Annuals of Internal Medicine 2020.12.08
On 9 March 2020, male twins who were 60 years old and considered homozygous because of their appearances and other personal characteristics developed symptoms that started with fever and nasal congestion; continued with fatigue, dyspnea, and dry cough; and, after 10 days, led to hospitalization. Nasopharyngeal swabs tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a real-time reverse transcriptase polymerase chain reaction assay. Neither twin had a history of chronic disease, cardiovascular risk factors, or long-term therapy. They lived at the same address and worked at the same location repairing automobiles in a body shop. Contact tracing identified 1 of their customers who interacted closely with them without protective measures as the likely source of their infections. The twins had similar presentations at admission (Table); both had mild interstitial pneumonia. However, because of limited resources during a surge in admissions, the diagnosis in twin 1 was based on lung ultrasonography that showed subpleural B-lines and chest radiography that showed bibasilar ground-glass opacification, whereas the diagnosis in twin 2 was based on a chest computed tomography scan that showed bilateral multifocal ground-glass opacities with 25% lung involvement. The same medical team provided care to both twins during the first 2 weeks of their hospital stays, where they were treated with supplemental oxygen, paracetamol, hydroxychloroquine, darunavir/cobicistat, and enoxaparin at prophylactic dosages. Despite having similar presentations and early treatment, the twins had different clinical courses. The Figure compares key clinical measures during the first 2 weeks of hospitalization, which was from admission to discharge for twin 1 and from admission to transfer to the intensive care unit for twin 2. Twin 1 was discharged without complications and recovered uneventfully. In contrast, twin 2 had a progressive increase in leukocyte count and C-reactive protein level associated with a variable increase in body temperature. Moreover, noninvasive ventilation was necessary because of a decrease in the Pao2/FIo2 ratio. After 3 days of ineffective ventilation, he was transferred to the intensive care unit where he reached his lowest Pao2/FIo2 value of 58 and was intubated and mechanically ventilated. He developed septic shock from an anaerobic bacterial infection that required vasopressors, antibiotics, steroids, and 4 days of invasive ventilation. His intensive care unit stay was followed by 17 days of uncomplicated hospitalization and a posthospitalization recovery that was slow but ended in full recovery of gas exchange without long-term consequences.
Discussion: Genetic factors are often proposed to explain differences in how COVID-19 affects people. For example, others have suggested that polymorphisms of ACE2 and TMPRSS2, differences in the ABO blood group system, and additional genetic factors may be associated with the susceptibility for acquiring SARS-CoV-2 and the severity of COVID-19 (1, 2). That possibility seems unlikely in the 2 patients we describe, especially if we assume no spontaneous mutations or epigenetic differences. In addition, other factors have been associated with an adverse prognosis, such as older age; cardiovascular risk factors; and chronic diseases of the lung, kidney, liver, or cardiovascular system (3). Our patients were identical in these respects. Moreover, some have proposed that environmental factors, such as air pollution, are associated with susceptibility to COVID-19 (4) and by extension may be related to disease severity. However, our patients lived at the same address and worked at the same job in the same workplace, so they probably had similar environmental exposures. Also, differences in the virus—for example, differences in the infecting dose (5) or viruses with different mutations—may explain differences in illness severity. We do not have direct information about these viral characteristics, but we believe both patients were infected by the same person, so they likely acquired the same virus. We also know that the number of polymerase chain reaction cycles needed to produce detectable viral RNA was similar (Table), which suggests that the viral load at diagnosis was similar.