COVID-19 vaccination prevents a more severe course and treatment with complement inhibitors reduce worsening hemolysis during the Omicron pandemic in patients with PNH: a single-center study

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Abstract

Objective

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by chronic complement-mediated hemolysis. The concentrated outbreak of coronavirus disease 2019 (COVID-19) in China after 6 December 2022, provided an opportunity to observe the disease course of PNH during an active Omicron infection epidemic.

Patients and method

Patients diagnosed with PNH at Peking Union Medical College Hospital (PUMCH) before 6 December 2022, were followed up until 10 April 2023. Clinical data related to coronavirus infection and hemolysis were recorded. Factors influencing the infection and severity rate of Omicron, as well as hemolysis provocation, were analyzed.

Results

In total, 131 patients with PNH were included in this retrospective analysis; 87.8% were infected with Omicron. Among them, 15.7% met the criteria for severity, and 1 patient died (0.87%). No protective factors were identified against Omicron infections. However, patients with severe Omicron infection ( n = 18) had a lower vaccination rate than those with non-severe infection ( n = 97; p = 0.015). Among those infected ( n = 115) with Omicron, there was a significant increase in lactate dehydrogenase (LDH) levels compared with those in the uninfected group ( n = 16, p = 0.000). Patients with severe infections ( n = 18) had even higher LDH increase rates than those without severe infections ( n = 97; p = 0.002). 10 (37.0%) patients treated with complement inhibitors developed breakthrough hemolysis (BTH). Patients treated with complement inhibitors ( n = 27) exhibited less severe hemolysis than treatment-naïve patients ( n = 104; p = 0.003).

Conclusions

Omicron infection exacerbates hemolytic attacks in patients with PNH. Vaccination helps mitigate the severity of Omicron infection, and using complement inhibitors reduces hemolysis exacerbation.

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Most cited references 60

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Chaomin Wu, Xiaoyan Chen, Yanping Cai … (2020)

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

David Khoury, Deborah Cromer, Arnold Reynaldi … (2021)

Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

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Author and article information

Journal

Journal ID (nlm-ta): Ann Med

Journal ID (iso-abbrev): Ann Med

Title: Annals of Medicine

Publisher: Taylor & Francis

ISSN (Print): 0785-3890

ISSN (Electronic): 1365-2060

Publication date (Electronic, pub): 1 January 2024

Publication date (Electronic, collection): 2023

Publication date PMC-release: 1 January 2024

Volume: 55

Issue: 2

Electronic Location Identifier: 2274510

Affiliations

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College , Beijing, China

Author notes

CONTACT Chen Yang elegant_yc@ 123456126.com

Bing Han hanbing_li@ 123456sina.com.cn Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College , Beijing, 100730, China

Author information

Bing Han https://orcid.org/0000-0002-9717-217X

Article

Publisher ID: 2274510

DOI: 10.1080/07853890.2023.2274510

PMC ID: 10763918

PubMed ID: 38163328

SO-VID: de8dad0b-ba6d-4c82-8668-774fd5c98095

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This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

COVID-19 vaccination prevents a more severe course and treatment with complement inhibitors reduce worsening hemolysis during the Omicron pandemic in patients with PNH: a single-center study

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Novel Coronavirus Disease COVID-19

Most cited references 60

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

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