Discussion
To help further understand COVID-19 infection and treatment, we studied 64 cases in Wenzhou. The epidemic information showed obviously that COVID-19 could spread from person to person, having family and community aggregation, which may cause public transmission. The result was in keeping with a familial cluster report [16]. We have 25 cases of Gen.2, a little less than Gen.1 (33 cases), which meant Wenzhou were still facing the press of importing cases, and the epidemic of local was still a potential threat that needed to pay attention. Regardless, the number of cases increase slowly donated to the strategy of city blockade that made by the government from Jan 25th and Feb 2nd [17 18].
In our cases, the majority cases (58, 90.63%) were ranged from 20–60 (median age was 44), few (5, 7.81%) were above 60. It was inconsistent with the cases reported in Wuhan[19 20], but similar to Korea[21]. The reasons were various: the aged had low immunity compared to the youngers and Wuhan had a great number of elders; the breakout of COVID-19 in short time challenged the hospital resource, while the cases we had in Wenzhou were imported by travelers transmitted from Wuhan or spread by close contacting to them, the main of those were young and middle aged; genomic and infectivity of virus may evolve after outbreak; furthermore, we may not be clear to the virus in early phase for information lacking. Notably, we reported the minimum age of patient with 26-months old, who got virus from mother, the pre-minimum age was reported as 6 months [22]. Thus, the whole population may be susceptible to COVID-19.
There were 51 light cases, 11 severity and 2 critical in 64 cases, no death. About half had basic disease, especially hypertension; the elders or with basic disease may have more serious conditions. Most cases (59, 92.19%) had fever, the average temperature was 38.1℃. Temperature was shown to have correlation to disease severity. Respiratory symptoms were seen in 45 cases (70.3%), as 28 (43.8%) had gastrointestinal symptoms. Above half (39, 60.9%) had Weakness, few (5, 7.8%) had muscular soreness. Importantly, 5 cases had no fever, just with mild symptoms like cough, pharyngalgia, stuffiness or nausea, but PCR tests were positive. One case even did not have any symptom. Among these 5 cases, 3 were definite as Gen.1, 2 were Gen.2, the latency of them ranged from 1-14. This important information indicted that the COVID-19 could be infected with no symptoms, and the latency of COVID-19 could be up to 14 days without showing any typical or obvious symptoms. COVID-19 was so craft that it may conceal in health groups, and had much more infectivity than SARS, it may probably cause pandemic, infecting more population than SARS absolutely.
All 64 cases were tested to be PCR positive in an interval more than 24h in respiratory samples (sputum or throat swabs). Although nucleic acid of PCR test had high specificity, due to the unclear course of infection and skill required to take swab samples, the sensitivity was not satisfied with only 30-40% in suspect patients (47.4%, 9/19)[23]. But it was showed by the lab information that the virus copies could be tested to reach highest at 7th day after disease onset. It was reported that in diagnosed cases, the virus could also be detected in 10% patients’ blood samples at acute period and 50% of feces[24]. Another report showed 88.9% (8/9) stool sensitivity while blood and urine were negative[23]. Saliva also had 91.7% (11/12) positive in diagnostic patients[25]. The PCR positive rate was highly depending on the sample quality and course of infection. Another problem was the safety. The doctor faced high infectivity risk during obtaining sample. And PCR test have its longtime cost disadvantage as well. Compared to PCR, chest CT was much more convenient and safety. In our study, 62 cases had varying degrees of lung symptoms by checking with chest CT, Pneumonia (62, 96.9%), Both lungs involvement (61, 95.3%), Ground-glass opacity (48, 75%), and Consolidation (42, 65.6%). One of two cases having no lung changes in CTs but had high fever as 38℃; the other one did not show any symptoms. Cases with normal CT and PCR positive had also been reported[26 27]. Thus, chest CT and PCR of nucleic acid shall be combined considered in clinical high suspicion. Besides, a few patients had rhythm and wave changed in their electrocardiography that may be caused by low potassium ion under the attack of virus.
It was also found that patients may have many lower indexes including WBC, LC, PLT, K+, Na+, OI, and high LDH, CRP, D-dimer (Figure 2 ), BNP and TNI were normal, consistent with a report of multi-center study[26]. Correlation analyzation showed that the severity had positive correlated to age, temperate, LDH, D-dimer and negative to LC and OI (Table 3, Figure 3 ). LDH and LC were good biomarkers for monitoring progress of disease in all classifications (Figure 5 ). The low potassium may be caused by feed less when fevering or vomiting, diarrhea by antivirus drug use, and would have influence with weakness, dyspnea. Thus, it was important to correct low potassium and keep a close obvious on it during treatment.
The average of hospital stay was 25.8 days, the temperature of fevers returned to normal with treatment in 1-5 days (2.7 days as average), 20 were discharged when data were collected. The average of COVID-19 nucleic acid test transforming to negative was 12.8 days. In early phase, the infected lungs presented changes like ground-glass, cloud turbulence or paving stone pattern, then developed as consolidation within more than 2 leaves later, having local pulmonary fibrosis if deteriorated. The inflammation could be absorbed in about 7-10 days if treated well. The triple therapy (Interferon, Lopinavir/ritonavir, Abidor) was confirmed to be effective in treating COVID-19 infection. Weakness and diarrhea during treatment may be related to virus attack or Lopinavir/ritonavir taken.
ACE2, Angiotensin I Converting Enzyme 2, was confirmed to be the cell entry receptor of COVID-19 as SARS-CoV[28]. The protein was expressed in endothelial cells, arterial smooth muscle cells, lung alveolar epithelial cells, lymphocyte, heart, kidney, testis, ovary, and gastrointestinal system[29]. It explained why COVID-19 could be detected in samples of respiratory and gastrointestinal system and blood as SARS[2] and lymphopenia caused. It also reminded us COVID-19 may have influence on sterility as SARS, needed to call attention. High expression of ACE2 was also related to hypertension and smoke, accord with the vulnerable and high mortality to elders, smokers and those who had basic disease of hypertension. The protein was involved in regulating of calcium-activated potassium channel activity by related to CALM1, CALM3, CHRNA9 and CHARNA10 (String Database), leading to low potassium in patients infected with COVID-19 and SARS, that may result in weakness, dyspnea and rhythm.
Due to close relative genomic and same virus receptor ACE2, COVID-19 had similarity clinical features to SARS, such as fever, high temperate, respiratory and gastrointestinal system mainly involved, similar chest CT change, low potassium, low LC, low OI, high LDH and so on. Most of infection were light cases, suggested that it was milder than SARS. But had much stronger infectivity, with high infectivity when in latency without any symptoms. Early diagnosis and treatment when symptom showed, would bring it a better outcome. We shall do a good job in public health management, strengthen health publicity and education to control further spread of the epidemic as possible. With the experience in handling SARS, we have confidence and do will defeat the COVID-19 in the end.