Innate and adaptive immunity to SARS-CoV-2 and predisposing factors.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has affected all countries worldwide. Although some symptoms are relatively mild, others are still associated with severe and even fatal clinical outcomes. Innate and adaptive immunity are important for the control of SARS-CoV-2 infections, whereas a comprehensive characterization of the innate and adaptive immune response to COVID-19 is still lacking and the mechanisms underlying immune pathogenesis and host predisposing factors are still a matter of scientific debate. Here, the specific functions and kinetics of innate and adaptive immunity involved in SARS-CoV-2 recognition and resultant pathogenesis are discussed, as well as their immune memory for vaccinations, viral-mediated immune evasion, and the current and future immunotherapeutic agents. We also highlight host factors that contribute to infection, which may deepen the understanding of viral pathogenesis and help identify targeted therapies that attenuate severe disease and infection.

Comparative analysis of epidemiological trends of COVID-19 in Shanghai and New York City

ObjectiveTo assess the effects of countermeasures against coronavirus disease 2019 (COVID-19) in Shanghai from March to May 2022 in comparison with epidemiological trend of COVID-19 in New York City. MethodsDaily confirmed cases, asymptomatic SARS-CoV-2 carriers, and daily deaths were obtained in the Shanghai Municipal Health Commission and the Center for Disease Control and Prevention (CDC) of the United States. Descriptive study was conducted by using these data. ResultsFrom March 1 to May 17, the number of daily asymptomatic SARS-CoV-2 infections in Shanghai was up to 58 times as large as that of daily confirmed cases;however, the number of daily confirmed cases in Shanghai was generally less than that in New York in the same time period. At the peak of the COVID-19 epidemic, the growth of daily attack rate in Shanghai was significantly lower than that in New York (P < 0.05). Moreover, the number of daily death was evidently less than that in New York. In addition, the vaccination rate in the elderly (aged 60 years) in Shanghai was evidently lower than that in New York (aged 65 years). ConclusionThe COVID-19 epidemics in Shanghai from March to May 2022 and in New York after December 2021 were both caused by the Omicron variant. Compared with the Delta variant, the Omicron variant has stronger replication ability and infectivity, resulting in challenges to the containment of the epidemic in metropolis such as Shanghai and New York City. The epidemic in New York City remained crucial due to absence of effective countermeasures, while that in Shanghai has been effectively contained with strict countermeasures. The prevention and control strategies may be adjusted along with the continual evolution of SARS-CoV-2 and increasing trend of imported COVID-19 cases.

Epidemiological characteristics of SARS-CoV-2 infection outbreak in Shanghai in the spring of 2022

Objective: To investigate the epidemiological characteristics and analyze the incidence trend of SARS-CoV-2 infection in Shanghai, China, and compare with the characteristics of the infection in Jilin Province of China during the same period in 2022 and Wuhan at the beginning of 2020.

The effects of hypertension on the prognosis of coronavirus disease 2019: a systematic review and meta-analysis on the interactions with age and antihypertensive treatment.

BACKGROUND: Hypertension and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) have been reported to be associated with the prognosis of COVID-19, but the findings remain controversial. Here, we conducted a systematic review to summarize the current evidence. METHODS: We retrieved all the studies by MEDLINE via PubMed, CENTRAL, and Embase using the MeSH terms until 30 April 2021. A fixed or random effect model was applied to calculate pooled adjusted odds ratio (AOR) with 95% confidence interval (CI). Interactive analysis was performed to identify the interaction effect of hypertension and age on in-hospital mortality. RESULTS: In total, 86 articles with 18 775 387 COVID-19 patients from 18 countries were included in this study. The pooled analysis showed that the COVID-19 patients with hypertension had increased risks of in-hospital mortality and other adverse outcomes, compared with those without hypertension, with an AOR (95% CI) of 1.36 (1.28-1.45) and 1.32 (1.24-1.41), respectively. The results were mostly repeated in countries with more than three independent studies. Furthermore, the effect of hypertension on in-hospital mortality is more evident in younger and older COVID-19 patients than in 60-69-year-old patients. ACEI/ARBs did not significantly affect the mortality and adverse outcomes of COVID-19 patients, compared with those receiving other antihypertensive treatments. CONCLUSION: Hypertension is significantly associated with an increased risk of in-hospital mortality and adverse outcomes in COVID-19. The effect of hypertension on in-hospital mortality among consecutive age groups followed a U-shaped curve. ACEI/ARB treatments do not increase in-hospital mortality and other poor outcomes of COVID-19 patients with hypertension.

Epidemic characteristics of local cases infected with SARS-CoV-2 in Yangpu District of Shanghai, China

Objective: To analyze the incidence and epidemic characteristics of local cases infected with SARS-CoV-2 in Yangpu District of Shanghai, China, and provide scientific evidence for the prevention and control of coronavirus disease-19 (COVID-19).

The role of interferon a on antiviral immunity in upper respiratory tract

Upper respiratory tract is directly connected with the external environment, and its natural immune system is the first line of defense against pathogens. In antiviral infection, interferon (IFN) is the main component of the antiviral natural immune system and IFN-a is a newly discovered immune effector molecule that is mainly produced in the mucosal barrier. IFN-a exerts a biological role through Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathway, and plays an important part in regulating innate and acquired immunity of respiratory mucosa. IFN-a principally expresses on the mucosal barrier with a long-lasting antiviral impact and controls immune-inflammatory damage, which is becoming a new focus of antiviral immunity research in the upper respiratory tract, especially in fighting against 2019 novel coronavirus diseases (COVID-19). Thus, we summarize the research progress of IFN-a antiviral immunity in the upper respiratory tract to provide new insight in the prevention and treatment of viral infection in the upper respiratory tract.

SARS-CoV-2 variants: origin, drivers and prevention measures

COVID-19 has emerged around the world since December 2019 and rapidly evolves as a major global public health challenge. SARS-CoV-2 is a positive single-stranded RNA virus with a relatively high natural mutation rate. The emergence of SARS-CoV-2 variants is generally considered as the outcome of a "mutation-selection-adaption" process. The enzyme APOBECs that is activated in the inflammatory microenvironment may facilitate viral mutagenesis. Currently, the major SARS-CoV-2 variants that impose public health significance are B.1.1.7, B.1.351, P.1, B.1.6.7.2, B.1.1.529 and so on, with probably increasing transmissibility, decreasing reactivity to the neutralizing antibodies, immune escape, and enhancing disease severity and mortality. Consequently, it warrants up-to-date countermeasures against evolving SARS-CoV-2, including tracing viral mutagenesis, developing vaccines against major variants, and enhancing social distancing.

Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics. METHODS: Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package "outbreaker". The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test. RESULTS: From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based sub-clusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became "pure" in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P < 0.001). SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart (P < 0.001). CONCLUSIONS: SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure. Travel restrictions might cause location-specific SARS-CoV-2 clustering. The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion.

Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/presymptomatic COVID-19 patients.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial. METHODS: We enrolled 193 SARS-CoV-2 infected subjects in Ningbo and Zhoushan, Zhejiang, China, from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and IgG against SARS-CoV-2 using colloidal gold-labeled and enzyme-linked immunosorbent assays. RESULTS: Of those, 31 were asymptomatic SARS-CoV-2 carriers, 148 symptomatic COVID-19 patients, and 14 presymptomatic COVID-19 patients. Compared to symptomatic COVID-19 patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower level of C-reactive protein, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (7.5 vs. 25.5 days, P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic patients than presymptomatic patients (P = 0.003) and asymptomatic carriers (P = 0.004). Viral shedding duration was longer in presymptomatic COVID-19 patients than in asymptomatic carriers (48.0 vs. 24.0 days, P = 0.002). Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89.0% vs. 61.0%, P = 0.028). In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with comorbidities. CONCLUSION: Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity should be contributable to innate and adaptive cellular immunity rather than humoral immunity. The severity of COVID-19 is associated with older age and comorbidities in familial clustering cases.

Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. METHODS: Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann-Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. RESULTS: The mean incubation was 8.67 (95% confidence interval, 6.78-10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86-12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. CONCLUSIONS: Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.