The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

SummaryWe report the first local transmission of the Delta SARS-CoV-2 variant in mainland China. All 167 infections could be traced back to the first index case. The investigation on daily sequential PCR testing of the quarantined subjects indicated the viral load of the first positive test of Delta infections was ∼1000 times higher than that of the 19A/19B strains infections back in the initial epidemic wave of 2020, suggesting the potential faster viral replication rate and more infectiousness of the Delta variant at the early stage of the infection. The 126 high-quality sequencing data and reliable epidemiological data indicated some minor intra-host single nucleotide variants (iSNVs) could be transmitted between hosts and finally fixed in the virus population during the outbreak. The minor iSNVs transmission between donor-recipient contribute at least 4 of 31 substitutions identified in the outbreak suggesting some iSNVs could quickly arise and reach fixation when the virus spread rapidly. Disease control measures, including the frequency of population testing, quarantine in pre-symptomatic phase and enhancing the genetic surveillance should be adjusted to account for the increasing prevalence of the Delta variant at global level.

Background: The number of coronavirus disease 2019 (COVID-19) cases has rapidly increased all over the world. Specific information about immunity in non-survivors with COVID-19 is scarce. This study aimed to analyse the clinical characteristics and abnormal immunity of the confirmed COVID-19 non-survivors. Methods: In this single-centered, retrospective, observational study, we enrolled 125 patients with COVID-19 who were died between January 13 and March 4, 2020 in Renmin Hospital of Wuhan University. A total of 414 randomly recruited patients with confirmed COVID-19 who were discharged from the same hospital during the same period served as control. The demographic, clinical characteristics and laboratory findings at admission, and treatment used in these patients were collected. The immunity-related risk factors associated with in-hospital death were tested by logistic regression models and Receiver Operating Characteristic (ROC) curve.

We recently reported that inhibitors against human dihydroorotate dehydrogenase (DHODH) have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells. However, there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019 (COVID-19) patients. In the present study, we evaluated Leflunomide, an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases, in treating COVID-19 disease with a small-scale of patients. Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included. Five of the patients were treated with Leflunomide, and another five were treated as blank controls without a placebo. All the patients accepted standard supportive treatment for COVID-19. The patients given Leflunomide had a shorter viral shedding time (median of 5 days) than the controls (median of 11 days, P = 0.046). The patients given Leflunomide also showed a significant reduction in C-reactive protein levels, indicating that immunopathological inflammation was well controlled. No obvious adverse effects were observed in Leflunomide-treated patients, and they all discharged from the hospital faster than controls. This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.

Recent reports have showed that a proportion of patients with Coronavirus Disease 2019 (COVID-19) presented elevated leukocyte count. Clinical data about these patients is scarce. We aimed to evaluate the clinical findings of patients with COVID-19 who have increased leukocyte at admission. We retrospectively collected the clinical data on the 52 patients who have increased leukocyte count at admission from the 619 patients with confirmed COVID-19 who had pneumonia with abnormal features on chest CT scan in Renmin Hospital of Wuhan University in Wuhan, China, from February 3 to March 3, 2020. The mean age of the 52 patients with increased leukocyte count was 64.7 (SD 11.4) years, 32 (61.5%) were men and 47 (90.4%) had fever. Compared with the patients with non-increased leukocyte count, the patients with increased leukocyte count were significantly older (P < 0.01), were more likely to have underlying chronic diseases (P < 0.01), more likely to develop critically illness (P < 0.01), more likely to admit to an ICU (P < 0.01), more likely to receive mechanical ventilation (P < 0.01), had higher rate of death (P < 0.01) and the blood levels of neutrophil count and the serum concentrations of CRP and IL-6 were significantly increased, (P < 0.01). The older patients with COVID-19 who had underlying chronic disorders are more likely to develop leukocytosis. These patients are more likely to develop critical illness, with a high admission to an ICU and a high mortality rate.

nCoV) has caused more than one hundred cases in Wuhan (WMHC 2020). During a retrospective study of recent pneumonia patients in our department, we found two patients who are likely being infected with the 2019-nCoV. During the hospitalization, those two patients were appropriately treated, and both were discharged within two weeks. Thus, we are reporting the clinical features and treatment regiment, and hope the information and experience can be shared.The two patients were a couple. The male was 38 years old, and was admitted to the hospital due to fever for one week and dyspnea for one day on Dec. 27, 2019. On admission, he had slight cough of a little green viscous sputum. He had been treated with normal anti-infective therapy in another hospital for 3 days, but did not respond it. After then, he visited our department. The radiography of the chest at the OPD suggested the right lung infection.He was previously healthy, and had a history of allergy to heartleaf houttuynia herb (a traditional Chinese medicine). Physical examination (PE) on admission: T: 37.4°C; P: 95 bpm; R: 20 bpm; and BP: 129/73 mmHg. The breath sounds of both lungs were coarse, and no dry or moist rales were auscultated. The heart and abdomen were unremarkable. Routine urine test: urine glucose: 1?; urine specific gravity: 1.03; protein: 1?; and the others were within the normal ranges. Routine stool test: occult blood (chemical method): weakly positive. The creatine kinase was within the normal range; lactate dehydrogenase: 279 U/L:; and procalcitonin was within the normal range.To figure out the potential pathogen of his infection, a panel of extra laboratory tests was performed, and the results are shown in Table 1. Through those tests, all clinically frequent pathogens are excluded.During the hospitalization, the CT scans of lungs and the dynamics of immune responses were closely monitored. Summary reports of serial CT scans and serial blood tests of the male patient are shown in Fig. 1 and Table 2.After admission, according to our clinical experience, the patient was given methylprednisolone 40 mg iv gtt for once, and then the fever subsided. The patient was given human gamma globulin 10 g iv gtt qd for five successive days, and then the dose was changed to 5 g. Considering the cause was unknown, we also used drugs to treat atypical pathogens, including moxifloxacin for mycoplasma and chlamydia, and oseltamivir and abidol hydrochloride for influenza A virus; meanwhile, the patient was given Chinese patent medicine Tanreqing iv gtt for adjunctive therapy. On Jan 10, 2020, the male patient was re-examined for all inflammatory indices and all showed normal, and he was discharged from hospital on the same day.The female patient was 38 years old and was admitted due to fever, cough, and vomiting for one day on Dec 30, 2019. On admission, she had no dyspnea, no chest distress, no expectoration, no pharyngalgia, no nasal discharge, nor nasal obstruction. She was previously healthy, and had no history of allergy to food or drug. PE on admission...

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To the Editor, No therapeutics has been proven effective for treatment of coronavirus disease 2019 (COVID-19). 1,2 China has explored important clinical trials on a host of possible effective treatment options including ozone therapy. We introduced our experience in treating two confirmed cases by ozone therapy-major autohemotherapy (MAH). 3 After the written informed consent was obtained, MAH was given to patients once daily for 7 consecutive days. Each time, 100 mL of venous blood was collected and mixed with O 3 gas at the 1:1 ratio of oxygen-ozone to blood volume, with the final concentration of oxygen-ozone being 20 μg/mL. The clinical study was approved by the Clinical Research Ethics Committee of Renmin Hospital of Wuhan University (WDRY2020-K020). CASE 1 A male of 53-year-old was admitted to Renmin Hospital of Wuhan University on 20 February 2020 due to mild fever and dyspnea for 7 days, accompanied by headache, runny nose, fatigue, and loss of appetite. On admission, he presented a clear consciousness with a body temperature of 37.5℃. Chest computed tomography (CT) imaging on 19 February 2020 revealed multiple small patchy shadows, linear interstitial changes, and consolidation in both lungs. He was confirmed COVID-19 on 21 February 2020 Lymphopenia, elevated C-reactive protein and interleukin 6, mild hypoxemia were noted in laboratory tests.