A longitudinal study of SARS-CoV-2 infected patients shows high correlation between neutralizing antibodies and COVID-19 severity

Abstract

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection from re-infection and, thus, for public health policy and for vaccine development against the COVID-19. Here, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum specimens from a cohort of 140 SARS-CoV-2 qPCR-confirmed patients, including patient with mild symptoms but also more severe form including those that require intensive care. We show that nAb titers were strongly correlated with disease severity and with anti-Spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers, whereas patients with milder disease symptoms displayed heterogenous nAb titers and asymptomatic or exclusive outpatient care patients had no or poor nAb levels. We found that the nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery, as compared to individuals infected with alternative coronaviruses. We show the absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAb against SARS-CoV-2 infection. Finally, we found that the D614G mutation in the Spike protein, which has recently been identified as the major variant now found in Europe, does not allow neutralization escape. Altogether, our results contribute to the understanding of the immune correlate of SARS-CoV-2 induced disease and claim for a rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2.

SARS‐CoV‐2 re‐infection risk in Austria

“…The coronavirus disease 2019 (COVID‐19) pandemic is a major public health crisis 1,2 . A key question concerning measures against COVID‐19 is the strength and durability of immunity against this disease in individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) 3‐10 . Vaccination strategies, considerations regarding herd immunity, and overall simulations for the pandemic depend on the efficacy and the time course of immunity against COVID‐19 5…”

“…Data on immune responses to COVID‐19 are limited by knowledge gaps regarding their dynamics over time and their clinical significance with reference to protection against re‐infections 3‐10 . There is evidence for re‐infections from numerous case reports, but it is occasionally challenging to differentiate true re‐infections from prolonged viral shedding that may last for up to about 4 months 5,11,12 .…”

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

“…Experimental data pertaining to neutralization of S(G614) and S(D614) pseudoviruses have been reported in abundance. The majority of experiments demonstrate similar neutralization of both S(D614) and S(G614) PVs by antibodies or patient antisera directed against one or the other S protein variant [ 28 , 35 , 51 , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] ], while in some cases S(G614) exhibited greater susceptibility to neutralization [ 51 , 57 ]. Similar neutralization or greater susceptibility of the S(G614) variant have been reproduced with live SARS-CoV-2 as well [ 47 , 48 ].…”

Dynamics of neutralizing antibody responses in acute-phase COVID-19: A potential relationship between disease progression and rapid neutralizing antibody response

“…Among these virus-specific antibodies, only those capable of blocking SARS-CoV-2 spike (S) protein-mediated viral attachment and/or entry of host cells, called neutralizing antibodies (NAbs), play an important role in virus clearance and have been considered as key immune products in the protection against or treatment of viral diseases. Severe COVID-19 can be associated with high neutralization titers in the sub-acute or later phases [4,5] ; however, whether the acquisition of neutralizing antibodies in the acute phase is related to disease severity is unclear.…”