Year 3 of COVID-19: Harsh Truths, Brutal Realities, and Glimmers of Hope.

Severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease 2019 (COVID-19), has now killed 1 of every 303 Americans. Whereas 4 vaccines are approved in the United States and masks are widely available, too few are fully immunized and most of the population has stopped wearing protective masks. The ongoing consequences of this include continued excess morbidity and mortality and the generation of immune-evading variants and subvariants, which in toto are injurious and ultimately self-defeating. Herein we briefly update and review COVID-19 vaccines, waning immunity, and new variants.

Prevention of monkeypox with vaccines: a rapid review.

The largest outbreak of monkeypox in history began in May, 2022, and has rapidly spread across the globe ever since. The purpose of this Review is to briefly describe human immune responses to orthopoxviruses; provide an overview of the vaccines available to combat this outbreak; and discuss the various clinical data and animal studies evaluating protective immunity to monkeypox elicited by vaccinia virus-based smallpox vaccines, address ongoing concerns regarding the outbreak, and provide suggestions for the appropriate use of vaccines as an outbreak control measure. Data showing clinical effectiveness (~85%) of smallpox vaccines against monkeypox come from surveillance studies conducted in central Africa in the 1980s and later during outbreaks in the same area. These data are supported by a large number of animal studies (primarily in non-human primates) with live virus challenge by various inoculation routes. These studies uniformly showed a high degree of protection and immunity against monkeypox virus following vaccination with various smallpox vaccines. Smallpox vaccines represent an effective countermeasure that can be used to control monkeypox outbreaks. However, smallpox vaccines do cause side-effects and the replication-competent, second-generation vaccines have contraindications. Third-generation vaccines, although safer for use in immunocompromised populations, require two doses, which is an impediment to rapid outbreak response. Lessons learned from the COVID-19 pandemic should be used to inform our collective response to this monkeypox outbreak and to future outbreaks.

Uncontrolled spread: Book review

One out of very 405 Americans is now dead (as of December 6, 2021) of a virus we could have and should have been prepared for. Pandemics are nothing new. They have always occurred throughout history, and always will. They have, and will, occur regularly, though unpredictably, throughout our lifetime. I have survived the 1957, 1968, and 2009 influenza pandemics – and thus far the SARS-CoV-2 pandemic.

Distinct Homologous and Variant-Specific Memory B-Cell and Antibody Response Over Time After Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccination.

The durability of protective humoral immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection is largely dependent on the generation and persistence of antigen-specific isotype-switched memory B cells (MBCs) and long-lived plasma cells that reside in the bone marrow and secrete high-affinity neutralizing antibodies. The reactivity of vaccine-induced MBCs to emerging clinically significant SARS-CoV-2 variants of concern (VoCs) is largely unknown. In a longitudinal cohort study (up to 6 months following coronavirus disease 2019 messenger RNA vaccination), we measured MBCs in concert with other functional antibody measures. We found statistically significant differences between the frequencies of MBCs responding to homologous and VoC (Beta, Gamma, and Delta) receptor-binding domains after vaccination that persisted over time. In concert with a waning antibody response, the reduced MBC response to VoCs could translate to a weaker subsequent recall immune response and increased susceptibility to the emerging SARS-CoV-2 variant strains after vaccination.

Advancing the Science of Vaccine Safety During the Coronavirus Disease 2019 (COVID-19) Pandemic and Beyond: Launching an International Network of Special Immunization Services.

Within 2 years after the start of the coronavirus disease 2019 (COVID-19) pandemic, novel severe acute respiratory syndrome coronavirus 2 vaccines were developed, rigorously evaluated in large phase 3 trials, and administered to more than 5 billion individuals globally. However, adverse events of special interest (AESIs) have been described post-implementation, including myocarditis after receipt of messenger RNA (mRNA) vaccines and thrombosis with thrombocytopenia syndrome after receipt of adenoviral vector vaccines. AESIs are rare (<1 to 10/100 000 vaccinees) and less frequent than COVID-19 complications, though they have associated morbidity and mortality. The diversity of COVID-19 vaccine platforms (eg, mRNA, viral vector, protein) and rates of AESIs both between and within platforms (eg, higher rate of myocarditis after mRNA-1273 vs BNT162b2 vaccines) present an important opportunity to advance vaccine safety science. The International Network of Special Immunization Services has been formed with experts in vaccine safety, systems biology, and other relevant disciplines to study cases of AESIs and matched controls to uncover the pathogenesis of rare AESIs and inform vaccine development.

Comparability of clinical trials and spontaneous reporting data regarding COVID-19 vaccine safety.

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.

Shoulder injury related to vaccine administration (SIRVA) after COVID-19 vaccination.

OBJECTIVE: The global fight against COVID-19 has required mass vaccination clinics as well as mass recruitment of personnel, including many who may not regularly administer intramuscular deltoid immunizations, potentially increasing the incidence of improper intramuscular injection. Shoulder injury related to vaccine administration (SIRVA) is a well-described, preventable injury resulting from improper injection into anatomic structures adjacent to the deltoid muscle leading to mechanical and chemical trauma augmented by an inflammatory immune response to the vaccine and/or adjuvants. SIRVA is best described in the setting of influenza vaccination, and little is known about it as it pertains to COVID-19 vaccination. This study aims to describe SIRVA in the current pandemic, increase clinician awareness, and offer considerations for prevention. METHODS: To identify clinical characteristics of patients with post-COVID-19-vaccination shoulder injuries, we performed a systematic review of the cases of vaccination-related shoulder injuries reported in the literature and conducted a review of the public Vaccine Adverse Event Reporting System (VAERS). RESULTS: We identified 305 cases of SIRVA in the VAERS database and 28 cases of SIRVA in the setting of COVID-19 vaccination from the literature (n = 333). Patients had a mean age of 51.8 years and a median of 51.5 (range: 19-90) years. Of these, 76.3% were female and 23.7% male. Most patients sought medical evaluation with 54 of the 305 VAERS cases reporting utilizing emergency services. Of patients with imaging-confirmed SIRVA (n = 95), the most common diagnoses were adhesive capsulitis and bursitis, and the most common symptoms were pain (97.7%) and limited range of motion (68.1%). Most patients reported requiring treatment with the majority receiving physical therapy (56.3%), followed by cortisone injection (34.4%). Other modalities used were non-steroidal anti-inflammatory drugs, oral steroids, and surgery. Only 5 patients from this group reported recovery while 60 stated they had not yet recovered. Of those, 23.3% reported disability. CONCLUSION: SIRVA should be regarded as an under-reported, significant cause of post-vaccination morbidity. In the setting of COVID-19 mass vaccination, clinicians must be aware of signs and symptoms of SIRVA as well as appropriate diagnostic modalities and treatment options. Additionally, standardization and proper education regarding injection technique and appropriate needle length is imperative to reducing harm.

Readability of COVID-19 vaccine information for the general public.

BACKGROUND: More than 130 million individuals in the United States have now received at least one dose of a COVID-19 vaccine. Currently, all adults in the Unites States now have access to one of three COVID-19 vaccines. As part of the vaccination procedure, Emergency Use Authorization (EUA) fact sheets, which contain information regarding the vaccine, are provided. The purpose of this study was to analyze the ease of reading (i.e., readability) of the EUA-approved fact sheets for the vaccines currently available in the United States, the V-Safe adverse event survey script, and the Centers for Disease Control and Prevention (CDC) website information on COVID-19 vaccines designed for the general public in the United States. METHODS: We acquired the Pfizer, Moderna, and Janssen EUA fact sheets, as well as the V-Safe survey script and the CDC website information regarding COVID-19 vaccines. These documents were analyzed for their complexity regarding the following readability factors: average length of paragraphs, sentences, and words; font size and style; use of passive voice; the Gunning-Fog index; the Flesch Reading Ease index; and the Flesch-Kincaid Grade Level index. RESULTS: Only the V-Safe adverse-event survey script met readability standards for adequate comprehension. The mean readability scores of the EUA fact sheets and the CDC website were as follows: Flesch Reading Ease score (44.35 avg); Flesch-Kincaid Grade Level (10.48 avg); and Gunning-Fog index (11.8 avg).These scores indicate that at least a 10th-grade level education would be required to understand these reading materials. CONCLUSION: The average person in the United States would have difficulty understanding the information provided in the EUA fact sheets and CDC COVID-19 vaccine website documents; however, the V-Safe survey was written at an adequate reading level. To ensure that the general public fully understands information regarding COVID-19 vaccines, greater care and effort should be given to the development of simplified information material.

Detection of SARS-CoV-2 peptide-specific antibodies in Syrian hamster serum by ELISA.

Golden Syrian hamsters are increasingly used as a permissive animal model for SARS-CoV-2 virus studies, but the lack of immunological assays and other immunological reagents for hamsters limits its full potential. Herein, we developed an ELISA method to detect antibodies specific to peptides and proteins derived from SARS-CoV-2 virus in immunized golden Syrian hamsters. Under optimized conditions, this assay quantitates antibodies specific for individual viral peptides, peptide pools, and proteins. Hence, this ELISA method allows investigators to quantitatively assess humoral immune responses at the peptide and protein levels and has potential application in the development of peptide-based vaccines to be tested in hamsters.

Vaccine safety in an era of novel vaccines: a proposed research agenda

Vaccines have outstanding efficacy and safety records, and the evolving science of vaccines is enabling us to better understand their mechanisms of action as well as the pathways that drive vaccine-related adverse events. This understanding is particularly crucial as novel vaccine antigens, platforms and adjuvants are increasingly being used. In this Comment article, Gregory Poland and Richard Kennedy outline the importance of continued funding and infrastructure support for research into vaccine safety to inform public health decisions and increase public trust in new vaccine technologies.

Book review

Throughout my own career as a physician-scientist and vaccinologists, past President of the Armed Forces Epidemiological Board, President of the Defense Health Board, and a prior member of every US national committee that deals with vaccines, as well as a participant in multiple tabletop exercises designed to improve our pandemic preparedness I have never ceased to be amazed at the conscious and collective “group-think” that pervades what passes for pandemic preparedness and planning. The chapter titles alone are concise and revealing summaries of critical aspects of our willful delusions about the pandemic, and our anemic responses (America the Vulnerable, Confusion and Subterfuge, Pandemics as National Security Threats, The Outbreak We Didn’t Want to See, Looking for Spread in the Wrong Places, the Zika Misadventure, the CDC Fails, Not Enough Tests and Not Enough Labs, Shortage after Shortage, Preparing for the Wrong Pathogen, Stay-at-Home Orders, A Plan Gone Awry, The Information Desert, Hardened Sites, Evidence Is Hard to Collect in a Crisis, Getting Drugs to Patients, the mRNA Breakthrough, A New Doctrine for National Security). Future pandemic planning should only be conducted with adult supervision, include experts other than the same people who have repeatedly failed the nation, involve checks and outside review, and include experts from outside the usual field – such as psychologists, futurists, supply chain and logistical experts, and others – and be chaired by persons such as Gottlieb who have a clear and comprehensive grasp on the multifaceted nature of the complexities involved in preparedness and response.