COVID-19 mitigation behaviors and policies limited SARS-CoV-2 transmission in the United States from September 2020 through November 2021 (preprint)

United States jurisdictions implemented varied policies to slow SARS-CoV-2 transmission. Understanding patterns of these policies alongside individuals behaviors can inform effective outbreak response. To do so, we estimated the time-varying reproduction number (Rt), a weekly measure of real-time transmission using US COVID-19 cases from September 2020-November 2021. We then assessed the association between Rt and policies, personal COVID-19 mitigation behaviors, variants, immunity, and social vulnerability indicators using two multi-level regression models. First, we fit a model with state-level policy stringency according to the Oxford Stringency Index, a composite indicator reflecting the strictness of COVID-19 policies and strength of pandemic-related communication. Our second model included a subset of specific policies. We found that personal mitigation behaviors and vaccination were more strongly associated with decreased transmission than policies. Importantly, transmission was reduced not by a single measure, but by various layered measures. These results underscore the need for policy, behavior change, and risk communication integration to reduce virus transmission during epidemics.

"Effect of COVID-19 Vaccination on Menstrual Cycle Patterns of Reproductive-Age Women: A Multi-centric Observational Study."

AIM: The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns and pre- and post-menstrual symptoms in women aged 18-45 years. BACKGROUND: COVID-19 vaccination was introduced to combat the dreadful impacts of human coronavirus infection. The two indigenously developed COVID-19 vaccines approved for use in India are COVISHILED and COVAXIN. OBJECTIVES: To investigate the effects of COVID-19 vaccination on the menstrual cycle, pre- and post-menstrual symptoms and to establish the correlation with the type of vaccine received. METHODS: Multi-centric observational study conducted in six institutes of national importance in different states of India over one year. A total of 5709 female participants fulfilling inclusion criteria were enrolled. Data about the impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on the menstrual cycle and its associated symptoms were obtained using all participants' online and offline interviews. RESULTS: Of 5709 participants, 78.2% received COVISHIELD and 21.8% COVAXIN. Of the total 5709 participants, 333(5.8%) developed post-vaccination menstrual disturbances, with 32.7% having frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleeding. A total of 301 participants noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of the menstrual cycle (p=0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to the COVISHIELD (5.3%) group. A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in the COVISHIELD group (p=0.031), with generalized weakness and body pains as the main complaints (p=0.001). No significant difference was observed in the incidence of COVID-19 infection with these vaccines. No significant associations were observed when comparing menstrual abnormalities among those with COVID-19 infection (p>0.05). CONCLUSIONS: COVISHILED and COVAXIN vaccines were associated with menstrual cycle disturbances and pre-and post-menstrual symptoms in a small proportion of participants, with 94.7% having no change in the amount of bleeding during menstruation post-vaccination. The menstrual irregularities observed were significantly higher with the COVAXIN vaccine. Others: Further, long-term studies are required to confirm that the impact of COVID-19 vaccination on the menstrual cycle may be short-lasting, with no severe effects on women's menstrual health.

A snapshot of socio-demographics and utilization of maternal health services by pregnant women living in urban slum settings in India: A baseline data representation (preprint)

Utilization of maternal health care services significantly influences maternal mortality rate. Although several studies are looking into demographic and socioeconomic factors and inequality in distribution and proper utilization of these services between rural and urban communities, there is a paucity of studies focusing on urban slums. This cross-sectional survey aims to examine the trends and determinants of utilization of maternal healthcare services during antenatal period in urban slums including assessment of fertility, family planning practices, dietary practices, quality of health, and impact of COVID on pregnancy, which was conducted in four urban slums of South Delhi, between April and June 2022 amongst pregnant women (aged 18-44 years). Data were collected from 250 currently pregnant women visiting the Anganwadi centers. The detailed methodology was adopted from the published study protocol. The data was collected electronically using SOMAARTH (developed by The INCLEN Trust International – IN) on an android-based platform, and the tools adopted from National Family Health Survey-5. The results revealed that out of 250 women, 98% were less than 40 years of age, and 169 (67%) were less than 28 years of age. About 93% of the sample population were educated and 234 (93%) were homemakers while the remaining engaged in various occupations. Of the 250 women, 54% had borne children, and 82% of them had a single child. While all the respondents knew about antenatal services, only 2.8% had a high level and the majority (78%) had a medium level of knowledge. Only 47% of women had exposure to media while 51% adopted some form of family planning practices. Of all the women who received antenatal care (ANC), 98%, 97%, and 94% had received iron and folic acid, tetanus toxoid, and ultrasound examination, respectively during the present pregnancy. Only 2 (15.4%) women had COVID exposure during pregnancy. This preliminary study indicates that exposure to media and adoption of family planning continues to be low. However, a majority knew ANC, and all had accessed the ANC services. Therefore, comprehensive strategies need to be planned to ameliorate women’s education and awareness about the importance of ANC and postnatal care. Also, public health infrastructure needs to be strengthened to improve the utilization of maternal services.

Challenges of COVID-19 Case Forecasting in the US, 2020-2021 (preprint)

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naive baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making. Author SummaryAs SARS-CoV-2 began to spread throughout the world in early 2020, modelers played a critical role in predicting how the epidemic could take shape. Short-term forecasts of epidemic outcomes (for example, infections, cases, hospitalizations, or deaths) provided useful information to support pandemic planning, resource allocation, and intervention. Yet, infectious disease forecasting is still a nascent science, and the reliability of different types of forecasts is unclear. We retrospectively evaluated COVID-19 case forecasts, which were often unreliable. For example, forecasts did not anticipate the speed of increase in cases in early winter 2020. This analysis provides insights on specific problems that could be addressed in future research to improve forecasts and their use. Identifying the strengths and weaknesses of forecasts is critical to improving forecasting for current and future public health responses.

Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response.

Understanding the molecular features of neutralizing epitopes is important for developing vaccines/therapeutics against emerging SARS-CoV-2 variants. We describe three monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during the first wave of the pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, poorly neutralized Beta, and failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these mAbs in complex with trimeric spike protein showed that all three mAbs bivalently bind spike with two mAbs targeting class 1 and one targeting a class 4 receptor binding domain epitope. The immunogenetic makeup, structure, and function of these mAbs revealed specific molecular interactions associated with the potent multi-variant binding/neutralization efficacy. This knowledge shows how mutational combinations can affect the binding or neutralization of an antibody, which in turn relates to the efficacy of immune responses to emerging SARS-CoV-2 escape variants.

COVID-19: Challenges, Preventive Measures and Remediation

This review highlights origin, symptoms, diagnosis, causative agents, mode of transmission and persistence of coronavirus disease (COVID-19) through human activities. In the current scenario researchers, doctors and scientists are striving to combat the transmission of COVID-19 among society. Origin and growth of pandemic has raised the serious concern to address the causative agents, mode of transmission, persistence, preventive measures, diagnosis and possibilities of treatment. The broad-spectrum antiviral antiphrastic, complementary and alternative medicines are currently proposed for possible eradication of the pandemic. The current world is relying on, prevention and control of infection through sanitization and quarantine and onwards waiting for appropriate virucidal agents, sanitizers and strategic vaccination and immunization to combat the pandemic of SARS-CoV-2. Eradication of COVID-19 under stringent guidelines of WHO regarding social practices, intensive care, administration of complementary medicines and innovation of vaccines are under active considerations across the world to combat the pandemic.

Microorganisms in Pathogenesis and Management of Guillain-Barré Syndrome (GBS)

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system encompassing clinically heterogenous group of diseases such as acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and others. Genetic aetiology of GBS remains unknown till today but in most cases is often triggered by a preceding microbial infection or vaccine in few instances. Recent studies have suggested an association of GBS with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections;however, the underlying mechanism remains undetermined. Massive vaccination drives carried out in the world for COVID-19 disease have also raised few concerns on the overall risk-benefit ratio regarding the development of GBS following vaccination. Molecular mimicry is the most commonly accepted immunopathogenic mechanism in GBS for infections including SARS-CoV-2;however, they do not explain all the cases. Impairment in the gut-brain axis due to altered gut microbiota has been linked to various neurological disorders, and with the close connection of immune system with gut microbiome, the development of GBS following gastrointestinal infections can be explained. This can facilitate the development of microbiome-targeted therapies such as prebiotics and probiotics together with immunotherapy for GBS management. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Using real-time data to guide decision-making during an influenza pandemic: A modelling analysis.

Influenza pandemics typically occur in multiple waves of infection, often associated with initial emergence of a novel virus, followed (in temperate regions) by a resurgence accompanying the onset of the annual influenza season. Here, we examined whether data collected from an initial pandemic wave could be informative, for the need to implement non-pharmaceutical measures in any resurgent wave. Drawing from the 2009 H1N1 pandemic in 10 states in the USA, we calibrated simple mathematical models of influenza transmission dynamics to data for laboratory confirmed hospitalisations during the initial 'spring' wave. We then projected pandemic outcomes (cumulative hospitalisations) during the fall wave, and compared these projections with data. Model results showed reasonable agreement for all states that reported a substantial number of cases in the spring wave. Using this model we propose a probabilistic decision framework that can be used to determine the need for preemptive measures such as postponing school openings, in advance of a fall wave. This work illustrates how model-based evidence synthesis, in real-time during an early pandemic wave, could be used to inform timely decisions for pandemic response.

Epidemiology, Risk Factors, Diagnosis and Treatment of Mucormycosis (Black Fungus): A Review.

The COVID-19 pandemic has shown an adverse effect worldwide, but in India, it has been observed during the second wave that people who recovered from COVID-19 infection developed a secondary infection because it grows in tandem with COVID-19 treatment. Meanwhile, news of a new deadly fungus has surfaced known as Mucormycosis (Black fungus). Mucormycosis is a fungal infection that invades the blood vessels and is caused by Mucormycetes, a group of fungi. Due to the post-pandemic effect of COVID-19 many fungal and bacterial diseases have affected the population. The reason behind the frequent development of opportunistic infections like mucormycosis is the use of steroids, oxygen masks, and antibiotics throughout the treatment of critically and severely ill patients with COVID-19. Inhaling filamentous fungi from the natural environment and a lack of supportive care units can be a risk factor for mucormycosis. It is usually found in people who are immunocompromised. Mucormycosis is more common in people with HIV/AIDS, COVID-19, congenital bone marrow disease, viral diseases, malignancies, severe burns, and irregularly or untreated and treated diabetes. This review emphasizes triggers that may precipitate mucormycosis related to corticosteroids, recent epidemiology, and incidence of mucormycosis. The infection was diagnosed and identified using a variety of cutting-edge medical techniques, including clinical diagnosis, histopathology, and serology. Many treatment methods, such as antifungal medications and therapies, have also been successfully used. The mortality rate, however, remains high due to an aggressive surgical excision or debridement and lack of early diagnosis.

Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple epitopes (preprint)

Development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. Current strategies for developing pan-coronavirus countermeasures have largely focused on the receptor binding domain (RBD) and S2 regions of the coronavirus Spike protein; it has been unclear whether the N-terminal domain (NTD) is a viable target for universal vaccines and broadly neutralizing antibodies (Abs). Additionally, many RBD-targeting Abs have proven susceptible to viral escape. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees using multiplexed panels of uniquely barcoded antigens in a high-throughput single cell workflow to isolate over 9,000 SARS-CoV-2-specific monoclonal Abs (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. We observed many instances of clonal coalescence between individuals, suggesting that Ab responses frequently converge independently on similar genetic solutions. Among the recovered antibodies was TXG-0078, a public neutralizing mAb that binds the NTD supersite region of the coronavirus Spike protein and recognizes a diverse collection of alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy chain-dominant binding pattern seen in other NTD supersite-specific neutralizing Abs with much narrower specificity. We also report the discovery of CC24.2, a pan-sarbecovirus neutralizing mAb that targets a novel RBD epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 provides protection against in vivo challenge with SARS-CoV-2, suggesting potential future use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.

Are we expecting too much for too long from the vaccinators? A qualitative study on perceived challenges of COVID-19 vaccinators of district Shahdol, India

Background: There is a paucity of knowledge regarding challenges faced by the coronavirus disease 2019 (COVID-19) vaccinators in resource constraint settings like district Shahdol, Central India. Hence, the present study was planned to explore the perceived challenges of vaccinators regarding COVID-19 vaccination. Methods: In October 2021, district health authorities conducted a one-day workshop with the auxiliary nurse midwives, staff nurses, and lady health visitors who work as vaccinators. It had three distinct but mutually connected phases. In the first phase, a free listing exercise was performed to list out their perceived challenges that are prominent and representative of their cultural domain. In the second phase, the pile-sorting exercise with the challenges mentioned in the above step was performed to produce similar data in the form of a matrix, based on a perceived similarity between them by multi-dimensional scaling analysis. In the final phase, the transcripts generated during the discussion on the free listing and pile sorting exercises was used for the thematic analysis to find plausible explanations for the findings. Result: A total of 15 vaccinators took part in the workshop. In the free listing exercise, a total of 14 items were identified as perceived challenges for COVID-19 vaccinators. The three items with the highest Smith's S value were overtime duty, no holidays, and lack of monetary incentive. The analysis of pile-sorting suggested that participants clustered their 14 perceived challenges into five groups;1) beneficiaries related, 2) vaccination schedule related, 3) lack of facilities at vaccination site, 4) lack of monetary incentive, and 5) issues related to digital data handling. Thematic analysis suggested that their main challenges were overtime duty, no monetary incentive, and lack of toilet, food, and transport facility at the session site. Conclusion: Vaccinators perceive overtime duty and lack of holidays as their top two challenges and expect monetary incentives for this. The study recommends better basic amenities like toilet facility, sustained and effective community engagement, a monetary incentive, and a better ecosystem for digital data handling for the vaccinators.

A cross-sectional study to describe the spectrum of ocular manifestations and risk factors of mucormycosis presenting to a tertiary hospital of East India.

Purpose: To report the clinico-demographic profile of rhino-orbito-cerebral mucormycosis (ROCM) in patients during the "second wave" of the COVID-19 pandemic in eastern India, and their ophthalmic manifestations at presentation to our tertiary institute. Methods: Cross-sectional study amongst patients presenting to our center based on their hospital records. Demographic information, history related to COVID-19, records of detailed ocular examination, and microbiological, radiological, and histopathological investigation were entered into an online worksheet and analyzed using SPSS 26.0. Results: A total of 219 patients with ROCM were treated from May to September 2021, and 110 of these had ocular manifestations at presentation (50.2%). The age of patients ranged from 22 to 83 years and the mean ± standard deviation (SD) age was 49.9 ± 12.9 years. Ninety (81.8%) patients had been diagnosed with diabetes mellitus, 31 (34%) had hypertension, and 10 had other comorbidities. The duration between the onset of COVID-19 and mucormycosis symptoms was 0 to 60 days with a mean ± SD interval of 20.9 ± 12.6 days. Fifty-six (50.9%) patients had a history of steroid use. Unrelenting ocular or facial pain was the most common presenting symptom, ptosis was the most common anterior segment manifestation, and ophthalmic artery occlusion was the most common posterior segment manifestation. Conclusion: Our data from eastern India reinforces the relationship between COVID-19, diabetes, corticosteroid use, and ROCM. Knowledge of various presenting anterior and posterior segment manifestations of the disease as described in the present study will guide clinicians to recognize the disease early and make every effort to prevent complications.

Patterns and Trajectories of Pulmonary Function in Coronavirus Disease 2019 Survivors: An Exploratory Study Conducted in Central India.

BACKGROUND: The ongoing pandemic of coronavirus disease 2019 (COVID-19) has negatively impacted respiratory health worldwide. The severity of the disease varies considerably, and patients may present with bronchitis, pneumonia, and acute respiratory distress syndrome. This study aims to quantify the parameters of the pulmonary function test (PFT) with regard to the severity of COVID-19 and understand the pattern of PFT in reference to the status of selected morbidities and body mass index. MATERIALS AND METHODS: This is a hospital-based, comparative, cross-sectional study. A total of 255 COVID-19 survivors underwent clinical assessment, a PFT, and a 6-minute walk test. Participants were divided into mild, moderate, and severe disease groups. The parameters were compared between these groups. The PFT and 6-minute walk tests were conducted using an NDD Digital computerized spirometer (NDD Meditechnik AG., Switzerland) and a fingertip pulse oximeter (Hasely Inc., India), respectively. RESULTS: All PFT parameters showed significant differential distribution among the severity groups (p<0.001) except for forced expiratory volume in 1 s/ forced vital capacity (FEV1/FVC) and forced expiratory flow (FEF) during 25%-75% expiration and peak expiratory flow (PEF). Among severe category participants forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC, were significantly reduced as compared to mild and moderate. Severity was significantly affected by age >50 years. Severe category participants were seen in 31% of normal, 58% of pre-obese, and 53% of obese participants; however, this difference was insignificant. A significant reduction in SPO2 on the 6-minute walk test was observed in severely sick participants. CONCLUSIONS: COVID-19 is associated with a mixed pattern of spirometry. Poor prognosis is associated with older age, obesity, and multimorbidity.

Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response (preprint)

A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.

Structural insights for neutralization of Omicron variants BA.1, BA.2, BA.4, and BA.5 by a broadly neutralizing SARS-CoV-2 antibody.

In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19-recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)-specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC50 ranging from 0.02 to 0.13 µg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.

Assessing the Compliance of Dental Clinicians towards Regulatory Infection Control Guidelines Using a Newly Developed Survey Tool: A Pilot Cross-Sectional Study in India.

Adherence to the dental practice regulatory guidelines instituted during the COVID-19 pandemic is essential to minimize the transmission of SARS-CoV-2 strains. Given the lack of a valid and reliable survey tool to assess the adherence to dental practice guidelines, this study aims to develop, validate, and test a survey tool on a pilot sample of dental clinicians practicing in India. A survey tool was developed/validated through a sequential phasic approach: Phase I- developing survey using conceptual and literature framework; Phase II: ascertaining its validity and reliability; Phase III: pilot testing; and Phase IV: assessing construct validity by exploratory factor analysis (EFA) on the responses collected in Spring 2021. The EFA was achieved using a traditional unweighted least squares extraction method through a varimax rotation with Kaiser normalization. A six-factor solution with 18 items (with the global reliability of 86%) related to screening, regular infection prevention measures, infection control inside the dental operatory, disinfection of the dental unit, disposal, and other COVID-19-specific preventive measures were extracted. Our sample had higher compliance with regard to providing alcohol-based hand scrubs, providing protective gear to attendees, collecting travel/medical history, and screening patients for COVID-19 symptoms. In contrast, less compliance was observed regarding the use of paperless forms of practice and rubber dams in the operatory. The use of a validated survey tool ensures the collection of reliable and valid data, which can serve as baseline data to measure the uptake and effectiveness of dental practice regulatory guidelines in a clinical setting and community dental health clinics.

COVID-19-Associated Mucormycosis in a Tertiary Care Hospital in India: A Case Series.

Mucormycosis is a disease that usually occurs in immunocompromised patients or those with uncontrolled diabetes mellitus. The second wave of the coronavirus disease 2019 (COVID-19) pandemic in India was accompanied by an unexpected rise in mucormycosis cases, ranging from the most commonly occurring Rhino-orbital-cerebral mucormycosis (ROCM) to rare cases of pulmonary and gastrointestinal mucormycosis. The majority of cases that presented to our hospital were individuals with underlying diabetes mellitus who received steroids for COVID-19 before being diagnosed with mucormycosis. In this case series, we present five rhino-orbital-cerebral mucormycosis cases that were histopathologically positive and treated at a tertiary-care hospital in India. Magnetic resonance imaging (MRI) of all of the patients demonstrated orbital apex syndrome and diffuse or focal infiltration of the cavernous sinus. Cases were treated with anti-fungal drugs, transcutaneous retrobulbar injection of amphotericin B (TRAM B), along with appropriate surgical excision and debridement of the involved tissue. The essential elements for successfully managing this fatal infection are control of the predisposing factors, early detection, anti-fungal drugs, and surgical debridement of the involved tissues.

Outcomes of Transcutaneous Retrobulbar Amphotericin B in Rhino-Orbital-Cerebral Mucormycosis Among Patients Recovering From COVID-19: A Preliminary Experience.

Background In this study, we aimed to assess the outcomes of transcutaneous retrobulbar injection of amphotericin B (TRAMB) in rhino-orbital-cerebral mucormycosis (ROCM) among patients recovering from coronavirus disease 2019 (COVID-19). Methodology This retrospective study was conducted at a tertiary care center in eastern India from May 29th to July 31st, 2021, and included post-COVID-19 patients admitted with stage 3 and 4a ROCM who underwent TRAMB. The details of the ophthalmic examination, laboratory investigations, and radiological examination were retrieved from patients records. Patients were given TRAMB (3.5 mg/mL) on alternate days till they underwent debulking surgery and resumed from the second postoperative day alternatively till the patients showed clinical stabilization or improvement. Results In total, 45 eyes of 41 patients were included in the study. The median number of injections given was six (minimum = 3; maximum = 10). Following was the distribution of number of injection needed in each eye: eight eyes (three injections), six eyes (four injections), seven eyes (five injections), three eyes (six injections), eight eyes (seven injections), 11 eyes (eight injections), and one eye had received nine and ten injections each. Overall, 21/32 (65.62%) eyes had improvement in proptosis whereas 9/32 (28.12%) had improvement in ptosis. Six patients had improvement in extraocular movement. In total, 25 eyes had no improvement whereas seven eyes had improvement in vision. Four eyes underwent exenteration. All nine patients with limited orbital disease had good improvement with fewer injections (median = 4). None of the patients undergoing TRAMB had an intracranial extension of disease. Moreover, 8.88% (4/45) of the eyes had post-TRAMB transient inflammation which resolved without any intervention. Finally, 3/41 of the patients died. Conclusions TRAMB can be considered as an useful therapeutic adjunct in managing ROCM. Further, it can halt the progression of the disease while awaiting definitive surgical intervention.

Patent intelligence of RNA viruses: Implications for combating emerging and re-emerging RNA virus based infectious diseases.

The recent outbreak of one of the RNA viruses (2019-nCoV) has affected most of the population and the fatalities reported may label it as a modern-day scourge. Active research on RNA virus infections and vaccine development had more commercial impact which leads to an increase in patent filings. Patents are a goldmine of information whose mining yields crucial technological inputs for further research. In this research article, we have investigated both the patent applications and granted patents, to identify the technological trends and their impact on 2019-nCoV infection using biotechnology-related keywords such as genes, proteins, nucleic acid etc. related to the RNA virus infection. In our research, patent analysis was majorly focused on prospecting for patent data related to the RNA virus infections. Our patent analysis specifically identified spike protein (S protein) and nucleocapsid proteins (N proteins) as the most actively researched macromolecules for vaccine and/or drug development for diagnosis and treatment of RNA virus based infectious diseases. The outcomes of this patent intelligence study will be useful for the researchers who are actively working in the area of vaccine or drug development for RNA virus-based infections including 2019-nCoV and other emerging and re-emerging viral infections in the near future.