Background The relationship of host immune response and viral replication with health outcomes in patients with COVID-19 remains to be defined. We aimed to characterize the medium and long-term clinical, virological, and serological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID. Methods Prospective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2, and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID-19 symptom questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized. Results Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2 months and 6 months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct = 38) and 3% (median Ct = 36) patients at 2 months and 6 months, respectively, but no reinfections were demonstrated. Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR [95%CI]) were lower peak S-IgG (0.80 [0.66-0.94]) and higher WHO severity score (2.57 [1.20-5.86]); 6-month predictors were lower peak S-IgG (0.89 [0.79-0.99]) and female sex (2.41 [1.20-4.82]); no association was found with prolonged viral RNA shedding. Conclusions Long-COVID is associated with weak anti-SARS-CoV-2 antibody response, severity of illness, and female gender. Late clinical events and persistent symptoms in the medium and long term occur in a significant proportion of patients hospitalized for COVID-19.

Background The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. Findings 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA ( p = 0•016) and SARS-CoV-2 viral load ( p <0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 [95%CI] [0•15–0•81], log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 [0•35–7•7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 [0•11–0•89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 [1•9–5] for S-IgG; and HR 3•0 [1•9–4•9] for N-IgG; log-rank p <0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 [0•41–6•0]) nor N-IgG (HR 0•96 [0•26–3•5]) responses in an adjusted propensity score analysis. Interpretation Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. Funding Instituto de salud Carlos III (Spain).

No abstract

Objectives The interdependencies of viral replication and the host immune response in patients with COVID-19 remain to be defined. We investigated the viral determinants of antibody response, the predictors of non-seroconversion, and the role of antibodies on viral dynamics. Methods Prospective study in patients hospitalized with microbiologically confirmed COVID-19 by real-time polymerase-chain-reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring SARS-CoV-2 RNA and antibodies (total and S-IgG/N-IgG), respectively. Results Of 132 patients included, 99 (75%) showed positive antibody titers after a median (Q1-Q3) of 11 (8-14) days. Median (Q1-Q3) follow-up was 74.5 (63.0-87.0) days. In adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load (p=0.009) and positively with time to viral clearance (p=0.004). Adjusted predictors of S-IgG levels were time to viral clearance (p&lt;0.001), bilateral lung infiltrates on admission (p=0.011), and the time-dependent SARS-CoV-2 RNA (p&lt;0.001) and SARS-CoV-2 RNA area under the curve (p=0.001). Thirty-three (25%) patients showed undetectable antibody titers. Patients who did not seroconvert had higher cycle threshold values of RT-PCR (38.0 vs 28.0; p&lt;0.001), shorter time to viral clearance (3.0 vs 41.0; p&lt;0.001) and were more likely to have SARS-CoV-2 only detected on fecal samples (p&lt;0.001). Non-seroconvertors had also lower levels of blood inflammatory biomarkers on admission and lower disease severity. Conclusions Viral replication determines the magnitude of antibody response to SARS-CoV-2 that, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.

Background Performance of point-of-care tests in different clinical scenarios and on different samples remains undetermined. We comprehensively evaluated the performance of the nasopharyngeal Panbio COVID-19 antigen Rapid-Test-Device. Method Prospective study including consecutive patients attending three primary care centers (PCC) and an emergency department. The antigen test was performed at point-of-care in nasopharyngeal and nasal swabs, and in saliva. Positive and negative percent agreement (PPA, NPA) were calculated with the RT-PCR assay as reference standard. Results Of 913 patients included, 296 (32.3%) were asymptomatic and 690 (75.6%) came from the PCC. Nasopharyngeal swabs were collected from 913, nasal swabs from 659, and saliva from 611 patients. RT-PCR was positive in 196 (21.5%) nasopharyngeal samples (NPS). Overall PPA (95% CI) in NPS was 60.5% (53.3-67.4), and it was lower in nasal swabs (44.7%) and saliva (23.1%). Test performance in NPS was largely dependent on the cycle threshold (Ct) in RT-PCR, with PPA of 94% for Ct≤25 and 80% for Ct&lt;30. In symptomatic patients, the PPA was 95% for Ct≤25; 85% for Ct&lt;30, and 89% for the symptom triad of fever, cough and malaise. Performance was also dependent on age, with PPA of 100% in symptomatic patients &gt;50 years with Ct&lt;25. In asymptomatic patients, the PPA was 86% for Ct&lt;25. In all cases, NPA was 100%. Conclusion The nasopharyngeal Panbio COVID-19 antigen test performed at point-of-care has a good sensitivity in symptomatic patients with Ct&lt;30 and older age. The test was useful to identify asymptomatic patients with lower Ct values.