We report here two families infected with COVID–19, with two totally different outcomes even both in the context of family clusters. The family cluster of COVID–19 infection refers to many family members infected, even all of them, which has been reported in several literatures (2–4). Known data demonstrated that SARS-CoV–2 holded strong infectious capacity and noticeably, the last three days of the incubation period was the highest risk of transmission (5). Family 1 demonstrated a typical family cluster of COVID–19 infection. The patient 1 is symptomatic but undiagnosed at initial. The transmission chain might be through patient 2 (infected by patient 1) in the incubation period. Then, the other three patients were infected by patient 2, although they were not in contact with patient 1, endorsing that asymptomatic cases in the incubation period may also lead to a family cluster of infection.
However, the index patient was the merely individual infected in family 2, though they closely contacted in family life. Considering that the patient was a healthy middle-aged male without underlying diseases, did not develop fever, and had mild pulmonary symptoms from onset to admission, we believed that the viral load exposed to the patient was not high or the virus might show low transmission ability. According to previous studies on the family cluster of COVID–19 infection, it is not difficult to find that the proportion of family members infected and the infection symptoms were quite variable, which might be associated with the viral load of COVID–19 patients contacted, the virus virulence, the immune state and physical condition of close contacts, and so on. (2–4)2–4
Additionally, the patient in family 2 developed into fatal stroke even without previous stroke risk factors. Because we did not know the previous conditions of cerebrovascular diseases and failed to perform a lumbar puncture for the etiological dection of cerebrospinal fluid (CSF) due to the rapid deterioration of his condition, we could not confirm that whether SARS-CoV–2 contributed to the development of stroke in the patient. However, no stroke high-risk factors and rapidly deteriorating cerebral infarction occurring after mild COVID–19 indirectly indicated that acute ischemic stroke might be associated with COVID–19. At least the inflammatory state after the onset of COVID–19 might be an inducement of stroke. Recent viral infections were reported to be associated with stroke, of which virus-induced inﬂammatory response is thought to be the predominant mechanism linking ischemic stroke with virus infection (6,7). The most commonly studied viruses related to increased risk of stroke include Epstein-Barr virus, herpes simplex virus (HSV)–1 and HSV–2, and cytomegalovirus. The stroke risk was highest during the ﬁrst 3 days after the diagnosis of respiratory tract infection and gradually decreased in subsequent weeks (8). Inﬂammatory cascades promote atherosclerosis, plaque rupture, and thrombosis, thereby leading to ischemic stroke (7,9). High-sensitive C-reactive protein might be an independent predictor of ischemic stroke, as in this patient with increased high-sensitive C-reactive protein as well as another important inflammatory marker serum amyloid A. According to a recent study, SARS-CoV–2 can bind to angiotensin-converting enzyme 2 (ACE2) and trigger functional changes in ACE2/Angiotensin Ⅱ Type 2 Receptor (AT2R), thereby resulting in an imbalance in the steady-state cytokine regulatory axis and a cytokine storm (10). ACE2 exists in nervous system and skeletal muscle. The expression and distribution of ACE2 suggest that SARS-CoV–2 can cause neurological symptoms through direct or indirect mechanisms. During the epidemic period of severe acute respiratory syndrome (SARS), there were also a few SARS patients with cerebral infarction (11,12). Umapathi et al (12) once described 5 severe SARS patients developed large artery ischaemic stroke, and thought that stroke occurring in the context of SARS infection was affected by many factors, including virus-induced inflammation of the vessel wall and hypercoagulability associated with virus infection. The D-dimer level of this patient also continued to increase, suggesting that there might also be virus-induced hypercoagulability. COVID–19 might be complicated with stroke and even had stroke as the first manifestation, especially in patients with asymptomatic or mild infection. If not found promptly and accepted into stroke unit conventionally, it would bring unpredictable consequences. However, the underlying mechanism regarding stroke attack in COVID–19 paients is still lack of in-depth study.
Given the importance of early detection of asymptomatic carrier and the possibility of COVID–19-related stroke, more and more attention should be paid to the the family cluster of COVID–19 infection, and we believe our experience warrants an increased vigilance against stroke and other thrombotic complications among COVID–19 patients in future outbreaks, especially in patients with mild symptoms or asymptomatic infection.