficult without testing for a specific virus. All ILI patients should undergo COVID-19 testing as per WHO revised strategies and Indian Medical Council Research guidelines. Objectives To assess the prevalence of SARS-CoV-2 infection in patients with ILIs during the present pandemic. Patients and methods A prospective study was conducted in a dedicated COVID-19 hospital, Bengaluru. All ILI patients visiting the Victoria Hospital underwent nasopharyngeal and oropharyngeal swab collection and were tested for SARS-CoV-2 as per the Indian Medical Council Research-approved protocol. Results In all, 12 062 patients attended the fever clinic in Victoria Hospital attached to Bangalore Medical College and Research Institute. Out of them, 1167 (12.67%) patients presented with ILI. Of the studied patients, 873 (78%) patients were under 50 years. Male patients constituted 67.09% of the study population. In the present study, 337 (30.55%) of the patients with ILI tested positive to SARS-CoV-2 antigen. Nearly 2/3rd of SARS-CoV-2-positive ILI patients were males and below 50 years. The positive rate of SARS-CoV-2 was higher in the noncontainment zone than the containment zones of ILI patients although statistically not significant (P=0.09). Conclusion Thirty percent of ILI patients were SARS-CoV-2 positive. Majority of SARS-CoV-2 positive tested ILI patients were men under the age of 50 years.

The new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) brings about the coronavirus disease 2019 (COVID-19) pandemic. It is a pathogen that causes extreme respiratory tract infection, especially as the world's populations had no previous immunity and there were little or no uniformly acceptable treatment options. The virus may persist to bring about considerable morbidity and mortality except an efficient vaccine is produced. Following erstwhile evidence and experience with SARS and Middle East respiratory syndrome, the major focus to vaccine development was the spike glycoprotein, regarded as the most important target for SARS-CoV-2 immunotherapies. Collaborative efforts were undertaken to ensure that manufacturing occurred as quickly as possible to salvage the situation. Three vaccine candidates were respectively made of one protein-based vaccine, a simian-derived adenovirus vector, and one messenger RNA vaccine. Two of them published their short-term analyses and effective results after their third trial phase. The messenger RNA vaccine was first confirmed in the USA and the adenovirus-derived vaccine in the UK. This paper gives a narrative review of the literature on the present knowledge about this new virus as it concerns the drawn-up plans of COVID-19 vaccines that are not only effective but safe following the new and established approaches to vaccine development.

The coronavirus disease 2019 (COVID-19) results from the infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and primarily affects the respiratory tissue. Since first reported from Wuhan, China in December 2019, the virus has resulted in an unprecedented pandemic. Vaccination against SARS-CoV-2 can control the further spread of the ongoing pandemic by making people immunised to SARS-CoV-2. Several vaccines have been approved for use in clinics, a lot many are in different stages of development. Diligent interpretations from the preclinical evaluation are crucial to identify the most effective and safest vaccine candidates. Multiple vaccine candidates/variants have been tested in small animal models with relative ease and further in non-human primate models before being taken into clinical development. Here, we review the state-of-the-art strategies employed for a thorough preclinical evaluation of COVID-19 vaccine candidates. We summarise the methods in place to identify indicators which make the vaccine candidate effective in controlling SARS-CoV-2 infection and/or COVID-19 and are safe for administration as inferred by their (1) biophysical/functional attributes (antigen expression, organization, functionality, and stability); (2) immunogenicity in animal models and protective correlates [SARS-CoV-2 specific binding/neutralising immunoglobulin titer, B/T-cell profiling, balanced T-helper type-1 (Th1) or type-2 (Th2) response (Th1:Th2), and anamnestic response]; (3) protective correlates as interpreted by controlled pathology of the respiratory tissue (pulmonary clinical and immunopathology); and finally, (4) strategies to monitor adverse effects of the vaccine candidates.

Introduction: Coronavirus Disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is ravaging the globe due to its rapid spread. Since providing fast results is of critical importance in a time of shortage of medical personnel and beds in isolation wards and to ensure timely treatment for patients, developing high quality rapid Point of Care (POC) diagnostics is essential. Aim: To compare the diagnostic performance of chip based real time Reverse Trancriptase Polymerase Chain Reaction (RTPCR) (TrueNat) which has a shorter turnaround time compared to conventional real time RT-PCR in samples of suspected COVID-19 patients. Materials and Methods: The present cross-sectional observational study was carried out in a tertiary care hospital in New Delhi, India. Five hundred randomly selected Oropharyngeal (OP) swabs samples received from May-July 2020, were included in the study to compare the diagnostic performance of chip based real time RTPCR (TrueNat) with conventional real time RT-PCR for diagnosis of SARS-CoV-2 infection. All statistical analysis was performed using STATA version 16.1 software (College station, Texas, USA). Results: The sensitivity of TrueNat test was 100% while the specificity was found to be 99.12% at 95% confidence intervals. The positive predictive value was 91.84% and the negative predictive value was 100%. Conclusion: The short turnaround time, good sensitivity and specificity makes TrueNat a reliable and affordable option to provide rapid results in cases requiring urgent interventions and to augment SARS-CoV-2 testing capacity at peripheral settings where sample load is less.

Introduction: In December 2019, a rapid spread of highly infectious, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was reported in Wuhan, China. The gold standard for diagnosis of SARS-CoV-2 infection is nucleic acid amplification technology by detecting its viral Ribonucleic Acid (RNA) from respiratory swabs (oropharyngeal and nasopharyngeal) by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) whose specificity is approximately 95%. Magnetic bead RNA extraction was benchmarked against the commercial QIAcube extraction platform. Aim: To compare the efficacy of nucleic acid extraction by manual method and automated magnetic bead-based method to detect SARS-CoV-2. Materials and Methods: The present cross-sectional observational study was conducted in the Department of Microbiology, Autonomous State Medical College, Firozabad, Uttar Pradesh, India. Duration of the study was from February 2022 to March 2022. A total of 470 oropharyngeal and nasopharyngeal samples were included in the present study to observe the efficacy of nucleic acid extraction by manual extraction and automated extraction for SARS-CoV-2. Data were entered in Microsoft Excel software and analysed using Statistical Package for the Social Sciences (SPSS) version 26.0. Results: During the present study period, a total of 470 individual samples were tested in 94 pools. Out of these 470 individuals, 331 were males (70.5%) and 139 were females (29.5%). All 94 pools were found negative by both automatic and manual extraction methods. Envelope (E) gene was found in one pool (1.06%) by the manual RNA extraction method. The E gene was absent in 93 pools (98.94%) by manual method. Internal control was found highest in 88 pools (93.62%) by the automated extraction method. Conclusion: Automated workflows avoid human error from the sample processing pipeline and also ensure as well as enhance the meaningful output, diagnostic precision, and testing capacity. Automated instruments are in wide usage because of their capability of processing thousands of samples per day with the support of minimal staff.

(1) Objective: We aimed to analyze and describe the management of acute biliary pancreatitis (ABP) during the coronavirus disease 2019 (COVID-19) pandemic. (2) Methods: This was a retrospective cohort study among patients with ABP during a control period (16 March 2019 to 15 March 2020; period 1) and a COVID-19 period (16 March 2020 to 15 March 2021; period 2). (3) Results: We included 89 patients with ABP, being 58 in period 1 and 31 in period 2. The mean patient age was 62.75 ± 16.59 years, and 51 (57.3%) patients were women. The Quick Sequential Organ Failure Assessment score for sepsis and World Society of Emergency Surgery Sepsis Severity Score were significantly higher among patients in period 2. Twenty-two patients (37.9%) in period 1 and six (19.3%) in period 2 underwent cholecystectomy. There were no significant differences in surgical interventions between the two periods. The hospital mortality rate was 3.4 and 19.3% in period 1 and period 2, respectively. Mortality was significantly higher in period 2. Conclusion: During the COVID-19 pandemic, we observed a significant reduction in the number of patients with ABP but increased severity and mortality. Multicenter studies with more patients are needed to obtain additional evidence regarding ABP management during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The current pandemic caused by the coronavirus disease 2019 (COVID-19) continues affecting millions of people worldwide. Various cardiovascular manifestations have been associated with COVID-19 but only a few case reports of Brugada syndrome in acute respiratory syndrome by SARS-CoV-2 were published. The diagnosis, prognosis, and treatment remain a challenge and represent a concern in terms of management in this population. We describe a case of a 66-year-old patient with COVID-19 presenting a coved type-1 Brugada pattern in electrocardiogram. Drug challenge was performed for the diagnosis of Brugada syndrome and electrophysiological study for risk stratification. < Learning objective: Brugada pattern can be unmasked during coronavirus disease 2019 (COVID-19) infection, regardless of fever. Supportive care and avoidance of drugs that may induce Brugada pattern and ventricular arrhythmias can prevent clinical complications in Brugada patients with COVID-19. In asymptomatic patients with suspected Brugada syndrome and a family history of sudden cardiac death, the correct diagnosis and risk stratification may be performed.> [ABSTRACT FROM AUTHOR]

Summary: Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference –0·5% [95% CI –9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase–quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti–SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

Abstract Introduction Increasing evidence indicate that coronavirus disease 2019 (COVID-19) is companied by renal dysfunction. However, the association of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced renal dysfunction with prognosis remains obscure. Materials and methods All 154 patients with COVID-19 were recruited from the Second People’s Hospital of Fuyang City in Anhui, China. Demographic characteristics and laboratory data were extracted. Renal dysfunction was evaluated and its prognosis was followed up based on a retrospective cohort study. Results There were 125 (81.2%) mild and 29 (18.8%) severe cases in 154 COVID-19 patients. On admission, 16 (10.4%) subjects were accompanied with renal dysfunction. Serum creatinine and cystatin C were increased and estimated glomerular filtration rate (eGFR) was decreased in severe patients compared with those in mild patients. Renal dysfunction was more prevalent in severe patients. Using multivariate logistic regression, we found that male gender, older age and hypertension were three importantly independent risk factors for renal dysfunction in COVID-19 patients. Follow-up study found that at least one renal function marker of 3.33% patients remained abnormal in 2 weeks after discharge. Conclusion Male elderly COVID-19 patients with hypertension elevates the risk of renal dysfunction. SARS-CoV-2-induced renal dysfunction are not fully recovered in 2 weeks after discharge.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has imposed an unprecedented burden on our healthcare system. Serological testing for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies serves as an useful marker for determining an infection by the virus in the recent past and the immune response. The immune response, including the humoral response to the infection is one of them and the knowledge in this area is still evolving. Virus specific antibodies are expected to help in eliminating the virus and to provide protective immunity against reinfection. Aim: To serially monitor the total antibody response to SARSCoV-2 in order to gain better insight into the duration of antibody persistence. Materials and Methods: This prospective observational study was conducted in 66 Healthcare Workers (HCW) with a history of Reverse Transcription-Polymerase Chain Reaction (RTPCR) proven COVID-19 infection. The study was conducted between May 2020 to April 2021 at the Suburban diagnostics Central Processing Laboratory, Mumbai, Maharashtra, India. Serum samples were serially examined for the presence of total antibodies against the Nucleocapsid (N) protein of SARS-CoV-2 upto 180 days postinfection. A further follow-up examination was done at 360 days. A qualitative Electrochemiluminescence Immunoassay (ECLIA) assay was used for assessment of the antibody response. The chi-square or Fisher-exact test was used to compare categorical variables and the Mann-Whitney U test, Kruskal Wallis test and student t-test were used to compare continuous variables across groups. For assessing relationship between variables, the Pearson test or linear regression were used as appropriate. Results: Out of 66 healthcare workers, 32 were male (48.5%) and 34 were females (51.5%) with the median age of 29.5 years. Out of 66 cases, 62 (94%) cases developed antibodies against SARS-CoV-2 at different time intervals, 48 cases during the 14-30 day interval, 10 cases during the 31-60 day interval, three cases during the 61-90 day interval and one case during the 90-120 days interval. Thirty one out of 35 (88%) cases that could be followed-up at 360 days showed persistence of antibodies. No patient reported symptoms which would warrant a repeat RT-PCR test. Conclusion: This study showed that the antibody response to SARS-CoV-2 virus was sustained for 12 months postinfection in most cases. The absence of fresh infection in these cases during the study period suggests that the antibodies might protect against reinfection with the virus. So, it may be safe to defer vaccination in postinfection cases by 6-9 months thereby saving precious resources. [ABSTRACT FROM AUTHOR]

Summary: The red blood cell distribution width (RDW), an indicator of anisocytosis has emerged as a potential tool for risk stratification of critically ill patients with sepsis. Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in this ongoing context of the Coronavirus Disease 2019 (COVID‐19) pandemic. The current systematic review and meta‐analysis aims to explore the utility of RDW in the prognosis of COVID‐19 patients. A comprehensive screening of electronic databases was performed up to 30th April 2021 after enrolling in PROSPERO (CRD42020206685). Observational studies or interventional studies, evaluating the impact of RDW in COVID‐19 outcomes (mortality and severity) are included in this meta‐analysis.Our search retrieved 25 studies, with a total of 18,392 and 3,446 COVID‐19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher RDW levels on admission in comparison to survivors and non‐severe patients (SMD = 0.46; 95%CI 0.31–0.71; I2 = 88% and SMD = 0.46; 95%CI 0.26–0.67; I2 = 60%, respectively). In a sub‐group analysis of 2,980 patients, RDW > 14.5 has been associated with increased risk of mortality (OR = 2.73; 95%CI 1.96–3.82; I2 = 56%). However, the evidences is of low quality. A higher level of RDW on admission in COVID‐19 patients is associated with increased morbidity and mortality. However, further studies regarding the cut‐off value of RDW are the need of the hour. [ABSTRACT FROM AUTHOR]

The importance of donor anonymity is recognized by numerous organizations, and is crucial for maintenance of the relationship between volunteer blood donors and blood transfusion services, and to prevent stigma and discrimination of the blood donor. Unfortunately, in the USA we have recently begun to encounter patients refusing blood based solely on the COVID-19 vaccination status or COVID-19 infection history of the blood donor. Refusing blood transfusions from COVID-19-vaccinated donors: are we repeating history? These same patients, some of whom are likely to imminently require blood, have refused to consent to transfusion unless they can be assured that the blood donor did not receive a COVID-19 vaccine, regardless of the risk of morbidity and mortality. [Extracted from the article]

Abstract Purpose Acute macular neuroretinopathy (AMN) is a visual-deteriorating rare clinical entity with an uncertain etiology. We aimed to report a case of AMN and underlying disease of acute myeloid leukemia (AML). Case presentation A thirty-five-year-old female patient with bone marrow biopsy confirmed AML, and bicytopenia, under chemotherapy, complained of sudden paracentral visual field defect in her right eye was referred. Visual acuity was 20/20 in both eyes. Posterior segment evaluation revealed multiple Roth’s spots. Optical coherence tomography (OCT) demonstrated hyper-reflectivity band, in the outer nuclear layer and outer plexiform layer, nasal to the fovea of the right eye, and hyperreflective patch in outer retina segmentation en-face OCT, suggestive of the diagnosis of AMN. Nine days after AMN diagnosis, dyspnea, malaise, and cough was initiated. Ground glass opacities in lung CT scan, beside reverse transcription polymerase chain reaction of severe acute respiratory syndrome coronavirus-2, was conclusive of coronavirus disease 2019 (COVID-19). The patient deceased after 6 days. Conclusion We report a rare case of AMN following AML. Our findings support the role of ischemia in the outer retina, of which AML may contributed to the pathophysiological process. The patient has deceased less than 2 weeks from AMN initiation.

COVID-19 pneumonia is a serious health issue in the current pandemic caused by SARS-CoV-2. PCR testing is limited due to a number of factors and imaging has role in decision-making for many of these patients. We present computed tomography chest images of patients hospitalized with suspicion of COVID-19 pneumonia and point out the common and uncommon features on imaging to assist management of these patients.

Novel coronavirus (nCoV) first emerged in Hubei province of China in December 2019. The virus initially known as 2019-nCoV was renamed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The associated disease is known as coronavirus disease 2019 (COVID-19). As the COVID-19 pandemic has unfolded, interest has grown in antibody testing as a way to measure how far the infection has spread and to identify individuals who may be immune. Molecular diagnostic tests like polymerase chain reaction are developed rapidly, however they are not able to fulfill all the requirements of an epidemic reaction. Hence, to complement molecular diagnostic tests, serology tests emerged as a vital aspect of the overall response by confirming the presence of antibodies during the early stage of the infection. Antibody tests help in assessing herd immunity, data about the ongoing phase of infection, identifying potential donors for convalescent plasma therapy, etc. This review currently focuses on giving an overview about the antibody tests in SARS-CoV-2 infections.

PURPOSE: Severe acute respiratory syndrome coronavirus2 (SARSCoV2) can affect eyes in various forms. Furthermore, ocular surface can act as potential port of entry and ocular secretions as possible route of transmission of SARSCoV2. The aims of the study are to identify ocular manifestation in confirmed coronavirus disease 2019 (COVID19) patients and to evaluate conjunctival secretions as the possible route of transmission of this disease. MATERIALS AND METHODS: A prospective, populationbased, observational study was done. Ocular symptoms and signs of every hospitalized patient with SARSCoV2 infection between September 15, 2020, and November 15, 2020, were recorded. Tear samples of the first 60 participants (30 each of patients with severe and moderate illness, can be removed) with ocular manifestations were selected for real-time polymerase chain reaction (RTPCR). Data were analyzed using the Statistical Package for the Social Science Software (SPSS) program, version 23. When comparing mean values, ttest was used otherwise Chisquare test. RESULTS: Out of 804 admitted patients during study period, 309 (38.4%) patients were identified with ocular manifestations, out of which 78% (241) had conjunctival hyperemia, 65.6% (203) had follicular reaction in palpebral conjunctiva, 58% (180) had chemosis, and 58% (99) had discharge and 18.4% (57) complained of burning in their eyes. Mean duration from systemic manifestation to onset of ocular symptoms was 4.52 ± 1.47 days while 8 patients (1%) had conjunctivitis as the presenting symptom. SARSCoV2 was detected in 18.3% patients (11 out of 60) using RTPCR. CONCLUSION: The presence of SARSCoV2 in ocular secretions of patients with ocular manifestations suggests that COVID19infected patients with ocular manifestations should wear protective glasses to prevent secretions contamination to healthy persons.

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic has imposed an unprecedented burden on our healthcare system. Serological testing for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies serves as useful marker for determining an infection by the virus in the recent past and the immune response. The immune response, including the humoral response to the infection is one of them and the knowledge in this area is still evolving. Virus specific antibodies are expected to help in eliminating the virus and to provide protective immunity against reinfection. Aim: To serially monitor the total antibody response to SARS-CoV-2 in order to gain better insight into the duration of antibody persistence. Materials and Methods: This prospective observational and analytical study was conducted in 66 Healthcare Workers (HCW) with a history of Reverse Transcription-Polymerase Chain Reaction (RT-PCR) proven COVID-19 infection. The study was conducted between May 2020 to April 2021 at the Suburban diagnostics Central Processing Laboratory, Mumbai, Maharashtra, India. Serum samples were serially examined for the presence of total antibodies against the Nucleocapsid (N) protein of SARS-CoV-2 upto 180 days postinfection. A further follow-up examination was done at 360 days. A qualitative Electrochemiluminescence Immunoassay (ECLIA) was used for assessment of the antibody response. The Chi-square or Fisher-exact test was used to compare categorical variables and the Mann-Whitney U test, Kruskal Wallis test and student t-test were used to compare continuous variables across groups. For assessing relationship between variables, the Pearson test or Linear regression were used as appropriate. Results: Out of 66 healthcare workers, 32 were male (48.5%) and 34 were females (51.5%) with the median age of 29.5 years. Out of 66 cases, 62 (94%) cases developed antibodies against SARS-CoV-2 at different time intervals, 48 cases during the 14-30 day interval, 10 cases during the 31-60 day interval, three cases during the 61-90 day interval and one case during the 90-120 days interval. Out of 35, 31 (88.6%) subjects could be followed-up at 360 days showed persistence of antibodies. No patient reported symptoms which would warrant a repeat RT-PCR test. Conclusion: This study showed that the antibody response to SARS-CoV-2 virus was sustained for 12 months postinfection in most cases. The absence of fresh infection in these cases during the study period suggests that the antibodies might protect against reinfection with the virus. So, it may be safe to defer vaccination in postinfection cases by 6-9 months thereby saving precious resources.

Background: Repeated re-positive of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) B.1.617.2 (Delta) variants of concern (VOC) in recovered coronavirus disease 2019 (COVID-19) patients have not been reported yet. Methods: We reported a rare case of repeated COVID-19 relapse during the post-discharge surveillance. Results: This case had long-term viral shedding for 79 days. Conclusions: This case highlights that longer observation and isolation periods need be considered for patients with SARS-CoV-2 delta VOC infection. [ABSTRACT FROM AUTHOR]

Introduction: In December 2019, a rapid spread of highly infectious, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was reported in Wuhan, China. The gold standard for diagnosis of SARS-CoV-2 infection is nucleic acid amplification technology by detecting its viral Ribonucleic Acid (RNA) from respiratory swabs (oropharyngeal and nasopharyngeal) by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) whose specificity is approximately 95%. Magnetic bead RNA extraction was benchmarked against the commercial QIAcube extraction platform. Aim: To compare the efficacy of nucleic acid extraction by manual method and automated magnetic bead-based method to detect SARS-CoV-2. Materials and Methods: The present cross-sectional observational study was conducted in the Department of Microbiology, Autonomous State Medical College, Firozabad, Uttar Pradesh, India. Duration of the study was from February 2022 to March 2022. A total of 470 oropharyngeal and nasopharyngeal samples were included in the present study to observe the efficacy of nucleic acid extraction by manual extraction and automated extraction for SARS-CoV-2. Data were entered in Microsoft Excel software and analysed using Statistical Package for the Social Sciences (SPSS) version 26.0. Results: During the present study period, a total of 470 individual samples were tested in 94 pools. Out of these 470 individuals, 331 were males (70.5%) and 139 were females (29.5%). All 94 pools were found negative by both automatic and manual extraction methods. Envelope (E) gene was found in one pool (1.06%) by the manual RNA extraction method. The E gene was absent in 93 pools (98.94%) by manual method. Internal control was found highest in 88 pools (93.62%) by the automated extraction method. Conclusion: Automated workflows avoid human error from the sample processing pipeline and also ensure as well as enhance the meaningful output, diagnostic precision, and testing capacity. Automated instruments are in wide usage because of their capability of processing thousands of samples per day with the support of minimal staff. [ABSTRACT FROM AUTHOR]

Summary: Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and lower seroconversion rates following coronavirus disease 2019 (COVID‐19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS‐CoV‐2 in non‐vaccinated patients with MM and COVID‐19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration‐approved enzyme‐linked immunosorbent assay methodology. Thirty‐five patients with COVID‐19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID‐19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6–94%) and 58·7% (21·4–91·8%) for COVID‐19‐positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID‐19‐positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID‐19 should be considered for booster vaccine doses. [ABSTRACT FROM AUTHOR]

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 has been declared a worldwide pandemic by the WHO. Within various multi-organ involvements, several ocular manifestations have been described. We report the case of a patient diagnosed with COVID-19 who presented with a progressive increase of bilateral cotton wool spots over a 1-week period, despite quick and complete recovery of systemic signs of the disease and no ocular symptoms. We followed the evolution of such lesions over a 3-month period. Here, we underline the importance of retinal screening even if no ocular symptom is reported. Furthermore, we demonstrate the essential role of fundus examination as a reflection of systemic vascular changes. [ABSTRACT FROM AUTHOR]

Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in the ongoing context of the COVID-19 pandemic. The platelet-to-lymphocyte count ratio (PLR), has emerged as a potential tool for risk stratification of critically ill patients with sepsis. The current systematic review explores the utility of PLR as a prognostic predictor of COVID-19 patients. We screened the electronic databases until May 15, 2021 after enrolling in PROSPERO (CRD42021220269). Studies evaluating the association between PLR on admission and outcomes in terms of mortality and severity among COVID-19 patients were included. We retrieved 32 studies, with a total of 2768 and 3262 COVID-19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher PLR levels on admission in comparison to survivors and non-severe patients (mean differences [MD] = 66.10; 95% confidence interval [CI]: 47.75-84.44; p < 0.00001 and MD = 86.74; 95% CI: 67.7-105.7; p < 0.00001, respectively). A higher level of PLR on admission in COVID-19 patients is associated with increased morbidity and mortality. However, the evidence is of low quality and further studies regarding the cut-off value of PLR are the need of the hour. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus Disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is ravaging the globe due to its rapid spread. Since providing fast results is of critical importance in a time of shortage of medical personnel and beds in isolation wards and to ensure timely treatment for patients, developing high quality rapid Point of Care (POC) diagnostics is essential. Aim: To compare the diagnostic performance of chip based real time Reverse Trancriptase Polymerase Chain Reaction (RTPCR) (TrueNat) which has a shorter turnaround time compared to conventional real time RT-PCR in samples of suspected COVID-19 patients. Materials and Methods: The present cross-sectional observational study was carried out in a tertiary care hospital in New Delhi, India. Five hundred randomly selected Oropharyngeal (OP) swabs samples received from May-July 2020, were included in the study to compare the diagnostic performance of chip based real time RTPCR (TrueNat) with conventional real time RT-PCR for diagnosis of SARS-CoV-2 infection. All statistical analysis was performed using STATA version 16.1 software (College station, Texas, USA). Results: The sensitivity of TrueNat test was 100% while the specificity was found to be 99.12% at 95% confidence intervals. The positive predictive value was 91.84% and the negative predictive value was 100%. Conclusion: The short turnaround time, good sensitivity and specificity makes TrueNat a reliable and affordable option to provide rapid results in cases requiring urgent interventions and to augment SARS-CoV-2 testing capacity at peripheral settings where sample load is less. [ABSTRACT FROM AUTHOR]

Introduction Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients. Material and methods All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient’s prognosis was followed up. Results On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia. Conclusions Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients.

In December 2019, China reported several cases of a new coronavirus disease (COVID-19). The COVID-19 outbreak, which was initially limited to Wuhan, China, has rapidly spread worldwide. Infection of the disease occurs through exposure to the virus through inhalation of respiratory droplets or if a person touches a mucosal surface after touching an object with the virus on it. The common symptoms of COVID-19 are fever, dry cough, dyspnea (difficult or labored breathing), fatigue, chest pain, and myalgia (muscle pain), etc. Real-time polymerase chain reaction is used to detect the virus in sputum, throat, nasal swabs, and secretion of lower respiratory samples. Early diagnosis, isolation, and supportive care are necessary for the treatment of the patients. The present review aims to provide recent information on COVID-19 related to its epidemiology, clinical symptoms, and management. This article also summarizes the current understanding of severe acute respiratory syndrome coronavirus-2 and its history of origin.

The coronavirus disease 2019 (COVID-19) outbreak was declared a pandemic on March 11, 2020. Several dental care facilities in affected countries have been completely closed or have been only providing minimal treatment for emergency cases. However, several facilities in some affected countries are still providing regular dental treatment. This can, in part, be a result of the lack of universal protocol or guidelines regulating the dental care provision during such a pandemic. This lack of guidelines can, on the one hand, increase the nosocomial COVID-19 spread through dental health care facilities, and on the other hand, deprive patients' in need of the required urgent dental care. Moreover, ceasing dental care provision during such a period will incense the burden on hospital emergency departments already struggle with the pandemic. This review article is aimed to develop guidelines for dental patients' management during and after the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the respiratory coronavirus disease 2019 (COVID-19). Coronaviruses are a large family of enveloped, positive-sense, single-stranded RNA viruses, which infect a broad range of vertebrate animals. The SARS-CoV-2 is spread primarily between people through close contact and through respiratory droplets produced from coughs or sneezes by the infected individuals. After entering into the human body, it enters human cells by binding to the angiotensin-converting enzyme 2 receptors, prominently present in lung, kidney, and gastrointestinal tract. Older people and people of all ages with severe chronic medical conditions such as diabetes, lung disease, and heart disease seem to be at higher risk of developing serious COVID-19 illness. There have been four pandemics caused by the emergence of new influenza viruses in the past century such as H1N1 Spanish flu (1918), H2N2 Asian flu (1957), the H3N2 Hong Kong flu (1968), and the H1N1 Swine flu (2009). Community interventions are important response strategies that can reduce the impact of disease. Widespread transmission of the virus could translate the situation into large numbers of people needing medical care at the same time. Better understanding of the complexity and dynamics of influenza pandemics reduces the further risk effect of such critical situations. Global efforts in tackling the virus at this time are focused all together on lessening the spread and impact of this virus.

Fulminant type 1 diabetes (FT1D) is a subtype of type 1 diabetes (T1D) that is characterized by the rapid progression to diabetic ketoacidosis against the background of rapid and almost complete pancreatic islet destruction. The HbA1c level at FT1D onset remains normal or slightly elevated despite marked hyperglycemia, reflecting the rapid clinical course of the disease, and is an important marker for diagnosis. FT1D often appears following flu-like symptoms, and there are many reports of its onset being linked to viral infections. In addition, disease-susceptibility genes have been identified in FT1D, suggesting the involvement of host factors in disease development. In most cases, islet-related autoantibodies are not detected, and histology of pancreatic tissue reveals macrophage and T cell infiltration of the islets in the early stages of FT1D, suggesting that islet destruction occurs via an immune response different from that occurring in autoimmune type 1 diabetes. From 2019, coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread worldwide and became a serious problem. Reports on the association between SARS-CoV-2 and T1D are mixed, with some suggesting an increase in T1D incidence due to the COVID-19 pandemic. When discussing the association between COVID-19 and T1D, it is also necessary to focus on FT1D. However, it is not easy to diagnose this subtype without understanding the concept. Therefore, authors hereby review the concept and the latest findings of FT1D, hoping that the association between COVID-19 and T1D will be adequately evaluated in the future.

A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis. [ABSTRACT FROM AUTHOR]

PURPOSE: Severe acute respiratory syndrome coronavirus2 (SARSCoV2) can affect eyes in various forms. Furthermore, ocular surface can act as potential port of entry and ocular secretions as possible route of transmission of SARSCoV2. The aims of the study are to identify ocular manifestation in confirmed coronavirus disease 2019 (COVID19) patients and to evaluate conjunctival secretions as the possible route of transmission of this disease. MATERIALS AND METHODS: A prospective, populationbased, observational study was done. Ocular symptoms and signs of every hospitalized patient with SARSCoV2 infection between September 15, 2020, and November 15, 2020, were recorded. Tear samples of the first 60 participants (30 each of patients with severe and moderate illness, can be removed) with ocular manifestations were selected for real-time polymerase chain reaction (RTPCR). Data were analyzed using the Statistical Package for the Social Science Software (SPSS) program, version 23. When comparing mean values, ttest was used otherwise Chisquare test. RESULTS: Out of 804 admitted patients during study period, 309 (38.4%) patients were identified with ocular manifestations, out of which 78% (241) had conjunctival hyperemia, 65.6% (203) had follicular reaction in palpebral conjunctiva, 58% (180) had chemosis, and 58% (99) had discharge and 18.4% (57) complained of burning in their eyes. Mean duration from systemic manifestation to onset of ocular symptoms was 4.52 ± 1.47 days while 8 patients (1%) had conjunctivitis as the presenting symptom. SARSCoV2 was detected in 18.3% patients (11 out of 60) using RTPCR. CONCLUSION: The presence of SARSCoV2 in ocular secretions of patients with ocular manifestations suggests that COVID19infected patients with ocular manifestations should wear protective glasses to prevent secretions contamination to healthy persons. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of ICU surge on mortality and to explore clinical and sociodemographic predictors of mortality.Design: Retrospective cohort analysis.Setting: NYC Health + Hospitals ICUs.Patients: Adult ICU patients with coronavirus disease 2019 admitted between March 24, and May 12, 2020.Interventions: None.Measurements and Main Results: Hospitals reported surge levels daily. Uni- and multivariable analyses were conducted to assess factors impacting in-hospital mortality. Mortality in Hispanic patients was higher for high/very high surge compared with low/medium surge (69.6% vs 56.4%; p = 0.0011). Patients 65 years old and older had similar mortality across surge levels. Mortality decreased from high/very high surge to low/medium surge in, patients 18-44 years old and 45-64 (18-44 yr: 46.4% vs 27.3%; p = 0.0017 and 45-64 yr: 64.9% vs 53.2%; p = 0.002), and for medium, high, and very high poverty neighborhoods (medium: 69.5% vs 60.7%; p = 0.019 and high: 71.2% vs 59.7%; p = 0.0078 and very high: 66.6% vs 50.7%; p = 0.0003). In the multivariable model high surge (high/very high vs low/medium odds ratio, 1.4; 95% CI, 1.2-1.8), race/ethnicity (Black vs White odds ratio, 1.5; 95% CI, 1.1-2.0 and Asian vs White odds ratio 1.5; 95% CI, 1.0-2.3; other vs White odds ratio 1.5, 95% CI, 1.0-2.3), age (45-64 vs 18-44 odds ratio, 2.0; 95% CI, 1.6-2.5 and 65-74 vs 18-44 odds ratio, 5.1; 95% CI, 3.3-8.0 and 75+ vs 18-44 odds ratio, 6.8; 95% CI, 4.7-10.1), payer type (uninsured vs commercial/other odds ratio, 1.7; 95% CI, 1.2-2.3; medicaid vs commercial/other odds ratio, 1.3; 95% CI, 1.1-1.5), neighborhood poverty (medium vs low odds ratio 1.6, 95% CI, 1.0-2.4 and high vs low odds ratio, 1.8; 95% CI, 1.3-2.5), comorbidities (diabetes odds ratio, 1.6; 95% CI, 1.2-2.0 and asthma odds ratio, 1.4; 95% CI, 1.1-1.8 and heart disease odds ratio, 2.5; 95% CI, 2.0-3.3), and interventions (mechanical ventilation odds ratio, 8.8; 95% CI, 6.1-12.9 and dialysis odds ratio, 3.0; 95% CI, 1.9-4.7) were significant predictors for mortality.Conclusions: Patients admitted to ICUs with higher surge scores were at greater risk of death. Impact of surge levels on mortality varied across sociodemographic groups. [ABSTRACT FROM AUTHOR]

A continual rise in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease (COVID-19) has become a global threat. The main problem comes when SARS-CoV-2 gets mutated with the rising infection and becomes more lethal for humankind than ever. Mutations in the structural proteins of SARS-CoV-2, i.e., the spike surface glycoprotein (S), envelope (E), membrane (M) and nucleocapsid (N), and replication machinery enzymes, i.e., main protease (Mpro) and RNA-dependent RNA polymerase (RdRp) creating more complexities towards pathogenesis and the available COVID-19 therapeutic strategies. This study analyzes how a minimal variation in these enzymes, especially in S protein at the genomic/proteomic level, affects pathogenesis. The structural variations are discussed in light of the failure of small molecule development in COVID-19 therapeutic strategies. We have performed in-depth sequence- and structure-based analyses of these proteins to get deeper insights into the mechanism of pathogenesis, structure-function relationships, and development of modern therapeutic approaches. Structural and functional consequences of the selected mutations on these proteins and their association with SARS-CoV-2 virulency and human health are discussed in detail in the light of our comparative genomics analysis.

Introduction: Lockdown imposed due to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused by coronavirus led to disruption of all aspects of life across the world with serious consequences in delivering of routine surgical services to the patients. Anaesthesiologists and surgeons in the study Institute devised clinical assessment based protocols for preanaesthesia assessment {not including routine preoperative Coronavirus Disease 2019 (COVID-19) Testing} to ensure timely conduct of elective surgeries as soon as patients started reporting to hospital. Aim: To evaluate the efficacy of various measures taken by anaesthesiologists and operation theatre team to impart surgical care during COVID-19 pandemic without increasing the risk of transmission of COVID-19 disease. Materials and Methods: A retrospective observational study was carried out with the idea of comparing the surgical workload of year 2020 (January to December 2020) with the previous year 2019 (January to December 2019). The study was conducted in the month of March 2021, in a 627-bedded secondary care multispeciality hospital in northern India. The data on total number of patients undergoing surgeries in year 2020 was compared with that of year 2019 on the basis of elective surgeries, emergency surgeries and different modalities of anaesthesia used to conduct all those surgeries. These variables from both the years were compared using chi-square tests and Statistical Package for Social Sciences (SPSS) trial version 23.0. Results: The total numbers of surgeries had reduced in year 2020 (3923 in 2019 vs 2500 in 2020) with highest reduction in the months of April and May 2020 (83.08 and 74.75%, respectively). However, with implementation of clinical assessment based protocols and targeted changes in anaesthesia practice, the decrease in elective surgeries came to statistically non significant levels by the month of September 2020. The difference in percentage of cases carried out under regional anaesthesia (4.23% in 2019 vs 3.24% in 2020) was statistically not significant (p-value=0.051). The emergency surgeries in 2019 were 805 vs 742 in 2020, percentage change from 2019 base data was -7.83. The incidence of COVID-19 infection during postoperative period was nil in the Institute. The incidence of COVID-19 infection among the staff was found to be similar to the patients reported to the hospital despite of handling elective surgical cases. Conclusion: Regular surgical care can be safely provided after thorough clinical assessment of the patients in this ongoing pandemic. This did not lead to increase in incidence of COVID19 infection in healthcare workers as shown in our data. Hence, preoperative COVID-19 testing should be performed only when indicated by clinical history and examination. However, more studies with multiple centres are required to validate these protocols and hence facilitate the formation of even more refined ones.

Purpose: Herein, we report a case of bilateral neuroretinitis and panuveitis in a patient recovered from coronavirus disease 2019 (COVID-19). Case presentation: A 37-year-old male patient with a history of recovered COVID-19, which was confirmed with nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), about one-month ago was referred with one-week history of bilateral severe vision loss. Visual acuity was counting fingers, and bilateral retinitis and panuveitis were revealed in ocular examination. The result of the vitreous sample using RT-PCR was positive for SARS-CoV-2 and negative for Herpesviridae viruses and mycobacterium tuberculosis. The patient was successfully treated with corticosteroid. Conclusion: We report a case of bilateral neuroretinitis and panuveitisin a recovered COVID-19 patient and positive RT-PCR of the vitreous sample. It is suggested to apply intraocular sampling and evaluation for COVID-19 in patients with the new-onset of uveitis and/or retinitis during the pandemic. [ABSTRACT FROM AUTHOR]

Nucleic acid detection is a necessary part of medical treatment and fieldwork. However, the current detection technologies are far from ideal. A lack of timely and accessible testing for identifying cases and close contacts has allowed severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), the causative virus of the ongoing coronavirus disease‐2019 (COVID‐19) pandemic, to spread uncontrollably. The slow and expensive detection of mutations—predictors for chronic diseases such as cancer—form a barrier to personalized treatment. A recently developed diagnostic assay is ideal and field‐ready—it relies on CRISPR‐Cas13. CRISPR‐Cas13 works similarly to other CRISPR systems: Cas13 is guided by a crRNA to cleave next to a specific RNA target sequence. Additionally, Cas13 boasts a unique collateral cleavage activity; collateral cleavage of a fluorescent reporter detects the presence of the target sequence in sample RNA. This system forms the basis of CRISPR‐Cas13 diagnostic assays. CRISPR‐Cas13 assays have >95% sensitivity and >99% specificity. Detection is rapid (<2 h), inexpensive ($0.05 per test), and portable—a test using lateral flow strips is akin to a pregnancy test. The recent adaptation of micro‐well chips facilitates high‐level multiplexing and is high‐throughput. In this review, we cover the development of CRISPR‐Cas13 assays for medical diagnosis, discuss the advantages of CRISPR‐Cas13‐based diagnosis over the traditional reverse transcription polymerase chain reaction (RT‐PCR), and present examples of detection from real patient samples. Highlights: In the CRISPR‐Cas13 system, Cas13 is guided by a crRNA to cleave sample RNA at a specific target sequence.Cas13 has collateral cleavage activity that when used with a fluorescent reporter detects a specific target sequence.CRISPR‐Cas13‐based diagnostics are highly sensitive (>95%), specific (>99%), rapid (<2 h), inexpensive ($0.05 per test), and portable‐recent adaptions of micro‐well chips facilitate high‐evel multiplexing and are high‐throughput.CRISPR‐Cas13‐based diagnostics have been validated in the detection of viral RNA and mutations in patient samples, including SARS‐CoV‐2 RNA during the ongoing COVID‐19 pandemic.CRISPR‐Cas13 is also applied to RNA editing, thereby creating a full system of diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]