Type I and III interferons are good markers to monitor COVID-19 pathophysiology.

The COVID-19 pandemic has caused millions of deaths and has resulted in disastrous societal and economic impacts worldwide. During SARS-CoV-2 infection, abnormal levels of pro-inflammatory cytokines have been observed and were associated to the severity of the disease. Type I (-α/ß) and Type III (IFN-λ) interferons are family members of cytokines that play an important role in fighting viral replication during the early phases of infection. The location and timing of the IFNs production have been shown to be decisive for the COVID-19 outcome. Despite the effectiveness of COVID-19 vaccines and with the emergence of new SARS-CoV-2 variants, a better understanding of the involvement of IFNs as players in antiviral immunity in the COVID-19 pathophysiology is necessary to implement additional potent prophylactic and/or therapeutic approaches. In this study, we investigated the role of type I and III IFN in COVID-19 pathophysiology. We first analyzed the IFN-α, IFN-ß and IFN- λ mRNA expression in nasopharyngeal swabs and blood samples from Moroccan patients infected with SARS-CoV-2 and secondly correlated these IFNs expressions with COVID-19 clinical and biological parameters. Our results showed that in the upper airways of patients with mild, non-severe, or severe COVID-19 manifestations, the IFN- α, - ß and - λ are expressed in the same manner as in controls. However, in blood samples their expression was downregulated in all groups. Univariate linear models with interferons as predictors to evaluate clinical-biological parameters highlighted that the main clinical-biological relations were found when testing: FiO2, Lymphocyte values and virus load. Furthermore, the multivariate models confirmed that quantifications of interferons during COVID-19 are good biological markers for tracking COVID-19 pathophysiology.

Mix-and-match COVID-19 vaccines trigger high antibody response after the third dose vaccine in Moroccan health care workers.

Recent studies have shown that in individuals who have received two doses of COVID-19 vaccine, the level of IgG antibodies decreased over time. In addition, the resurgence of the epidemic due to variants has led the authorities in several countries, including Morocco, to extend the third dose to the entire adult population. In this study, we included 43 healthcare workers (HCWs) who were vaccinated with three doses. They were vaccinated with ChAdOx1 nCoV-19 for the first two doses and with BNT 162b2 or BBIBP-CorV vaccine for the third dose. Humoral response was assessed on the day of injection of the third dose of vaccine and one month after the third dose by measuring anti-receptor-binding domain (RBD) IgG levels. Seven months after the second dose, the median titer of anti-RBD IgG was higher in the group with a history of SARS-CoV-2 infection than in the group with no history of infection (1038 AU/mL vs. 76.05 AU/mL, respectively, p = 0.003). One month after the third dose, a significant increase in median level of anti-RBD in both groups was observed: from 76.05 AU/mL to 6127 AU/mL in the group with no history of infection and from 1038 AU/mL to 14,412 AU/mL in the group with history of infection. Notably, the BNT 162b2 vaccine elicits a high titer of anti-RBD antibody compared to the BBIBP-CorV vaccine. Median antibody titers were 21,991 AU/mL and 3640 AU/mL for BNT 162b2 and BBIBP-CorV vaccines, respectively (p = 0.0002). 23% of HCWs were infected with SARS-CoV-2 within the first two months after the third dose injection. However, all these patients developed mild symptoms and tested negative by RT-qPCR between 10 and 15 days after the onset of symptoms. Our findings support that the third dose of COVID-19 vaccine significantly improves the humoral response and protects against the severe disease.

Kinetics of SARS-CoV-2 IgM and IgG Antibodies 3 Months after COVID-19 Onset in Moroccan Patients.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious global public health problems. Characterization of the immune response, particularly antibodies to SARS-CoV-2, is important for establishing vaccine strategies. The purpose of this study was to evaluate longitudinally the kinetics of anti-SARS-CoV-2 antibodies against spike protein (S1) for up to 3 months in a cohort of 169 COVID-19 patients. We enrolled COVID-19 patients at two regional hospitals in Casablanca, Morocco, between March and September 2021. Blood samples were collected and N-specific IgM and S-specific IgG levels were measured by a commercial Euroimmun ELISA. IgM antibodies were assessed 2-5 (D00), 9-12 (D07), 17-20 (D15), and 32-37 (D30) days after symptom onset; IgG antibodies were assessed at these time points plus 60 (D60) and 90 (D90) days after symptom onset. We found that at 3 months after symptom onset, 79% of patients had detectable SARS-CoV-2-specific IgG antibodies, whereas their IgM seropositivity was 19% by 1 month after symptom onset. The IgM level decreased to 0.34 (interquartile range [IQR] 0.19-0.92) at 1 month after symptom onset, whereas the IgG level peaked at D30 (3.10; IQR 1.83-5.64) and remained almost stable at D90 (2.95; IQR 1.52-5.19). IgG levels were significantly higher in patients older than 50 years than in those younger than 50 at all follow-up time points (P < 0.05). Statistical analysis showed no significant difference in median anti-S1 antibody levels among infected patients based on gender or comorbidities. This study provides information on the longevity of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients.

Anti-SARS-CoV-2 Antibody Responses 5 Months Post Complete Vaccination of Moroccan Healthcare Workers.

Data about the duration of antibodies after vaccination show that the protection against SARS-CoV-2 infection begins to decline over time. This study aims to determine anti-SARS-CoV-2 anti-S IgG levels in healthcare workers five months after the second vaccination dose. We collected samples from 82 participants who were fully vaccinated with ChAdOx1 nCoV-19 or BBIBP-CorV. We assessed anti-SARS-CoV-2 IgG antibodies using a Euroimmun ELISA and an Abbott Architect ™ SARS-CoV-2 IgG test. Of the 82 participants, 65.85% were seropositive for IgG using ELISA, and 86.59% were positive for IgG according to the Abbott Architect ™ test. Individuals vaccinated with the ChAdOx1 nCoV-19 vaccine had a median anti-S1 antibody level of 1.810 AU/mL [interquartile range (IQR), 1.080-3.7340] and 171.7 AU/mL [79.9-684.6] according to the Euroimmun ELISA and Abbott Architect test, respectively. These tests indicated that people vaccinated with BBIBP-CorV had a median anti-S1 antibody level of 1.840 AU/mL [0.810-2.960] and 126.7 AU/mL [54.9-474.3], respectively. Statistical analysis showed no significant difference between the positivity rates of the vaccinated individuals, either for gender or for age. In addition, we found no significant difference between the two vaccines. Our study provides information on the longevity of the anti-SARS-CoV-2 IgG antibodies in people at least five months after vaccination.

The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong?

The outbreak of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has emerged in China in December 2019 and rapidly spread to more than 196 countries worldwide. The physiopathology of human SARS-CoV-2 has not been completely understood, but its pathogenesis has been linked to a disproportionate response of the immune system. Just as described for SARS and MERS, an uncontrolled systemic inflammatory response, known as cytokine release syndrome (CRS) was observed in severe COVID-19 patients. It results from the release by immune and non-immune effector cells of substantial amounts of pro-inflammatory cytokines and appears to contribute to SARS-CoV-2 pulmonary inflammation and extensive lung damage. In addition, hyper-coagulation and thrombosis resulted from the important release of pro-inflammatory cytokines contribute to the lethality of subjects severely infected with SARS-CoV-2. It is therefore essential to have a deep understanding of the various cytokines involved in this exacerbated immune response, and that could be targeted by potential immunological treatments. The aim of this review was to gather the current knowledge about the role of pro-inflammatory cytokines, namely IL-1ß, IL-6, IL-8, IL-17 and TNFα in SARS-CoV-2 CRS, the probable causes and clinical outcomes of this phenomenon in severe cases of COVID-19.