COVID-19 pneumonia with back pain: Presentation of an acute pulmonary embolism associated with novel coronavirus infection in an outpatient setting.

The Chinese Center for Disease Control and Prevention reported 80% of coronavirus infections were mild cases; hence, most cases will be managed in an outpatient setting. COVID-19 is associated with a hypercoagulable state; therefore, further research should be done on outpatient use of anticoagulation for VTE/PE prophylaxis in these patients.

INTRODUCTION

The emergence of COVID‐19, caused by the SARS‐CoV‐2 Virus, has created a global pandemic and strained our entire healthcare system around the world. As the medical community continues to learn more about this highly contagious disease, the most common cause for hospitalization is severe respiratory distress. , However, according to the Chinese Center for Disease Control and Prevention, 80% of cases caused by COVID‐19 are mild cases. In conjunction with the majority of the cases being mild, evolving literature suggests the novel virus causes a proinflammatory and hypercoagulable state. , As a result there is propagation of the inflammatory process, vascular relaxation, and vasodilation. More specifically, COVID‐19 can cause pulmonary and systemic inflammation leading to multi‐organ dysfunction resulting in acute respiratory distress syndrome (ARDS) or venous thrombus embolism (VTE). , One study in the North‐of‐France outlined the increased prevalence of pulmonary embolisms (PE) in ICU patients with COVID‐19 during their hospitalization. While this study brought awareness to the development of PE in high risk patients, a subsequent case report from the United States highlighted an association between COVID‐19 and PE in a patient who had no known risk factors.

To date, there are no case reports that detail COVID‐19 positive patients with no known VTE risk factors who develop PE late in their disease course in an outpatient setting. This case illustrates the clinical features of the development of PE in a patient after diagnosis with COVID‐19 within an outpatient setting. This observation supports the need for further research into risk stratifying patients in an outpatient setting who may benefit from the use of oral anticoagulants to prevent VTE in COVID‐19 positive patients.

CASE REPORT

34‐year‐old male with a history of Graves’ disease status post thyroidectomy one year ago on levothyroxine presents via telehealth to the primary care office for a hospital follow‐up. Patient reports that on 17 March 2020 he spiked a fever of 102°F coupled with myalgias, intermittent nonproductive cough, and headaches. He took Ibuprofen for the fever and pain which started to improve. On 21 March 2020, his fever returned with a new symptom of nonbloody diarrhea without abdominal pain. His symptoms quickly progressed to generalized weakness and extreme fatigue. He had two positive COVID‐19 contacts. He continued to worsen, so he sought medical attention in the emergency room on 22 March 2020.

Upon presentation to the emergency room (ER) his vital signs were as follows: temperature (Temp) 102.5°F, heart rate (HR) 121 bpm, blood pressure (BP) 128/75 mm Hg, and pulse oxygen (SpO2) 90% on room air. His physical examination was unremarkable for everything except for noticeable “fatigue.” He was found to have a unilateral left lower lobe infiltrate on chest x‐ray (CXR) in which he was placed on oxygen at 2 L nasal cannula. His saturations began to slowly improve. His blood work resulted a normal white blood cell count with a low absolute lymphocyte count; the remaining comprehensive metabolic panel (CMP) was unremarkable with a negative influenza swab. Due to the paucity of testing at the time in Western New York, he was not tested for COVID‐19. When he was able to maintain 94% oxygen saturations on room air, he was discharged on oral azithromycin for 5 days. Given his positive contact, he was assumed to have COVID‐19 despite the unilateral CXR and encouraged to self‐isolate for 14 days.

On April 2nd at his appointment, patient stated that his myalgias and fever had improved since completing his antibiotic and he was feeling much better. However, 2 days ago he developed a new symptom of pleuritic‐like chest pain with mild shortness of breath (SOB) but, no fever, chills, sore throat, or cough. He admitted to having severe back pain and described not being able to lay on his right side due to the excruciating pain. His right sided pleuritic chest pain began to worsen which was now accompanied by hematuria. His back pain increased and was unrelieved by muscle relaxants that he took on his own, so he was sent back to the ER later that evening for further work up.

While in the ER his vital signs were as follows: Temp 98.9°F, HR 100 bpm, BP 107/92, and SpO2 96% on room air. His physical examination was unremarkable as was his complete blood count and cardiac enzymes. His computed tomography (CT) chest with IV contrast demonstrated bilateral air space disease with combination multifocal pneumonia and atelectasis as well as a right lower lobe pulmonary embolus. CT abdomen/pelvis disclosed a mildly enlarged prostate but otherwise unremarkable imaging. Patient was discharged on a novel oral anticoagulant. Prior to the patient's diagnosis of a PE, he had no known risk factors for PE or venous thrombosis embolism (VTE). He was still mobile after he developed symptoms, albeit less than his normal activity but not immobilized.

During his hospital follow‐up, his symptoms of pleuritic chest pain and hematuria had resolved. Pertinent positives on physical examination included HR 93 bpm, Temp 98.1°F, and SpO2 90% with fine crackles in the right lower lung field. The remaining parts of the physical examination were normal. He was later sent for antibody testing in which he was positive for SARS‐CoV‐2 IGG antibodies.

DISCUSSION

COVID‐19 Pneumonia and PE

Our understanding of COVID‐19 is constantly evolving, but several studies have documented the role of inflammatory markers in patients with COVID‐19 that make them more hypercoagulable. , , Studies out of France have demonstrated that patients with COVID‐19 are more likely to develop pulmonary emboli within 6 days in the ICU compared to patients with similar disease severity who were admitted prior to the pandemic. Among 107 COVID‐19 patents admitted to ICU, there was an increase in pulmonary embolisms during their stay in the tertiary care unit. Furthermore, the frequency of pulmonary embolisms in COVID‐19 patients was two times higher than patients admitted to the ICU with influenza pre‐pandemic with similar severity entrance scores. Our patient also developed a PE after being diagnosed with COVID‐19 which is consistent with the VTE disease burden, but our patient had no known risk factors for VTE. He was not admitted to a higher level of care as mentioned in the previous study. This is important to note because, some research studies have suggested that patients may have a mortality benefit from anticoagulation. , This mortality benefit has not been extrapolated to the outpatient setting and could have great implications if found to prevent development of PE secondary to COVID‐19. This also could widen the research efforts to determine if COVID‐19 VTE is a contributor of postmortem deaths not just respiratory failure.

Hematuria and PE

Another interesting point in our case is the presentation of hematuria early in his symptom onset. This could be related to the high degree of human angiotensin‐converting enzyme (ACE) receptors in the kidney. One study detailed the relationship between ACE and COVID‐19 in which the virus creates an increased ACE/ACE2 ratio that potentially influences kidney damage by decreasing the hydrolyzing effects of bradykinin within the Kinin‐Kallikrein system. The development of hematuria in a patient could be a sign of increased COVID‐19 viral load or suggests that the patient is at increased risk for VTE/PE. By activating the Kinin‐Kallikrein system, micro‐clots within the renal system cause hematuria which potentially may precede the development of more life‐threatening VTEs as seen in our patient. If a prediction score or risk stratification model was to be created for adverse outcomes pertaining to COVID‐19, hematuria should be considered as one of those predicting factors.

The development of VTE in COVID‐19 is a result of activation of coagulation pathways which clinically can present as a PE. Our patient developed a PE roughly 14 days after the onset of his first symptoms and 9 days after his diagnosis of COVID‐19. He also presented to the emergency room with new onset hematuria with a relatively benign CT Pelvis. His presentation of PE and hematuria can potentially be explained by the biochemical imbalance of ACE/ACE2. Unfortunately, inflammatory markers such as D‐Dimer, ESR, or Ferritin were not completed, but his presentation of hematuria and new onset PE is likely a result of the brewing cytokine storm at the time. The connection of hematuria to increased COVID‐19 viral load or degree of inflammatory state can potentially lead to the prediction of the development of VTE/PE late in the disease course in mild‐to‐moderate outpatient COVID‐19 cases.

Outpatient diagnostic challenges

It is not uncommon for people with pneumonia to present with back pain or pleuritic‐like chest pain due to the focal lesion. The unique finding in our patient is that he started to have back pain two days prior to his appointment, but it was on the opposite side of where his infiltrates were described. His new back pain could be related to an evolving COVID‐19 pneumonia in which he may have just now began to develop the bilateral nature of the pneumonia or due to a developing PE. Prior to his hematuria, his complaints of pleuritic chest pain could have been a result of his evolving COVID‐19 pneumonia or new onset PE. He had no risk factors for VTE/PE, no surgeries and was still mobile. This poses a diagnostic challenge in caring for assumingly healthy COVID patients in an outpatient setting.

Coronavirus is normally described as causing a bilateral pneumonia; however, our patient did not present with bilateral disease on his first presentation to the ER. Research has shown that CXR is insensitive in the detection of positive COVID‐19 cases in the early phase of the disease 11. This means that our patient on March 22nd most likely was in the early phase of the disease process. The study from France reported the development of a PE among critically ill patients within a median time from ICU admission of 6 days, but ranging from 1 to 18 days. PE development appears to occur in nonhospitalized patients with moderate COVID‐19 symptoms within an outpatient setting as demonstrated by our case. A similar case was published of a patient with no known VTE risk factors who presented to the ER with an acute subsegmental PE as a result of COVID‐19. These two cases identify the hypercoagulable state of these patients.

It would have been ideal if our patient was tested for COVID‐19 at his first presentation to the emergency room; however, the lack of testing capacity within the region excluded him from being tested. Eventually, he was sent for SARS‐CoV‐2 IGG antibodies 6 weeks later in which he tested positive.

CONCLUSION

This case is one of the first to report the development of a PE in a sequential fashion of a patient infected with SARS‐CoV‐2 with mild‐to‐moderate COVID‐19 symptoms with no known VTE risk factors in an outpatient setting. Awareness of the potential timeline in which patient's develop PE’s is important for outpatient clinicians to be aware of so they can better triage their patients and prevent adverse outcomes. Further research should be done on the usage of anticoagulant medications in an outpatient setting for VTE/PE prophylaxis in mild‐to‐moderate COVID‐19 infections for a short course during the active phase.

CONFLICT OF INTEREST

None declared.

AUTHOR CONTRIBUTIONS

KD, is a General Internal Medicine/Preventive Medicine Physician at the Community Health Center of Buffalo, Inc She was directly involved in the care of the patient in the above case report. The author revised the article critically for important intellectual content. The author agreed to be accountable for all aspects of the work ensuring the questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved prior to publication.

ETHICAL APPROVAL

In accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards, ethical approval is not required for case reports.