Immunity to SARS-CoV-2 up to 15 months after infection

BackgroundInformation concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset. MethodsThe levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison. FindingsFollowing a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months. ConclusionThe data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies. FundingEU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

BackgroundThe longevity of the immune response against SARS-CoV-2 is currently debated. We thus profiled the serum anti-SARS-CoV-2 antibody levels and virus specific memory B- and T-cell responses over time in convalescent COVID-19 patients. MethodsA cohort of COVID-19 patients from the Lombardy region in Italy who experienced mild to critical disease and Swedish volunteers with mild symptoms, were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, specific memory B- and T-cell responses were tested in selected patient samples. ResultsAnti-SARS-CoV-2 antibodies were present in 85% samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM or IgA antibodies declined after 1 month while levels of specific IgG antibodies remained stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses were developed in vast majority of the patients tested, regardless of disease severity, and remained detectable up to 6-8 months after infection. ConclusionsAlthough the serum levels of anti-SARS-CoV-2 IgG antibodies started to decline, virus-specific T and/or memory B cell responses increased with time and maintained during the study period (6-8 months after infection). FundingEuropean Unions Horizon 2020 research and innovation programme (ATAC), the Italian Ministry of Health, CIMED, the Swedish Research Council and the China Scholarship Council.

Prolonged low-dose methylprednisolone in patients with severe COVID-19 pneumonia

BackgroundIn hospitalized patients with COVID-19 pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for ICU and mortality. MethodsWe conducted a multicenter, observational study to explore the association between exposure to prolonged, low-dose, MP treatment and need for ICU referral, intubation or death within 28 days (composite primary endpoint) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. ResultsFindings are reported as MP (n=83) vs. control (n=90). The composite primary endpoint was met by 19 vs. 40 [adjusted hazard ratio (HR) 0.41; 95% confidence interval (CI): 0.24-0.72]. Transfer to ICU and need for invasive MV was necessary in 15 vs. 27 (p=0.07) and 14 vs. 26 (p=0.10), respectively. By day 28, the MP group had fewer deaths (6 vs. 21, adjusted HR=0.29; 95% CI: 0.12-0.73) and more days off invasive MV (24.0 {+/-} 9.0 vs. 17.5 {+/-} 12.8; p=0.001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the two groups (p=0.84). ConclusionIn patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Randomized controlled studies are needed to confirm these findings. RegistrationClinicalTrials.gov. Identifier: NCT04323592

Clinical presentation and evolution of COVID-19 in immunosuppressed patients. Preliminary evaluation in a North Italian cohort on calcineurin-inhibitors based therapy

The clinical course of COVID-19 in patients undergoing chronic immunosuppressive therapy is yet poorly known. We performed a monocentric cross-sectional study describing the clinical course of COVID-19 in a cohort of patients from northern Italy treated with calcineurin-inhibitors for organ transplantation or rheumatic diseases. Data were collected by phone call and clinical chart review between March 27th- 31st 2020. COVID-19 related symptoms, rynopharingeal swab, therapeutic changes and outcome were assessed in 384 consecutive patients (57% males; median age 61 years, IQR 48-69). 331 patients (86%) received solid organ transplantation (kidney n=140, 36%, heart n=100, 26%, lung n=91, 24%) and 53 (14%) had a rheumatic disease. Calcineurin inhibitors were the only immunosuppressant administered in 46 patients (12%). 14 patients developed a "confirmed COVID-19" (swab positivity) and 14 a "clinical COVID-19" (only typical symptoms). Fever (75%) and diarrhoea (50%) were the most common symptoms. Fourteen patients were hospitalized and 11 have already been dismissed. No patient required start/changes of the O2 therapy or developed superinfection. Only one patient, with metastatic lung cancer, died. In conclusion, COVID-19 showed a mild course in our cohort, with low mortality. Calcineurin inhibitor-based immunosuppressive regimens appear safe in this context and should not be discontinued.

Clinical and immunological evaluation of 12-month azithromycin therapy in chronic lung allograft rejection.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the leading cause of morbidity/mortality in lung-transplant recipients (LTRs). Recent studies demonstrated that azithromycin (AZI) can improve graft function in BOS. We here investigated whether a 12-month course of AZI could more efficiently impact the course of BOS if administered early in BOS development. METHODS: Using a retrospective study, we examined AZI effects on graft function in 62 LTRs: 25 with potential BOS (BOS 0-p) and 37 with BOS grade 1-3. Response was defined as a ≥ 10% FEV(1) increase. Bronchoalveolar (BAL) neutrophilia and levels of IL-8, 8-isoprostane and other plasma cytokines were analyzed as parameters of lung or systemic inflammation. RESULTS: After 12-month AZI, 13 patients were responders, 35 had graft function stabilization, and 14 further deteriorated. The frequency of responders was significantly higher in LTRs with BOS 0-p (44%) than in those with BOS grade 1-3 (6%). No association was found between BAL features and AZI response while a significant decrease in plasma levels of IL-8, MCP-1, I-309, MIP-1α, and TNF-α was detected. CONCLUSIONS: Long-term AZI can improve or stabilize lung graft function in LTRs with BOS, but the treatment impacts the course of the disease more efficiently if administered in BOS 0-p.