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As of January 20, 2021, a total of 24,135,690 cases of coronavirus disease 2019 (COVID-19) and 400,306 associated deaths had been reported in the United States (https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days). On December 18, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Moderna COVID-19 vaccine administered as 2 doses, 1 month apart to prevent COVID-19. On December 19, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of Moderna COVID-19 vaccine (1). As of January 10, 2021, a reported 4,041,396 first doses of Moderna COVID-19 vaccine had been administered in the United States, and reports of 1,266 (0.03%) adverse events after receipt of Moderna COVID-19 vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS). Among these, 108 case reports were identified for further review as possible cases of severe allergic reaction, including anaphylaxis. Anaphylaxis is a life-threatening allergic reaction that occurs rarely after vaccination, with onset typically within minutes to hours (2). Among these case reports, 10 cases were determined to be anaphylaxis (a rate of 2.5 anaphylaxis cases per million Moderna COVID-19 vaccine doses administered), including nine in persons with a documented history of allergies or allergic reactions, five of whom had a previous history of anaphylaxis. The median interval from vaccine receipt to symptom onset was 7.5 minutes (range = 1-45 minutes). Among eight persons with follow-up information available, all had recovered or been discharged home. Among the remaining case reports that were determined not to be anaphylaxis, 47 were assessed to be nonanaphylaxis allergic reactions, and 47 were considered nonallergic adverse events. For four case reports, investigators have been unable to obtain sufficient information to assess the likelihood of anaphylaxis. This report summarizes the clinical and epidemiologic characteristics of case reports of allergic reactions, including anaphylaxis and nonanaphylaxis allergic reactions, after receipt of the first dose of Moderna COVID-19 vaccine during December 21, 2020-January 10, 2021, in the United States. CDC has issued updated interim clinical considerations for use of mRNA COVID-19 vaccines currently authorized in the United States (3) and interim considerations for preparing for the potential management of anaphylaxis (4).

Cases of apparent secondary immune thrombocytopenia (ITP) after SARS-CoV-2 vaccination with both the Pfizer and Moderna versions have been reported and reached public attention. Public alarm was heightened following the death of the first identified patient from an intracranial hemorrhage, which was reported on the Internet, then in USA Today1 and then in The New York Times.2 Described below, we have collected a series of cases of very low platelet counts occurring within 2 weeks of vaccination in order to enhance our understanding of the possible relationship, if any, between SARS-CoV-2 vaccination and development of ITP with implications for surveillance and management. Twenty case reports of patients with thrombocytopenia following vaccination, 17 without pre-existing thrombocytopenia and 14 with reported bleeding symptoms prior to hospitalization were identified upon review of data available from the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), agencies of the U.S. Department of Health and Human Services (HHS) Vaccine Adverse Events Reporting System (VAERS), published reports,3, 4 and via direct communication with patients and treating providers. These cases were investigated as suspicious for new onset, post-vaccination secondary ITP; we could not exclude exacerbation of clinically undetected ITP. Search terms relating to “decreased platelet count”, “immune thrombocytopenia”, “hemorrhage”, “petechiae”, and “contusion” were utilized to identify cases reported in VAERS. The reports describing 19 of 20 patients included age (range 22–73 years old; median 41 years) and gender (11 females and 8 males). Nine received the Pfizer vaccine and 11 received the Moderna vaccine. All 20 patients were hospitalized and most patients presented with petechiae, bruising or mucosal bleeding (gingival, vaginal, epistaxis) with onset of symptoms between 1–23 days (median 5 days) post vaccination. Platelet counts at presentation were available for all 20 cases with the majority being at or below 10 × 109/L (range 1–36 × 109/L; median 2 × 109/L). One patient had known ITP in remission; another had mild–moderate thrombocytopenia in 2019 with note of positive anti-platelet antibodies, a third had previous mild thrombocytopenia (145 × 109/L) while a fourth had inherited thrombocytopenia with baseline platelet counts of 40–60 × 109/L. Three other patients had known autoimmune conditions including hypothyroidism, Crohns disease, or positive tests for anti-thyroglobulin antibodies. Treatment for suspected ITP was described in 15 of the cases, including corticosteroids n = 14, intravenous immune globulin (IVIG) n = 12, platelet transfusions n = 8, rituximab n = 2, romiplostim = 1, vincristine = 1, and aminocaproic acid (Amicar) n = 1; combination therapy was used in most patients. Initial outcomes were reported in 16 cases. An improvement in the platelet count was described in patients treated with platelet transfusion alone (n = 1), corticosteroids alone (n = 1), corticosteroids + platelet transfusion (n = 3), corticosteroids + IVIG (n = 3), corticosteroids + IVIG + platelet transfusion (n = 5), corticosteroids +IVIG + rituximab + vincristine + romiplostim (n = 1). The index patient passed away after a cerebral hemorrhage, as mentioned, notwithstanding having received emergent treatment with IVIG, steroids, rituximab and platelet transfusions. Another patient had no improvement in platelet counts after 3 days, but treatment details are not specified. Five additional patients with ”thrombocytopenia” or ”immune thrombocytopenia” post vaccination were identified in VAERS (last accessed 2/5/21), but either available information is insufficient for inclusion or the clinical scenarios suggest alternative processes contributing to thrombocytopenia. One 59 year-old man was identified with ”thrombocytopenia” at an unspecified time after receiving the Pfizer vaccine without additional details regarding platelet count, clinical course, or treatment. A 44 year-old woman was hospitalized for nausea, vomiting and chest pain on the day that she received the Pfizer vaccine. Her laboratory values included a platelet count of 85 × 109/L and a peak troponin level of 4 ng/mL (normal < = 0.04 ng/mL). The patient was diagnosed with myocarditis but did not require treatment for thrombocytopenia. Her platelets were 61 × 109/L on discharge, but subsequent platelet counts were not reported. The third is a patient without age or gender reported who was found to have thrombocytopenia, neutropenia and a pulmonary embolism at an unspecified time following the Pfizer vaccine. This patient was hospitalized and passed away; no additional details were available. A fourth patient, a 37-year-old man, had ”thrombocytopenia requiring hospitalization, meds and platelet infusion” 4 days following the Moderna vaccine with no details regarding presenting symptoms, platelet count, treatment or outcome. The last patient is an 80 year-old man with multiple medical problems including recent transcatheter aortic valve replacement, hypothyroidism, and diverticulosis who presented 6 days after the Pfizer vaccine with bloody diarrhea, hemoglobin 8.7 g/dL and platelets 60 × 109/L. He received several units of packed red blood cells and two units of platelets with improvement to 101 × 109/L and was discharged 5 days later. There were a handful of reports with minimal additional details alluding to a male who passed away in December from brain hemorrhage following the Pfizer vaccine – these could be describing the index patient. We did not attempt to obtain information on patients with pre-existing active ITP who received a SARS-CoV-2 vaccine for this report. We identified additional reports of post-vaccination bruising or bleeding unrelated to the injection site, but no mention of platelet counts, or thrombocytopenia, was provided. Note, VAERS was last accessed on January 29, 2021 for this search. Fourteen patients reported ”petechiae”/”bruising” of whom three were evaluated in the office and one presented to the emergency room. There have been 51 reports of” bleeding”/”hemorrhage” (vaginal n = 11, conjunctival n = 13, cerebral n = 6, gingival n = 2, gastrointestinal n = 5, epistaxis n = 12, and cutaneous n = 2). There were 31 patients who did not seek additional evaluation, seven were seen via office visits, while 13 presented to the emergency room or were hospitalized. Two patients passed away in the hospital. No additional details are available. Are these case of primary ITP coincident with or secondary ITP as a result of vaccination? In either case, the clinical presentations and the favorable response to “ITP-directed” therapies in most of the treated patients, such as corticosteroids and IVIG suggest an antibody-mediated platelet clearance mechanism that is operative in ITP. Is the relationship between vaccination and thrombocytopenia coincident or causal? It is not surprising that 17 possible de novo cases would be detected among the well over 20 million people who have received at least one dose of these two vaccines in the United States as of February 2, 2021. This would be less than one case in a million vaccinated persons, consistent with the absence of cases seen in the more than 70 000 subjects enrolled in the combined Pfizer and Moderna vaccine trials.5, 6 If we assume that these reports identify 17 cases of secondary ITP that developed following vaccination, this extrapolates to 17 × 6 (because only cases that occurred during the first 2 months [December 2020 – January 2021] following vaccine rollout are captured) × 15 to cover the fraction of the population that has been vaccinated [20 million of the 300+ million total US population]) = approximately 1500 cases of post-vaccine secondary ITP/year. There are approximately 50 000 adults who are diagnosed with ITP in the US each year. If we explored the temporal relationship of the 17 cases occurring within 1-2 weeks of vaccination, then we could extrapolate by multiplying by 26 or 52 weeks to look at the rate of ITP per year if the cases are totally ‘coincidental’. This would be approximately 39,000 to 78,000 cases of ITP per year which is not far from the estimated total baseline incidence per year. Thus, the incidence of an immune-mediated thrombocytopenia post SARS-CoV-2 vaccination appears either less than or roughly comparable to what would be seen if the cases were coincidental following vaccination, perhaps enhanced somewhat by heightened surveillance of symptomatic patients. These estimates are very rough so this information should be considered very preliminary. It also assumes that all cases of clinically significant ITP are reported. The incidence of secondary ITP following other types of vaccines provides an inconsistent picture. It is estimated that approximately 1:40 000 children develop secondary ITP after receiving measles-mumps-rubella (MMR) vaccine.7 Well-documented cases of acquired immune thrombocytopenia have been reported after varicella and other vaccinations as well, including one described in this issue of the American Journal of Hematology following Shingrix recombinant Zoster vaccine.8-10 On the other hand, the only case–controlled study of adult recipients of all vaccines published 10 years ago was interpreted as indicating no discernable increase in ITP within 1 year post vaccination.11 In the absence of pre-vaccination platelet counts and given the variable time post vaccination to discovery of thrombocytopenia, it is impossible to precisely estimate the incidence of secondary ITP post SARS-CoV-2 vaccination at this time. However, it is notable that all but one of the cases identified thus far occurred after the initial dose of SARS-CoV-2 vaccine. One would assume that if the vaccination was unrelated to development of ITP, case occurrences would divide more evenly between the two doses. It is also likely that the actual incidence of thrombocytopenia, including mild asymptomatic cases, may be higher and go unreported. Even in view of the uncertain relationship between SARS-CoV-2 vaccination and secondary ITP, it is worth considering possible mechanisms by which this might occur. Thrombocytopenia has been reported after treatment with some anti-sense oligonucleotides,12, 13 but it would seem that a far higher, sustained level of RNA reaching dendritic cells in lymph nodes and elsewhere would be required to generate an immune response than is likely seen based on a single intramuscular injection. This is also inconsistent with the very rapid onset of thrombocytopenia in the index and additional cases. Another possibility is that some individuals may have pre-formed antibodies, including those directed against poly-ethylene-glycol or to other components of the outer lipid layer of the nanoparticles. This presumes that antibodies directed against a novel antigen formed by attachment of vaccine particles on a small number of platelets trigger a reaction involving “all” platelets, which seems unlikely. Recent articles identified antibodies detected post Covid-19 infection that activated platelets14 and an ITP-like syndrome following natural infection15, 16; both findings require confirmation and the relationship to the post vaccination ITP cases reported here is uncertain. Third, some patients may have had mild “compensated” thrombocytopenia of diverse causes, for example, pre-existing ITP or hereditary thrombocytopenia. For example, one of the patients reported in this issue of the American Journal of Hematology had a documented borderline platelet count (145 × 109/L) 2 months prior to receipt of the vaccine raising the question of pre-existing subclinical ITP.3 The other patient reported in this issue of the American Journal of Hematology had chronic, hereditary thrombocytopenia, with a last known exacerbation 12 years prior to the present episode.4 An additional patient identified in VAERS had platelets of 55–115 × 109/L in 2019. Severe thrombocytopenia in these patients or others may have been induced by enhancement of macrophage-mediated clearance or impaired platelet production as part of a systemic inflammatory response to vaccination.8, 17 This is compatible with patients in whom severe thrombocytopenia was first noted 1–3 days post-vaccination. Transient drops in platelet counts post vaccinations for influenza and other viruses is a not uncommon observation in patients with ITP and other causes of thrombocytopenia. Lastly, post-vaccination ITP remains possible, especially in those with onset 1-2 weeks after exposure. One patient in our series had a normal platelet count documented in the week prior to receipt of the vaccine and only developed symptomatology 13 days post vaccination compatible with vaccine related secondary ITP. The reported cases also provide insight into diagnosis and treatment. Most of the patients responded to treatment with corticosteroids and IVIG but showed little benefit from platelet transfusion, a pattern consistent with that of ITP. There was no response in the two patients treated with rituximab but they were only evaluable for up to 2 weeks; in addition, rituximab would impair the response to vaccination, if given within days to 2 weeks of the vaccination and for at least 4-6 months subsequently. The first of two patients (with sufficient information available) continued to have a platelet count of 1–2 × 109/L and died of intracranial bleeding 16 days post vaccination and 13 days post presentation of ITP despite receiving platelet transfusions, steroids, IVIG, and rituximab. The second patient presented 1 day after vaccination and still had a count of 1 × 109/L 7 days later despite receiving the same combination of the four ITP treatments; however, she responded following addition of vincristine and romiplostim. The suggestion might be (from this very limited information) to give IVIG and high dose steroids as initial treatment. If this does not work and the platelet count remains very low, it would seem appropriate to institute other treatments within the first week including a thrombopoietic agent perhaps starting above the lowest dose often recommended to initate therapy and potentially vinca alkaloids depending upon response. Excluding rituximab from initial treatment seems appropriate in most cases given that response can take up to 8 weeks18 and response to vaccination can be impaired. Once a platelet response is seen, patients could be managed as if they were typical cases of primary ITP. Whether such cases will prove to be self-limiting or persist and lead to chronic ITP remains uncertain. In summary, we cannot exclude the possibility that the Pfizer and Moderna vaccines have the potential to trigger de novo ITP (including clinically undiagnosed cases), albeit very rarely. Distinguishing vaccine-induced ITP from coincidental ITP presenting soon after vaccination is impossible at this time. Additional surveillance is needed to determine the true incidence of thrombocytopenia post vaccination. If the incidence of thrombocytopenia post vaccination is higher than that based on available case reports, we anticipate that many more cases will be reported in the coming weeks as a higher proportion of the population is vaccinated. It may be worthwhile to see whether exacerbations of other conditions considered to have an autoimmune pathophysiology occur as well to gain a better understanding of host response to vaccination. Notwithstanding these concerns, the incidence of symptomatic thrombocytopenia post vaccination is well below the risk of death and morbidity from SARS-CoV-2 infection as also described on the Platelet Disorder Support Association (PDSA) website in the statement from the Medical Advisory Board. We echo recommendations from the PDSA and the American Society of Hematology that strongly encourage reporting this and other potential complications through VAERS and in any other way deemed appropriate. Finally, we recommend immediately checking a platelet count in anyone who reports abnormal bleeding or bruising following vaccination and consulting a hematologist. Management of vaccination in patients with pre-existing ITP is complex and is not explored here. The opinion of the Medical Advisory Board of PDSA is that in most, but not necessarily all, patients the benefit of vaccination exceeds the risk of exacerbating ITP. At this time, for patients with ITP it appears reasonable to obtain a baseline count before vaccination and then obtain additional platelet count(s) following vaccination based on patient clinical and treatment history. In patients who present with severe thrombocytopenia soon after vaccination in the absence of other likely causes, we believe it would be appropriate to pursue aggressive treatment for presumed ITP. Whether to administer a second dose of vaccine or whether a change to a different vaccine is warranted in patients who develop thrombocytopenia or substantial worsening of pre-existing thrombocytopenia with the initial dose requires further study. Eun-Ju Lee, James B Bussel, and Douglas B Cines contributed to the data acquisition, interpretation of data and wrote the manuscript. Terry Gernsheimer, Craig Kessler, Marc Michel, Michael D Tarantino, John W Semple, Donald M Arnold, Bertrand Godeau, Michele P Lambert provided input on the manuscript and approved the final version for submission. E.L., and J.W.S. declare no conflict of interest. D.B.C. has received relevant research support from Alexion and Aplagon, and served as a consultant to Rigel, Dova, and CSL Behring. T.G. has received honoraria from Amgen; has acted as a consultant for Amgen, Dova Pharmaceuticals, Biogen, Cellphire, Fujifilm, Rigel, Shionogi, and Principia; and has received research support from Principia. C.K. has served on advisory boards for Novartis, Rigel, Dova, Pfizer. M.M. has received research support from GSK, and received fees from LFB. M.D.T. has received research funding from Grifols and Novo Nordisk; is on advisory boards for Biogen, Grifols, Kedrion, Novo Nordisk, Pfizer, and Takeda; is a speaker for Amgen, Grifols, Octapharma, and Takeda; and reviews grants for Pfizer. D.M.A. has received research funding from Novartis, Bristol-Myers Squibb, and Rigel and has acted as a consultant for Novartis, Principia, and Rigel. B.G. served as an expert for Amgen, Novartis, LFB and Roche; has received research support from Amgen and Roche. M.P.L. has served on advisory boards for Octapharma and Shionogi, has acted as a consultant for Amgen, Novartis, Shionogi, Dova, Principia, Argenx, Rigel and Bayer, and has received research funding from Sysmex, Novartis, Rigel and Astra Zeneca. J.B.B. has served on advisory boards and/or consulted for Amgen, Novartis, Dova, Rigel, UCB, Argenx, Momenta, Regeneron, RallyBio, and CSL-Behring. None. Not applicable Table S1: Patients with reported thrombocytopenia post SARS/CoV-2 vaccination Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

RNA is a large group of functionally important biomacromolecules. In striking analogy to proteins, the function of RNA depends on its structure and dynamics, which in turn is encoded in the linear sequence. However, while there are numerous methods for computational prediction of protein three-dimensional (3D) structure from sequence, with comparative modeling being the most reliable approach, there are very few such methods for RNA. Here, we present ModeRNA, a software tool for comparative modeling of RNA 3D structures. As an input, ModeRNA requires a 3D structure of a template RNA molecule, and a sequence alignment between the target to be modeled and the template. It must be emphasized that a good alignment is required for successful modeling, and for large and complex RNA molecules the development of a good alignment usually requires manual adjustments of the input data based on previous expertise of the respective RNA family. ModeRNA can model post-transcriptional modifications, a functionally important feature analogous to post-translational modifications in proteins. ModeRNA can also model DNA structures or use them as templates. It is equipped with many functions for merging fragments of different nucleic acid structures into a single model and analyzing their geometry. Windows and UNIX implementations of ModeRNA with comprehensive documentation and a tutorial are freely available.

The novel coronavirus outbreak was declared a pandemic in March 2020. We are reviewing the COVID-19 vaccines authorized for use in the United States by discussing the mechanisms of action, administration, side effects, and efficacy of vaccines developed by Pfizer, Moderna, and Johnson & Johnson. Pfizer and Moderna developed mRNA vaccines, encoding the spike protein of SARS-CoV-2, whereas Johnson & Johnson developed an adenovirus vector-based vaccine. Safety has been shown in a large cohort of participants in clinical trials as well as the general population since emergency approval of vaccine administration in the US. Clinical trial results showed the Pfizer and Moderna vaccines to be 95.0%, and the Johnson & Johnson vaccine to be 66.0% effective in protecting against moderate and symptomatic SARS-CoV-2 infection. It is important to keep medical literature updated with the ongoing trials of these vaccinations, especially as they are tested among different age groups and upon the emergence of novel variants of the SARS-CoV-2 coronavirus.

Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.

Importance: In response to the coronavirus disease 2019 (COVID-19) pandemic, 2 mRNA vaccines (Pfizer-BioNTech and Moderna) received emergency use authorization from the US Food and Drug Administration in December 2020. Some patients in the US have developed delayed localized cutaneous vaccine reactions that have been dubbed "COVID arm." Objective: To describe the course of localized cutaneous injection-site reactions to the Moderna COVID-19 vaccine, subsequent reactions to the second vaccine dose, and to characterize the findings of histopathologic examination of the reaction. Design, Setting, and Participants: This retrospective case series study was performed at Yale New Haven Hospital, a tertiary medical center in New Haven, Connecticut, with 16 patients referred with localized cutaneous injection-site reactions from January 20 through February 12, 2021. Main Outcomes and Measures: We collected each patient's demographic information, a brief relevant medical history, clinical course, and treatment (if any); and considered the findings of a histopathologic examination of 1 skin biopsy specimen. Results: Of 16 patients (median [range] age, 38 [25-89] years; 13 [81%] women), 14 patients self-identified as White and 2 as Asian. The delayed localized cutaneous reactions developed in a median (range) of 7 (2-12) days after receiving the Moderna COVID-19 vaccine. These reactions occurred at or near the injection site and were described as pruritic, painful, and edematous pink plaques. None of the participants had received the Pfizer-BioNTech vaccine. Results of a skin biopsy specimen demonstrated a mild predominantly perivascular mixed infiltrate with lymphocytes and eosinophils, consistent with a dermal hypersensitivity reaction. Of participants who had a reaction to first vaccine dose (15 of 16 patients), most (11 patients) developed a similar localized injection-site reaction to the second vaccine dose; most (10 patients) also developed the second reaction sooner as compared with the first-dose reaction. Conclusions and Relevance: Clinical and histopathologic findings of this case series study indicate that the localized injection-site reactions to the Moderna COVID-19 vaccine are a delayed hypersensitivity reaction. These reactions may occur sooner after the second dose, but they are self-limited and not associated with serious vaccine adverse effects. In contrast to immediate hypersensitivity reactions (eg, anaphylaxis, urticaria), these delayed reactions (dubbed "COVID arm") are not a contraindication to subsequent vaccination.

SUMMARY: The diverse functional roles of non-coding RNA molecules are determined by their underlying structure. ModeRNA server is an online tool for RNA 3D structure modeling by the comparative approach, based on a template RNA structure and a user-defined target-template sequence alignment. It offers an option to search for potential templates, given the target sequence. The server also provides tools for analyzing, editing and formatting of RNA structure files. It facilitates the use of the ModeRNA software and offers new options in comparison to the standalone program. AVAILABILITY AND IMPLEMENTATION: ModeRNA server was implemented using the Python language and the Django web framework. It is freely available at http://iimcb.genesilico.pl/modernaserver. CONTACT: iamb@genesilico.pl.

The Moderna mRNA-1273 vaccine was authorized by the Food and Drug Administration for emergency use during the ongoing COVID-19 pandemic in December 2020.1 Out of 15,185 participants in the phase III Coronavirus Efficacy (COVE) trials who received at least one dose of the Moderna vaccine, 228 (1.5%) reported hypersensitivity adverse events, including injection site rash and urticaria.2 Although we have seen an eruptive, morbilliform rash that manifests 48 hours postvaccination that is similar to a drug rash (Fig 1), we report 4 cases of “COVID arm”: a localized erythematous rash surrounding the injection site that manifests days after the first dose of the Moderna COVID-19 vaccine.

Use of all COVID-19 vaccines authorized under an EUA, including the Moderna COVID-19 vaccine, should be implemented in conjunction with ACIP's interim recommendations for allocating initial supplies of COVID-19 vaccines (3). The ACIP recommendation for the use of the Moderna COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available.

Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.

The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5'-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5'-UTR and the downstream 3'-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine (Ψ) complicates some of these optimization processes because Ψ is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly.

INTRODUCTION: A worldwide vaccination campaign is underway to bring an end to the SARS-CoV-2 pandemic; however, its success relies heavily on the actual willingness of individuals to get vaccinated. Social media platforms such as Twitter may prove to be a valuable source of information on the attitudes and sentiment towards SARS-CoV-2 vaccination that can be tracked almost instantaneously. MATERIALS AND METHODS: The Twitter academic Application Programming Interface was used to retrieve all English-language tweets mentioning AstraZeneca/Oxford, Pfizer/BioNTech and Moderna vaccines in 4 months from 1 December 2020 to 31 March 2021. Sentiment analysis was performed using the AFINN lexicon to calculate the daily average sentiment of tweets which was evaluated longitudinally and comparatively for each vaccine throughout the 4 months. RESULTS: A total of 701 891 tweets have been retrieved and included in the daily sentiment analysis. The sentiment regarding Pfizer and Moderna vaccines appeared positive and stable throughout the 4 months, with no significant differences in sentiment between the months. In contrast, the sentiment regarding the AstraZeneca/Oxford vaccine seems to be decreasing over time, with a significant decrease when comparing December with March (p<0.0000000001, mean difference=-0.746, 95% CI=-0.915 to -0.577). CONCLUSION: Lexicon-based Twitter sentiment analysis is a valuable and easily implemented tool to track the sentiment regarding SARS-CoV-2 vaccines. It is worrisome that the sentiment regarding the AstraZeneca/Oxford vaccine appears to be turning negative over time, as this may boost hesitancy rates towards this specific SARS-CoV-2 vaccine.

with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

Resenha do livro:SANTOS, Boaventura de Sousa. Introdução a uma ciência pós-moderna. Rio de Janeiro, Graal, 1989.

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O livro de Mario Alighiero Manacorda trata da relação marxismo e educação. A parte central do livro é fruto de pesquisa realizada por Manacorda em 1960. No Brasil, foi traduzido e editado pela primeira vez em 1991. Para esclarecer o pensamento marxista sobre o ensino, Manacorda parte da análise filológica dos primeiros textos de Marx e Engels. Conclui: há necessidade de se enfrentar a sociedade capitalista de modo a eliminar a propriedade privada, a divisão do trabalho, a exploração e a unilateralidade do homem, para atingir o pleno desenvolvimento das forças produtivas e a recuperação da unilateralidade. Eis os princípios da pedagogia marxiana.

Il ‘Panegirico’ di Plinio nella critica moderna was published in Band 33/1. Teilband Sprache und Literatur (Allgemeines zur Literatur des 2. Jahrhunderts und einzelne Autoren der trajanischen und frühhadrianischen Zeit) on page 387.