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SARS-CoV-2 and Influenza Coinfection in a Deployed Military Setting—Two Case Reports

Image of Illustration reveals ultrastructural morphology exhibited by coronaviruses. Click to open a larger version of the image. This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19). (Credit: Alissa Eckert, MSMI; Dan Higgins, MAMS)

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Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is responsible for a global pandemic with over 46 million cases worldwide, including over 9 million in the U.S. and 83,000 in the DoD as of 2 November 2020.1,2 COVID-19 presents as a broad spectrum of disease progression and manifestations ranging from asymptomatic carriage/colonization to acute respiratory distress syndrome leading to severe complications or death. Risk factors for severe disease include several comorbidities: older age (≥65 years), hypertension (HTN), cardiovascular disease, smoking, chronic respiratory disease, cancer, diabetes (DM), obesity (BMI ≥ 30 kg/m2), and male sex.3–6 Additionally, some workplace exposures pose significant risks of infection among workers based on close contacts with high risk populations (e.g., COVID-19 patients, factory workers).Deployment may place service members at higher risk for respiratory infections; for example, a high-profile COVID-19 outbreak on the USS Theodore Roosevelt during deployment was recently described.8

In contrast to COVID-19, the military faces seasonal influenza every year. Risk factors of seasonal influenza overlap with those associated with COVID-19 (e.g., immune suppressed, older age, comorbidities), as do clinical presentations (fever, cough, headaches, and malaise).9 Fortunately, influenza-associated deaths among the U.S. military have been relatively few. This is most likely because of the good preexisting health status of the US military, prompt detection of influenza with rapid influenza diagnostic tests (RIDTs), several effective antiviral therapeutics for early treatment and chemoprophylaxis, and a robust, compulsory vaccination program. The seasonal influenza vaccine has been shown to reduce the risk for influenza illness and associated morbidity and mortality worldwide.10

Coinfection with both SARS-CoV-2 and influenza was reported early in the pandemic, when 46 (49%) of a case series of 93 critically ill COVID-19 cases from Wuhan, China were found to be coinfected with influenza virus.11 Several case reports and case series documenting similar coinfections have been published since then.12–15 Although one meta-analysis estimated that only 3% of COVID-19 cases are coinfected with another virus,16 the impact of coinfections is uncertain due to substantial heterogeneity between populations and environments. This report describes a case series of the first 2 coinfections of COVID-19 and seasonal influenza in the deployed setting, specifically at a U.S. Army Role I Military Treatment Facility (MTF) within the U.S. Central Command (CENTCOM) area of responsibility (AOR). The threats, challenges, and mitigation strategies for these coinfections in the deployed setting are also described.

Case 1

On 8 October 2020, a 56 year old white male contractor, presented to a Role I clinic with symptoms of anorexia, fever, chills, and headache which began 3 days prior. His initial vital signs were unremarkable (blood pressure [BP]: 112/72; pulse [P]: 96; respiratory rate [RR]: 18; peripheral capillary oxygen saturation [SpO2]: 97% RA; temperature [T]: 97o F). He did not display respiratory distress. The QuickVue® rapid point-of-care antigen test was positive for influenza type A; a COVID-19 test was performed but results were not immediately available. He had not received the 2020–2021 seasonal influenza vaccine. He was immediately placed on isolation and antiviral treatment with osteltamivir was initiated. His past medical history was significant for hypertension and obstructive sleep apnea (no continuous positive airway pressure was required). His routine medications included amlodipine, hydrochlorothiazide, and losartan. He did not report any allergies to medications. His physical exam was unremarkable. Subsequently, he tested positive for COVID-19 by nasopharyngeal swab from the Biofire® (reverse transcription polymerase chain reaction [RT-PCR]). On day 6 of the illness, he developed a non-productive cough and myalgias. He completed his course of osteltamivir without issues. On day 9 of illness, the patient complained of “body stiffness” and was prescribed ibuprofen as needed. The remaining course of infection was unremarkable and afebrile. There were no anti-pyretics prescribed for the 24 hours prior to release from isolation and the symptoms were improving. No further testing or diagnostics were required. His condition did not warrant hospitalization. Three close contacts were identified. One contact had symptoms compatible with COVID-19 and was tested; this test came back positive, so the contact was also considered a confirmed case and was isolated for 10 days. At this point, further contact tracing was performed. The 2 other contacts remained asymptomatic during their 14-day quarantine. Ten days after symptom onset, Case 1 returned to duty as per Centers for Disease Control and Prevention (CDC) recommendations.17

Case 2

On 9 October 2020, a 34 year old white male Army officer was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive for COVID-19 by the Biofire® RT-PCR. He was placed in isolation with precautions. He did not report any significant past medical history, comorbidities, or medications. His initial vital signs revealed an elevated blood pressure but were otherwise unremarkable (BP: 143/76; P: 83; RR: 16; SpO2: 97%; T:97o F). He continued to be asymptomatic until 2 days later when he complained of myalgias. He did not display any respiratory distress or other symptoms. Since myalgias are a classic symptom of seasonal influenza, the provider ordered a QuickVue® rapid influenza antigen test, which was positive for influenza type B, so the provider started him on the antiviral osteltamivir. He had not received the 2020–2021 seasonal influenza vaccine. His vital signs were stable throughout the illness and the initial elevated blood pressure normalized. His physical exam was unremarkable. On the next day (day 4 from the inititation of quarantine), he complained of new onset nausea and vomiting after taking the osteltamivir. As nausea and vomiting are common side effects of osteltamivir, the provider adjusted the timing of the medicine and prescribed ondansetron as needed for nausea. On day 7, his blood pressure increased to 144/62 and the patient complained of ageusia and anosmia (loss of taste and smell, respectively). On day 8, symptoms also included slight fatigue, but he had no respiratory distress and his vital signs were normal. He completed the course of Tamiflu®. On day 9, he complained of a cough and shortness of breath plus diarrhea, but his vital signs remained normal (BP: 112/80; P: 68; RR: 18; SpO2 98%; T: 96o F) and his physical exam was unremarkable. His symptoms improved through supportive care.

Throughout the remaining course of illness, the patient remained afebrile and improved with no anti-pyretics 24 hours prior to release from isolation. There were no indications for further testing or diagnostics. His course of illness did not warrant hospital admission. Six close contacts were identified; all 6 remained asymptomatic during the 14-day quarantine. Ten days after symptom onset, Case 2 was returned to duty.

Editorial Comment

This report describes the first 2 confirmed cases of COVID-19 and influenza coinfection among U.S. personnel deployed within the CENTCOM AOR. Because seasonal influenza and COVID-19 both present with a wide variety of clinical manifestations and overlapping symptoms, providers should consider the possibility of infection with influenza, COVID-19, or coinfection among patients with respiratory illnesses. While both influenza and COVID-19 may result in severe complications and death, patients with influenza and COVID-19 coinfection have been found to have more than 2 times the odds of death compared to those affected by COVID-19 alone.18 Although standards of fitness required for deployment typically result in a generally healthy deployed population,19 there are some civilian and contractor personnel who may deploy with chronic medical conditions. Additionally, there may be environmental and occupational factors which place personnel at increased risk of infection and transmission during deployment. Some examples of this elevated risk are seen in the current case reports, including the civilian contractor who was at higher risk for occupational exposure as a linguist based on daily interaction with host nation partners, in addition to the congregate living and work settings which exist during deployments.

A Role I medical facility has limited laboratory capability in the deployed environment. The current case reports demonstrate the importance of maintaining an index of suspicion and of early testing for the multiple possible etiologic agents in order to both provide the most appropriate care and to implement effective measures to interrupt disease transmission. Rapid, point-of-care diagnostic test capabilities which include both influenza and COVID-19 can help guide antiviral treatment, implementation of effective prevention and control measures, and other clinical decisions such as antibiotic use and additional diagnostic testing. These tests should preferably be collected within 4 days of symptom onset using nasopharyngeal specimens. Rapid influenza molecular assays are recommended over antigen detection tests,20 and several multiplex nucleic acid detection assays have received Emergency Use Authorization to detect both SARS-CoV-2 and influenza types A and B viruses.21 However, false negative COVID-19 tests may also occur, particularly among those who are coinfected with influenza.13 The local epidemiology of SARS-CoV-2 and influenza viruses should influence clinical and public health decisions. When both viruses are circulating widely, providers may consider presumptive treatment, even in the context of a negative influenza test, based on mission requirements and the clinical situation. Public health may recommend quarantine for close contacts of confirmed influenza cases even if SARSCoV-2 tests are pending or negative. To enhance active case finding efforts, all close contacts of confirmed or probable cases of COVID-19 should be tested.22

The best way to prevent influenza is through annual vaccination. The fact that neither of the 2 cases had received the 2020–2021 vaccine underscores the importance of this intervention. In outpatients with uncomplicated influenza, antiviral treatment has been shown to significantly reduce illness duration, lower respiratory tract complications requiring antibiotics, and hospitalizations for any cause.23,24 Health care personnel should ensure that antiviral treatment is available and prioritized for those who are at high risk for influenza complications. Antiviral chemoprophylaxis of influenza is generally not recommended for widespread or routine use except for control of institutional influenza outbreaks, in hospitalized patients, or among outpatients with complications or progressive disease.20 Clinicians should also ensure that other treatment issues are considered for coinfected patients, such as the higher mortality seen among patients with influenza pneumonia after corticosteroid treatment.25

While this report includes only 2 cases, and further research on influenza and COVID-19 co-infection is certainly warranted, it nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats. This is particularly important in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade Commanders’ execution of critical missions. This requires command emphasis and support of FHP measures including: vaccination, physical distancing, use of face coverings, hygiene and sanitation, contact tracing, isolation and quarantine, medical therapeutics, rapid diagnostic testing, and host nation partnerships. These case reports also highlight the importance of identifying symptomatic persons quickly enough to test, trace, and treat for both COVID-19 and influenza. Understanding the risks and epidemiologic trends of infectious diseases will enhance Commanders’ ability to mitigate the risk of these diseases in deployed forces.

Author affiliations: COL Paul O. Kwon, U.S. AMEDDAC, Fort Jackson, SC; MAJ Nathan A. Fisher, U.S. CENTCOM, Camp Arifjan, Kuwait; COL James D. Mancuso, Uniformed Services University of the Health Sciences, Bethesda, MD.

Disclaimer: The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University, the U.S. Army, or the U.S. Department of Defense.

References

1. Johns Hopkins University & Medicine. Coronavirus resource center. https://coronavirus.jhu.edu/. Updated 2 November 2020. Accessed 2 November 2020.

2. US Department of Defense. Coronavirus: DOD Response (DOD COVID-19 Cumulative Totals). https://www.defense.gov/explore/spotlight/coronavirus/. Updated 30 October 2020. Accessed 2 November 2020.

3. Webb Hooper M, Napoles AM, Perez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA. 2020;323(24):2466-2467.

4. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310.

5. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020. 

6. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. NEngl J Med. 2020;382(18):1708–1720.

7. Baker MG, Peckham TK, Seixas NS. Estimating the burden of United States workers exposed to infection or disease: A key factor in containing risk of COVID-19 infection. PLoS One. 2020;15(4):e0232452.

8. Kasper MR, Geibe JR, Sears CL, et al. An outbreak of COVID-19 on an aircraft carrier. N Engl J Med. 2020.

9. Sanchez JL, Cooper MJ. Influenza in the US military: An overview. J Infectious Diseases & Treatment. 2016;2(1):1–5.

10. Epperson S, Davis CT, Brammer L, et al. Update: Influenza activity—United States and worldwide, May 19–September 28, 2019, and composition of the 2020 southern hemisphere influenza vaccine. MMWR Morb Mortal Wkly Rep. 2019;68(40):880–884.

11. Ma S, Lai X, Chen Z, Tu S, Qin K. Clinical characteristics of critically ill patients co-infected with SARS-CoV-2 and the influenza virus in Wuhan, China. Int J Infect Dis. 2020;96:683–687.

12. Singh B, Kaur P, Reid RJ, Shamoon F, Bikkina M. COVID-19 and Influenza Co-Infection: Report of Three Cases. Cureus. 2020;12(8):e9852.

13. Wu X, Cai Y, Huang X, et al. Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia, China. Emerg Infect Dis. 2020;26(6):1324–1326.

14. Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J Med Virol. 2020.

15. Azekawa S, Namkoong H, Mitamura K, Kawaoka Y, Saito F. Co-infection with SARS-CoV-2 and influenza A virus. IDCases. 2020;20:e00775.

16. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect.2020;81(2):266–275.

17. Centers for Disease Control and Prevention (CDC). Duration of Isolation and Precautions for Adults with COVID-19. Department of Health and Human Services. https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html.Updated 19 October 2020. Accessed 18 December 2020.

18. Stowe J, Tessier E, Zhao H, et al. Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design. medRxiv. https://www.medrxiv.org/content/10.1101/2020.09.18.20189647v2. Updated 22September 2020. Accessed 3 November 2020.

19. U.S. Central Command. MOD FIFTEEN TO USCENTCOM INDIVIDUAL PROTECTION AND INDIVIDUAL-UNIT DEPLOYMENT POLICY. https://media.defense.gov/2020/Aug/29/2002487210/-1/-1/0/USCENTCOM%20MOD%2015.PDF. Updated 9 April 2020. Accessed 3 November 2020.

20. Uyeki T, Bernstein H, Bradley J, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Inf Dis. 2019;68(6):e1-e47.

21. Centers for Disease Control and Prevention: National Center for Immunization and Respiratory Diseases (NCIRD). Table 4. Multiplex Assays Authorized for Simultaneous Detection of Influenza Viruses and SARS-CoV-2 by FDA. https://www.cdc.gov/flu/professionals/diagnosis/table-flu-covid19-detection.html. Updated 20 October 2020. Accessed 3 November 2020.

22. Centers for Disease Control and Prevention (CDC). Contact Tracing for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/php/contacttracing/contact-tracing-plan/contact-tracing.html. Updated 16 December 2020. Accessed 19 December 2020.

23. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomized controlled trials. Lancet. 2015;385(9979):1729–1737.

24. Malosh RE, Martin ET, Ortiz JR, Monto AS. The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review. Vaccine. 2018;36(1):141–147.

25. Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019;23(1):99.

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