Query: covid vaccine symptoms

title: COVID 19 coronavirus vaccine design using reverse vaccinology and machine learning
abstract: To ultimately combat the emerging COVID 19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS CoV 2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane protein, have been tested for vaccine development against SARS and MERS. We further used the Vaxign reverse vaccinology tool and the newly developed Vaxign ML machine learning tool to predict COVID 19 vaccine candidates. The N protein was found to be conserved in the more pathogenic strains (SARS/MERS/COVID 19) but not in the other human coronaviruses that mostly cause mild symptoms. By investigating the entire proteome of SARS CoV 2, six proteins, including the S protein and five non structural proteins (nsp3, 3CL pro, and nsp8 10) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS CoV 2, SARS CoV, and MERS CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC I and MHC II T cell epitopes, and linear B cell epitopes localized in specific locations and functional domains of the protein. Our predicted vaccine targets provide new strategies for effective and safe COVID 19 vaccine development.

title: A Review of the Progress and Challenges of Developing a Vaccine for COVID 19
abstract: A novel coronavirus, which has been designated as severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) was first detected in December 2019 in Wuhan China and causes the highly infectious disease referred to as COVID 19. COVID 19 has now spread worldwide to become a global pandemic affecting over 24 million people as of August 26th, 2020 and claimed the life of more than 800,000 people worldwide. COVID 19 is asymptomatic for some individuals and for others it can cause symptoms ranging from flu like to acute respiratory distress syndrome (ARDS) pneumonia and death. Although it is anticipated that an effective vaccine will be available to protect against COVID 19, at present the world is relying on social distancing and hygiene measures and repurposed drugs. There is a worldwide effort to develop an effective vaccine against SARS CoV 2 and, as of late August 2020, there are 30 vaccines in clinical trials with over 200 in various stages of development. This review will focus on the eight vaccine candidates that entered Phase 1 clinical trials in mid May, including AstraZeneca/Oxford's AZD1222, Moderna's mRNA 1273 and Sinovac's CoronaVac vaccines, which are currently in advanced stages of vaccine development. In addition to reviewing the different stages of vaccine development, vaccine platforms and vaccine candidates, this review also discusses the biological and immunological basis required of a SARS CoV 2 vaccine, the importance of a collaborative international effort, the ethical implications of vaccine development, the efficacy needed for an immunogenic vaccine, vaccine coverage, the potential limitations and challenges of vaccine development. Although the demand for a vaccine far surpasses the production capacity, it will be beneficial to have a limited number of vaccines available for the more vulnerable population by the end of 2020 and for the rest of the global population by the end of 2021.

title: COVID 19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning
abstract: To ultimately combat the emerging COVID 19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS CoV 2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane (M) protein, have been tested for vaccine development against SARS and MERS. However, these vaccine candidates might lack the induction of complete protection and have safety concerns. We then applied the Vaxign and the newly developed machine learning based Vaxign ML reverse vaccinology tools to predict COVID 19 vaccine candidates. Our Vaxign analysis found that the SARS CoV 2 N protein sequence is conserved with SARS CoV and MERS CoV but not from the other four human coronaviruses causing mild symptoms. By investigating the entire proteome of SARS CoV 2, six proteins, including the S protein and five non structural proteins (nsp3, 3CL pro, and nsp8 10) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS CoV 2, SARS CoV, and MERS CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC I and MHC II T cell epitopes, and the predicted linear B cell epitopes were found to be localized on the surface of the protein. Our predicted vaccine targets have the potential for effective and safe COVID 19 vaccine development. We also propose that an "Sp/Nsp cocktail vaccine" containing a structural protein(s) (Sp) and a non structural protein(s) (Nsp) would stimulate effective complementary immune responses.

title: Vaccine repurposing approach for preventing COVID 19: can MMR vaccines reduce morbidity and mortality?
abstract: The coronavirus disease (COVID 19) is resulting in millions of infected individuals with several hundred thousands dead throughout the world. Amidst all the havoc, one interesting observation in the present COVID 19 pandemic is the negligible symptoms in the young; particularly children below 10 years of age. We assume the extensive pediatric vaccination with MMR vaccines followed globally could have resulted in innate immune responses, e.g. induction of interferons (IFNs) and activated natural killer (NK) cells, thereby offering natural immunity against SARS CoV 2 in the young population. Possible cross protective innate immunity offered by MMR vaccination prompted us to suggest repurposing MMR vaccination for immuno prophylaxis against COVID 19.

title: Side effects of BNT162b2 mRNA COVID 19 vaccine: A randomized, cross sectional study with detailed self reported symptoms from healthcare workers
abstract: Concerns are prevailing about the safety and side effects from BNT162b2 mRNA COVID 19 vaccine.  A randomized, cross sectional study was performed to investigate the side effects of BNT162b2 vaccine using an independent online questionnaire gathering responses from healthcare workers (HCWs) with detailed review of organ systems.  Of all HCWs, 87.98% (1245/1415) completed the survey. Of them, 64.5 (803/1245) received BNT162b2 mRNA vaccine and reported at least one or more symptoms (classified based on organ systems and occurrence rate) post vaccination. Of these, 640/803 (79.7% were able to continue activities of daily living (ADL) 103/803 (12.83% were temporarily unable to perform ADL, 99/803 (12.33% temporarily took off from work, only 20/803 (2.49% required help from an outpatient provider, 5/803 (0.62% required help from emergency department, and 2/803 (0.25% required hospitalization. Despite, 97.61% had no intention to skip the second dose and 92.9% had already received it.  The commonly reported symptoms (occurrence in the descending order) include soreness, fatigue, myalgia, headache, chills, fever, joint pain, nausea, muscle spasm, sweating, dizziness, flushing, feelings of relief, brain fogging, anorexia, localized swelling, decreased sleep quality, itching, tingling, diarrhea, nasal stuffiness, and palpitations. Despite, there is remarkable acceptance for the second dose among HCWs.

title: Non life threatening adverse effects with COVID 19 mRNA 1273 vaccine: A randomized, cross sectional study on healthcare workers with detailed self reported symptoms
abstract: There are concerns regarding the side effects of the new coronavirus disease 2019 (COVID 19) mRNA 1273 vaccine among healthcare workers (HCWs) in the United States. The objective of the study was to investigate the side effects of the mRNA 1273 vaccine with detailed review of organ systems. A randomized, cross sectional study using an independent online survey questionnaire was conducted to collect responses from HCWs. Of all participants, 87.8% (1116/1271) provided complete responses. Of them, 38.7% (432/1116) received the mRNA 1273 vaccine, among which, 89.35% were females; 425 of these 432 mRNA 1273 vaccine recipients (98.34% reported at least one or more symptoms. The results were classified based on the frequency of symptoms reported postvaccination. Of these, 254/432 (58.8% were able to continue their daily routine activities. 108/432 (25% temporarily had trouble to perform daily activities, 120/432 (27.78% required transient time off from work, 17/432 (3.94% required help from an outpatient provider, 1/432 (0.23% required help from emergency department, and none of them were hospitalized. Despite the wide array of self reported symptoms, 97.02% of the HCWs did not intend to skip the second dose of vaccine. Among all the symptoms reported, localized pain, generalized weakness, headache, myalgia, chills, fever, nausea, joint pains, sweating, localized swelling at the injection site, dizziness, itching, rash, decreased appetite, muscle spasm, decreased sleep quality, and brain fogging were the most commonly reported symptoms (in descending order of occurrence) Most of the symptoms reported were nonlife threatening. Despite the wide array of self reported symptoms, there appears to be a higher acceptance for this vaccine.

title: Can Unconventional Immunomodulatory Agents Help Alleviate COVID 19 Symptoms and Severity?
abstract: Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS CoV 2) is the cause of the respiratory infection known as COVID 19. From an immunopathological standpoint, coronaviruses such as SARS CoV 2 induce increased levels of a variety of T helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin 1 (IL 1) IL 6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti inflammatory and/or Th2 immune response to counteract COVID 19 symptoms and severity.  Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS CoV 2) is the cause of the respiratory infection known as COVID 19. From an immunopathological standpoint, coronaviruses such as SARS CoV 2 induce increased levels of a variety of T helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin 1 (IL 1) IL 6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti inflammatory and/or Th2 immune response to counteract COVID 19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low dose oral interferon alpha, microdose DNA, low dose thimerosal, and phytocannabinoids.

title: Trained immunity as a novel approach against COVID 19 with a focus on Bacillus Calmette Guerin vaccine: mechanisms, challenges and perspectives
abstract: COVID 19 is a severe health problem in many countries and has altered day to day life in the whole world. This infection is caused by the SARS CoV 2 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID 19. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette Guerin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID 19. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS CoV 2 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID 19 severity.

title: COVID 19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact
abstract: Several COVID 19 vaccine candidates are in the final stage of testing. Interim trial results for two vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS) It remains unknown whether this efficacy is mediated predominately by lowering SARS CoV 2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP) A vaccine with high VESYMP but low VESUSC has uncertain population impact.  We developed a mathematical model of SARS CoV 2 transmission, calibrated to demographic, physical distancing and epidemic data from King County, Washington. Different rollout scenarios starting December 2020 were simulated assuming different combinations of VESUSC and VESYMP resulting in up to 100% VEDIS with constant vaccine effects over 1 year. We assumed no further increase in physical distancing despite expanding case numbers and no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported.  Rollouts of 1M vaccinations (5,000 daily) using vaccines with 50% VEDIS are projected to prevent 30% 58% of infections and 38% 58% of deaths over one year. In comparison, vaccines with 90% VEDIS are projected to prevent 47% 78% of the infections and 58% 77% of deaths over one year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a 'symptom reducing' vaccine will require twice as many people vaccinated than a 'susceptibility reducing' vaccine with the same 90% VEDIS to prevent 50% of the infections and death over one year. Delaying the start of the vaccination by 3 months decreases the expected population impact by approximately 40%  Vaccines which prevent COVID 19 disease but not SARS CoV 2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

title: mRNA COVID 19 vaccine is well tolerated in patients with cutaneous and systemic mastocytosis with mast cell activation symptoms and anaphylaxis