High levels of antibodies and inflammatory mediators may predict severe COVID-19

The 2019 coronavirus disease pandemic (COVID-19), caused by severe acute coronavirus 2 respiratory syndrome (SARS-CoV-2), has spread rapidly around the world. To date, over 138.3 million cases have been confirmed and over 2.9 million deaths have been reported.

New study published on bioRxiv* Preprint server reports on biomarkers can help predict the progression of a viral disease to dangerous levels early enough to allow for timely intervention.

Predicting the progression of COVID-19

The generally asymptomatic nature of COVID-19, together with the high infectivity of the virus, encourages its spread. In a significant minority of cases, the disease progresses and becomes severe or critical, requiring intensive medical care.

In such cases, the patient quickly worsens and develops severe inflammatory lung disease, which results in acute respiratory distress syndrome (ARDS). This is often accompanied by other multi-organ dysfunctions and sepsis.

The risk of severe disease is much higher in older adults over the age of 80 and people with concomitant diseases such as hypertension, diabetes or obesity. The outcome may be effective viral clearance or a hyperintense inflammatory response leading to severe lung damage, organ failure and chronic sequelae, prolonged illness, or death.

The present study considers clinical, virological, and immunological markers in patients hospitalized with COVID-19 to identify mild, moderate, and severe disease. These features were monitored at the time of diagnosis and at various points for up to six months from the onset of confirmed infection.

Study details

The study included 24 hospitalized patients, of whom over 80% were men, and the mean age was 61 years. Half of them met the criteria for obesity, with a body mass index (BMI) over 30. More than 40% had hypertension.

The average length of hospital stay was eight days. Every fifth person needs admission to the intensive care unit. One-third were diagnosed with severe COVID-19.

There were 92 nasopharyngeal swab samples giving viral ribonucleic acid (RNA), taken at different times. That is, 24 were derived from a polymerase chain reaction assay at admission; 18 were from day 3, 13 from day 5, day five and 16 days one month. Finally, 16 were collected in three months.

Virus tests

Almost all patients were initially positive, with a median viral load> 2000 copies / 10,000 cells. One patient was negative, probably due to poor sampling. With a decrease in viral load over time, 80% of patients were negative within a month of diagnosis.

The virus persisted in five patients, as shown by positive tests after one and three months. All five had severe COVID-19, along with underlying cardiovascular disease, hypertension, or diabetes.

Viral loads

In the acute phase, patients with severe disease showed a slight decrease in viral load during the first six days, which became significant only after that period. In contrast, early and marked reductions have been reported in patients with mild or moderate disease.

Antibody level

Over a hundred serum samples were available for antibody testing, following almost the same collection pattern as nasopharyngeal swabs. Anti-SARS-CoV-2 IgA levels were variable at baseline, progressively increasing until day 6 and then decreasing until month 6. The highest levels at baseline and later were in patients with severe COVID-19.

The same pattern was visible for IgM and for IgG. The increase in IgG levels was much slower until the sixth day, but then gradually decreased to very low titers in the 6th month. At this point, however, levels were fourfold higher than in uninfected controls, at ~16 versus 4.5 μg / mL, respectively.

Cytokine level

Mean levels for nine cytokines, measured in 18 patients, including TNF-α, IL-6, IL-8, IL-1β, and MIP-1α, showed differences between inflammatory and other cytokines.

Higher levels of IL-6, IL-8 and MIP-1β were initially associated with severe disease. High levels were maintained for inflammatory markers such as IL-6, IL-8, IP-10, TNF-α, and sCD25 throughout the study period in severe COVID-19 compared with mild to moderately ill patients.

However, for MIP-1β, IL-1β, MIP-1α, and IFN-γ, the levels of some of them were higher by one and three months among those with mild or moderate disease compared to those with severe disease.

At six months, no difference was observed between the different groups.

High levels of antibodies and cytokines were found in patients with ARDS compared to those without this complication, as well as mechanical ventilation and admission to the ICU. Viral load did not initially show such a correlation.

What are the implications?

The persistence of viral RNA in five patients, all of whom had either severe COVID-19, or underlying chronic disease, or both, suggests the need to understand the clinical importance of the presence of the virus in different parts of the body, whether plasma, intestinal, or upper respiratory tract.

If this is known, it could help you to keep an eye on acutely infected patients, as well as to monitor them after the acute symptoms subside.

The results show that the following markers are associated with severe disease: high titers of specific IgA, IgM, IgG, and high levels of the cytokines IL-6, IL-8, and MIP-1β, at the time of admission; and prolonged presence of viral RNA in the upper respiratory tract for the first few days after diagnosis.

The rapid decline in IgA and IgM antibodies after the acute infection phase divides IgG, but at a slower rate. However, at 6 months, the titers of specific IgG antibodies remained higher relative to naive individuals, indicating lasting immunity.

This resonates with other studies that show persistent antibodies to IgG up to eight months after the onset of infection. The correlation of such antibodies with neutralizing activity is unknown and remains an urgent research question.

The role of hyperactive inflammation in the damage caused by infection is underlined by the high level of inflammatory cytokines observed in this study. The individual parts for which each is responsible have yet to be clarified.

This small study presents interesting findings that need to be confirmed and monitored to identify and quantify the predictive value of these markers of serious COVID-19 before clinical deterioration occurs.

* Important notice

bioRxiv publishes preliminary scientific reports that have not been reviewed and should therefore not be considered final, direct clinical practice / health-related behavior, or treated as established information.