N Engl J Med. Correspondence to NPJ Vaccines. J Hepatol. Tarakji B, Umair A, Alakeel R et al. When this vaccine was first introduced in the United States in 1955, it used a weakened form of the polio virus that in very rare cases aboutone in 2.4 million recipients became activated and caused paralysis. The annual initiative from UAB Employee Wellness provides a free, 15-minute health screening to all benefit-eligible UAB, UAB Hospital, UAB LLC, UAB Health System/UA Health Services Foundation and Cooper Green employees. Hundt MA, Deng Y, Ciarleglio MM, Nathanson MH, et al. 2021. https://www.fda.gov/media/150320/download. "Many people worry that these vaccines were rushed into use and still do not have full FDA approval they are currently being distributed under Emergency Use Authorizations," Goepfert said. 2004;43(9):150310. 2021;397(10285):163745. Google Scholar. FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine. Etesevimab is a neutralizing antibody with 2 identical light and 2 identical heavy chains also isolated from the convalescent plasma of SARS-COV-2 survivors. As of January 2022, sotrovimab is the only available monoclonal antibody believed effective against the omicron variant, illustrating the dependence of the efficacy of monoclonal antibodies on viral structure. https://doi.org/10.1038/nrd.2017.243. Oral side effects of COVID-19 vaccine. Unlike many medications, which are taken daily, vaccines are generally one-and-done. Efficacy and safety of the RBD-dimer-based Covid-19 vaccine ZF2001 in adults. 2021;325(15):15351544. Sawires L. Effects of the influenza vaccine on the oral cavity. The side effects seen in these studies, and again in the nationwide rollouts that began in December 2020, "were tolerability issues," Goepfert said: "mainly things like arm pain and fatigue and headache. Chills and swollen lymph nodes can also occur. Bell's Palsy After 24 Hours of mRNA-1273 SARS-CoV-2 Vaccine. https://doi.org/10.1007/s10900-020-00958-x. Oral side effects of COVID-19 vaccine. N Engl J Med. 2016;64(6):140315. 2021;325(24):24482456. The trigger for anaphylaxis after administration of the Pfizer-BioNTech or Moderna mRNA vaccines is not yet clear. In patients 30years or younger who were ultimately diagnosed with vaccine-associated myocarditis, 89% reported chest pain (including pressure or discomfort), 98% had an elevated troponin level, and 72% had an abnormal EKG. sharing sensitive information, make sure youre on a federal Int Immunopharmacol. The dose authorized is 12mg/kg for those less than 30kg and 8mg/kg up to 800mg for those heavier than 30kg. Would you like email updates of new search results? SARS-CoV-2 emerged in December 2019 and led to the COVID-19 pandemic. Epub 2020 Jul 23. Mallapaty S. Chinas COVID vaccines have been crucial - now immunity is waning. Mei R, Raschi E, Forcesi E, Diemberger I, et al. Live-attenuated measles virus (MV) vaccines are safe and effective, and high coverage in two-dose regimens has successfully interrupted endemic transmission in large geographic areas. An ecological study of 663, 602 residents in Argentina reported a higher rate of reinfection after SinoPharm and also did not record adverse events [106]. 2021;73(11):e40829. Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page. GBS is a rare side effect that can cause the immune system to attack healthy . People react differently after being vaccinated. When TSS was also reported in individuals who received the Johnson & Jonson vaccine (a human adenovirus vector vaccine), an association between the adenovirus vector and the formation of anti-platelet factor 4 antibodies was proposed [96]. Early indications are that Delta infections bring more severe side effects than other forms of COVID, but that vaccines are still protective against Delta. https://doi.org/10.1126/sciimmunol.aaf7643, Stephenson KE, Le Gars M, Sadoff J, de Groot AM, et al. Fact sheet for health care providers emergency use authorisation (EUA) of bamlanivimab and etesevimab authorized use treatment. Our description of substances and their effects is not exhaustive and presents our knowledge as of June 2022. 2022 Aug 17;19(16):10228. doi: 10.3390/ijerph191610228. 2021 John Wiley & Sons A/S. The concern is that pre-treating with pain medications that reduce fevers and inflammation (like acetaminophen and ibuprofen) could dampen your immune system's response to the vaccine. Myocarditis or pericarditis typically develop within 7days of receiving the Pfizer-BioNTech or Moderna vaccines (74% of cases for the 1st dose, 90% for the 2nd) if they are going to develop [85]. Common COVID-19 vaccine side effects include: Redness or soreness at injection site. JAMA. CanSinBio is a DNA vaccine like Johnson & Johnson. eCollection 2022. Ann Med Health Sci Res 2014; 4: 829. That is not to say that there have never been safety issues with vaccines. (2023)Cite this article. "Medicines you take every day can cause side effects" that reveal themselves over time, including long-term problems as levels of the drug build up in the body over months and years, Goepfert said. Granados Villalpando JM, Romero Tapia SJ, Baeza Flores GDC, Ble Castillo JL, Juarez Rojop IE, Lopez Junco FI, Olvera Hernndez V, Quiroz Gomez S, Ruiz Quiones JA, Guzmn Priego CG. Among men, the highest incidence and mortality was seen in ages 40 to 49 with 4.3 cases per million vaccines doses and 0.7 deaths per million vaccine doses, respectively [97]. The most reported adverse-event was injection-site pain. Google Scholar. https://doi.org/10.1056/NEJMoa2102685. https://doi.org/10.1136/heartjnl-2020-317056. (Photo by: Andrea Mabry) In his nearly 30 years studying vaccines, Paul Goepfert, M.D., director of the Alabama Vaccine Research Clinic at theUniversity of Alabama at Birmingham, has never seen any vaccine as effective as the three COVID vaccines from Pfizer, Moderna, and Johnson & Johnson currently available in the United States. Their data shows that in Australia: over half the participants report no side effects (around 55%) just under half report any side effect (around 44%) less than 1% report visiting a doctor or emergency department after being vaccinated Case series report that self-limited chills and fevers are the main adverse events [9]. That is not to say that there have never been safety issues with vaccines. The Oxford-AstraZeneca vaccine is not approved for use in the United States but is in many parts of the world. Hepatitis B vaccination and associated oral manifestations: A non-systematic review of literature and case reports. Epub 2022 Sep 12. https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/reactogenicity.html. Ann Med Health Sci Res 2014; 4: 829. An analysis of 50,000 hospitalized patients with COVID who received convalescent plasma through the FDAs Early Access Program reported transfusion reactions (n=78), thromboembolic or thrombotic events (n=113, 75 judged unrelated), and cardiac events (n=677; 597 judged unrelated), mainly myocarditis and acute coronary syndrome [10]. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/reactogenicity.html. 2022;71:90. Disruption of CCR5 signaling to treat COVID-19-associated cytokine storm: case series of four critically ill patients treated with leronlimab. 2021 May 7;18(9):4965. doi: 10.3390/ijerph18094965. 2022;327(4):33140. Yang B, Fulcher JA, Ahn J, Berro M, et al. But in each instance, these have appeared soon after widespread use of the vaccine began. Sputnik Light can be stored at 28C, compared to Sputnik V, which must be stored at below 18C. The most common systemic adverse event was fatigue (546 [8.2%] participants in the vaccine group and 248 [7.0%] in placebo group). 3 things to know, New B Well UAB app now offers resources to employees, Caring for patients, Blazers through COVID-19, Blazer-created mental health app puts wellness in student hands, Resiliency training gives all students the tools to bounce back, Get a discounted rate on personal training certification through URec partnership, Ombuds offers a collaborative approach for resolving conflict at work, Employees finding help for anxiety in myStrength app, EACC to increase free sessions to 15 per year beginning Nov. 1, Savings can buy peace of mind. 2021;398(10296):21322. University of Florida, 2018. Google Scholar. Unauthorized use of these marks is strictly prohibited. In 1976, a vaccine against swine flu that was widely distributed in the United States was identified in rare cases (approximatelyone in 100,000) as a cause of Guillain-Barr Syndrome, in which the immune system attacks the nerves. By looking up grey literature, I have found only one study where only three participants (9%) who received the influenza vaccine got oral side effects associated with flu-like symptoms, thus implying that no statistically significant relationship could be established.3 Owing to the mass vaccination strategies of COVID-19, dentists among other clinical specialists are supposed to provide care to the recently vaccinated patients - at this moment, Hill's criteria of causal inference and rigorous anamnestic recording should be strictly followed before jumping to irrelevant conclusions. https://doi.org/10.1001/jamacardio.2021.3471. That is the most troubling unknown for me.. Many Americans say they want to make sure the shot is safe before getting vaccinated. Association between COVID-19 and myocarditis using hospital-based administrative data - United States, March 2020-January 2021. Sato K, Mano T, Niimi Y, Toda T, Iwata A, Iwatsubo T. Int J Infect Dis. Secondary Outcome Measures : https://doi.org/10.1093/cid/ciaa449. Nurse researcher Kristen Choi, PhD, experienced first-hand a "worst-case scenario" of potential side effects after receiving an experimental COVID-19 vaccine in a phase III trial. (Photo by: Steve Wood)The side effects seen in these studies, and again in the nationwide rollouts that began in December 2020, were tolerability issues, Goepfert says, mainly arm pain, fatigue and headache. Mol Ther. Lets talk about lipid nanoparticles. medRxiv.2021.05.07.21256652. Epub 2021 Sep 4. 1;5(4):e227038. Circulation. Senefeld JW, Johnson PW, Kunze KL, Bloch EM, et al. 2021;301(1):E3789. Please enable it to take advantage of the complete set of features! Health Canada and PHAC review the reports to determine whether the vaccine may have played a role. However, the results of the Blaze-1 trial determined that none of the 3 tested bamlanivimab monotherapy groups (700mg, 2800mg, 7000mg) produced a significant decrease in viral load at day 11 of infection compared to placebo [32] and, based on this, the FDA revoked bamlanivimabs monotherapy EUA in February 2021. Fischer S, Gerriets T, Wessels C, Walberer M, et al. Vaccines stimulate the production of antibodies that interact with a specific part of the virus (the epitope). J Transl Autoimmun. As of this writing, the Moderna, Pfizer, Johnson & Johnson, and Novavax (a protein vaccine not discussed here) are approved by the FDA. Try these four Rs to break free. Hodson R. Vaccines. Haq HN, Khan H, Chaudhry H, Nimmala S, Demidovich J, Papudesi BN, Potluri SD. A retrospective trial of 1827 patients with confirmed COVID-19 hospitalized between March 14, 2020, and April 23, 2020, reported transaminase elevations five times above the upper limit of normal as an independent predictor of mortality in patients who received an unspecified combination of lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab [27]. The Oxford-AstraZeneca and Johnson & Johnson vaccines are both DNA vaccines that use adenovirus as a vector. BNT162b2; Bell's palsy; COVID-19; Vaccine; mRNA-1273; side effects. Without integrating itself into the host DNA, the sequence is transcribed into mRNA and translated into the amino acid sequence for the S protein, which is subsequently expressed on the surface of host cells inducing an immune response [42]. For comparison, incidence of anaphylaxis to succinylcholine, vancomycin, and piperacillin/tazobactam have been estimated at 1.11, 0.57, and 0.35 per 1,000,000 administrations, respectively [90]. ECG changes were seen in 87% of patients with ST elevations being the most common finding. And the vaccine was quickly removed from use.. seeing spots or floaters vision loss What are most common side effects from COVID-19 vaccines? Sotrovimab binds to the S2 subunit [16]. Myocarditis associated with mRNA COVID-19 vaccination. Data supporting these associations come from the Vaccine Adverse Event Reporting System (VAERS). Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Another study compared the efficacy of sotrovimab in 546 hospitalized patients with SARS-CoV-2 to 0.9% saline and used the composite endpoint of length-of-stay and recurrent admissions and reported infusion-related adverse events in 18 patients (10%) who received sotrovimab and 14 patients (13%) who received saline. -, Polack FP, Thomas SJ, Kitchin N, et al. UAB Health Systems senior director of Infection Prevention breaks down the chain of transmission and how we all can lower our risk of getting sick. Side Effects of mRNA-Based and Viral Vector-Based COVID-19 Vaccines among German Healthcare Workers. In 48 patients in Wuhan, China, IL-6 levels were correlated with the degree of SARS-CoV-2 viremia and an independent predictor of mortality [24]. This site needs JavaScript to work properly. After a few rounds of translation, the LNP and mRNA are destroyed, and the APC stops manufacturing the S protein [59]. The LNP-mRNA complex is neutral and is taken up by endocytosis into the cell. Lancet Infect Dis. Evid Based Dent. All had chest pain, troponin elevation, and abnormal cardiac MRI (most commonly late gadolinium enhancement). If it happens, healthcare providers can effectively and immediately treat the reaction. The background incidence of myocarditis in this age group is 0.2 to 1.9 per million persons [77, 87]. The site is secure. 1953;98(6):64156. "Up to 10 percent of people who have COVID experience side effects such as difficulty thinking, pain, tiredness, loss of taste and depression. https://doi.org/10.1007/s00441-014-1850-8. Kang Y, Chen T, Mui D, Ferrari V, et al. The existence of variants complicates this goal. Nature. The Johnson & Johnson COVID-19 Vaccine (Ad26.COV2.S) is the third vaccine to receive EUA by the FDA for the prevention of COVID-19 in patients 18years of age and older [49]. Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. UAB - The University of Alabama at Birmingham, Vaccine side effects show up within weeks if at all, Our COVID vaccine experience during the past six months, survey of parents with children ages 12-15, in the New England Journal of Medicine here, British governments regulatory agency here, vaccines are still protective against Delta, My Health Rewards offers incentives for making healthy choices, Reduce stress with this quick, self-paced office ergonomics course, Check out the winners of the 2022 Wellness Week photo/video activity, Discover 12 outdoor oases hiding in plain sight, Find opportunities for mindfulness and health during Wellness Week Oct. 17-21, Wellscreens are back register for yours today, An infection prevention expert explains how to avoid COVID, flu and the next pandemic, Achieve mental clarity through mindfulness meditation this spring. 2020;60(9):113146. Taking OTC pain medications ahead of your shot to try and decrease symptoms is not recommended by the CDC, because it's not clear how that could affect the vaccine's effectiveness. 2021;10(333):51120. A review on oral manifestations of COVID-19 disease. (2023). The biological mechanism underlying this association is not fully understood. Post-vaccine symptoms are typically mild and resolve quickly without the need to use any medication. Background rates of five thrombosis with thrombocytopenia syndromes of special interest for COVID-19 vaccine safety surveillance: Incidence between 2017 and 2019 and patient profiles from 38.6 million people in six European countries. 4 patients (2 in the ZF2001 group and 2 in the placebo group) developed hypersensitivity reactions. https://stacks.cdc.gov/view/cdc/115700. The day Dr. Elizabeth Dawson was diagnosed with COVID-19 in October, she awoke feeling as if she had a bad hangover. Established by a committee of individuals from across the university and UAB Medicine, Wellness Week is designed to help the UAB community prioritize rest, well-being, mindfulness, movement and good nutrition. Clipboard, Search History, and several other advanced features are temporarily unavailable. As of June 12, 2021, more than 2.33 billion COVID vaccine doses have been administered worldwide, according to the New York Times vaccinations tracker. 2021;23(11):e30529. It binds to a region in the RBD that overlaps with the region bamlanivimab targets. This paper, along with its companion that covers xenobiotics and alternative remedies, is an update to . Diffuse ST elevations were seen in 9 (60%) of the patients at time of hospital admission. https://doi.org/10.1093/cid/ciaa1583. PLoS One. https://doi.org/10.4161/mabs.2.3.11782. Sir, vaccine hesitancy (VH) is an emerging public health challenge nourished by misinformation. The https:// ensures that you are connecting to the But knowing the cause can help you determine. Most people also need a booster dose to help improve the protection from the first 2 doses of the vaccine. Cumulative adverse event reporting of anaphylaxis after mRNA COVID-19 vaccine (Pfizer-BioNTech) injections in Japan: the first-month report. Huang Y, Yang C, Xu XF, et al. Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of REGEN-COV (casirivimab and imdevimab).2021. https://www.fda.gov/media/145611/download. Viruses may be able to mutate away from that structure. https://doi.org/10.1001/jama.2021.1967. All symptoms resolved after medical treatment without sequelae. Wan EYF, Chui CSL, Lai FTT, Chan EWY, Li X, Yan VKC, Gao L, Yu Q, Lam ICH, Chun RKC, Cowling BJ, Fong WC, Lau AYL, Mok VCT, Chan FLF, Lee CK, Chan LST, Lo D, Lau KK, Hung IFN, Leung GM, Wong ICK. Montgomery J, Ryan M, Engler R, Hoffman D, et al. Any risk is frightening, especially for a parent. After intramuscular injection, antigen presenting cells (APCs) internalize the LNPs and translate the mRNA into the S protein. Chen X, Zhao B, Qu Y, Chen Y, et al. Beyond taking medication, there are some home remedies that can help you cope with the side effects. J Med Virol. In 1976, a vaccine against swine flu that was widely distributed in the United States was identified in rare cases (approximately one in 100,000) as a cause of Guillain-Barr Syndrome, in which the immune system attacks the nerves. Of the 1991 cases reported to VAERS between December 14, 2020, and August 31, 2021, following at least 1 dose of the Pfizer-BioNTech or Moderna vaccines, in individuals older than 12years of age, 1626 met the CDCs definition of probable or confirmed myocarditis: 1,136 (70%) after the Pfizer-BioNTech vaccine and 490 (30%) after the Moderna vaccine. They also have idiosyncratic side effects and variable and varying efficacy, reflecting their specificity for certain S protein sequences. Nat Rev Immunol. Smallpox vaccination and myopericarditis: a clinical review. Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA COVID-19 vaccines in the US-December 14, 2020-January 18, 2021. SCB-2019 is a recombinant protein vaccine that contains antigenic subunits of the S protein with adjuvants AS03 (-tocopherol, squalene and polysorbate 80 in an oil-in-water emulsion) or CpG/Alum (a toll-like receptor agonist complexed with aluminum). Article About one in 100,000 people receiving the AstraZeneca COVID vaccine have experienced a clotting disorder known as thrombotic thrombocytopenia, including 79 cases among more than 20 million people receiving this vaccine in the United Kingdom, and 19 deaths. COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. 2021;6(12):144650. We don't know why that is, how long these symptoms will last or if there are effective ways to treat them. https://doi.org/10.1016/j.jhep.2016.02.004. JAMA Netw Open. The only vaccine program that might compare with the scale and speed of the COVID rollout is the original oral polio vaccine in the 1950s, Goepfert says. Women reported more adverse events than men (P<0.001), more AEs occurred after the first dose than the second dose (P<0.001), and the number of AEs decreased with age (P<0.001). Fields virology: emerging viruses. Last year, a national cross-sectional survey-based study found out that aversion to the potential side effects of vaccines was the most frequent cause for VH among population groups in the UK.1 The oral side effects following the administration of vaccines like polio and diphtheria were inconsistently reported with a low level of confidence; they have never been reported independently, eg they emerged typically in conjunction with other dermatologic and systemic symptoms.2 The oral side effects of non-orally administered vaccines including influenza vaccine are extremely rare. An open, non-randomised, phase 1/2 trial on the safety, tolerability, and immunogenicity of single-dose vaccine Sputnik Light for prevention of coronavirus infection in healthy adults. Of 23 patients who received one subcutaneous injection of 700mg leronlimab on a compassionate use basis, 17 recovered at day 30 although IL-6 levels did not decrease after administration. https://doi.org/10.1093/infdis/jiu396. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 1859 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. In December 2021, the FDA issued an EUA for sotrovimab [12], bamlanivimab/etesevimab [13], and casirivimab/imdevimab [14] to treat non-hospitalized immunosuppressed patients who are at high risk for progression of COVID-19 symptoms. 3. You wouldn't expect any of these vaccines to have any long-term side effects. Here we provide a narrative review of the biologic therapeutics used or proposed to treat COVID-19 during the last 3years. J Am Coll Cardiol. UAB also encourages applications from individuals with disabilities and veterans. https://doi.org/10.1161/CIRCULATIONAHA.122.059970. Side effects of the coronavirus (COVID-19) vaccination Very common side effects in the first day or two include: having a painful, heavy feeling and tenderness in the arm where you had your injection feeling tired headache, aches and chills diarrhoea, nausea and vomiting mild flu-like symptoms MAbs. Others could be more systemic, such as low-grade fever, achiness, or fatigue that ranges from mild to severe. You can also search for this author in DNA vaccines introduce viral DNA into host cells that codes for a protein or proteins integral to viral function (for SARS-CoV-2 usually the S protein). Castells MC, Phillips EJ. The common side effects for the Moderna and Pfizer-BioNTech Covid vaccines include things like pain and swelling on your arm where you get the shot, and flu-like symptoms including fatigue, headache, fever and chills. RECOVERY Collaborative Group. The following outcomes were selected and defined by the authors based on information from regulatory authorities, previous studies, large-scale adverse events initiatives: febrile seizure, aseptic. ), More recently, an even more rare side effect myocarditis, or inflammation of the heart muscle has been reported in people receiving Pfizer and Moderna COVID-19 vaccines. ", The long-term side effects of COVID infection are a major concern. 2021;25(3):16631669. In non-hospitalized patients with COVID-19 treatment with 2800mg bamlanivimab and 2800mg etesevimab infused over a total of 1h reduced viral load at day 11 compared with saline placebo. Immune Netw. For the Pfizer vaccine, myocarditis was most common during the 7days after the second Pfizer-BioNTech dose for males and females aged 1617, at 105.86 [95% CI, 91.65122.27] and 10.98 [95% CI, 7.1616.84] cases per million doses, respectively. MMWR Morb Mortal Wkly Rep. 2021;70(35):12281232. JAMA. https://doi.org/10.1002/jcph.1693. Vaccines are just designed to deliver a payload and then are quickly eliminated by the body, Goepfert said. MAbs. The most common side effects of the COVID-19 vaccines include: redness, pain, or. The most common adverse events attributed to tocilizumab are an increased incidence of opportunistic infections, reflecting immunosuppression, and clinically insignificant dyslipidemia [28]. The baseline rates for myocarditis in those age groups are 1.34 [95% CI, 1.051.72] and 0.42 [95% CI, 0.270.66] cases per million persons, respectively. Iftikhar H, Noor SMU, Masood M, Bashir K. Cureus. The S protein is composed of a region that attaches to the ACE2 receptor (the receptor binding domain (RBD) or S1) and a region that facilitates fusion of the host and virus membranes (S2) [6]. 2022 Mar 1;60(2):224-228. People who already had COVID are more likely to experience swollen lymph nodes after vaccination. Michael A. Chary is supported by the Loan Repayment Program (National Institute for Drug Abuse, National Institutes of Health). Thank you for visiting nature.com. J Med Internet Res. Wu S, Huang J, Zhang Z, Wu J, et al. Vok Z, Kiss Z, Surjn G, Surjn O, et al. A study from Buenos Aires, Argentina evaluated adverse events in healthcare workers (median age 35years, 67% females) that received Sputnik V. The most reported adverse events were pain at the injection site (57%), redness and swelling, (11%) new or worsened muscle pain (58%), fever (40%), and diarrhea (5%). Out of 8,674,378 administered doses, 16 associated cases of myocarditis were reported to VAERS. Repeat dosing produced injection site reactions in 35% of the casirivimab and imdevimab group (252 people) compared to 16% in the placebo group (38 people). Accessed 26 Feb 2022 from https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-01-05/02-covid-su-508.pdf. https://doi.org/10.1002/pds.5419. Radiology. -. Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of a randomized, blinded, placebo-controlled, Phase 2 clinical trial in adults at high risk of viral exposure.