25 discharged patients with COVID-19 infection were back hospitalized because of the virus mRNA recurrence. The median age of these 17 females and 8 males was 28 years (16.25~42), including 6 children under 12 years old.
21 of them had no comorbidity and 22 patients had the history of residing in Hubei province. Besides, 24 of them were once non-severe patient with the common symptoms of fever (17/25) and cough (14/25) at onset. Overall, with 14 (13-18.5) days of the hospital stay, as well as 13 (10.5-16.5) days of antivirus treatment, the patients all discharged in 2 (1-3.8) days after two consecutive negative results on virus mRNA RT-PCR detection, as well as improvements on chest computed tomography (CT) evidence.
With 14/25 of cloacal swab samples and rest of Nasal Swabs or oropharynx swab samples testing, these patients presented the repeated positive COVID-19 mRNA within 3 (2-7) days after the hospital. Notably, the median time from their last negative result to turning positive was 6 (4-10) days.
These patients were then hospitalized again and continued the quarantine protocol. All these patients were asymptomatic and chest CT scanning indicated that 12 of them even showed improvement while rest of them represented with no obvious change compared with previous images. With a few days of prophylactic intervention with Chinese herbal medicine, the RT-PCR results of virus mRNA detection were all turning to negative in both nasopharyngeal swab and cloacal swab samples.
Furthermore, correlation analysis indicated that there was a significant inverse correlation existed between serum D Dimer level and the duration of antiviral treatment (r=-0.637, p=0.002), while lymphocyte concentration significantly positively correlated (r=0.52, p=0.008) with the duration of virus reversal. These implied that the imperfect antivirus therapy probably was responsible for the recurrence of COVID-19 virus.
NOT PEER REVIEWED:
https://www.medrxiv.org/content/10.1101/2020.03.06.20031377v1.full.pdf
It has been reported that SARS-CoV directly infects monocytes, macrophages and T lymphocytes in human.17 The PLD may also be secondary to activation of T lymphocytes.18
Our findings showed that CD4 and CD8 T lymphocytes have significant difference (p < 0.01) between mild (Non-ICU) and severe or critical (ICU) cases without glucocorticoid treatment indicating COVID-19 directly effected on immune system is possible.
COVID-19 has spread rapidly since it was first identified in Wuhan and has been shown to have a wide spectrum of severity as SARS-CoV-2 binds to ACE2 receptors in 10-20 fold higher affinity than SARS-CoV binds to the same receptors.7,19 The report shows SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2.8 Therefore, it is necessary to further study whether lymphocytes have ACE2 receptor and TMPRSS2 expression during the developmental stage since the PLD exists. A SARS-CoV-2 RT-PCR assay for lymphocyte subsets in severe or critical cases should be followed up. Our findings also suggest that lymphocyte subsets should be analyzed at admission immediately no matter how COVID-19 affected lymphocytes through directly or indirectly. When patients are confirmed as COVID-19, clinicians should order tests for lymphocyte subsets in order to intervene early in the consequences of the PLD.
Conclusions
...The mortality rate is 4.6% in Wuhan, 1.9% in Beijing, and 0.9% in Shanghai. Our findings showed that the levels of lymphocytes were 0.8 (IQR, 0.6-1.1) 109/L in Wuhan, 1.0 (IQR, 0.7-1.4) 109/L in Beijing, and 1.1 (IQR, 0.8-1.5) 109/L in Shanghai before admission to hospitals, respectively, indicating that cellular immune function might relate to the mortality.
NOT PEER REVIEWED:
https://www.medrxiv.org/content/10.1101/2020.03.08.20031229v1.full.pdf