Our case demonstrated that co-infection of influenza and SARS-CoV-2 could occur in patients with no known direct exposure to COVID-19. The patient presented with non-specific symptoms that were clinically indistinguishable from illnesses caused by other respiratory pathogens, and the rapid antigen tests in the ED confirmed influenza A infection. He lives alone and independently at home in western Iowa, has no recent travel history or visits to any healthcare facilities other than a local dialysis center three times a week for routine dialysis. At the time of his presentation, there was only one confirmed, travel-related case in the county where the patient lives, and the patient denied any direct contact with the first infected person. Although there was no community spread case in the county where the patient lives, community transmitted cases were reported both in western Iowa and Omaha, Nebraska, at the time of this patient's presentation. Given the increase in the rapid community transmission of the COVID-19 pandemic, infectious disease team recommended that concomitant infection of COVID-19 needed to be ruled out in this high-risk patient with multiple comorbidities even when there was a lack of clear history of exposure and his symptoms could be easily explained by his positive rapid influenza antigen test. The local health department was notified of the positive COVID-19 results for the investigation of the source of infection. On March 21, 2020, this case was declared as the second confirmed case and the first confirmed community transmitted case in the area12.
The severity of clinical presentations of COVID-19 ranges widely from asymptomatic, mild to severe illnesses requiring hospitalization and intensive care. As many infected persons remain asymptomatic or only develop mild symptoms, many cases go unidentified and unreported. In a study that analyzed the COVID-19 outbreak on the Diamond Princess cruise ship, 634 out of 3,063 tested people were found to be positive for SARS-CoV-2, and an estimated 17·9% of the infected remained asymptomatic throughout13. Another study on 565 Japanese nationals evacuated from Wuhan, China, found that people remained asymptomatic in 30·8% of the confirmed COVID-19 cases, an even higher percentage14.
Around 14% of all infected cases worldwide progress to severe illness7, and as of April 23, 2020, in 183,559 of 2,630,778 confirmed cases (6·97%) worldwide, patients eventually died3. Older adults (age >65 years) and patients with underlying medical conditions such as heart disease, lung disease, diabetes, and renal disease are at higher risk from severe COVID-19 illness15. In the United States, the preliminary description of outcomes among patients with COVID-19 indicates that fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years, 1% to 3% among persons aged 55-64 years, <1% among persons aged 20–54 years, and no fatalities among persons aged ≤19 years16.
The most common symptoms of COVID-19 patients are fever (91·7%), cough (75%) fatigue (75%), and gastrointestinal symptoms (GI) (39·6%)17,18. Our patient initially developed mild fever, cough, and shortness of breath, but on admission (illness day 3) and during hospitalization, his main complaints were fatigue and diarrhea. The patient is unfortunately not eligible for the clinical trial of remdesivir at the University of Nebraska Medical Center due to his ESRD but has been improving clinically with dialysis and supportive care. By illness day 4 (hospital day 2), his shortness of breath, dry cough, and abdominal pain have improved. Since illness day 5 (hospital day 3), his severe diarrhea also improved with oral loperamide after Clostridium.difficile infection was ruled out.
A study done on 8274 close contacts in the Wuhan region where the virus was first discovered showed that 5·8% of COVID-19 patients had other respiratory pathogen co-infections19. In another study by Xia and colleges on 20 confirmed pediatric COVID-19 cases in Shanghai, China, 6 out of 20 children were coinfected with another respiratory pathogen20. In a recent research letter published on April 15, the rate of co-infections of COVID-19 with other respiratory pathogens was reported to be as high as 21% 21. Given the increase in the rapid community transmission of the pandemic, the threshold for suspicion and testing for SARS-CoV-2 infection should be low in patients with fever, respiratory symptoms, or other symptoms that are fitting for COVID-19, even when there is evidence of infections by other respiratory pathogens22-24. Any missed COVID-19 cases can lead to significant adverse public health consequences. This case highlights the fact that co-infection of SARS-CoV-2 and other respiratory pathogens can occur in patients with no known direct COVID-19 exposure, and that it is important to test for COVID-19 in high-risk patients even when other etiologies could explain the symptoms.
Lessons learned from this case
1) There should be a high index of suspicion for SARS-CoV-2 infection in patients with fever and respiratory symptoms even when the patient is tested positive for other respiratory pathogens. Any missed COVID-19 cases will put the patient, other patients, health care providers, and the whole community at risk. A high index of suspicion, early testing, and a multidisciplinary approach to patient care are crucial for the treatment of COVID-19 pneumonia, especially in patients with multiple comorbidities.
2) With adequate testing and appropriate triaging of patients with suspected COVID-19, health care providers can be better-prepared in various health care settings, including imaging centers, dialysis facilities, and long-term care institutions.
3) With the widespread community transmission of COVID-19 in the U.S., patients presenting with other less typical symptoms including GI symptoms such as nausea, vomiting, and abdominal pain should also raise the clinicians’ suspicion for possible COVID-19 infection.