Possible cancer-causing capacity of COVID-19: Is SARS-CoV-2 an oncogenic agent?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown diverse life-threatening effects, most of which are considered short-term. In addition to its short-term effects, which has claimed many millions of lives since 2019, the long-term complications of this virus are still under investigation. Similar to many oncogenic viruses, it has been hypothesized that SARS-CoV-2 employs various strategies to cause cancer in different organs. These include leveraging the renin angiotensin system, altering tumor suppressing pathways by means of its nonstructural proteins, and triggering inflammatory cascades by enhancing cytokine production in the form of a "cytokine storm" paving the way for the emergence of cancer stem cells in target organs. Since infection with SARS-CoV-2 occurs in several organs either directly or indirectly, it is expected that cancer stem cells may develop in multiple organs. Thus, we have reviewed the impact of coronavirus disease 2019 (COVID-19) on the vulnerability and susceptibility of specific organs to cancer development. It is important to note that the cancer-related effects of SARS-CoV-2 proposed in this article are based on the ability of the virus and its proteins to cause cancer but that the long-term consequences of this infection will only be illustrated in the long run.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.e., severe) or infection ward (i.e., moderate) and after 7 days of antiviral therapy. COVID-19 patients were treated with either favipiravir or Kaletra (FK group, 11 severe and 11 moderate) or dexamethasone plus remdesivir (DR group, 7 severe and 10 moderate) for 7 days in a pilot study. Eight healthy control subjects were also enrolled. The frequency of PD-1+ and CTLA-4+ lymphocytes in whole blood was evaluated by flow cytometry. Patients on DR therapy had shorter hospital stays than those on FK therapy. The frequency of PD-1+ lymphocytes in the FK group at baseline differed between COVID-19 patients and healthy controls, while the frequency of both PD-1+ and CTLA-4+ cells increased significantly 7 days of FK therapy. The response was similar in both moderate and severe patients. In contrast, the frequency of PD-1+ and CTLA-4+ lymphocytes varied significantly between patients and healthy controls before DR treatment. DR therapy enhanced PD-1+ but not the CTLA-4+ frequency of these cells after 7 days. We show that the frequency of PD-1 and CTAL-4-bearing lymphocytes during hospitalization was increased in Iranian ICU COVID-19 patients who received FK treatment, but that the frequency of CTLA-4+ cells was higher at baseline and did not increase in patients who received DR. The effectiveness of DR treatment may reflect differences in T-cell activation or exhaustion status, particularly in CTLA-4-expressing cells.

Effectiveness of different vaccine platforms in reducing mortality and length of ICU stay in severe and critical cases of COVID-19 in the Omicron variant era: A national cohort study in Iran.

Various severe acute respiratory syndrome coronavirus 2 vaccines with different platforms have been administered worldwide; however, their effectiveness in critical cases of COVID-19 has remained a concern. In this national cohort study, 24 016 intensive care unit (ICU) coronavirus disease-2019 (COVID-19) admissions were included from January to April 2022. The mortality and length of ICU stay were compared between the vaccinated and unvaccinated patients. A total of 9428 (39.25%) patients were unvaccinated, and 14 588 (60.75%) patients had received at least one dose of the vaccine. Compared with the unvaccinated, the first, second, and third doses of vaccine resulted in 8%, 20%, and 33% lower risk of ICU mortality in the adjusted model, with risk ratio (RR): 0.92, 95% confidence interval (CI): 0.84-1.001, RR: 0.80, 95% CI: 0.77-0.83, and RR: 0.67, 95% CI: 0.64-0.71, respectively. The mean survival time was significantly shorter in the unvaccinated versus the fully vaccinated patients (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.88); p < 0.001). All vaccine platforms successfully decreased the hazard of ICU death compared with the unvaccinated group. The duration of ICU stay was significantly shorter in the fully vaccinated than in unvaccinated group (MD, -0.62, 95% CI: -0.82 to -0.42; p < 0.001). Since COVID-19 vaccination in all doses and platforms has been able to reduce the risk of mortality and length of ICU-stay, universal vaccination is recommended based on vaccine availability.

Effectiveness of Borage plus syrup on COVID-19 patients in intensive care units.

Introduction: COVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting. Materials and methods: A pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020-December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-ß and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. Results: All the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05). Conclusion: Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.

Immunophenotype and function of circulating myeloid derived suppressor cells in COVID-19 patients.

The pathogenesis of coronavirus disease 2019 (COVID-19) is not fully elucidated. COVID-19 is due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes severe illness and death in some people by causing immune dysregulation and blood T cell depletion. Increased numbers of myeloid-derived suppressor cells (MDSCs) play a diverse role in the pathogenesis of many infections and cancers but their function in COVID-19 remains unclear. To evaluate the function of MDSCs in relation with the severity of COVID-19. 26 PCR-confirmed COVID-19 patients including 12 moderate and 14 severe patients along with 11 healthy age- and sex-matched controls were enrolled. 10 ml whole blood was harvested for cell isolation, immunophenotyping and stimulation. The immunophenotype of MDSCs by flow cytometry and T cells proliferation in the presence of MDSCs was evaluated. Serum TGF-ß was assessed by ELISA. High percentages of M-MDSCs in males and of P-MDSCs in female patients were found in severe and moderate affected patients. Isolated MDSCs of COVID-19 patients suppressed the proliferation and intracellular levels of IFN-γ in T cells despite significant suppression of T regulatory cells but up-regulation of precursor regulatory T cells. Serum analysis shows increased levels of TGF-ß in severe patients compared to moderate and control subjects (HC) (P = 0.003, P < 0.0001, respectively). The frequency of MDSCs in blood shows higher frequency among both moderate and severe patients and may be considered as a predictive factor for disease severity. MDSCs may suppress T cell proliferation by releasing TGF-ß.

Effectiveness of Borage plus syrup on COVID-19 patients in intensive care units

Introduction COVID-19 (coronavirus disease-2019) still causes a high rate of death globally with no definite curative treatment described. The traditional plant Borage (Borago officinalis L.) is a good source of gamma-linolenic (GLA). We hypothesized that Borage plus syrup (BPS) would be beneficial in severe COVID-19 patients within an intensive care unit (ICU) setting. Materials and methods A pilot single center, randomized trial with no placebo was undertaken. A total of 60 PCR-positive severe COVID-19 participants admitted to ICU from June 2020–December 2020 at Masih Daneshvari Hospital Tehran-Iran gave informed consent. The participants were randomly assigned to either Borage Plus Syrup (BPS, 5 ml for 5 days) (n = 30) or standard care (IFN-β and favipiravir) as a control group (n = 30). Pao2/Fio2, serum ferritin, CRP, bilirubin, IL-6, TNF-α, ALT, AST, PCT and serum IL-8 was measured upon admission and on release. Results All the measured parameters decreased significantly with BPS treatment. In the control group, most parameters significantly improved apart from AST and PCT. In addition, the suppression of serum TNF levels in the BPS group was greater than that seen in the control group (P ≤ 0.05). Moreover, the length of ICU stay was significantly lower in the BPS group compared with the control group (P ≤ 0.05). Conclusion Our study shows that addition of BPS to the standard treatment regime of COVID-19 patients in ICU improved outcomes and reduced the length of ICU treatment. Natural products could be considered as new approaches for reducting the harmful consequences of COVID-19.

Evaluation of Myeloid-derived Suppressor Cells in the Blood of Iranian COVID-19 Patients.

The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran. Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry. COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8.  A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39). COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSCs, lung, serum IL-8, and other inflammatory biomarkers should be measured.

Do Low-Density Granulocytes Induce Lymphopenia in Patients with COVID-19?

No abstract No abstract No abstract No abstract No abstract.

Blood Purification Techniques, Inflammatory Mediators and Mortality in COVID-19 Patients.

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

Decreased serum levels of angiotensin converting enzyme (ACE)2 and enhanced cytokine levels with severity of COVID-19: normalisation upon disease recovery.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Circulating soluble angiotensin-converting enzyme (sACE2)2, the main receptor for SARS-CoV-2, together with components of the renin-angiotensin system promote infection and disease severity. OBJECTIVE: This pilot study followed the time-course of sACE2 levels in relation to systemic cytokines in severe and moderate COVID-19 patients treated with remdesivir/dexamethasone in combination. METHODS: Peripheral blood was obtained upon admission from 30 patients (12 with moderate disease and 18 with severe disease) and 14 patients with PCR-confirmed mild COVID-19. Severe and moderate patients were treated with remdesivir (200mg/first day and 100mg/day for the remaining days) and dexamethasone (100mg/day). 6 healthy control subjects (HC) were also enrolled. Serum interleukin (IL)-6 and IL-8 and sACE2 levels were measured by ELISA at baseline and during treatment in severe and moderate patients and at baseline in mild and HCs. RESULTS: Baseline sACE2 levels were lower in severe (p = 0.0005) and moderate (p = 0.0022) patients than in patients with mild COVID-19 and in HC (p = 0.0023 and p = 0.0012 respectively). Treatment significantly increased sACE2 levels in patients with moderate disease (p = 0.0156) but only 50% of patients with severe disease showed enhanced levels compared to baseline. Systemic IL-6 and IL-8 levels were higher in all patient groups compared with HC and were not significantly affected over time or by remdesivir/dexamethasone treatment for 5 days. CONCLUSION: Serum sACE2 levels increase in severe COVID-19 patients as they recover over time whilst circulating cytokines are unaffected. Future studies should link these results to clinical outcomes.

The Immunopathogenesis of Neuroinvasive Lesions of SARS-CoV-2 Infection in COVID-19 Patients.

The new coronavirus disease COVID-19 was identified in December 2019. It subsequently spread across the world with over 125 M reported cases and 2.75 M deaths in 190 countries. COVID-19 causes severe respiratory distress; however, recent studies have reported neurological consequences of infection by the COVID-19 virus SARS-CoV-2 even in subjects with mild infection and no initial neurological effects. It is likely that the virus uses the olfactory nerve to reach the CNS and that this transport mechanism enables virus access to areas of the brain stem that regulates respiratory rhythm and may even trigger cell death by alteration of these neuronal nuclei. In addition, the long-term neuronal effects of COVID-19 suggest a role for SARS-CoV-2 in the development or progression of neurodegerative disease as a result of inflammation and/or hypercoagulation. In this review recent findings on the mechanism(s) by which SARS-CoV-2 accesses the CNS and induces neurological dysregulation are summarized.

Immune cell profiling and antibody responses in patients with COVID-19.

BACKGROUND: Although there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses. METHODS: In this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed. RESULTS: The white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells. CONCLUSION: Our results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.

Nutritional Impact and Its Potential Consequences on COVID-19 Severity.

Background: During late 2019 a viral disease due to a novel coronavirus was reported in Wuhan, China, which rapidly developed into an exploding pandemic and poses a severe threat to human health all over the world. Until now (May 2021), there are insufficient treatment options for the management of this global disease and shortage of vaccines. Important aspects that help to defeat coronavirus infection seems to be having a healthy, strong, and resilient immune system. Nutrition and metabolic disorders, such as obesity and diabetes play a crucial role on the community health situation in general and especially during this new pandemic. There seems to be an enormous impact of lifestyle, metabolic disorders, and immune status on coronavirus disease 2019 (COVID-19) severity and recovery. For this reason, it is important to consider the impact of lifestyle and the consumption of well-defined healthy diets during the pandemic. Aims: In this review, we summarise recent findings on the effect of nutrition on COVID-19 susceptibility and disease severity and treatment. Understanding how specific dietary features might help to improve the public health strategies to reduce the rate and severity of COVID-19.

Decreased neutrophil-mediated bacterial killing in COVID-19 patients.

The coronavirus disease COVID-19 was first described in December 2019. The peripheral blood of COVID-19 patients have increased numbers of neutrophils which are important in controlling the bacterial infections observed in COVID-19. We sought to evaluate the cytotoxic capacity of neutrophils in COVID-19 patients. 34 confirmed COVID-19 patients (29 severe, five mild disease), and nine healthy controls were recruited from the Masih Daneshvari Hospital (Tehran, Iran) from March to May 2020. Polymorphonuclear (PMN) cells were isolated from whole blood and incubated with green fluorescent protein (GFP)-labelled methicillin-resistant Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). Bacterial growth was determined by measuring the florescence of co-cultures of bacteria and neutrophils and reported as the lag time before exponential growth. The number of viable bacteria was determined after 70 hours as colony-forming units (CFU). The immunophenotype of tested cells was evaluated by flow cytometry. Isolated neutrophils have higher surface expression of CD16 and CD62L with negative markers for PMN-MDSC. Bacterial growth in the presence of SA (22 ± 0.9 versus 9.2 ± 0.5 h, P < .01) and PA (12.4 ± 0.6 versus 4.5 ± 0.22, P < .01) was significantly reduced in COVID-19 patients. After 70 h incubation of PMN with bacteria (SA and PA), CFUs were significant increased in COVID-19 patients SA (2.6 ± 0.09 × 108 CFU/mL-severe patients and 1.4 ± 0.06 × 108 CFU/mL-mild patients, P < .001) and PA (2.2 ± 0.09 × 109 CFU/mL-severe patients and 1.6 ± 0.03 × 109 CFU/mL-mild patients, P < .001). Gentamycin proliferation assays confirmed the presence of intracellular bacteria. Reduced bacterial killing by neutrophils from COVID-19 patients may be responsible for the high bacterial yield seen in these patients.

Increased Serum Levels of Soluble TNF-α Receptor Is Associated With ICU Mortality in COVID-19 Patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has infected over 112M patients and resulted in almost 2.5M deaths worldwide. The major clinical feature of severe COVID-19 patients requiring ventilation is acute respiratory distress syndrome (ARDS) possibly associated with a cytokine storm. Objectives: To elucidate serum levels of TNF-α and soluble TNF-Receptor 1 (sTNFR1) in patients with severe and mild COVID-19 disease as determinants of disease severity. Methods: We determined serum TNF-α and sTNFR1 concentrations in 46 patients with laboratory-confirmed COVID-19 (17 patients with severe disease within the intensive care unit [ICU] and 29 non-severe, non-ICU patients) and 15 healthy controls upon admission using ELISA. Subjects were recruited between March-May 2020 at the Masih Daneshvari Hospital Tehran, Iran. Results: Serum levels of sTNFRI were significantly higher in ICU patients (P<0.0001) and non-ICU patients (P=0.0342) compared with healthy subjects. Serum sTNFR1 were significantly higher in ICU patients than in non-ICU patients (P<0.0001). Serum TNF-α levels were greater in ICU and non-ICU patients than in the healthy subjects group (p<0.0001). The sTNFRI concentration in ICU (r=0.79, p=0.0002) and non-ICU (r=0.42, p=0.02) patients positively correlated with age although serum sTNFRI levels in ICU patients were significantly higher than in older healthy subjects. The sTNFRI concentration in ICU patients negatively correlated with ESR. Conclusions: The study demonstrates higher sTNFRI in ICU patients with severe COVID-19 disease and this be a biomarker of disease severity and mortality. Future studies should examine whether lower levels of systemic sTNFR1 at admission may indicate a better disease outcome.

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.

Comparative evaluation of SARS-CoV-2 IgG assays against nucleocapsid and spike antigens.

BACKGROUND: There are few studies to compare antibody response against anti-spike (S) and anti- nucleoprotein (N) SARS-CoV-2. OBJECTIVE: The aim of this study was to evaluate the IgG antibody production against S and N antigens of the virus and their correlation with the time and severity of the disease. METHODS: The IgG antibodies against S and N antigens of SARS-CoV-2 in serum specimens of 72 symptomatic patients who tested real-time reverse transcription polymerase chain reaction positive for SARS-CoV-2 were detected using the ELISA technique. Different antibody response was compared and the correlation with the time from disease onset and the severity was evaluated. RESULTS: Forty-eight of 72 (67%) patients tested positive for anti-SARS-CoV-2 antibodies, while 24 (33%) did not have detectable antibodies. Comparison of antibody levels for N and S antibodies showed that they correlate with each other well (r= 0.81; P< 0.001). However, sensitivity of anti-S SARS-CoV-2 IgG and anti-N SARS-CoV-2 IgG was 30% and 60%, during the first 7 days after symptom onset (r= 0.53; P= 0.111), but increased to 73% and 68% at more than 1-week post symptom onset (r= 0.89, P= 0.111), respectively. Cases with positive IgG response showed a decreased CD8+ T cells percentage compared to the negative IgG groups (26 ± 14 vs. 58 ± 32, p= 0.066 in anti-N IgG group and 28 ± 15 vs. 60 ± 45, p= 0.004 in anti-S IgG group, respectively). CONCLUSION: Nearly one-third of the confirmed COVID-19 patients had negative serology results. Lower percent positivity at early time points after symptom onset (less than 1 week) was seen using anti-S SARS-COV-2 IgG kit compare to the anti-N SARS-CoV-2 IgG; therefore, clinicians should interpret negative serology results of especially anti-S SARS-CoV-2 IgG with caution.

COVID-19: Molecular and Cellular Response.

In late December 2019, a vtiral pneumonia with an unknown agent was reported in Wuhan, China. A novel coronavirus was identified as the causative agent. Because of the human-to-human transmission and rapid spread; coronavirus disease 2019 (COVID-19) has rapidly increased to an epidemic scale and poses a severe threat to human health; it has been declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). This review aims to summarize the recent research progress of COVID-19 molecular features and immunopathogenesis to provide a reference for further research in prevention and treatment of SARS coronavirus2 (SARS-CoV-2) infection based on the knowledge from researches on SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV).

Correction to: Silent hypoxia: higher NO in red blood cells of COVID-19 patients.

An amendment to this paper has been published and can be accessed via the original article.