Convalescent Plasma The Experience And Journey From Blockbuster To Incognito: A Single Centre Experience

BACKGROUND: Convalescent plasma has been used to provide passive immunotherapy to patients with Covid-19 with a high level of safety. Very few efficacy studies were available, and due to COVID being a relatively new disease, its exact therapeutic role was unclear. This observational study on the impact of Covid convalescent plasma (CCP) on clinical outcomes attempts to evaluate the effectiveness of convalescent Covid 19 plasma therapy in the treatment of Covid 19 patients at the tertiary care center in the Uttarakhand state of India. METHODS: CCP was collected by plasmapheresis/ whole blood from willing Covid-recovered donors who underwent pre-donation testing including ABO and RhD grouping, mandatory blood screening tests for HIV, HBV, HCV, syphilis and Malaria, Haemoglobin estimation and Covid IgG assay. Hospitalized patients with severe Covid-19 pneumonia who received these CCP units were followed up and the outcome (Recovery/death) was observed. RESULTS: A total of 63 patients who received CCP were included in the study. Out of the total, 13 (20.7 %) were females and 50 (79.3 %) were males and their ages ranged from 24 to 80 years with a median age of 53 years. The period between the start of symptoms and hospitalization ranged from 1 to 14 days with an average duration of 4.7 days. Symptoms on presentation included Fever 53/63 (84.1 %), Tachypnoea 60/63 (95.2 %) and Cough 42/63 (66.7 %). Among these patients, 22/63 (34.9 %) were on non-invasive ventilation (NIV), 6/63 (9.5 %) on non-rebreather mask (NRBM) and 32/63 (50.8 %) were on Ventilator support. The infused convalescent plasma had a Mean IgG value of 57.3 AU with a range of (10-142 AU). A total of 37 (58.7 %) patients were lost to Covid-19 infection and 26 (41.3 %) were discharged from the hospital in a healthy state. CONCLUSION: The use of convalescent plasma in addition to standard treatment in our study on patients with severe pneumonia due to Covid-19 did not demonstrate reduced mortality of Covid 19 patients amidst numerous variables. The results showed that the use of convalescent plasma as a treatment option in the present conditions needs a serious re-evaluation. Studies on a strictly defined recipient group and transfusion of CCP units, with adequate antibody titer and/or neutralization activity, must be analyzed for future works.

Biochemical and HDX Mass Spectral Characterization of the SARS-CoV-2 Nsp1 Protein.

A major challenge in defining the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to better understand virally encoded multifunctional proteins and their interactions with host factors. Among the many proteins encoded by the positive-sense, single-stranded RNA genome, nonstructural protein 1 (Nsp1) stands out due to its impact on several stages of the viral replication cycle. Nsp1 is the major virulence factor that inhibits mRNA translation. Nsp1 also promotes host mRNA cleavage to modulate host and viral protein expression and to suppress host immune functions. To better define how this multifunctional protein can facilitate distinct functions, we characterize SARS-CoV-2 Nsp1 by using a combination of biophysical techniques, including light scattering, circular dichroism, hydrogen/deuterium exchange mass spectrometry (HDX-MS), and temperature-dependent HDX-MS. Our results reveal that the SARS-CoV-2 Nsp1 N- and C-terminus are unstructured in solution, and in the absence of other proteins, the C-terminus has an increased propensity to adopt a helical conformation. In addition, our data indicate that a short helix exists near the C-terminus and adjoins the region that binds the ribosome. Together, these findings provide insights into the dynamic nature of Nsp1 that impacts its functions during infection. Furthermore, our results will inform efforts to understand SARS-CoV-2 infection and antiviral development.

Intranasal administration of adenoviral vaccines expressing SARS-CoV-2 spike protein improves vaccine immunity in mouse models.

The ongoing SARS-CoV-2 pandemic is controlled but not halted by public health measures and mass vaccination strategies which have exclusively relied on intramuscular vaccines. Intranasal vaccines can prime or recruit to the respiratory epithelium mucosal immune cells capable of preventing infection. Here we report a comprehensive series of studies on this concept using various mouse models, including HLA class II-humanized transgenic strains. We found that a single intranasal (i.n.) dose of serotype-5 adenoviral vectors expressing either the receptor binding domain (Ad5-RBD) or the complete ectodomain (Ad5-S) of the SARS-CoV-2 spike protein was effective in inducing i) serum and bronchoalveolar lavage (BAL) anti-spike IgA and IgG, ii) robust SARS-CoV-2-neutralizing activity in the serum and BAL, iii) rigorous spike-directed T helper 1 cell/cytotoxic T cell immunity, and iv) protection of mice from a challenge with the SARS-CoV-2 beta variant. Intramuscular (i.m.) Ad5-RBD or Ad5-S administration did not induce serum or BAL IgA, and resulted in lower neutralizing titers in the serum. Moreover, prior immunity induced by an intramuscular mRNA vaccine could be potently enhanced and modulated towards a mucosal IgA response by an i.n. Ad5-S booster. Notably, Ad5 DNA was found in the liver or spleen after i.m. but not i.n. administration, indicating a lack of systemic spread of the vaccine vector, which has been associated with a risk of thrombotic thrombocytopenia. Unlike in otherwise genetically identical HLA-DQ6 mice, in HLA-DQ8 mice Ad5-RBD vaccine was inferior to Ad5-S, suggesting that the RBD fragment does not contain a sufficient collection of helper-T cell epitopes to constitute an optimal vaccine antigen. Our data add to previous promising preclinical results on intranasal SARS-CoV-2 vaccination and support the potential of this approach to elicit mucosal immunity for preventing transmission of SARS-CoV-2.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

An update on SARS-CoV-2 immunization and future directions.

Millions of people have died as a result of SARS-CoV-2, which was first discovered in China and has since spread globally. Patients with SARS-CoV-2 infection may show a range of symptoms, including fever, coughing, and shortness of breath, or they may show no symptoms at all. To treat COVID-19 symptoms and avoid serious infections, many medications and vaccinations have been employed. However, to entirely eradicate COVID-19 from the world, next-generation vaccine research is required because of the devastating consequences it is having for humanity and every nation's economy. Scientists are working hard to eradicate this dangerous virus across the world. SARS-CoV-2 has also undergone significant mutation, leading to distinct viral types such as the alpha, beta, gamma, delta, and omicron variants. This has sparked discussion about the effectiveness of current vaccines for the newly formed variants. A proper comparison of these vaccinations is required to compare their efficacy as the number of people immunized against SARS-CoV-2 globally increases. Population-level statistics evaluating the capacity of these vaccines to reduce infection are therefore being developed. In this paper, we analyze the many vaccines on the market in terms of their production process, price, dosage needed, and efficacy. This article also discusses the challenges of achieving herd immunity, the likelihood of reinfection, and the importance of convalescent plasma therapy in reducing infection.

Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants.

The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.

TiO2 based Photocatalysis membranes: An efficient strategy for pharmaceutical mineralization.

Among the various emerging contaminants, pharmaceuticals (PhACs) seem to have adverse effects on the quality of water. Even the smallest concentration of PhACs in ground water and drinking water is harmful to humans and aquatic species. Among all the deaths reported due to COVID-19, the mortality rate was higher for those patients who consumed antibiotics. Consequently, PhAC in water is a serious concern and their removal needs immediate attention. This study has focused on the PhACs' degradation by collaborating photocatalysis with membrane filtration. TiO2-based photocatalytic membrane is an innovative strategy which demonstrates mineralization of PhACs as a safer option. To highlight the same, an emphasis on the preparation and reinforcing properties of TiO2-based nanomembranes has been elaborated in this review. Further, mineralization of antibiotics or cytostatic compounds and their degradation mechanisms is also highlighted using TiO2 assisted membrane photocatalysis. Experimental reactor configurations have been discussed for commercial implementation of photoreactors for PhAC degradation anchored photocatalytic nanomembranes. Challenges and future perspectives are emphasized in order to design a nanomembrane based prototype in future for wastewater management.

Serologic Surveillance for SARS-CoV-2 Infection among Wild Rodents, Europe.

We report results from serologic surveillance for exposure to SARS-CoV-2 among 1,237 wild rodents and small mammals across Europe. All samples were negative, with the possible exception of 1. Despite suspected potential for human-to-rodent spillover, no evidence of widespread SARS-CoV-2 circulation in rodent populations has been reported to date.Esitämme tulokset serologisesta tutkimuksesta, jossa seulottiin SARS-CoV-2 tartuntojen varalta 1,237 luonnonvaraista jyrsijää ja piennisäkästä eri puolilta Eurooppaa. Kaikki näytteet olivat negatiivisia, yhtä näytettä lukuun ottamatta. SARS-CoV-2:n läikkymisen ihmisistä jyrsijöihin on arveltu olevan mahdollista, mutta todisteet viruksen laajamittaisesta leviämisestä jyrsijäpopulaatioissa puuttuvat.

Wild Red Deer (Cervus elaphus) Do Not Play a Role as Vectors or Reservoirs of SARS-CoV-2 in North-Eastern Poland.

Several studies reported a high prevalence of SARS-CoV-2 among white-tailed deer in North America. Monitoring cervids in all regions to better understand SARS-CoV-2 infection and circulation in other deer populations has been urged. To evaluate deer exposure and/or infection to/by SARS-CoV-2 in Poland, we sampled 90 red deer shot by hunters in five hunting districts in north-eastern Poland. Serum and nasopharyngeal swabs were collected, and then an immunofluorescent assay (IFA) to detect anti-SARS-CoV-2 antibodies was performed as well as real-time PCR with reverse transcription for direct virus detection. No positive samples were detected. There is no evidence of spillover of SARS-CoV-2 from the human to deer population in Poland.

Omicron variant: Current insights and future directions.

The global COVID-19 outbreak has returned with the identification of the SARS-CoV-2 Omicron variant (B.1.1.529) after appearing to be persistently spreading for the more than past two years. In comparison to prior SARS-CoV-2 variants, this new variant revealed a significant amount of mutation. This novel variety may have a greater rate of transmissibility which might impede the effectiveness of current diagnostic equipment as well as vaccination efficacy and also impede immunotherapies (Antibody / monoclonal antibody based). WHO designated B.1.1.529 as a variant of concern on November 26, 2021, identified as Omicron. The Omicron variant transmission method and severity, on the other hand, are well defined. The global spread of Omicron, which has now seized many nations, has resulted in numerous speculations regarding its origin and degree of infectivity. The following sections will go over its potential for transmission, omicron structure, and impact on COVID-19 vaccines, how it is different from delta variant and diagnostics.

ClusTRace, a bioinformatic pipeline for analyzing clusters in virus phylogenies.

BACKGROUND: SARS-CoV-2 is the highly transmissible etiologic agent of coronavirus disease 2019 (COVID-19) and has become a global scientific and public health challenge since December 2019. Several new variants of SARS-CoV-2 have emerged globally raising concern about prevention and treatment of COVID-19. Early detection and in-depth analysis of the emerging variants allowing pre-emptive alert and mitigation efforts are thus of paramount importance. RESULTS: Here we present ClusTRace, a novel bioinformatic pipeline for a fast and scalable analysis of sequence clusters or clades in large viral phylogenies. ClusTRace offers several high-level functionalities including lineage assignment, outlier filtering, aligning, phylogenetic tree reconstruction, cluster extraction, variant calling, visualization and reporting. ClusTRace was developed as an aid for COVID-19 transmission chain tracing in Finland with the main emphasis on fast screening of phylogenies for markers of super-spreading events and other features of concern, such as high rates of cluster growth and/or accumulation of novel mutations. CONCLUSIONS: ClusTRace provides an effective interface that can significantly cut down learning and operating costs related to complex bioinformatic analysis of large viral sequence sets and phylogenies. All code is freely available from https://bitbucket.org/plyusnin/clustrace/.

The phylodynamics of SARS-CoV-2 during 2020 in Finland.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections and fatalities globally since its emergence in late 2019. The virus was first detected in Finland in January 2020, after which it rapidly spread among the populace in spring. However, compared to other European nations, Finland has had a low incidence of SARS-CoV-2. To gain insight into the origins and turnover of SARS-CoV-2 lineages circulating in Finland in 2020, we investigated the phylogeographic and -dynamic history of the virus. Methods: The origins of SARS-CoV-2 introductions were inferred via Travel-aware Bayesian time-measured phylogeographic analyses. Sequences for the analyses included virus genomes belonging to the B.1 lineage and with the D614G mutation from countries of likely origin, which were determined utilizing Google mobility data. We collected all available sequences from spring and fall peaks to study lineage dynamics. Results: We observed rapid turnover among Finnish lineages during this period. Clade 20C became the most prevalent among sequenced cases and was replaced by other strains in fall 2020. Bayesian phylogeographic reconstructions suggested 42 independent introductions into Finland during spring 2020, mainly from Italy, Austria, and Spain. Conclusions: A single introduction from Spain might have seeded one-third of cases in Finland during spring in 2020. The investigations of the original introductions of SARS-CoV-2 to Finland during the early stages of the pandemic and of the subsequent lineage dynamics could be utilized to assess the role of transboundary movements and the effects of early intervention and public health measures.

Clinical Characteristics of 100 Patients With COVID-19-Associated Mucormycosis From a Tertiary Care Center in North India.

Background Fungal infection in patients with coronavirus disease 2019 (COVID-19) has emerged as a new challenge in healthcare facilities. This study aimed to describe the demographic and clinical characteristics of COVID-19-associated mucormycosis (CAM). Methodology This retrospective, single-center case series included patients who were hospitalized and diagnosed with COVID-19 and mucormycosis at the All India Institute of Medical Sciences, Rishikesh (North India) from April 15, 2021, onwards and last followed up on June 30, 2021. Demographic, clinical, laboratory, radiological, microbiological, pathological, and outcome data were then collected and analyzed. Results Of the 100 consecutive inpatients with CAM, 95 (95%) had diabetes mellitus. At the onset of illness, the most common manifestations were facial swelling (85%), eye swelling (83%), headache (68%), pain around the eyeball (67%), malaise (57%), and fever (50%). The most common organ involved on examination was the nose and paranasal sinus (96%), followed by the orbit (83%), palate (19%), and cranial nerves (7%). Pulmonary involvement was seldom observed (1%). Predominant pathological findings were the presence of aseptate hyphae (75%), necrosis (75%), angioinvasion (36%), and perineural invasion (2.6%). During the last follow-up, 13 patients died, with 11 (84.6%) having severe COVID-19 and two (15.3%) having moderate COVID-19. Conclusions Steroid use and diabetes mellitus are the significant risk factors of CAM. Patients with CAM usually present with face/eye swelling with radiological involvement of the nose and sinus and may die because of severe COVID-19.

Experimental Infection of Mink with SARS-COV-2 Omicron Variant and Subsequent Clinical Disease.

We report an experimental infection of American mink with SARS-CoV-2 Omicron variant and show that mink remain positive for viral RNA for days, experience clinical signs and histopathologic changes, and transmit the virus to uninfected recipients. Preparedness is crucial to avoid spread among mink and spillover to human populations.

Introduction and rapid spread of SARS-CoV-2 Omicron variant and the dynamics of its sub-lineages BA.1 and BA.1.1, December 2021, Finland (preprint)

Multiple introductions of SARS-COV-2 Omicron variant BA.1. and BA.1.1. lineages to Finland were detected early December 2021, and comprised the majority over Delta variant in 3 weeks in the capital region. Our sequence analysis demonstrates emergence of a large cluster of BA.1.1 in community transmission.

Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages, Finland, December 2021.

Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.

Zoonotic spill-over of SARS-CoV-2: mink-adapted virus in humans.

OBJECTIVES: This work aimed to analyse possible zoonotic spill-over of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the spill-over of mink-adapted SARS-CoV-2 from farmed mink to humans after adaptation that lasted at least 3 months. METHODS: Next-generation sequencing and a bioinformatic approach were applied to analyse the data. RESULTS: In an isolate obtained from an asymptomatic patient testing positive for SARS-CoV-2, we found four distinguishing mutations in the S gene that gave rise to the mink-adapted variant (G75V, M177T, Y453F, and C1247F) and others. CONCLUSIONS: Zoonotic spill-over of SARS-CoV-2 can occur from mink to human.

Surgical Diseases Management during COVID-19 Crisis at a Tertiary Care Hospital of India: Our Institutional Strategy.

Introduction In response to the national coronavirus disease 2019 (COVID-19) pandemic, all hospitals and medical institutes gave priority to COVID-19 screening and to the management of patients who required hospitalization for COVID-19 infection. Surgical departments postponed all elective operative procedures and provided only essential surgical care to patients who presented with acute surgical conditions or suspected malignancy. Ample literature has emerged during this pandemic regarding the guidelines for safe surgical care. We report our experience during the lockdown period including the surgical procedures performed, the perioperative care provided, and the specific precautions implemented in response to the COVID-19 crisis. Materials and Methods We extracted patient clinical data from the medical records of all surgical patients admitted to our tertiary care hospital between the March 24th, 2020 and May 31st, 2020. Data collected included: patient demographics, surgical diagnoses, surgical procedures, nonoperative management, and patient outcomes. Results Seventy-seven patients were included in this report: 23 patients were managed medically, 28 patients underwent a radiologic intervention, and 23 patients required an operative procedure. In total eight of the 77 patients died due to ongoing sepsis, multiorgan failure, or advanced malignancy. Conclusion During the COVID-19 lockdown period, our surgical team performed many lifesaving surgical procedures and appropriately selected cancer operations. We implemented and standardized essential perioperative measures to reduce the spread of COVID-19 infection. When the lockdown measures were phased out a large number of patients remained in need of delayed elective and semi-elective operative treatment. Hospitals, medical institutes, and surgical leadership must adjust their priorities, foster stewardship of limited surgical care resources, and rapidly implement effective strategies to assure perioperative safety for both patients and operating room staff during periods of crisis.

Determinants of COVID-19 Vaccination Willingness among Health Care Workers: A Quick Online Survey in India.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused a large number of deaths along with severe socio-economic effects. The vaccine is considered to be the last hope to control viral transmission. This study aimed to explore the determinants of health care workers' (HCWs) willingness to take the COVID-19 vaccination. METHODS: A structured, pre-validated, and pre-tested questionnaire was administered online to 599 HCWs including physicians, residents, and nurses from different types of healthcare set-ups across India. Information was collected regarding vaccine acceptability, attitude toward vaccination, and reasons for hesitancy. The chi-square test, followed by multinomial regression analysis, was applied to determine the factors associated with HCWs' vaccination willingness. RESULTS: It was found that 73 % (n=437) of HCWs were willing to accept the vaccines, while 10.85% (n=65) refused and 16.2% (n=96) needed more time to decide. Gender (P<0.001), occupation (P=0.040), working as front-line workers (P=0.008), vaccine manufacturing country preferences (P<0.001), and perceived risk of catching COVID-19 in the next 6 months (P=0.005) had a significant association with intent to receive vaccination (the response were "yes" vs. "no" and "not sure"). The reasons for vaccine hesitancy were vaccine safety and efficacy concerns, antivaccine attitude and beliefs, personal choice, and not wanting to take a vaccine before others. CONCLUSION: The majority of HCWs agreed to take COVID-19 vaccines once available. Nevertheless, providing support to manage evolving vaccine environments will help change the perception of HCWs who refuse or are reluctant to take the vaccines.