Association between SARS-CoV-2 infection and several key respiratory and non-respiratory complications

In a recent study posted to Preprints with The Lancet, researchers assessed the intensity of association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risks of various respiratory and non-respiratory complications.

Study: Complications Following SARS-CoV-2 Infection in Victoria, Australia: A Record Linkage Study. Image Credit: RONNACHAIPARK/Shutterstock

The coronavirus disease 2019 (COVID-19) pandemic has imposed a profound global burden on the healthcare system. Evidence from previous studies suggests the role of SARS-CoV-2 infection in inducing cardiac, vascular, and neurological pathologies apart from respiratory illnesses.

The present study was designed to measure hospitalization rates and the major reasons for admissions following the onset of COVID-19.

Study design

The researchers used a primary cohort composed of SARS-CoV-2-confirmed cases between 25 January 2020 and 31 May 2021; the data was captured from the transmission and response epidemiology victoria (TREVi) database (a population-linked dataset). This cohort was linked to the Victorian admitted episodes dataset (VAED) and Victorian death index (VDI). Record linkages were performed through the Center for Victorian data linkages at the Victorian Government Department of Health.

Two different study designs were used 1) a retrospective cohort study to ascertain the rate of hospitalizations of COVID-19 cases and the identification of clinical reasons for hospitalizations following one year of onset of COVID-19 illness and 2) self-controlled case series which assessed the epidemiological link between SARS-CoV-2 infection and major respiratory and non-respiratory complications. The researchers also conducted a sensitivity analysis.

The outcomes of interest were identified by International Classification of Disease version 10 Australian Modification (ICD-10-AM) diagnoses codes. A Poisson regression model estimated incident rate ratios (IRR) and 95% confidence intervals for risk comparison post-exposure with a baseline period before SARS-CoV-2 infection.

Findings

The researchers observed that out of the 20,594 SARS-CoV-2-positive cases notified during the study protocol, 12.11% were hospitalized with COVID-19 symptoms. Hospitalized COVID-19 cases were proportionally female, older, and required an interpreter compared to non-hospitalized cases. Of the hospitalized cases, 19% showed symptoms at the onset of infection, and 1% were registered as dead.

On the analysis of a cohort of 20,594 COVID-19 cases, researchers observed that 21.07% were admitted to the hospital for one year following the onset of illness. In the first 12 days of onset of illness, there were 25% hospital admissions, which rose to 50% by the first 115 days. In the hospitalized cases, the common reasons for admissions were viral pneumonia (10.5%), SARS-CoV-2 infection (4.6%), cough (3.0%), unspecified fever (2.5%), dyspnoea (2.3%), and unspecified chest pain (1.4%).

Primary analysis revealed that from 365 to 60 days before the onset of illness (baseline period), SARS-CoV-2 infection was strongly associated with various respiratory and non-respiratory-complications. In the period between three to < 90 days of SARS-CoV-2 infection, the risk for myocarditis and pericarditis, coagulative disorder, thrombocytopenia, acute renal failure, and cerebral infarction was significantly elevated compared to the baseline.

Following the 90 days of COVID-19 onset, the risk for venous thrombotic events was seven-fold higher compared to baseline (pulmonary embolism: IRR 6.37, embolism of the lower limb: IRR 5.47, phlebitis: IRR 2.82, and thrombophlebitis: IRR 11.66). The researchers observed five embolism cases or thrombosis of other veins like splanchnic vessels while there was no such case in the baseline period. Among all cases, only one was hospitalized following >14 days of COVID-19 onset with a range between 4 to 66 days.

Within 90 days of the onset of COVID-19, 24 cases were assessed having cerebral infarction with the principal condition including respiratory viral pneumonia (29.17%), non-specific cerebral infarction (29.17%), and hemorrhage or infarction non-specific stroke (12.50%). Cases of cerebral infarction due to the central vein or portal vein thrombosis were not observed.

Respiratory events such as infectious (IRR 15.16) and non-infectious (IRR 9.09) events, combined asthma, and chronic obstructive pulmonary disease (COPD) (IRR 6.11) were elevated markedly following 90 days of the onset of the COVID-19 illness.

While performing sensitivity analysis, the researchers observed profound increased risks for acute myocardial infarction (AMI) (IRR 5.08) and intracerebral hemorrhage (IRR 10.17) following a three to <7 day period of COVID-19 onset. Between 14 and < 90 days following onset of COVID-19, venous thromboembolic event risk was elevated (IRR 5.45 for 14 to < 30 days; and IRR 4.36 for 30 to < 90 days). Hospitalizations owing to the risk of respiratory illnesses were observed to be the highest during 30 days of onset of COVID-19 illness thereafter returning to a baseline level.

Conclusion

The results of this study demonstrated that SARS-CoV-2 infection substantially raised the risk of several complications beyond the respiratory illness, including pericarditis and myocarditis, AMI, pulmonary embolism, coagulative disorders, thrombocytopenia, and acute renal failure.

The evidence from this study highlighted that improved understanding of these COVID-19-related complications might aid early diagnosis and treatment of patients with SARS-CoV-2 infection history and help reduce the public health burden on individuals and health services due to COVID-19. Further research is warranted for quantifying the risk of complications to assess the mechanism of SARS-CoV-2-infection-induced complications identified in this analysis and develop interventions to prevent these complications.

*Important notice

Preprints with The Lancet publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.