MERS-CoV infection elicits long-lasting specific antibody, T and B cell immune responses in recovered individuals.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronaviruses and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. While MERS-CoV-specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels. METHODS: Serological and flow cytometric analysis of MERS-CoV-specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses. RESULTS: Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T and B cell responses up to 6.9 years post-infection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B cell subsets with antibody-independent functions as demonstrated by their ability to produce TNF-α, IL-6, and IFN-γ cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17 and IFN-γ. CONCLUSIONS: MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.

Mouth rinses efficacy on salivary SARS-CoV-2 viral load: A randomized clinical trial.

Considering the global trend to confine the COVID-19 pandemic by applying various preventive health measures, preprocedural mouth rinsing has been proposed to mitigate the transmission risk of SARS-CoV-2 in dental clinics. The study aimed to investigate the effect of different mouth rinses on salivary viral load in COVID-19 patients. This study was a single-center, randomized, double-blind, six-parallel-group, placebo-controlled clinical trial that investigated the effect of four mouth rinses (1% povidone-iodine, 1.5% hydrogen peroxide, 0.075% cetylpyridinium chloride, and 80 ppm hypochlorous acid) on salivary SARS-CoV-2 viral load relative to the distilled water and no-rinse control groups. The viral load was measured by quantitative reverse transcription PCR (RT-qPCR) at baseline and 5, 30, and 60 min post rinsing. The viral load pattern within each mouth rinse group showed a reduction overtime; however, this reduction was only statistically significant in the hydrogen peroxide group. Further, a significant reduction in the viral load was observed between povidone-iodine, hydrogen peroxide, and cetylpyridinium chloride compared to the no-rinse group at 60 min, indicating their late antiviral potential. Interestingly, a similar statistically significant reduction was also observed in the distilled water control group compared to the no-rinse group at 60 min, proposing mechanical washing of the viral particles through the rinsing procedure. Therefore, results suggest using preprocedural mouth rinses, particularly hydrogen peroxide, as a risk-mitigation step before dental procedures, along with strict adherence to other infection control measures.

The Effect of Short Treatment with Nigella Sativa on Symptoms, the Cluster of Differentiation (CD) Profile, and Inflammatory Markers in Mild COVID-19 Patients: A Randomized, Double-Blind Controlled Trial.

The current study investigated the impact of different doses of Nigella sativa seeds on the symptoms, the cluster of differentiation profile group, and inflammatory markers of mild COVID-19 cases. METHODS: The study was a double-blind placebo-controlled clinical trial. Patients with mild and asymptomatic SARS-CoV-2 infection patients were randomly subdivided into seven subgroups: Group (GP) 1: received charcoal capsules as a control group, and GP 2: received three capsules of whole Nigella sativa seeds daily, two capsules in the morning and one in the evening; GP 3: received three capsules of whole Nigella sativa seeds every 12 h, GP 4: received five capsules in the morning and four capsules of whole Nigella sativa seeds in the evening, GP 5: received one capsule of Nigella sativa powder every 12 h; GP 6: received two capsules of Nigella sativa powder every 12 h; GP 7: received three capsules of Nigella sativa powder every 12 h; all treatment course was for ten days. Inflammatory parameters were assessed before and after interventions. RESULTS: 262 subjects were included in the final analysis. No significant difference was detected regarding age, gender, and nationality. No significant differences were detected between the inflammatory marker in all groups. The WBCs showed a significant difference between before and after the intervention. While for procalcitonin, a significant difference was demonstrated in groups 1,4, and 6. CONCLUSIONS: The current randomized clinical trial did not reveal a significant effect of ten days of treatment with various doses of Nigella sativa on symptoms, differentiation profile, and inflammatory markers of patients with COVID-19. As a natural product, the effect of Nigella sativa on disease requires weeks to manifest itself.

Vitamin D Status and Mortality from SARS CoV-2: A Prospective Study of Unvaccinated Caucasian Adults.

COVID-19 and a low vitamin D state share common risk factors, which might explain why vitamin D deficiency has been linked with higher COVID-19 mortality. Moreover, measures of serum vitamin D may become lower during systemic inflammatory responses, further confounding the association via reverse causality. In this prospective study (recruited over 12 months), we examined whether the association between a low vitamin D state and in-hospital mortality due to SARS-CoV-2 pneumonia in unvaccinated subjects is explained by (i) the presence of shared risk factors (e.g., obesity, advanced age) or (ii) a reduction in serum 25(OH)D due to COVID-19 (i.e., reverse causality). In this cohort of 232 (mean age = 56 years) patients (all had SARS-CoV-2 diagnosed via PCR AND required supplemental oxygen therapy), we failed to find an association between serum vitamin D and levels of CRP, or other inflammatory markers. However, the hazard ratio for mortality for subjects over 70 years of age (13.2) and for subjects with a serum 25(OH)D level less than 30 nmol·L-1 (4.6) remained significantly elevated even after adjustment for gender, obesity and the presence of diabetes mellitus. Subjects <70 years and >70 years had significantly higher mortality with a serum 25(OH)D less than 30 nmol·L-1 (11.8% and 55%), than with a serum 25(OH)D greater than 30 nmol·L-1 (2.2% and 25%). Unvaccinated Caucasian adults with a low vitamin D state have higher mortality due to SARS CoV-2 pneumonia, which is not explained by confounders and is not closely linked with elevated serum CRP.

Clinical Presentation of Asymptomatic and Mild SARS-CoV-2 Infection in Riyadh, Saudi Arabia.

BACKGROUND: There is substantial evidence that most SARS-CoV-2 infections are mild or even asymptomatic, yet they can transmit the virus to others. The current study described the clinical presentation of mild COVID-19 cases isolated in the ministry of health (MOH) quarantines in Riyadh, Saudi Arabia. METHODS: A cross-sectional study targeted the SARS-CoV-2 PCR +ve asymptomatic and mild COVID-19 patients isolated in the Saudi MOH quarantines in Riyadh city between July and December 2020. The confirmed COVID-19 patients were enrolled and interviewed by telephones after obtaining the informed consent. RESULTS: The study included 223 patients with a mean age of 32.5±10.7 years old. The majority were male 156 (70%). Only 27 [12.1%; 95% CI = (8.1-17.1%)] were asymptomatic. General fatigue was the most common reported symptom, 43.5%, followed by headache with 42.6%, and cough by 38.1%. Anosmia and ageusia were reported by 33.2% and 31.4%, respectively. The least common reported symptoms were vomiting, earache, and nausea with 1.8%, 4.0%, and 7.6%, respectively. CONCLUSION: The top five clinical manifestations of mild COVID-19 cases were general fatigue, headache, cough, anosmia, and ageusia. Only 12% of confirmed COVID-19 cases were asymptomatic.

Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients.

The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.

Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review.

The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.