Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection

Abstract:

To understand the roles of acute phase viral dynamics and host immune responses in PASC, we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR. Participants self-collected nasal specimens up to 21 times within the first 28 days after symptom onset; Interviewer-administered clinical questionnaires and blood samples were collected at enrollment and days 9, 14, 21, 28, and month 4 and 8 post-symptom.

Defining PASC as the presence of any symptom new or worse since infection reported at their 4-month visit, we compared viral markers (quantity and duration of viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-a, IFN-a, IFN-g, MCP, IP-10, and Spike IgG) over the acute period.

In comparison to those who fully recovered, those who developed PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA, infectious virus, and N-antigen, longer duration of viral shedding, and lower Spike-specific IgG levels within the first 10 days of the acute phase of illness. No significant differences were identified among a panel of host immune markers, though there was a trend toward higher initial levels of certain markers (e.g., MCP-1, IFN-a, and IFN-g) in those who went on to develop PASC.

Early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC. These findings highlight the importance of understanding the early biological markers from acute SARS-CoV-2 infection in the natural history of PASC.

Source: Scott LuMichael J. PelusoDavid V. GliddenMichelle C. DavidsonKara LugtuJesus Pineda-RamirezMichel TassettoMiguel Garcia-KnightAmethyst ZhangSarah A. GoldbergJessica Y. ChenMaya Fortes-CobbySara ParkAna MartinezMatthew SoAidan DonovanBadri ViswanathanRebecca HohKevin DonohueDavid R. McIlwainBrice GaudiliereKhamal AnglinBrandon C. YeeAhmed ChennaJohn W. WinslowChristos PetropoulosSteven G. DeeksMelissa Briggs-HagenRaul AndinoClaire M. MidgleyJeffrey N. MartinSharon SaydahJ. Daniel Kelly. Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection. https://www.medrxiv.org/content/10.1101/2023.07.14.23292649v1.full-text (Full text)

Natural history of long-COVID

Abstract:

Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test.

Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.

Source: Hastie, C.E., Lowe, D.J., McAuley, A. et al. Natural history of long-COVID in a nationwide, population cohort study. Nat Commun 14, 3504 (2023). https://doi.org/10.1038/s41467-023-39193-y https://www.nature.com/articles/s41467-023-39193-y (Full text)