Dr. Douglas S. Paauw
Let’s start with a case:
A 37-year-old woman is seen in clinic for a 5-day history of cough, fever, chest tightness, and onset of dyspnea on the day of her office visit.
An exam reveals her blood pressure is 100/60 mm Hg, her pulse is 100 beats per minute, her temperature is 38.7° C, her oxygen saturation is 93%, and her respiratory rate is 20 breaths per minute.
Auscultation of the chest revealed bilateral wheezing and rhonchi. A nasopharyngeal swab is sent for COVID-19 and is negative; she also tests negative for influenza.
Her hemoglobin level is 13 g/dL, hematocrit was 39%, platelet count was 155,000 per mcL of blood, and D-dimer level was 8.4 mcg/mL (normal is less than 0.4 mcg/mL.) Her white blood cell count was 6,000 per mcL of blood (neutrophils, 4,900; lymphocytes, 800; basophils, 200). Her chest x-ray showed bilateral lower lobe infiltrates.
What do you recommend?
A. Begin azithromycin plus ceftriaxone
B. Begin azithromycin
C. Begin oseltamivir
D. Obtain chest CT
E. Repeat COVID-19 test
With the massive amount of information coming out every day on COVID-19, it is hard to keep up with all of it, and sort out accurate, reviewed studies. We are in a position where we need to take in what we can and assess the best data available.
In the case above, I think choices D or E would make sense. This patient very likely has COVID-19 based on clinical symptoms and lab parameters. The negative COVID-19 test gives us pause, but several studies show that false negative tests are not uncommon.
Long et al. reported on 36 patients who had received both chest CT and real-time reverse transcription polymerase chain reaction (rRT-PCR) for COVID-19.1 All were eventually diagnosed with COVID-19 pneumonia. The CT scan had a very high sensitivity (35/36) of 97.2%, whereas the rRT-PCR had a lower sensitivity (30/36) of 83%. All six of the patients with a negative COVID-19 test initially were positive on repeat testing (three on the second test, three on the third test).
There are concerns about what the sensitivity of the rRT-PCR tests being run in the United States are. At this point, I think that, when the pretest probability of COVID-19 infection is very high based on local epidemiology and clinical symptoms, a negative COVID rRT-PCR does not eliminate the diagnosis. In many cases, COVID-19 may still be the most likely diagnosis.
Early in the pandemic, the symptoms that were emphasized were fever, cough, and dyspnea. Those were all crucial symptoms for a disease that causes pneumonia. GI symptoms were initially deemphasized. In an early study released from Wuhan, China, only about 5% of COVID-19 patients had nausea or diarrhea.2 In a study of 305 patients focused on gastrointestinal symptoms, half of the patients had diarrhea, half had anorexia and 30% had nausea.3 In a small series of nine patients who presented with only GI symptoms, four of these patients never developed fever or pulmonary symptoms.3
On March 14, the French health minister, Olivier Véran, tweeted that “taking anti-inflammatory drugs (ibuprofen, cortisone …) could be an aggravating factor for the infection. If you have a fever, take paracetamol.” This was picked up by many news services, and soon became standard recommendations, despite no data.
There is reason for concern for NSAIDs, as regular NSAID use has been tied to more complications in patients with respiratory tract infections.4 I have never been a proponent of regular NSAID use in patients who are infected, because the likelihood of toxicity is elevated in patients who are volume depleted or under physiologic stress. But at this time, there is no evidence on problems with episodic NSAID use in patients with COVID-19.
Another widely disseminated decree was that patients with COVID-19 should not use ACE inhibitors and angiotensin II receptor blockers (ARBs). COVID-19 binds to their target cells through ACE2, which is expressed by epithelial cells of the lung, intestine and kidney. Patients who are treated with ACE inhibitors and ARBs have been shown to have more ACE2 expression.
In a letter to the editor by Fang et al. published in Lancet Respiratory Medicine, the authors raised the question of whether patients might be better served to be switched from ACE inhibitors and ARBs to calcium-channel blockers for the treatment of hypertension.5 A small study by Meng et al. looked at outcomes of patients on these drugs who had COVID-19 infection.6 They looked at 417 patients admitted to a hospital in China with COVID-19 infection. A total of 42 patients were on medications for hypertension. Group 1 were patients on ACE inhibitors/ARBs (17 patients) and group 2 were patients on other antihypertensives (25 patients). During hospitalization 12 patients (48%) in group 2 were categorized as having severe disease and 1 patient died. In group 1 (the ACE inhibitor/ARB–treated patients) only four (23%) were categorized as having severe disease, and no patients in this group died.
Vaduganathan et al. published a special report in the New England Journal of Medicine strongly arguing the point that “[u]ntil further data are available, we think that [renin-angiotensin-aldosterone system] inhibitors should be continued in patients in otherwise stable condition who are at risk for, being evaluated for, or with COVID-19”.7 This position is supported by the American Heart Association, the American College of Cardiology, the American College of Physicians, and 11 other medical organizations.
Take-home messages
- Testing isn’t perfect – if you have strong suspicion for COVID-19 disease, retest.
- GI symptoms appear to be common, and rarely may be the only symptoms initially.
- NSAIDs are always risky in really sick patients, but data specific to COVID-19 is lacking.
- ACE inhibitors/ARBs should not be avoided in patients with COVID-19.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact Dr. Paauw at [email protected].
References
1. Long C et al. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? Eur J Radiol. 2020 Mar 25;126:108961.
2. Zhou F et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62.
3. Tian Y et al. Review article: Gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther. 2020;00:1–9.
4. Voiriot G et al. Risks related to the use of nonsteroidal anti-inflammatory drugs in community-acquired pneumonia in adult and pediatric patients. J Clin Med. 2019;8:E786.
5. Fang L et al. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Mar 11. doi:10.1016/S2213-2600(20)30116-8.
6. Meng J et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020 Dec;9(1):757-60.
7. Vaduganathan M et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020 Mar 30. doi: 10.1056/NEJMsr2005760.