key: cord-0683222-aekhd3tb authors: Kadali, Renuka Ananth Kalyan; Janagama, Ravali; Peruru, Sharanya; Gajula, Viswanath; Madathala, Rajasekhar R.; Chennaiahgari, Nikhita; Malayala, Srikrishna V. 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 date: 2021-05-05 journal: J Med Virol DOI: 10.1002/jmv.26996 sha: d1d96240489531c9fe0d995a5d637a24a9489872 doc_id: 683222 cord_uid: aekhd3tb 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. Severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) were thought to have emerged in China, with bats as their original carriers. 1 SARS-CoV-2 is transmitted via respiratory droplets from face-to-face contact or contaminated surfaces. Although the role of aerosol spread in humans remains unclear, this mode of transmission is still a major concern. 2 Common symptoms in hospitalized patients with coronavirus disease 2019 (COVID- 19) infection include fever, dry cough, shortness of breath, fatigue, myalgia, nausea, vomiting or diarrhea, headache, weakness, anosmia, ageusia, and rhinorrhea. 3 Common complications 4-10 with COVID-19 infection include pneumonia, acute respiratory distress syndrome, acute liver failure, cardiac abnormalities with troponin elevation, acute heart failure dysrhythmias, myocarditis, prothrombotic coagulopathy resulting in venous and arterial thromboembolic events, acute renal failure, neurologic manifestations, including impaired consciousness and acute cerebrovascular disease such as stroke, and shock. The overwhelming systemic inflammation and multiorgan failure with high mortality is secondary to "cytokine storm syndrome" (pediatric inflammatory multisystem syndrome in children, which is an immune deregulation characterized by perpetuated activation of lymphocytes and macrophages, resulting in secretion of large quantities of cytokines). 11, 12 As of February 22, 2021 , the number of deaths related to COVID-19 infection in the United States was 500 000. 13 The Moderna COVID-19 mRNA-1273 vaccine was authorized by the Food and Drug Administration (FDA) in the United States to prevent COVID-19 infection on December 18, 2020. On December 19, 2020 , the Advisory Committee on Immunization Practices issued an interim recommendation for the use of a twodose regimen of mRNA-1273 vaccine (which was shown to have 94.1% efficacy in prevention of COVID-19 illness, including severe disease) in persons aged 18 years or older. [14] [15] [16] The first phase of the vaccination program was primarily focused on healthcare workers (HCWs) nationwide (who were at the forefront and took the vaccine as a challenge) and on long-term care facility (LTCF) residents. The Moderna COVID-19 vaccine, mRNA-1273 (100 μg) is administered intramuscularly as a series of two doses (0.5 ml each), given 28 days apart. 17 A large population-based study described that allergic reactions to vaccines generally occur at a rate of 1.31 (95% confidence interval, 0.90-1.84) cases per million vaccine doses, with no fatalities reported. 18 Current reports from the Centers for Disease Control and Prevention (CDC) suggest that anaphylactic reactions to the mRNA-1273 vaccine may occur more frequently than to other vaccines. 19 Overall, the COVID-19 messenger RNA (mRNA)-based vaccination program has generated many concerns, questions, and continuing arguments about the safety issues of both new mRNA vaccines among HCWs and the general population in the United States. However, there are limited data and literature on the side effects that specifically focus on a detailed review of organ systems and the demographic factors, such as age, gender, education level, and ethnicity. The objective of the present study was to analyze the safety and more detailed side effect profile of the mRNA-1273 vaccine using a self-reported online survey questionnaire among HCWs. Therefore, we chose a random population of HCWs and in- (2) communities of HCWs via social media. Informed consent was obtained at the beginning of the survey. Participants who voluntarily agreed and consented to proceed and who chose to receive one of the two mRNA-based COVID-19 vaccines were automatically allowed to move forward to answer subsequent questions about the side effects and other variables. Those who chose "None of them" were diverted to a disqualified page. The study obtained feedback in anonymous mode regarding the side effects and benefit profile during the postvaccination period. This study included the healthcare providers and workers in healthcare settings (Phase 1a vaccine recipients who may be exposed to suspect or confirmed COVID-19 patients or infective materials) that have received one or two doses of the mRNA-based COVID-19 vaccine. (1) Those who received one or two doses of the mRNA-based COVID-19 vaccine but belong to one of the following: (a) Phase 1a "long-term care facility" residents and staff. (2) Those who did not receive mRNA-based COVID-19 vaccine. The (7) Decrease in memory 1.62% (7) Ear pain 1.62% (7) Food intolerance 1.62% (7) Hives 1.62% (7) Increased appetite 1.62% (7) Increased urine production 1.62% (7) Depression 1.39% (6) Numbness 1.39% (6) Urgent need to urinate 1.16% (5) Extremely rare frequency The generalized symptoms that were primarily reported are Approximately 94.21% (407/432) of HCWs reported sore arm or pain at the injection site as their primary localized side effect, followed by swelling by 15.05% (65), itching by 14.58% (63), rash** by 13 .43% (58), lymphadenopathy (axillary or regional or cervical or ipsilateral supraclavicular) by 4.17% (18) , residual skin discoloration by 3.47% (15) , and bleeding by 0.46% (2) of the recipients (432). Myalgia (muscle pain) was reported by 54.17% (234), arthritis or joint pain by 24.77% (107), and muscle stiffness/spasm by 11.11% (48) of the recipients (432). Nausea was reported by 26 (14), vomiting by 3.01% (13), constipation by 1.62% (7), food intolerance by 1.62% (7), and trouble swallowing by 0.23% (1) of the recipients (432). 3.7 | Head/eyes/ears/nose/mouth/throat symptoms Nasal stuffiness was reported by 6.48% (28), sore throat by 6.02% Decreased appetite*** was reported by 13.19% (57), heat or cold intolerance by 8.56% (37), increased thirst by 3.24% (14) , increased appetite by 1.62% (7), and increased urine production by 1.62% (7) of the recipients (432). Palpitations/racing heart was reported by 8.1% (35), blood pressure changes by 1.85% (8), chest pain by 1.85% (8) , and syncope by 0.93% (4) of the recipients (432). Shortness of breath was reported by 2.31% (10), and cough by 3.47% (15) of the recipients (432). Among the 432 recipients, 1.62% (7) reported hives, 0.93% (4) reported atopic eczema, 0.69% (3) reported hay fever, 0.46% (2) reported swelling in the mouth/throat, 0.46% (2) reported asthma exacerbation, 0.23% (1) swelling of the lips, and 0.23% (1) reported anaphylaxis. We obtained information on chronic medical problems among the study participants ( A total of 2.08% (9) participants reported improvement or resolution of symptoms from their chronic medical problems after receiving the vaccination. The present study aimed to analyze the safety and more detailed (8) Chronic alcohol intake 1.62% (7) Chronic smoking (or quit within last 5 years) 1.39% (6) such as heart disease, cancer, stroke, probable pulmonary embolism, and otherwise frail health were thought to be the causes of death. The common adverse reactions to the mRNA vaccines, such as fever, nausea, and diarrhea, may have contributed to fatal outcomes in some of the frail patients. 20 However, in our study; since the response data was first hand (directly from the vaccine recipients), no data on deaths were collected which was reflected as if there were no reports of deaths from the mRNA-1273 vaccine in our study. Therefore, we recommend following the CDC guidelines that everyone who is vaccinated should be observed for at least 15 minutes after receiving the vaccine, with epinephrine available at the vaccination site in case it is needed. It is the inactive ingredient or the excipient (including egg protein, gelatin, formaldehyde, thimerosal, or neomycin), but not the active ingredients, that are attributable for the allergic reactions. | 4427 examples including rare cases of Bell's palsy and other neurologic disease that were reported after COVID vaccination; however, so far, there is no clear suggestion that the vaccine played any role). 23 We reviewed the symptomatology from the original trial conducted by Moderna which was released by FDA in its briefing document before the approval of COVID-19 mRNA-1273 vaccine. 24 Though, the percentages of several high-frequent symptoms in both the trial group and our study are almost similar, their reported list of symptomatology is certainly narrower in comparison to our detailed complete review of the organ systems (Tables 2 and 3 Hence, we tried to avoid the response fatigue from our survey respondents and limited or avoided the questions focusing on the severity level of every adverse effect. Therefore, the severity of each symptom was not gauged quantitatively in the study. The first-dose efficacy of 92.1% was reported for the mRNA-1273 vaccine. 24 Having such a highly protective first dose, the benefits derived from a scarce supply of vaccine could be maximized by deferring second doses until all priority group members are offered at least one dose. 25 Thereby, choosing alternative dosing regimens may also prevent the side effects associated with second dose of the vaccine. Our findings about side effects with BNT162b2 mRNA vaccine were reported in a parallel sub-study. 26 A more detailed review of organ systems on HCWs in this study after receipt of the mRNA-1273 vaccine in comparison to what the CDC is collecting through the VAERS showed that sore arm or localized pain, generalized weakness or fatigue, headache, myalgia or muscle pain, chills, fever, nausea, joint pain, sweating, localized swelling at the injection site, dizziness, itching, rash, decreased appetite, muscle stiffness or spasm, decreased sleep quality, and brain fogging are the most commonly reported symptoms (in the descending order of occurrence), followed by flushing, heat or cold intolerance, palpitations, diarrhea, nasal stuffiness, and sore throat as other predominant symptoms. Most of the symptoms reported during the early phase of post-vaccination period were non-life threatening. The high acceptance rate towards the second dose of vaccine is a positive sign and can be encouraging for future vaccine recipients to end the deadly pandemic, irrespective of side effects. The acceptability or tolerance of symptoms perceived might be higher in HCWs with their higher level of education (Table 1 ) and experience in the healthcare field. There is no available objective data to compare and analyze the tolerance rate for HCWs, but this can certainly be considered as a question for future or subsequent studies among nonhealthcare worker population using a similar questionnaire. Having a highly protective first-dose efficacy of 92.1% with the mRNA-1273 vaccine, vaccine researchers may consider to perform studies on alternative dosing regimen which may also help prevent several side effects associated with second dose of the vaccine. Origin and cross-species transmission of bat coronaviruses in China Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis Coagulation abnormalities and thrombosis in patients with COVID-19 Cardiovascular complications in COVID-19 Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China Incidence of venous thromboembolism in hospitalized patients with COVID-19 Incidence of acute kidney injury in COVID-19 infection: a systematic review and meta-analysis Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis COVID-19 infection and stroke risk Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome COVID-19 pandemic and children: a review United States at a Glance Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine-United States Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States Risk of anaphylaxis after vaccination in children and adults Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine-United States First month of COVID-19 vaccine safety monitoring-United States mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach Census and 2017 American Community Survey 1-year estimates 19 vaccines: safety, side effects and coincidence. Harvard Health Blog FDA Briefing Document: Moderna COVID-19 vaccine. Vaccines and Related Biological Products Advisory Committee Meeting. 2020 Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine Side effects of BNT162b2 mRNA COVID-19 vaccine: A randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers The authors are indebted to Dr. Folarin for the timely COVID-19 updates and preparedness meetings at our health system, Dr. Ramu G. Sudhagoni for significant contributions with suggestions on the statistical analysis and critical reading of the manuscript, and to Sailaja Kadali (a student from Richard Montgomery High School, Maryland) for her assistance with sorting data obtained from secured Survey Monkey web source, percentage calculations of the obtained data, and her excellent secretarial assistance. The authors declare that they are no conflict of interests. The views in this article are those of the authors and not of their institutions, pharmaceutical companies, vaccine manufacturing companies, or the CDC, NIAID, NIH, and DHHS. All authors contributed significantly to this study. The exempt approval for this web-based survey study was obtained from the Institutional Review Board at Cape Fear Valley Health System, 1638 Owen Drive, Fayetteville, NC 28304. https://orcid.org/0000-0003- Ravali Janagama https://orcid.org/0000-0002-7601-7648