Durability of the humoral immune response in recovered COVID-19 patients

BackgroundThe immunological factors involved in protection against the disease caused by SARS-CoV-2 are insufficiently defined and understood. However, previous knowledge pertaining to the related SARS virus and other human coronaviruses may prove useful. Population-based serosurveys measuring anti-SARS-CoV-2 antibodies may provide a pattern for estimating infection degrees and observing the development of the epidemic. In this study, we aimed to investigate the persistence of antibody against the SARS-CoV-2 in recovered patients in Al Madinah region of Saudi Arabia.Materials and methodsA total of 150 recovered COVID-19 patients participated in this study. All the patients tested positive for the presence of SARS-CoV-2 RNA, using qualitative RT-PCR. An ELISA was used to measure anti-Spike (S) IgG antibodies in serum samples and screen for their persistence at various time points post-infection.ResultsThe patients were categorized as asymptomatic (27.3%), mild (28%) and moderate (44.7%) according to the disease severity. Amongst them, 35.3% were females (n = 53) and 64.7% were males (n = 97). Significant anti-S IgG antibody levels were observed among the different groups, with the patients in moderate group exhibiting the highest levels followed by the mild group; while the lowest levels were detected among the asymptomatic. There was a significant positive correlation between the patients’ age and anti-S IgG antibody concentrations (Pearson r = 0.45; p < 0.001).ConclusionOur findings provide a solid evidence to support the use of an anti-S IgG ELISA as a diagnostic tool to indicate SARS-CoV-2 infection. IgG seropositivity was sustained in recovered patients up to a hundred days' post-infection, the latest time point for antibody measurement in our study. Ours is the first report in Saudi Arabia to investigate the durability of humoral immune response in recovered COVID-19 patients.     

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka,Bangladesh

BackgroundCOVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients.Methodology/Principal findingsThis longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases.Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases.Conclusion/SignificanceWe report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.     

Seroprevalence of COVID-19 in Riyadh city during the early increase of COVID-19 infections in Saudi Arabia,June 2020

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 and caused a global pandemic of the Coronavirus Disease 2019 (COVID-19). More than 170 million cases have been reported worldwide with mortality rate of 1–3%. The detection of SARS-CoV-2 by molecular testing is limited to acute infections, therefore serological studies provide a better estimation of the virus spread in a population. This study aims to evaluate the seroprevalence of SARS-CoV-2 in the major city of Riyadh, Saudi Arabia during the sharp increase of the pandemic, in June 2020. Serum samples from non-COVID patients (n = 432), patients visiting hospitals for other complications and confirmed negative for COVID-19, and healthy blood donors (n = 350) were collected and evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). The overall percentage of positive samples was 7.80% in the combined two populations (n = 782). The seroprevalence was lower in the blood donors (6%) than non-COVID-19 patients (9.25%), p = 0.0004. This seroprevalence rate is higher than the documented cases, indicating asymptomatic or mild unreported COVID-19 infections in these two populations. This warrants further national sero-surveys and highlights the importance of real-time serological surveillance during pandemics.     

Shorter leukocyte telomere length is associated with severity of COVID-19 infection.

The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology.     

Antibody profile in symptomatic/asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected Saudi persons

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected persons could be symptomatic or asymptomatic. Asymptomatic and symptomatic patients can transmit SARS-CoV-2. This study aimed to study the humoral immune response in Saudis who are Covid-19 symptomatic and asymptomatic patients. We created three types of enzyme-linked immunosorbant assays (ELISAs) to reveal IgG and IgM antibodies (Abs) against SARS-CoV-2. The developed ELISAs were designed to detect Abs against SARS-CoV-2 N, S and N + S proteins. A number of Covid-19 symptomatic (1 5 3) and asymptomatic (84) RT–PCR-confirmed patient sera were used to evaluate the ELISAs and to determine the IgG and IgM antibody profile in those patients. The sensitivity and specificity of these ELISAs were evaluated using pre-Covid-19 pandemic serum samples. The results revealed the existence of anti-SARS-CoV-2 IgG and IgM Abs in Covid-19 symptomatic and asymptomatic Saudi persons. The use of SARS-CoV-2 N and S proteins in the same ELISA greatly increased the detectability of infection. In conclusion, the Covid-19 symptomatic and asymptomatic Saudi persons demonstrated both IgG and IgM antibody profile with higher titer in symptomatic patients. The use of N + S proteins as antibody capture antigens greatly increased the ELISA sensitivity.     

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 < 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.     

SARS-CoV-2 infection negatively affects ovarian function in ART patients

Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1β were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor β (Erβ), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3β-hydroxysteroid dehydrogenase (3β-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.     

Assessment of global asymptomatic SARS-CoV-2 infection and management practices from China

With ongoing research, it was found that asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was widespread in coronavirus disease 2019 (COVID-19) populations. Studies have confirmed asymptomatic patients with COVID-19 have potential infectivity, and most of the transmission occurred before symptoms appear. Asymptomatic infection rates varied widely in different countries and regions. Identifying the asymptomatic infected persons and cutting off the infection source is an effective way to prevent the spread of this disease. However, asymptomatic patients have hidden clinical symptoms, and screening based only on the clinical symptoms of COVID-19 can easily lead to a missed diagnosis. Therefore, determining asymptomatic infection patients by SARS-CoV-2 nucleic acid testing is the gold standard. A series of prevention and control measures adopted by the Chinese government, especially the “Four Early” policy, have achieved outstanding achievements, which are worth learning from by other countries.     

The concentrations of essential/toxic elements in serum of COVID-19 patients are not directly related to the severity of the disease

BackgroundIn recent months, the current COVID-19 pandemic has generated thousands of studies directly or indirectly related with this disease and/or the coronavirus SARS-CoV-2 causing the infection. On August 22, 2022, the database PUBMED included 287,639 publications containing the term COVID-19. However, in spite of the importance of trace elements in human health, including the immune system, data on the levels of metals/metalloids in COVID-19 patients is very limited.MethodsThe concentrations of As, Cd, Cr, Cu, Hg, Fe, Mg, Mn, Pb, Se, V and Zn were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in 126 serum samples of individuals infected with SARS-CoV-2, as well as in 88 samples of non-infected individuals. Participants were divided into four groups: i) individuals COVID-19 positive (COVID-19 +) with an asymptomatic infection course; ii) individuals suffering mild COVID-19; iii) individuals suffering severe COVID-19, and iv) individuals COVID-19 negative (COVID-19-) (control group). The occurrence of the analyzed metals/metalloids was evaluated along with the biochemical profile, including blood cell counts, lipids, proteins and crucial enzymes.ResultsSerum levels of Mg, V, Cr, Cu, Cd, and Pb were higher in COVID-19 positive patients than those in the control group. Although no significant differences were observed between the different groups of patients, the concentrations of Cd, Pb, V and Zn showed a tendency to be higher in individuals with severe COVID-19 than in those showing mild symptoms or being asymptomatic. Arsenic and Hg were rarely detected, regardless if the subjects were infected by SARS-CoV-2, or not. The current results did not show significant differences in the levels of the rest of analyzed elements according to the severity of the disease (asymptomatic, mild and severe).ConclusionsIn spite of the results here obtained, we highlight the need to reduce the exposure to Cd, Pb and V to minimize the potential adverse health outcomes after COVID-19 infection. On the other hand, although a protective role of essential elements was not found, Mg and Cu concentrations were higher in severe COVID-19 patients than in non-infected individuals.     

Incidence and impact of cardiac arrhythmias in coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

BackgroundStudies have shown that cardiac arrhythmias may occur in up to 44% of patients with severe coronavirus disease 2019 (COVID-19) and has been associated with an increased risk of death. This systematic review and meta-analysis aimed to evaluate the incidence of cardiac arrhythmias in patients with COVID-19 and their implications on patient prognosis.MethodsWe performed a systematic literature search from PubMed, SCOPUS, Europe PMC, Cochrane Central Databases, and Google Scholar + Preprint Servers. The primary endpoint of the study was poor outcomes including mortality, severe COVID-19, and the need for ICU care.ResultsA total of 4 studies including 784 patients were analyzed. The incidence of arrhythmia in patients with COVID-19 was 19% (9–28%; I²: 91.45). Arrhythmia occurred in 48% (38–57%; I²: 48.08) of patients with poor outcome and 6% (1–12%; I²: 85.33%) of patients without poor outcome. Patients with COVID-19 experiencing arrhythmia had an increased risk of poor outcome (RR 7.96 [3.77, 16.81], p < 0.001; I²: 71.1%). The funnel-plot analysis showed an asymmetrical funnel plot with most of the studies on the right side of the effect estimate. The regression-based Egger’s test showed indication of small-study effects (p = 0.001).ConclusionCardiac arrhythmias were significantly associated with an increased risk of poor outcome in COVID-19. Arrhythmias were observed in 19% of patients with COVID-19 and in 48% of patients with COVID-19 and poor outcomes.     

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.     

Sex differences in immune responses to SARS-CoV-2 in patients with COVID-19

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3⁺ and CD8⁺ T cell proportions. The lower CD4⁺ T cell proportions and higher CD8⁺ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4⁺ T cell proportion was negatively associated with the CD8⁺ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4⁺ T cell and CD8⁺ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.     

Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2pos subjects

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2^pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2^pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with combined assays of 44-plex CyTOF, RNA-seq and Olink. Notably, both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations, while certain parameters including more severely decreased frequencies of CD107a^low classical monocytes, intermediate monocytes, non-classical monocytes and CD62L^hi CD8⁺ T_naïve cells, reduced plasma STC1 level but an increased frequency of CD4⁺ NKT cells combined to distinguish the latter. Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage, a likely lymphocyte exhaustion and immunosuppression, yielding mechanistic insights into SSIS fate determination, which could potentially improve SARS-CoV-2 management.Subject terms: Mechanisms of disease, Immunology     

Humoral Immunity against SARS-CoV-2 and the Impact on COVID-19 Pathogenesis

It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge.     

Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan,China

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.     

Heart rate variability as a marker of cardiovascular dysautonomia in post-COVID-19 syndrome using artificial intelligence

IntroductionCardiovascular dysautonomia comprising postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH) is one of the presentations in COVID-19 recovered subjects. We aim to determine the prevalence of cardiovascular dysautonomia in post COVID-19 patients and to evaluate an Artificial Intelligence (AI) model to identify time domain heart rate variability (HRV) measures most suitable for short term ECG in these subjects.MethodsThis observational study enrolled 92 recently COVID-19 recovered subjects who underwent measurement of heart rate and blood pressure response to standing up from supine position and a 12-lead ECG recording for 60 s period during supine paced breathing. Using feature extraction, ECG features including those of HRV (RMSSD and SDNN) were obtained. An AI model was constructed with ShAP AI interpretability to determine time domain HRV features representing post COVID-19 recovered state. In addition, 120 healthy volunteers were enrolled as controls.ResultsCardiovascular dysautonomia was present in 15.21% (OH:13.04%; POTS:2.17%). Patients with OH had significantly lower HRV and higher inflammatory markers. HRV (RMSSD) was significantly lower in post COVID-19 patients compared to healthy controls (13.9 ± 11.8 ms vs 19.9 ± 19.5 ms; P = 0.01) with inverse correlation between HRV and inflammatory markers. Multiple perceptron was best performing AI model with HRV(RMSSD) being the top time domain HRV feature distinguishing between COVID-19 recovered patients and healthy controls.ConclusionPresent study showed that cardiovascular dysautonomia is common in COVID-19 recovered subjects with a significantly lower HRV compared to healthy controls. The AI model was able to distinguish between COVID-19 recovered patients and healthy controls.