Clinical characteristics and severity of beta and delta variants of SARS-CoV-2 and the effect of vaccine on delta variants.

Background: The Delta variant of concern (VOC) is rapidly becoming the dominant strain globally. We report the clinical characteristics and severity of hospitalized patients infected with Delta and Beta VOCs during the local outbreak in Harbin, Heilongjiang Province, China, and the effect of vaccines on the Delta variant. Methods: We collected a total of 735 COVID-19 patients from the First Affiliated Hospital of Harbin Medical University, including 96 cases infected with the Delta VOC and 639 cases infected with the Beta VOC. Demographic, clinical characteristic and laboratory findings were collected and compared. Results: Differences in viral shedding, IgG and IgM levels, and the neutrophil-to-lymphocyte ratio were noted between the Delta and Beta VOCs (p < 0.05). Survival analysis of the two groups revealed longer viral shedding of the Delta VOC (p < 0.05). For the Delta VOC, the longer the vaccination period, the lower the IgG and IgM levels. IgM levels were higher in the convalescent plasma group, whereas lymphocyte counts were lower. Conclusions: Delta VOC virus shedding was longer compared with Beta VOC shedding. Vaccination with inactivated vaccines can reduce the severe illness rate of the Delta VOC. IgG and IgM levels are reduced as the time period between the first and second vaccine doses increases.

Clinical characteristics of 310 SARS-CoV-2 Omicron variant patients and comparison with Delta and Beta variant patients in China.

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread, data on the clinical characteristics of infected patients are limited. In this study, the demographic, clinical characteristics, and laboratory data of 310 SARS-CoV-2 Omicron variant patients treated at Haihe Hospital of Tianjin were collected and analyzed. Information on these patients was compared to 96 patients with the Delta variant of concern (VOC) and 326 patients with the Beta VOC during the previous coronavirus disease 2019 (COVID-19) outbreak in Harbin. Of the 310 patients infected with the Omicron variant, the median age was 35 years. Most patients were clinically classified as mild (57.74%), and the most common symptoms were cough (48.71%), fever (39.35%), and sore throat (38.26%). The results for different vaccination groups in the Omicron group showed that the median of "SARS-CoV-2 specific IgG" after 2 or 3 doses of vaccination was higher than the unvaccinated group (all Ps â€‹< â€‹0.05). Older age was associated with a higher proportion of moderate cases and lower asymptomatic and mild cases based on clinical classifications. Compared to the Delta and Beta groups, the median age of the Omicron group was younger. The total number of asymptomatic patients and mild patients in the Omicron virus group was higher than the Delta and Beta groups (60.97% vs. 54.17% vs. 47.55%). This study presented the clinical characteristics of the first group of patients infected with the Omicron variant in Tianjin, China, and compared their clinical features with patients infected by the Delta and Beta variants, which would increase our understanding of the characteristics of SARS-CoV-2 Omicron variant.

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial.

Recombinant human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody JS016 showed neutralizing and therapeutic effects in preclinical studies. The clinical efficacy and safety of the therapy needed to be evaluated. In this phase 2/3, multicenter, randomized, open-label, controlled trial, hospitalized patients with moderate or severe coronavirus disease 2019 (COVID-19) were randomly assigned in a 1:1 ratio to receive standard care or standard care plus a single intravenous infusion of JS016. The primary outcome was a six-level ordinal scale of clinical status on day 28 since randomization. Secondary outcomes include adverse events, 28-day mortality, ventilator-free days within 28 days, length of hospital stay, and negative conversion rate of SARS-CoV-2 nucleic acid on day 14. A total of 199 patients were randomized, and 197 (99 in the JS016 group and 98 in the control group) were analyzed. Most patients, 95 (96%) in the JS016 group and 97 (99%) in the control group were in the best category on day 28 since randomization. The odds ratio of being in a better clinical status was 0.31 (95% confidence interval [CI], 0.03 to 3.19; P = 0.33). Few adverse events occurred in both groups (3% in the JS016 group and 1% in the control group, respectively; P = 0.34). SARS-CoV-2 neutralizing antibody JS016 did not show clinical efficacy among hospitalized Chinese patients with moderate to severe COVID-19 disease. Further studies are needed to assess the efficacy of the neutralizing antibody to prevent disease deterioration and its benefits among groups of patients specified by disease course and severity. (This study has been registered at ClinicalTrials.gov under identifier NCT04931238.).

Continuous Renal Replacement Therapy With oXiris Filter May Not be an Effective Resolution to Alleviate Cytokine Release Syndrome in Non-AKI Patients With Severe and Critical COVID-19.

In this study, we aimed to determine whether continuous renal replacement therapy (CRRT) with oXiris filter may alleviate cytokine release syndrome (CRS) in non-AKI patients with severe and critical coronavirus disease 2019 (COVID-19). A total of 17 non-AKI patients with severe and critical COVID-19 treated between February 14 and March 26, 2020 were included and randomly divided into intervention group and control group according to the random number table. Patients in the intervention group immediately received CRRT with oXiris filter plus conventional treatment, while those in the control group only received conventional treatment. Demographic data were collected and collated at admission. During ICU hospitalization, the concentrations of circulating cytokines and inflammatory chemokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were quantitatively measured daily to reflect the degree of CRS induced by SARS-CoV-2 infection. Clinical data, including the severity of COVID-19 white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet (PLT), C-reaction protein (CRP), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), albumin (ALB), serum creatinine (SCr), D-Dimer, fibrinogen (FIB), IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, number of hospital days and sequential organ failure assessment (SOFA) score were obtained and collated from medical records, and then compared between the two groups. Age, and SCr significantly differed between the two groups. Besides the IL-2 concentration that was significantly lower on day 2 than that on day 1 in the intervention group, and the IL-6 concentrations that were significantly higher on day 1, and day 2 in the intervention group compared to the control group, similar to the IL-10 concentration on day 5, there were no significant differences between the two groups. To sum up, CRRT with oXiris filter may not effectively alleviate CRS in non-AKI patients with severe and critical COVID-19. Thus, its application in these patients should be considered with caution to avoid increasing the unnecessary burden on society and individuals and making the already overwhelmed medical system even more strained (IRB number: IRB-AF/SC-04).

Cytokine levels in sputum, not serum, may be more helpful for indicating the damage in the lung and the prognosis of severe COVID-19 - A case series.

PURPOSE: To describe the relationship between the severity of lung damage and cytokine levels in sputum, bronchoalveolar lavage fluid (BALF), serum. METHOD: Eight severe patients infected with coronavirus disease 2019 (COVID-19) were admitted and their cytokines and chest computed tomography (CT) were analyzed. RESULTS: Compared with in serum, IL-6 and TNF-α in sputum and in BALF show more directly reflect the severity of COVID-19 critical patients. The gradient ratio of IL-6 levels may predict the prognosis of severe patients. CONCLUSION: Cytokine levels in the sputum may be more helpful for indicating lung damage. Local intervention through the respiratory tract is expected to benefit patients with severe COVID-19.

Cytokine Storm May Not Be the Chief Culprit for the Deterioration of COVID-19.

COVID-19 is spreading and ravaging all over the world, and the number of deaths is increasing day by day without downward trend. However, there is limited knowledge of pathogenesis on the deterioration of COVID-19 at present. In this study we aim to determine whether cytokine storm is really the chief culprit for the deterioration of COVID-19. The confirmed COVID-19 patients were divided into moderate group (n = 89), severe group (n = 37), and critical group (n = 41). Demographic data were collected and recorded on admission to ICU. Clinical data were obtained when moderate, severe, or critical COVID-19 was diagnosed, and then compared between groups. The proportion of enrolled COVID-19 patients was slightly higher among males (52.5%) than females (47.5%), with an average age of 64.87 years. The number of patients without comorbidities exceed one third (36.1%), and patients with 1, 2, 3, 4 kinds of comorbidities accounted for 23.0%, 23.0%, 13.1%, and 4.9%, respectively. IL-6, IL-10, TNF, and IFN-γ, including oxygenation index, sequential organ failure assessment score, white blood cell count, lymphocyte count, lymphocyte percentage, platelet, C-reaction protein, lactate dehydrogenase, creatine kinase isoenzyme, albumin, D-Dimer, and fibrinogen showed significant difference between groups. Some, but not all, cytokines and chemokines were involved in the deterioration of COVID-19, and thus cytokine storm maybe just the tip of the iceberg and should be used with caution to explain pathogenesis on the deterioration of COVID-19, which might be complex and related to inflammation, immunity, blood coagulation, and multiple organ functions. Future studies should focus on identification of specific signaling pathways and mechanisms after severe acute respiratory syndrome coronavirus 2 infections (IRB number: IRB-AF/SC-04/01.0).

COVID-19 patient with an incubation period of 27 d: A case report.

BACKGROUND: As a highly contagious disease, coronavirus disease 2019 (COVID-19) is wreaking havoc around the world due to continuous spread among close contacts mainly via droplets, aerosols, contaminated hands or surfaces. Therefore, centralized isolation of close contacts and suspected patients is an important measure to prevent the transmission of COVID-19. At present, the quarantine duration in most countries is 14 d due to the fact that the incubation period of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is usually identified as 1-14 d with median estimate of 4-7.5 d. Since COVID-19 patients in the incubation period are also contagious, cases with an incubation period of more than 14 d need to be evaluated. CASE SUMMARY: A 70-year-old male patient was admitted to the Department of Respiratory Medicine of The First Affiliated Hospital of Harbin Medical University on April 5 due to a cough with sputum and shortness of breath. On April 10, the patient was transferred to the Fever Clinic for further treatment due to close contact to one confirmed COVID-19 patient in the same room. During the period from April 10 to May 6, nucleic acid and antibodies to SARS-CoV-2 were tested 7 and 4 times, respectively, all of which were negative. On May 7, the patient developed fever with a maximum temperature of 39℃, and his respiratory difficulties had deteriorated. The results of nucleic acid and antibody detection of SARS-CoV-2 were positive. On May 8, the nucleic acid and antibody detection of SARS-CoV-2 by Heilongjiang Provincial Center for Disease Control were also positive, and the patient was diagnosed with COVID-19 and reported to the Chinese Center for Disease Control and Prevention. CONCLUSION: This case highlights the importance of the SARS-CoV-2 incubation period. Further epidemiological investigations and clinical observations are urgently needed to identify the optimal incubation period of SARS-CoV-2 and formulate rational and evidence-based quarantine policies for COVID-19 accordingly.

Exploration of transmission chain and prevention of the recurrence of coronavirus disease 2019 in Heilongjiang Province due to in-hospital transmission.

The coronavirus disease 2019 (COVID-19) epidemic is a major public health emergency characterized by fast spread, a wide range of infections, and enormous control difficulty. Since the end of December 2019, Wuhan has become the first core infection area of China's COVID-19 outbreak. Since March 2020, the domestic worst-hit areas have moved to the Heilongjiang Province due to the increased number of imported COVID-19 cases. Herein, we reported the major COVID-19 outbreak, which caused a rebound of the epidemic in Harbin, China. After the rebound, different levels of causes for the recurrence of COVID-19, including city-level, hospital-level, and medical staff-level cause, were investigated. Meanwhile, corresponding countermeasures to prevent the recurrence of the epidemic were also carried out on the city level, hospital level, and medical staff level, which eventually showed the effect of infection control function in a pandemic. In this study, we described the complete transmission chain, analyzed the causes of the outbreak, and proposed corresponding countermeasures from our practical clinical experience, which can be used as a valuable reference for COVID-19 control.

SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid Organs.

While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. In situ hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of Il6, Il8 and Il1b genes in infected primary macrophages and DCs in vitro, and SARS-CoV-2-NP+ macrophages and DCs also manifested high levels of IL-6 and IL-1ß, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.

Standardization of critical care management of non-critically ill patients with COVID-19.

The large global outbreak of coronavirus disease 2019 (COVID-19) has seriously endangered the health care system in China and globally. The sudden surge of patients with severe acute respiratory syndrome coronavirus 2 infection has revealed the shortage of critical care medicine resources and intensivists. Currently, the management of non-critically ill patients with COVID-19 is performed mostly by non-intensive care unit (ICU) physicians, who lack the required professional knowledge, training, and practice in critical care medicine, especially in terms of continuous monitoring of the respiratory function, intervention, and feedback on treatment effects. This clinical problem needs an urgent solution. Therefore, here, we propose a series of clinical strategies for non-ICU physicians aimed at the standardization of the management of non-critically ill patients with COVID-19 from the perspective of critical care medicine. Isolation management is performed to facilitate the implementation of hierarchical monitoring and intervention to ensure the reasonable distribution of scarce critical care medical resources and intensivists, highlight the key patients, timely detection of disease progression, and early and appropriate intervention and organ function support, and thus improve the prognosis. Different management objectives are also set based on the high-risk factors and the severity of patients with COVID-19. The approaches suggested herein will facilitate the timely detection of disease progression, and thus ensure the provision of early and appropriate intervention and organ function support, which will eventually improve the prognosis.

Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection.

It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.

Decreased T Cell Levels in Critically Ill Coronavirus Patients: Single-Center, Prospective and Observational Study.

BACKGROUND: Since Dec. 2019, the COVID-19 pandemic has been an outbreak. T cells play an important role in dealing with various disease-causing pathogens. However, the role of T cells played in COVID-19 patients is still unknown. Our study aimed to describe the immunologic state of the critically ill COVID-19 patients. METHODS: A total of 63 patients with confirmed COVID-19 pneumonia were admitted to the Department of Intensive Care Unit of the First Affiliated Hospital of Harbin Medical University. The immunologic characteristics (lymphocyte apoptosis, the expression of PD-1 and HLA-DR in T cells, T cell subset levels, redistribution and the production of inflammatory factors) as well as their laboratory parameters were compared between severe group and critical group. RESULTS: The level of T cells in peripheral blood was decreased in critical patients compared with that in severe patients, but the expression levels of PD-1 (CD4+: 24.71% VS 30.56%; CD8+: 33.05% VS 32.38%) and HLA-DR (T cells: 36.28% VS 27.44%; monocytes: 20.58% VS 23.83%) in T cells were not significantly changed, and apoptosis and necrosis were not different in lymphocytes (apoptosis: 1.04% VS 1.27%; necrosis: 0.67% VS 1.11%), granulocytes, or monocytes between those two groups. CONCLUSION: There is severe immunosuppression in critically ill COVID-19 patients. Redistribution of T cells might be the main reason for lymphocytic decline. Decreasing the infiltration of T lymphocytes in the lung may be beneficial for the treatment of COVID-19.