2019 冠状病毒病和登革热：两例病例报告
抽象的
本世纪的疫情让受影响国家的医疗系统不堪重负，所有资源都被转移到了 2019 冠状病毒病上。2019 冠状病毒病在发病初期可以表现为任何其他急性发热性未分化疾病。在热带地区，临床医生越来越难以在不使用诊断手段的情况下区分这些发热性疾病。在这次疫情中，许多热带疾病被忽视和漏报。登革热在马尔代夫是一种地方性流行病，登革热病毒全年都在传播。关于登革热病毒和严重急性呼吸系统综合症冠状病毒 2 合并感染的报道很少，在合并感染的情况下，疾病的结果和动态可能会发生改变。我们描述了临床表现和一系列实验室检查结果，并强调了登革热感染中不常见的非典型发现。
病例 1 是一名 39 岁的亚洲男性，在感染登革热第 6 天出现警示症状。根据医院规程进行的严重急性呼吸道综合征冠状病毒 2 逆转录聚合酶链反应检测结果呈阳性。病例 2 是一名 38 岁的亚洲男性，在发病第 5 天因急性呼吸道感染症状入院，严重急性呼吸道综合征冠状病毒 2 逆转录聚合酶链反应检测结果呈阳性。对进行性白细胞减少和血小板减少的评估显示登革热血清学检测呈阳性。
临床医生在对 2019 冠状病毒病病例进行可能的热带疾病鉴别诊断时必须认真谨慎，特别是当患者出现血液浓缩、血小板减少和转氨酶升高且天冬氨酸表达高于丙氨酸转氨酶时，这在登革热感染中很常见。在治疗 2019 冠状病毒病和登革热合并感染患者时，静脉输液时必须小心谨慎，因为 2019 冠状病毒病患者更容易出现肺水肿。及时诊断和适当的治疗对于避免严重登革热感染的严重并发症至关重要。对 2019 冠状病毒病患者重复并重新确认登革热血清学检查很重要，以避免出现假阳性。在当前疫情期间，必须谨慎小心，不要忽视该地区其他地方性热带疾病。
介绍
2019 年冠状病毒病 (COVID-19) 大流行始于 2019 年 12 月下旬。已报告确诊病例超过 1900 万，死亡人数超过 70 万。目前，全球仅有 12 个国家未受到 COVID-19 的影响 [1]。马尔代夫于 2020 年 3 月 7 日确诊首例 COVID-19 病例 [2]。大多数确诊病例无症状，在有症状的病例中，大多数病情轻度至中度，少数病情危重。迄今为止，马尔代夫已确诊超过 4769 例 COVID-19 病例，19 人死亡 [3]。几种虫媒病毒感染和其他热带疾病在马尔代夫流行 [4,5,6,7,8,9,10,11,12,13]。其中，最常见的诊断是登革热感染，因为市售血清学快速诊断检测试剂盒的广泛使用 [14]。每年，马尔代夫的登革热疫情都会达到报告病例数的峰值，尤其是在雨季。造成这种情况的因素包括由于城市拥挤导致的病媒控制不力，以及对堆积垃圾的分类力度有限，而这些垃圾是潜在的病媒滋生地 [15]。由于过去 7 个月 COVID-19 疫情一直是人们关注的焦点，因此许多现有问题（如登革热）被忽视了。如果严重登革热未被发现，可能会致命 [16,17,18]。这些类型包括登革出血热（除了出血外，还会发生血浆渗漏）和多系统受累的扩大性登革热综合征。这些类型现在统称为严重登革热 [19]。许多登革热流行的国家都担心 COVID-19 大流行期间登革热疫情可能造成的灾难性影响 [20,21,22]，而其他国家则表示登革热和 COVID-19 在临床和实验室发现方面有相似之处 [23]。一份报告显示，一例 COVID-19 病例的登革热血清学检测结果为假 [24]。也有报道称，血清学重叠导致登革热血清学检测呈假阳性 [25]。关于登革热病毒和严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 合并感染的报道很少 [24,26]。本文中，我们描述了临床表现和系列实验室检查特征，并强调了登革热和登革出血热与 SARS-CoV-2 合并感染时不常见的非典型发现。
病例介绍
一名 39 岁的亚裔男性移民工人因过去 6 天持续高烧、眶后头痛、疲劳和肌痛而到急诊室就诊。他还抱怨右上腹疼痛、呕吐和便溏。没有皮疹、关节痛或出血病史。体格检查时，他脱水，记录的生命体征为体温 37.5°C，心率为每分钟 80 次，血压为 113/78 毫米汞柱，脉压为 35 毫米汞柱，呼吸频率为每分钟 20 次，毛细血管再充盈时间少于 2 秒，室内空气中的氧饱和度为 98%。全身检查无异常，除右上腹压痛和肝脏跨度正常外。床边腹部超声检查显示胆囊壁水肿。表 1 列出了入院时的实验室检查和系列实验室概况，结果显示血液浓缩为 19% 和转氨酶升高。登革热快速检测 (SD BIOLINE Dengue DUO®) 显示非结构蛋白 1 (NS1) 呈阴性，免疫球蛋白 (Ig)M 和 IgG 呈阳性。后来，登革热酶联免疫吸附试验 (ELISA) IgM 和 IgG（Panbio®Standard Diagnostics）呈阳性，再次证实了这一点。按照医院入院方案进行的 COVID-19 逆转录聚合酶链反应 (rRT-PCR)（LiferiverTM2019-nCoV 实时多重 RT-PCR 试剂盒）呈阳性，循环阈值为 28.35。患者被送入 COVID-19 机构并被隔离，诊断为 COVID-19 合并登革热出血热 I 级。由于患者生命体征稳定，血液浓缩略有增加，因此对其采取口服液体的保守治疗。发病第 5 天，患者出现干咳和喉咙痛，为此进行了胸部 X 光检查，未发现异常。每天对患者进行监测，以观察其是否出现登革热的警告信号，包括血液浓缩。患者住院期间一切顺利，在完成 14 天的强制隔离期后出院。
一名 38 岁的亚裔男性，过去 5 天出现间歇性发热和全身性头痛。发热后 3 天内，他还出现喉咙痛、味觉障碍和嗅觉丧失。作为 COVID-19 患者的密切接触者，他咨询了一家在线诊所，并被转诊到医院进行评估。检查时，他出现脱水症状，体温为 37.4°C，脉搏为每分钟 84 次，血压为 100/60 mmHg，脉压为 40 mmHg，呼吸频率为每分钟 21 次，毛细血管再充盈时间少于 2 秒，室内空气中的氧饱和度为 97%。其他全身检查无异常。由于 SARS-CoV-2 rRT-PCR 检测呈阳性（Ct 值为 24.45），他被收治并隔离。他的实验室参数列于表 2，显示白细胞减少和血小板减少。鉴于总白细胞计数和血小板呈减少趋势，要求进行登革热快速检测，结果显示 NS1 阴性和 IgM/IgG 阳性。抗登革热 IgM 和 IgG 的登革热 ELISA 血清学检测呈阳性，再次证实了这一点。因此，患者被诊断为 COVID-19 登革热。患者血液浓缩程度很低，由于他能够充分摄入液体，因此给他口服液体进行治疗，并每天监测是否出现登革热的警告信号或 COVID-19 的严重程度恶化。患者入院后没有出现任何发烧高峰。患者的血小板逐渐改善，症状在 1 周内消退。患者完成 14 天强制隔离期后出院。
讨论
这里我们描述了两例登革热和 COVID-19 合并感染病例。第一例患者出现登革热症状，入院 5 天后出现 COVID-19 症状。第二例患者入院时患有轻度 COVID-19，在病程中，由于血液浓缩程度轻度增加以及白细胞和血小板计数逐渐下降，因此被检测出登革热阳性。在合并感染中，一种病毒可以抑制或增强另一种病毒，导致疾病的临床表现不同。
The COVID-19 pandemic has spread across the globe, including areas where other tropical diseases are endemic such as the Maldives [6,8,9,10,15]. Clinicians are challenged with the additional burden of possible coinfections with other tropical diseases that have the potential to complicate the course of illness [26]. Coinfections with COVID-19 have been reported with multiple bacteria and viruses [27,28,29,30,31]. Nevertheless, coinfection with dengue viruses and SARS-CoV-2 are still scarce, with only a few reports describing false-positive dengue serology [24,32]. The healthcare system of the Maldives is stretched and may not respond adequately to a dual outbreak because of limited manpower and infrastructure [33]. Every year, the Maldives experiences a dengue outbreak during the monsoons. From the year 2011, an average of 1543 cases have been reported annually [15]. In 2018, 3494 cases were reported, and in 2019, 5023 cases were reported, which was a record number for the Maldives [34]. Despite an expected increase in cases, so far only 225 cases have been reported, while dengue cases are on the rise in other endemic regions [34,35]. We postulate that healthcare providers are more focused on COVID-19, which has resulted in lower rates of testing or reporting of dengue virus. In addition, individuals with mild symptomatic dengue infections perhaps are not visiting hospitals because of the pandemic and lockdowns. COVID-19 may present as an undifferentiated acute febrile illness [36]. In one study, 87.9% of COVID-19 patients presented with fever, 67.7% presented with cough, and 13.7% of patients had headache [37]. Nevertheless, information regarding the frequency of fever in dengue infection is limited in most prospective studies, mostly due to confounders within the study designs where fever remains an inclusion criterion. Fever can be absent in the elderly population or, if present, can occur over 90% of the time [38]. Cough in dengue infection has been reported in 67% of cases, which can be due to pleural effusion observed during plasma leakage in dengue hemorrhagic fever (DHF) [39,40]. Headache in dengue infection has been reported in 89% of cases and more commonly in DHF [41]. Bleeding in COVID-19 has been reported to be associated with morbidity, but frequency of bleeding manifestations in COVID-19 remains low [42]. In contrast, bleeding in dengue infection occurs more frequently and is associated with increasing severity [41]. The hematological profile in COVID-19 and dengue infection are similar. Neutrophils are increased early in both infections with leukopenia and thrombocytopenia. The discrepancy in the hematological profile in both infections is lymphopenia, which is observed in COVID-19 during the course of illness in contrast to a reverse neutrophil-to-lymphocyte ratio in dengue infection. Transaminitis is observed in both infections; however, the expression of aspartate aminotransferase is greater than alanine transaminase in dengue infection [43,44]. Our first case was initially diagnosed as dengue fever with warning signs, and COVID-19 was detected during the screening process before admission [45]. On day 5 of admission, he developed a non-productive cough and sore throat that could be attributed to COVID-19. The cough could also be due to dengue-related pleural effusion, which was not evident on his chest X-ray in posterior–anterior view. However, a chest X-ray in lateral decubitus view is more sensitive to detect minimal effusion [46]. In our second case, the patient was admitted with a diagnosis of mild COVID-19. With a depleting trend of leukocytes and platelets, dengue serology was performed, which was positive. Case 1 had a hemoconcentration of 19% and gall bladder wall edema suggestive of plasma leakage [47]. As there was no bleeding manifestation, this case was classified as DHF grade 1 [48]. In case 1, liver biochemistry revealed an atypical profile with alanine transaminase expression greater than that of aspartate aminotransferase, which may be due to coinfection. However, initially in case 2, we observed mild transaminitis with an elevation of aspartate aminotransferase expression compared with that of alanine transaminase, which is consistent with dengue infe

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