Vaccine Supply Forecasting and Optimization using Deterministic and Probabilistic Approaches

When the pandemic was at its peak, it was a quite difficult task for the government to schedule vaccine supply in various districts of a state. This task became further difficult when vaccines were required to be supplied to various Covid Vaccination Centers (CVCs) at a granular level. This is because there was no data regarding the trend being acquired at each CVC and the population distribution is non-uniform across the district. This led to the arousal of an ambiguous situation for a certain period and hence mismanagement. Now that we have sufficient data across each CVC, we can work on a time series analysis of vaccine requirements in which we can essentially forecast the number of administered doses and optimize the wastage at all atomic CVC levels. © 2023 IEEE.

Performance Evaluation of Different RT-PCR Kits for the Direct Detection of SARS-CoV-2 in Preheated Specimens

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created high demand for molecular kits and consumables for mass screening of suspected individuals. Direct real-time polymerase chain reaction (RT-PCR) assay without nucleic acid extraction has several advantages in saving testing time and cost and helps in the rapid reporting of SARS-CoV-2. The present study evaluated the analytical performance of four SARS-CoV-2 RT-PCR for direct RT-PCR testing using preheated specimens.Methods A total of 100 clinical specimens were selected and divided into three different groups: (1) group I: 20 SARS-CoV-2 positive specimens with high viral load, viz., low Ct values (< 30 Ct), (2) group II: 50 SARS-CoV-2 positive specimens with low viral load, viz., high Ct values (> 30 Ct), and (3) group III: 30 SARS-CoV-2 negative specimens. Specimens were heat-inactivated at 70 >= C for 10 minutes and cooled down at 4 >= C and were evaluated for standard and direct RT-PCR method by using ViralDtect-II Multiplex Real-Time PCR kit, TaqPath COVID-19 Combo kit, COVIDsure Pro Multiplex RT-PCR kit, and Hi-PCR Coronavirus (COVID-19) Multiplex Probe PCR kit.Results Results showed that except ViralDtect-II kit, the other three TaqPath COVID-19 Combo kit, COVIDsure Pro kit, and Hi-PCR Coronavirus (COVID-19) RT-PCR kit were able to amplify all the SARS-CoV-2 genes in the direct RT-PCR method using preheated specimens. In group I specimens, 100% sensitivity was observed in all three RT-PCR kits. In group II specimens, COVIDsure Pro kit was found to be superior among other kits.Conclusion Direct RT-PCR method during pandemic situation is valuable and cost effective for the detection of SARS-CoV-2. All three TaqPath COVID-19 Combo kit, COVIDsure Pro kit, and Hi-PCR Coronavirus (COVID-19) RT-PCR kit can be used for direct RT-PCR method and COVIDsure Pro kit performance was found to be superior among all.

Requirement for booster doses in healthy, cancer and immunosuppressed patients infected with the ancestral or variant SARS-CoV-2

Introduction: Current SARS-CoV-2 vaccines are effective at preventing COVID-19 or limiting disease severity in healthy individuals, but effectiveness is lower among patients with cancer or immunosuppression. Vaccine effectiveness wanes with time and varies by vaccine type. Moreover, current vaccines are based on the ancestral SARS-CoV-2 spike protein sequence, and emerging viral variants evade vaccine induced immunity. Booster doses partially overcome these issues, but there are limited clinical data on the durability of protection afforded by boosters - especially against SARS-CoV-2 variants. Methods: Here we describe a mechanistic mathematical model for vaccination-induced immunity in patients with cancer and use it to predict vaccine effectiveness taking into account current and possible future viral, host and vaccine characteristics. Crucially, this allows predictions over time frames currently not reported in the clinical literature. The model incorporates the infection of lung epithelium by SARS-CoV-2, the response of innate and adaptive immune cells to infection, the production of pro-and anti-inflammatory cytokines, the activation of the coagulation cascade. The model further accounts for the interactions between the virus, immune cells and tumor cells as well as for vaccination-induced immunity and anti-cancer therapies. Results: Model predictions were validated with available clinical data. The model predicts that for healthy individuals vaccinated and boosted with mRNA-1273, BNT-162b2a, and Ad26.COV2.S, robust immunogenicity against the ancestral and delta variant extends beyond a year. Immunogenicity is enhanced following booster vaccination in patients with cancer on various anti-cancer therapies and for patients without cancer on immunosuppressive agents. However, our model predicts that more than one booster dose will be required for patients with cancer, or on immunosuppression, to maintain protective immunity against current and hypothetical future variants. SARS-CoV2 variants with enhanced binding to target cells, reduced affinity for vaccine-generated antibodies or reduced immunogenicity resulted in lower antibody levels and more severe disease compared with variants with enhanced viral replication or internalization rates. Conclusion: For patients with cancer and immunosuppressed individuals, SARS-CoV2 variants with enhanced ability to bind to target cells, altered antibody affinity or reduced immunogenicity could lead to breakthrough infections even after a single booster dose. Our mathematical model is useful for anticipating and planning future vaccinations in patients with cancer.

Performance Analysis of Different Real Time-Pcr Kits for the Diagnosis of Sars-Cov-2 Virus

Background: At present the whole world is facing pandemic of the COVID-19 disease caused by SARS-CoV-2 virus. Rapid and correct laboratory diagnosis is indispensable to stop its spread and break the chain of transmission. In India, ICMR has approved numerous RT-PCR kits for the diagnosis of COVID-19 but an independent performance analysis of these kits is not done till date. We comparatively evaluated performance of ten COVID-19 RT-PCR kits and we conclude that all RT-PCR kits can be used for the routine diagnosis of COVID-19 patients. Methods:Performance analysis of the selected kits was done on the basis of number of target genes in the kit, labelled fluorophores, internal control, total RT-PCR run time, threshold cycle and result interpretation. Among all the selected kits, some have target regions of E gene and N gene and others have RdRP gene, Orf 1ab gene, and S gene. Some kits have primer probes for human RNase P gene while others included internal control to check correct sample collection and RNA extraction procedure. All kits uses reverse transcription reaction and total RT-PCR run time is in the range of 67 minute to 135 minutes. Threshold cut-off of those kits falls within the range of ≤34 to ≤40. Once internal control is inter- preted as valid and all target genes detected together then the test is interpreted as positive. Results:Our analysis indicate that some kits prove better than others on the basis of more number of SARS -CoV-2 genes target in their kit, all tests look good to diagnose positive samples, negative sample and inconclusive samples. Conclusions:Considering our analysis, we conclude that all RT-PCR kits can be used for the routine diagnosis of sympto- matic COVID-19 patients.

Incidence of Non Amplification of N Gene of SARS-CoV-2 using Commercially Available Real Time Polymerase Chain Reaction Kit and its Comparison with Two Other Different Kits

Introduction: Novel Coronavirus Disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has resulted in an unprecedented global pandemic. Real Time Polymerase Chain Reaction (RT-PCR) tests are being used in the diagnosis of COVID-19 worldwide however mutations in the SARS-CoV-2 genome have generated many SARS-CoV-2 genome variants and which may affect the correct Reverse transcriptase-Real time Polymerase Chain Reaction (RT-PCR) diagnosis. Aim: To confirm and study the incidence of the non amplification of the SARS-CoV-2 Nucleocapsid gene (N gene) target among known SARS-CoV-2 positive samples. Materials and Methods: This retrospective observational study was carried out at the State Virology Laboratory, Gandhi Medical College, Bhopal, Madhya Pradesh, India during January 2021 to May 2021. During the study period, a total of 159 SARS-CoV-2 positive samples were failed to amplify the N gene target. To investigate the non amplification of N gene target of SARSCoV-2, a total of 20 samples were selected and retested using the initially used RT-PCR kit (VIRALDTECT RT-PCR kit) and also with the two different RT-PCR kits (TaqPath RT-PCR kit and Hi-PCR RT-PCR kit) which also contain primers/probes for the SARS-CoV-2 N gene target. Results: Amplification and detection of the SARS-CoV-2 N target gene was not observed in VIRALDTECT RT-PCR test results. In contrast, amplification was detected in the N gene target of SARS-CoV-2 while using the TaqPath and Hi-PCR kits. Obtained results confirm the failure of the annealing of VIRALDTECT kit N gene primer/probe and suggest the possible mutation event in the SARS-CoV-2 N gene among the N gene non amplified samples. Conclusion: Present study reports, the incidence of non amplification of SARS-CoV-2 N gene, where the RT-PCR kit failed to detect N gene target and seriously affect RT-PCR diagnosis. Hence, the study emphasises the revalidation of commercially available SARS-CoV-2, RT-PCR kits to identify these kinds of failure incidence.

A tale of survival: Covid-19, disseminated cryptococcus, and cytomegalovirus disease in an abo-incompatible kidney transplant recipient

Introduction: We present a rare case of Collapsing Focal Segmental Glomerulosclerosis (FSGS) in Covid-19 (COVAN), disseminated Cryptococcus and CMV infection in a kidney transplant recipient with dialysis dependent acute kidney injury and successful renal and critical illness recovery. Case Description: 63yo black male with an ABO incompatible kidney transplant 8yrs ago, baseline creatinine (Cr) of 1.4 mg/dl with acute Covid-19 infection with presenting Cr of 5.5 mg/dl and nephrotic range proteinuria (5.9gm/gm). Started hemodialysis on day 21 of the acute illness. Normal imaging, stable anti-ABO titers and transplant kidney biopsy with collapsing FSGS and ATN. Blood cultures ordered for persistent fevers were positive for Cryptococcus neoformis. Biopsy of painful indurated skin of the left flank revealed variably sized yeast forms within the dermis consistent with cutaneous Cryptococcus. Treated with amphotericin B/flucytosine followed by fluconazole with clearance of fungemia, resolution of fever and improvement of skin lesions. Immunosuppression was continued with reduced dose of tacrolimus and prednisone 10mg/day. Antimetabolite was discontinued. Persistent weakness and diarrhea lead to testing for CMV with PCR at 51,000copies/ml, treated with IV ganciclovir with complete resolution of symptoms. Discharged home on maintenance dialysis with valganciclovir and fluconazole prophylaxis. He returned on day 70 of illness with a Cr of 1.2 mg/dl, a 24hour urine collection with a creatinine clearance of 28 ml/min and 2gms of proteinuria. Dialysis was discontinued due to renal recovery. At last clinic follow up, day 100 from diagnoses, Cr remains stable at 1.7 mg/dl off dialysis. Discussion: Immune dysregulation in the setting of acute Covid-19 infection coupled with long term immunosuppression may have contributed to multiple opportunistic infections. Optimal approach for immunosuppression in KTRs with acute Covid-19 infection is still evolving. Our patient was successfully treated without stopping all immunosuppression. Our case underscores importance of having low threshold to test for various opportunistic infections even in the setting of active Covid-19 infection. While data on COVAN in KTRs is limited, our case shows potential for renal recovery even in a high immunologic risk kidney transplant recipient.

Investigation of different commercially available real time-polymerase chain reaction kits for SARS-CoV-2 diagnosis

Introduction: The whole world is facing an ongoing global health emergency of COVID-19 disease caused by the SARS-CoV-2. Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) is a gold standard in the detection of SARS-CoV-2 infection. Presently, many single tube multiple gene target RTPCR kits have been developed and are commercially available for Corona Virus Disease 2019 (COVID-19) diagnosis. Aim: To evaluate the performance of seven COVID-19 RT-PCR kits (DiagSure, Meril, VIRALDTECT II, TruPCR, Q-line, Allplex and TaqPath) which are commercially available for COVID-19 RT-PCR diagnosis. Materials and Methods: This observational study was conducted at the State Virology Laboratory (SVL), Gandhi Medical College, Bhopal, Madhya Pradesh, India. Seven commercially available kits have been evaluated on the basis of: (i) number of SARS-CoV-2 specific gene target;(ii) human housekeeping genes as internal control;(iii) RT-PCR run time;and (iv) kit performances to correctly detect SARS-CoV-2 positive and negative RNA samples. A total of 50 RNA samples (left over RNA) were included, master mix preparation, template addition and RT-PCR test has been performed according to kits literature. At the end of PCR run, mean and standard deviation of obtained cut-off of all kits were calculated using Microsoft Excel. Results: All seven RT-PCR kits performed satisfactory regarding the reproducibility and they could correctly identify 30 positive and 20 negative RNA samples. RNA samples (group C) having low viral loads with a high Cycle threshold (Ct) value (>30) were also detected by all these seven kits. Obtained Ct values of each group was in parallel range in comparison with the initial testing Ct values. Kits were found to be superior which contains primers and probes for three SARS-CoV-2 specific gene targets, have human housekeeping gene as internal control and taking less time to complete RT-PCR. Conclusion: All seven COVID-19 RT-PCR kits included in this study demonstrated satisfactory performance and can be used for the routine molecular diagnosis of COVID-19 disease.

EVOLUTION OF MANAGEMENT IN THE INFORMATION TECHNOLOGY DOMAIN TO INCREMENTAL AND TANGIBLE OUTCOME-BASED MODE: ACCELERATED BY THE POSITIVE INFLUENCE OF COVID-19

Management, as the study of the organization and the organizational phenomenon has been an evolving body of knowledge that has particularly been maturing to inculcate the intricacies of knowledge work and the knowledge worker. The trend has been continuous, but the form and messaging have crystallized more with the advent of the twentieth century. Management in Information Technology has also embraced this evolution as it is necessitated by the demands of the knowledge work. From a linear sequential management model to iterative feedback and feed forward driven management methodology, the journey has been continuous. The study analyzed this trend which clearly showed the evolution but also inherent inertia in adapting to this evolution, thus creating limits to the opportunities that it provides. So, the journey from the waterfall model of software development in the Information Technology domain to a 'V-model' (software development model), where software development is plotted against software testing and then the iterative models evolved to Agile methodology. But in run-time, the mode to implement Agile through Sprint, scrum, etc. became a mini waterfall. The requirement analysis was based on Work Breakdown Structure, which should ideally have been User story and acceptance criterion, the resource loading, and inherent effort estimation and resource utilization were role-based, such as Project Manager, Technical Architect, Team Leader, Developer, Tester, etc., though it should have been Scrum Master and Scrum Members. Bell curve is being used habitually to measure resource performance within the team. Individual sprints were not leading to production release, which is how it was envisioned but there was some staging environment created where the sprints ended and then did a common User Acceptance Testing which is followed by deployment to production much like the waterfall model. To add to this, puritanical Agile practitioners were necessitating all scrum members to be in the same room for an effective stand-up or scrum meeting, which is almost impossible to achieve in the current onsite-offshore model of engagement. This created more fissures than opportunities to align. So, the inherent inertia and the puritanical interpretation of the methodologies resulted in falling back to the same trap and not reaping the benefits of the natural evolution of management in The Information Technology which was taking its organic spread to lead us to improved effectiveness. But with the onset of COVID 19 pandemic, the Information Technology industry had to take immediate steps, which was, the same steps that were being dictated by the organic spread of the management evolution but were being resisted by this inherent inertia combined with the puritanical approach. Here, the study has analyzed the steps and implications dictated by COVID 19 pandemic in the Information Technology domain, and how it needs to be conceptualized to ensure it is utilized as an enabler for the next phase of The Information Technology management growth, particularly in terms of knowledge work and the knowledge worker.

Optimizing treatment for COVID-19using computational modeling: Implications for cancerpatients

Emerging retrospective analyses show that cancer patients are more likely to develop severe COVID-19. Thecauses for these worse outcomes are unclear, but data suggest that cancer therapies, which can suppress theimmune system, are not responsible for increased COVID-19 severity. An alternative hypothesis is that commonmolecular pathways are altered in cancer and COVID-19, resulting in worsened disease outcomes. Our previouswork demonstrated that activated renin angiotensin signaling (RAS) modulates the tumor microenvironment, resulting in worse outcomes and therapy resistance. Inhibition of this pathway using angiotensin receptor blockers(ARBs) or angiotensin converting enzyme inhibitors (ACEIs) can improve the outcomes of cancer therapies.Similarly, there is great interest in understanding the implications of RAS in COVID-19 progression because a keycomponent of this system, ACE2, is also the docking site for the SARS-CoV-2 virus. Indeed, multiple clinical trialsare currently evaluating whether ARBs/ACEIs benefit or harm COVID-19 patients. To help guide administration ofthese drugs, we adapted our existing computational modeling framework of the cancer microenvironment usingavailable data to simulate COVID-19 progression in patients. Using a systems biology approach, we mechanisticallymodeled the interaction of the RAS and coagulation pathways with COVID-19 infection. We further explored theefficacy of various antiviral, antithrombotic, and RAS-targeted treatment regimens to identify synergisticcombinations as well as optimal schedules for therapy. The system is complex, given that viral binding of ACE2interferes with its antiinflammatory signaling. When ACE2 is bound by the virus, its local activity decreases, leadingto immune dysregulation and risk of coagulopathy, predictors of COVID-19 severity and mortality. To optimizecombination treatments for cancer patients who contract COVID-19, multiple simulations were run by combiningdifferent therapeutics currently in clinical trials to predict their effects on viral load, thrombosis, oxygen saturation, and cytokine levels. These include ARBs, ACEIs, antiviral drugs, antithrombotic agents, and anti-inflammatory drugs(e.g., anti-IL6/6R). Our simulations predict that i) there is an optimal timing for treatment with antiviral drugs such asremdesivir, related to immune activation;ii) combinations of antiviral and antithrombotic drugs are able to preventlung damage, increase blood oxygen levels, and inhibit thromboembolic events;and iii) RAS modulators can have apositive effect when added to the treatment regimen. Effective strategies for COVID-19 treatment identified by this insilico analysis will be further analyzed in combination with cancer therapeutics (e.g., immune checkpoint blockers, chemotherapy) to provide guidelines for optimal clinical management of both cancer and COVID-19.

Intelligent network topology based post-pandemic reintroduction policies for offices

COVID-19 has touched almost all facets of modern life. As part of this global shift, many employers have recommended employees work from home in an effort to curb the spread of infection. When organizations bring workers back to the office, the specific policies for personnel reintroduction will shape both productivity and the spread of disease. This study explores the secondary social and energy impacts of potential reintroduction policies. Using a socio-organizational network inferred from an office in Redwood City, California, we define social, epidemic resistance, and energy metrics which are used to compare the character of personnel reintroduction plans. Our notable findings are, first, that the choice of which occupants return has a large effect on modeled network-level epidemic resistance. Second, where the occupants are located can significantly impact overlap in space-use within smaller spatial zones - a concept related to social distancing. In summary, this work is a critical first step in demonstrating the value of intelligent occupant network topology based reintroduction schemes in offices that can minimize: disease spread, socio-organizational disruptions and building energy use impacts. © 2020 ACM.