Plateau State has confirmed seven cases of Monkey Pox virus from the latest report.
The state epidemiologist, Mrs. Martina Nuwan stated this yesterday in her office in Jos, while giving an update on the spread of the virus in the state.
Nuwan said out of the 24 suspected samples they took, seven were confirmed positive while the results of two that were taken on Thursday were still pending.
She said there was a call from Bassa Local Government Area (LGA) of the state on a suspected case, which the states surveillance team is handling currently.
According to her, all the seven cases were treated at the Bingham University Teaching Hospital (BUTH), Jos and the Jos University Teaching Hospital (JUTH), with no death recorded.
She said though the primary source of transmission of the virus is from animals, the secondary source of transmission is from humans and contaminated environments like surfaces and clothes of an infected person.
She stated that everybody is vulnerable to Monkey Pox disease, including infants and the aged, saying that research has shown that most of the people that were infected by the virus are between the ages of 30 and 50 years.
Generally, she added, the male has the highest number of infection compared to their female counterpart, but most of the victims in Plateau State, are females.
She said Monkey Pox symptoms are not different from most of the viral diseases, saying that there were some clinical manifestations like fever, weakness of the body and the most topical one is rash on the face of an infected person before spreading to other parts of the body.
It can be all over the body, but 95% is found on the face, she further added.
The epidemiologist said, some precautionary measures that people need to take against contacting the virus are to avoid direct contact with animals and people with manifestations of the symptoms, and also avoid contact with beddings and other materials contaminated with the virus.
She advised infected persons to isolate themselves when such symptoms are manifesting and encouraged people to always go to hospital when they discovered any abnormalities in their body.
On the cure for the virus, Nuwan said for there is no vaccine for the virus but it is believed that the Small Pox vaccine could also prevent the Monkey Pox since they are similar virus, and is curable.
Nuwan said the state government through Ministry of Health has an Enhance Surveillance Team and the Public Health Emergency Response Centre that are coordinating emerging and reemerging diseases like the Monkey Pox.
World Health Organisation declared monkey Pox a public health emergency of international concern this year.
WASHINGTON, D.C. (September 27, 2022)The Department of Health and Human Services (HHS) Health Sector Cybersecurity Coordination Center (HC3) has alerted the health care industry to a monkeypox-themed phishing campaign targeting health care providers, including home health agencies. Health care companies that fail to adequately protect their patient's private health information and violate the Health Insurance Portability and Accountability Act (HIPAA) could face fines from the Office of Civil Rights and/or prosecution from their state attorney general's office.
In the alert, HC3 said the phishing attempt carried a subject ofData from (Victim Organization Abbreviation): "Important read about -Monkey Pox (Victim Organization) (Reference Number)." If someone tries to download the attached pdf, it launches a program that tries to harvestOutlook, O365 or other mail credentials.
The alert recommends organizations implement certain protective actions such as:
This alert reminds us that our cyber adversaries, foreign-based criminal gangs and hostile nation-state intelligence services, continue to prey on our culture of care by sending phishing emails based upon current urgent health care issues, said John Riggi, the American Hospital Associations national advisor for cybersecurity and risk. These insidious emails targeting well-intentioned health care workers lure the recipients to click on malicious links, download malware and provide credentials, ultimately leading to the theft of patient data or hospital funds.
Last week, the FBI issued an alert identifying a scheme in which stolen employee credentials were being used to divert and steal millions of dollars in hospital funds, Riggi continued. In this multi-faceted and complex cyber threat environment, multi-factor authentication, phishing tests and verbal authentication for payment instruction changes are essential.
Read more about protecting your business from cyber threats here.
In a recent study posted to the medRxiv* preprint server, researchers investigated the differences in vaccination- and previous infection-induced immunities against the Omicron BA.2 and BA.4/5 subvariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Since November 2021, the SARS-CoV-2 Omicron subvariants have increased the number of coronavirus disease 2019 (COVID-19) cases due to their increased transmissibility and immune evasion capabilities. The Netherlands experienced a surge in cases during the dominance of the BA.1 Omicron subvariant during late 2021, followed by subsequent BA.2, BA.4, and BA.5 dominance periods from early- to mid-2022.
The Omicron subvariants have mutations in the spike protein residues, resulting in increased humoral immunity evasion. Studies have shown that the BA.4 and BA.5 subvariants exhibit the highest degree of neutralization escape, raising concerns about the recurrence of severe COVID-19 outcomes.
The present study examined the effect of vaccination- and prior infection-induced immune status on the occurrence of BA.2 and BA.4/5 between May and July 2022 the transition phase between BA.2 and BA.4/5 predominance.
The researchers used SARS-CoV-2-positive test results from national community testing performed between 2 May to 24 July 2022 and carried out spike (S)-gene target failure (SGTF). The pseudonymized demographic and vaccination status information was also procured from the national community testing register.
The SGTF test was performed using TaqPath COVID-19 real-time polymerase chain reaction (RT-PCR). Combined with quantification cycles less than or equal to 30 to amplify the open reading frame 1 a and b (ORF1ab) and nucleocapsid (N) genes, the inability to detect the S-gene is a proxy for variants containing S 69/70 deletion, such as the Omicron subvariants BA.4 and BA.5. Samples that were non-SGTF were considered to be BA.2 positive, while SGTF samples were BA.4/5 since SGTF cannot distinguish between BA.4 and BA.5.
Whole genome sequencing (WGS) of random SGTF samples was also carried out to see the proportion of BA.4 to BA.5 samples. A combination of WGS and SGTF results from previous infections was used to determine the variants of previous SARS-CoV-2 infections. The immune status groups were defined according to vaccination history and prior infections. The BA.2 and BA.4/5 infections were correlated to these immune status groups using various statistical analyses.
The results found that irrespective of vaccination status, the frequency of BA.4/5 cases was higher than BA.2 cases among individuals with previous infections, suggesting higher immune evasion by BA.4/5. BA.2 and BA.4/5 showed no association with vaccination status, implying that vaccines granted equal protection against all three subvariants.
Prior infection with the BA.1 subvariant presented lower and shorter protective effects against BA.4/5 than BA.2. The authors noted that a similar study from Denmark and other in vitro studies corroborated their results on BA.1 infection-induced immunity being ineffective against BA.4/5. They also discussed studies from the United Kingdom and Portugal, which substantiate their findings about similar vaccination-induced immunity against BA.2 and BA.4/5.
However, the authors believe that the evasion exhibited by BA.2 and BA.4/5 from prior infection-induced immunity is smaller than those seen for BA.1 or the Delta variant, which indicates high antibody escape between the earlier variants of concern than between Omicron subvariants.
The study had a few limitations. Based on the lack of confidence in the previous infection information, the authors believe some individuals might have been misclassified as not previously infected. Additionally, the BA.4 and BA.5 infections could not be separated for the entire dataset due to a lack of WGS data. Furthermore, the 90% threshold used for the TaqPath RT-PCR tests could have resulted in the misclassification of the subvariants. The authors believe, however, that these limitations are unlikely to change the results significantly.
To summarize, the study found that BA.4/5 exhibits higher antibody escape than BA.2 against immunity induced by previous infections from other subvariants such as BA.1, irrespective of vaccination status. Vaccination was seen to grant uniform protection against BA.2 and BA.4/5 infections.
The findings are significant as they suggest that vaccination provides better immunity against the Omicron subvariants than humoral immunity from previous infections. Therefore, vaccine updates and investigation of immune evasion by emergent subvariants should be prioritized.
medRxiv publishes 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.
The Covid-19 pandemic wretched havoc in most parts of the world, leading to detrimental consequences.
Its outbreak led to serious loss of lives. As of today September 2022, the virus had claimed over 6.6 million lives. The numbers usually vary by region, and with time, influenced by healthcare system quality, government response, testing volume, initial outbreak, population characteristics etc.
Different nations have put measures to curb the spread of the pandemic, such as restriction of movements, quarantine measures, vaccination and putting on of the face masks.
The pandemic led to a lot of challenges to the global travel industry, with restrictions and travel guidelines enforced in different economies. However, it is significant and encouraging that there is stabilization of the travel activities in different parts of the country.
In countries such as China, the travel activities were low in February. However, there has been consistent recovery in place. Entry restrictions for different international travels have also been place in some countries but have since been abolished. That means that the visitors are no longer required to document and present vaccination proof or negative Covid-19 test.
Moreover, there have been considerable decline in the reported cases of the virus, suggesting a low contraction rate of the novel virus. However, one of the fundamental questions we need to ask ourselves is; is the world free from Covid-19 pandemic, are we out of the hood yet? The answer to this question is subjective, depending on where one exists.
An individual who dwells in an area where numerous deaths have been experienced would probably disregard the notion and plead with the government to intensify measures to curb the spread of the virus, while an individual living in an area regarded as Covid-19 free regions would nod in agreement that we have finally fought the fight and won the battle.
However, in it is crucial to dig deep and analyze the probability of finally being free from the pandemic, because any relaxation on the containment measures would lead more spread to low risk regions.
While the world continues to fight the highly contagious virus, countries such as New Zealand have shown their potential to contain and defeat the deadly virus. Amid this, New Zealand together with other countries such as Vatican, Fiji, Tanzania, Montenegro, St Kitts and Nevis, Seychelles, Timor-Leste and Papua New Guinea have provided a ray of hope that the crisis might improve in future. The countries have been declared as free from the virus so far and they have been successful in containing the Covid-19 pandemic spread.
Despite the milestone attained, the Director General of WHO warned that we have not reached a completely free virus state. The roll out of therapies and vaccines has assisted in stemming out deaths as well as hospitalization. Even though the deaths from Covid-19 have reached their lowest rates currently, it is important to remain consistent in containing the virus and reap from the hard work towards preventing the spread of the virus.
Countries should take a hard look at their policies and effectively strengthen them for the Corona virus and the future viruses. There should also be a 100 percent vaccination of the high risk groups and to continue to test the virus. As such, with more than one million deaths in 2022 alone, the pandemic is an emergency globally and within several countries.
The global picture
The majority of countries across the world reported falling covid-19 infection numbers. Many countries have extended their overall reporting intervals, making reporting of the identified cases viable and easy. Several countries in the world adopted the vaccination, a means to increase immunity and prevent contraction or severe cases of Covid-19.
Through this, many countries are able to contain the virus because the newly reported cases are relatively low across the continents.
As of June 2022, the countries that have more than 50 percent of its population infected include Andorra, San Marino and Iceland. On the other hand, countries that have between 40 and 50 percent of infection rate of the population are Seychelles, Cyprus, Israel, Switzerland and Georgia. However, countries with less than 1 percent population infected are Algeria, Gambia, Haiti, Cambodia, China and Tanzania.
In general, the overall cases of Covid-19 cases have declined. Most countries have also relaxed their Covid-19 containment measures such as putting on of face masks, restricting movements and enforcing vaccination. Travelling is also easy across the globe, with fewer requirements on the testing of the virus before travelling.
There has been improvement on the overall health of people, with few people getting exposed to the virus. The number of deaths has also declined significantly. Trade, sports activities and tourism has improved with more people visiting their tourist destination. The virus is currently top of the issues that worry the world leaders based on the latest research. Therefore, the major way of handling the issues is through vaccination to prevent further spread, especially in high risk countries.
The Covid-19 situation in Africa
With the population of more than one billion in Africa, the number of coronavirus across Africa has been found to be small compared to different continents. The World Health Organization estimates that about 8.7 million cases, with 75 percent of the cases experienced in Tunisia, Morocco and South Africa.
Fatalities have been low compared to other continent, with the WHO reporting a 2 percent of the overall cases in the world. The success of curbing the spread and intensity of the virus is not the full story. Most of the Africans are worse off than they were at the start of 2020.
The effect of the virus in Africa has majorly been an impact of secondary and tertiary effects. The current challenge in the continent is getting vaccines to countries that have low income and ascertaining that people get vaccinated.
However, as was the case with Ebola, concerning fears and myths, the lack of trust that several Africans have in their governments is justified on how people perceive initiatives such as vaccine drives. This is quite understandable given the political environments that many different people have grown up in. However, it is a challenge to clear for preventing the spread of the Covid-19 in African continent.
Kenya not in a bad shape
The Covid-19 pandemic has been a defining global health crisis of our time as well as the greatest challenge the world has faced since World War II. Since its outbreak in Asia, the virus has spread in almost all continents. Cases emerged in Asia, Europe, America and Africa.
Kenya has not been exempted from the challenges posed by the virus. Despite the severe case experienced before, the current corona case in Kenya points to a scenario that has been contained. The reported cases of Covid-19 have been low.
The government has also relaxed the containment measures such as wearing masks in public. Putting on of masks in outdoor places is deemed optional. However, an individual is required to put on the masks when in confined or closed spaces like aircraft, offices, markets, churches and supermarkets. All in order meetings have also been given a go ahead and they can continue at full capacity if the participants are fully vaccinated.
The Kenyan government has approved the vaccine in a bid to curb the spread of the virus. The move is aimed at preventing contracting the contagious disease and deaths. The vaccines are available for the Kenyan citizens, with the vaccines such as Moderna, Oxford, Johnson and Johnson and Pfizer available. The Kenyan government has not put travel restrictions. Thus, citizens across the world are permitted to enter as long as they are above the age of 12.
Those entering must show proof of negative PCR test conducted not less than 72 hours before departure.
The overall reported Covid-19 cases in the world has reduced. There are few cases compared to the time of its outbreak in Asia. The number of deaths has also declined significantly, and as such, many economies have opted to relax Covid-19 containment measures.
This is good news because the world economies can trade seamlessly, and other economic activities that spur economic growth have resumed. The reduction in the Covid-19 cases is therefore an achievement for most world economies. If the current state is anything to go by, then soon, normalcy will return and there will be total abolition of measures to curb the virus, including vaccination.
Chris DiazBusiness Leader and Brand Africa TrusteeTwitter: @DiazchrisAfrica
Latest: UAE mask rules dropped in most public places as authorities relax Covid restrictions
Face masks will no longer be mandatory in many indoor places and quarantine rules will be eased as part of a major overhaul of the UAE's Covid-19 safety measures being brought into force on Wednesday.
People will only be required to wear face coverings in places of worship, hospitals and on public transport - which includes buses, metros and taxis, - the authorities said in a televised briefing on Monday.
The relaxation of Covid-19 protocols comes amid a sharp drop in infection rates in recent months.
But other rules remain in place to help to win the fight against the disease.
Here is The Nationals guide to the latest Covid-19 rules.
Members of the public have been required to wear masks in indoor settings, such as at malls and when entering restaurants and cafes, under safety rules in place since the early stages of the pandemic.
In February, however, authorities lifted the requirement to wear face coverings outside.
Now wearing masks will be optional in most indoor settings.
From Wednesday, schools nationwide will not require children or teachers to wear masks.
Airlines are to decide on whether or not masks are obligatory.
Staff at restaurants and other eateries would still be required to wear masks while working.
Vaccinated people and those with exemptions will be required to have tests once every 30 days to keep Al Hosn app green. It was every 14 days previously.
Those who are unvaccinated must take a PCR test every seven days to maintain green status.
Active green pass status is required to enter many public buildings in the capital, including malls, supermarkets and restaurants.
Al Hosn allows the user to show proof they have taken a coronavirus vaccine, or had a recent test.
People in Abu Dhabi have been required to display proof of their Green status since August 20, 2021, to enter supermarkets, malls and gyms, among other premises.
Covid-19 PCR testing stations inside three Majid Al Futtaim malls in Dubai are now open to public. All photos by Pawan Singh / The National
The UAE will require people who catch Covid-19 to quarantine at home for five days instead of 10 under the relaxed measures confirmed on Monday.
People exposed to infected cases must take a PCR test, while vulnerable groups are asked to undertake a test and monitor their condition for seven days.
People exposed to infected cases must undergo a PCR test. Vulnerable people exposed to an infected person are advised to undergo a lab test and monitor their condition for seven days.
As of March 25, quarantine is not required for those who came in close contact with a positive case of Covid-19. The directive was issued by the National Emergency Crisis and Disasters Management Authority (Ncema).
However, they must undergo a PCR test on day one and seven, or when the contact starts showing symptoms of Covid-19.
Each emirate has the freedom to set its own rules and in Dubai, close contacts of positive cases who are not experiencing any symptoms do not have to take a PCR test.
Abu Dhabi Public Health Centre advises family members of positive cases to avoid contact with the patient and conduct PCR tests when required. All household members are urged to stay at home until the patient returns a negative tests.
From Wednesday, schools nationwide will not require children or teachers to wear masks.
Classrooms emptied and pupils switched to distance learning in the early months of the pandemic.
The UAE has sought to ease safety rules in recent months, including a widespread return to in-person education.
In early April, the Abu Dhabi Department of Education and Knowledge relaxed school-related Covid-19 prevention protocols.
The protocols removed classroom and bubble closure requirements.
As of February, passengers flying to Abu Dhabi and Dubai from all countries do not require a PCR test before flying if fully vaccinated.
Those not vaccinated must present a negative Covid-19 result issued within 48 hours of their flight or a valid medical certificate demonstrating they had recovered from Covid-19 within one month of their arrival.
It is now no longer mandatory to take a PCR test upon arrival in Abu Dhabi International Airport.
The UAE lifted a ban on overseas travel for unvaccinated Emiratis in April.
Citizens must present a negative result from a PCR test taken within 48 hours of travel under the updated Covid-19 safety measures announced on Wednesday.
They must also complete travel forms in Al Hosn app to turn their application status green.
Authorities had prevented unvaccinated citizens from travelling from January 10 as part of efforts to limit the spread of the virus.
If travelling from the UAE, passengers must check the requirements of the country they are travelling to because these change frequently.
When travelling from Dubai with Emirates airline, a PCR test before departure is not needed, unless the destination requires it.
When travelling from Abu Dhabi with Etihad Airways, you need to take a test only if it is required at your final destination.
Updated: September 27, 2022, 8:52 AM
A report from StatisticsKorea showed that 5,030 people died from Covid-19 in 2021, which is five times more than the Covid-19 related deaths in 2020.
The Covid-19 death rate per 100,000 people was 9.8, an increase of 7.9 from the previous year's 1.9.
By age, the Covid-19 death rate per 100,000 people was highest among those in their 80s with 124, followed by 70s (36.7), 60s (11.5), and 50s (3.1). Deaths over 60 years old accounted for 92.4 percent of the total fatalities last year.
The report also showed men had a higher mortality rate from Covid-19 than women. The Covid-19 death rate per 100,000 people for men was 10.4, which was higher than the mortality rate for women (9.2).
By month, more than half of the deaths occurred in November and December of last year, with the two months accounting for 2,985 deaths.
Seoul had the highest Covid-19 death rate per 100,000 people at 19.3, followed by Gyeonggi Province (11.5) and South Chungcheong Province (8.4). Compared to 2020, the Covid-19 death rate per 100,000 people increased in all cities except Daegu.
On Tuesday, Korea added 39,425 new Covid-19 infections, including 308 cases from abroad, bringing the total caseload to 24,673,663, according to the Korea Disease Control and Prevention Agency (KDCA).
Tuesday's figure was some 21.5 percent lower than a week ago, and the lowest figure for any Tuesday since July 12.
The nation also reported 26 more Covid-19 deaths, raising the death toll to 28,272. The fatality rate stood at 0.11 percent. The number of critically ill patients came to 401, down 26 from the previous day, the KDCA said.
The government has also started accepting advance reservations for booster vaccinations using an improved bivalent vaccine that can also respond to the Omicron variant from Tuesday.
The improved vaccine is a vaccine developed to respond to both the initial Corona 19 virus and Omicron variant (BA.1). The government plans to use Moderna's bivalent vaccine for the booster shots.
Those aged 60 and over, with weakened immunity, and patients in long-term care hospitals and facilities are given priority in receiving the vaccine.
According to the KDCA, about 44.67 million among 52 million Koreans have been fully vaccinated. In addition, about 33.59 million people had received their first booster shots, and 7.42 million had their second booster shots.
Background: Studies exploringfactors predicting postoperative ICU requirement in patients with coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) were not found in the literature. The aim was to evaluate the demographic profile, comorbidities, pattern of steroid received, airway assessment, and intraoperative hemodynamic perturbations associated with ICU requirement amongst patients scheduled for sinonasal debridement.
Methods: This is a retrospective cohort study. All CAM patients of 18 years were included.The patients characteristics, comorbidities, pattern of steroid received, airway assessment, intraoperative hemodynamic perturbations, and outcome data were retrieved.
Results: A total of 130 patients were included. Thirty got admitted to ICU, out of which 26 expired. Amongst the various comorbidities, diabetes was the most common (93.85%) and was associated with higher chances of ICU requirement. Of patients with a history of steroid intake,71% had a significantly higher risk of ICU admission. Out of 30 patients admitted to ICU, 87% (n=26) received invasive ventilation, and the rest were admitted for observation only.
Conclusion: Middle age, uncontrolled diabetes, history of steroid intake, increased levels ofserum creatinine with low potassium, and increased total leucocyte count are the independent risk factors predicting postoperative ICU admission amongst patients with CAM scheduled for sinonasal debridement.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is associated with a wide range of bacterial and fungal infections that co-exist during or following the disease [1-5]. One of these infections is mucormycosis, which is angioinvasive in nature. A sharp surge in cases occurred during the COVID-19 pandemic. Specifically, the prevalence of COVID-19-associated mucormycosis (CAM) has varied from 0.005 to 1.7 per million population globally [6]. The prevalence of CAM in India is nearly 80 times the average in other developed countries [7]. Researchers have pointed to the ample presence of Mucorales in Indian communities, the large number of diabetic patients, and the neglect of regular health check-ups in the country as probable explanations for this outcome [8].
Anesthesiologists often encounter CAM patients when they are scheduled for neurosurgery, ophthalmological surgery, or oro-sinonasal debridement [9]. Patients scheduled for sinonasal debridement often have associated difficult airways in addition to the aforementioned comorbidities [10]. We conducted a literature search that retrieved no studies that have explored the various factors and anesthetic concerns relating to patients scheduled for surgery for the management of CAM.
In the present retrospective observational cohort study, we evaluated the demographic profiles, comorbidities, patterns of steroid and other treatments, airway assessments, and intraoperative hemodynamic perturbations and complications associated with postoperative ICU visits by patients scheduled for either elective or emergency sinonasal debridement for CAM during the second wave of COVID-19 pandemic (March-May, 2021) in India.
The participants included patients who were scheduled for sinonasal debridement in the ENT operation theater (OT). The duration of the study was from May 24 (i.e., the inception of the mucormycosis) through July 31, 2021. During this period, the University College of Medical Sciences and Guru Tegh Bahadur Hospital in New Delhi, India, was the designated facility for the management of CAM cases following the second wave of COVID-19 in the country. We undertook this retrospective cohort study following approval from theInstitutional Ethics Committee For Human Research, University College of Medical Sciences, New Delhi, India, for conducting human research (IECHR-2021-50-16-R1).
We included all the adult patients (those over 17 years old) diagnosed with CAM scheduled for sinonasal debridement surgery during the study period in our sample and excluded obstetric and pediatric patients. We retrieved the case files retrospectively from the medical records department and coded them so as to maintain anonymity. The data was extracted manually. The data covered the patients characteristics, laboratory and radiological investigations, and treatments, such as patterns of steroid use, preoperative airway assessments, anesthetic practices including intraoperative hemodynamic parameters, blood loss, and outcomes. The data was checked twice, and a third researcher adjudicated the differences in their interpretations.
The demographic profiles of the patients in our sample included age, gender, American Society of Anesthesiologists (ASA) physical status classification, duration of surgery, co-morbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and diabetes mellitus, and the duration of the hospital stay prior to surgery (i.e., total days from hospital admission till the day of surgery). We also recorded baseline laboratory and radiological investigations before the surgery as well as the details regarding any previous use of oxygen therapy or steroids for the management of COVID-19. For those with a history of steroid use, we also recorded the dose, duration, and time since ceasing this treatment. We noted from the case files the patients complete airway assessments, such as mouth opening, Mallampati grade (MPG), thyromental distance in the preoperative period, and Cormack-Lehane (CL) grading at the time of intubation as well as the method for securing the airway, whether awake fiberoptic bronchoscopy, fiberoptic bronchoscopy following induction of anesthesia, or use of any airway adjunct such as a stylet, McCoy laryngoscope, bougie, video laryngoscope, or tracheostomy. We also recorded from the case files the results of routine blood examination, including complete blood count, total leucocyte count (TLC), coagulation profile, and serum biochemical test (including renal and liver function and electrolytes) of the patients.
We noted from the case file as well any hemodynamic perturbations (i.e., hypotension or bradycardia) during the intraoperative period. We defined hypotension and bradycardia as a drop in the systolic blood pressure of 20% and heart rate of 20%, respectively, below the baseline recorded on the operation theatre table before the induction of anesthesia. When necessary, hypotension was managed with IV fluids and vasopressors, and bradycardia with 0.6 mg of atropine IV. As per the records, the absence of tachycardia or hypertension indicated an adequate depth of anesthesia with optimum neuromuscular blockade, and analgesia was maintained throughout the surgery. For the patients who experienced hemodynamic perturbations, we noted any history of steroid treatment for COVID-19 and the time since the treatment had ceased.
We further recorded the other treatments that the patients had received retrospectively from their case files, including amphotericin, anticoagulants, and steroids. We noted as well the outcome, that is, whether the patients were sent to a ward or the ICU and, if so, any critical event or final outcome. The factors mandating postoperative ICU admission for elective/emergency postoperative ventilation or for observation included the presence of various comorbidities, significant intraoperative blood loss, intraoperative hemodynamic perturbations, and prolonged duration of surgery. In cases of morbidity or mortality, we noted from the case files the evident cause, such as acute respiratory distress syndrome (ARDS), heart failure, septic shock, coagulopathy, or acute kidney injury, and the number of days on a ventilator. We compared the various preoperative parameters, including demographic characteristics, comorbidities, preoperative investigations, airway assessment, and intraoperative parameters between the patients who required ICU and those who did not to identify the independent predictors of ICU admission among the patients scheduled for sinonasal debridement to treat CAM.
We analyzed the data with IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). We present the descriptions of variables as means, medians (IQRs), or proportions depending on the nature of the data. Since we retrieved the data retrospectively, we omitted the rows that contained three or more missing variables from the analysis, and we replicated the rows with one or two missing variables with the mean, IQR, or mode, again depending on the nature of the data. We used multivariate forward logistic regression to explore the association of such factors as clinical characteristics and laboratory parameters with the risk of ICU requirement and mortality. We included all of the parameters in the regression model after removing multicollinearity and estimating the probability of entry at 0.05. We considered p-values of less than 0.05 to be significant.
A total of 160 patients were scheduled for various mucormycosis surgeries during the study period, sinonasal debridement being the most common procedure. Out of 160 patients, 130 were scheduled for sinonasal debridement and all had a history of COVID-19 and, hence, were labeled to have CAM. Of these 130 patients, only 10 patients had received COVID-19 vaccination (one dose only). Table 1 shows the demographic profile. CAM was seen in the age group of 40 to 60 years and the middle-aged group had significantly more chances of postoperative ICU admission with more preponderance in males. The mean duration of surgery was two hours.
Amongst the various comorbidities, diabetes was the most common (94%) in these patients with more risk of ICU requirement in diabetic patients as compared to any other comorbidity. Sixty-five percent of patients had other comorbidities like hypertension, COPD, chronic kidney disease, coronary arterial disease, or cerebrovascular accident.
Out of 130, 92 patients had a history of steroid intake, of which 93% (n=28) had a significantly higher risk of ICU admission (p-value < 0.005). The average mean duration of steroid intake was 14-20 days. Four patients out of 130 were found to be currently on steroid treatment. The mean time since the stoppage of steroids was found to be 10-20 days. None of the patients who had received steroids earlier were observed to have developed hemodynamic perturbations intraoperatively. Also, four patients who were currently on steroids at the time of surgery also did not report any hemodynamic disturbance. Only 29% of patients had received oxygen therapy during their management of COVID-19. Of the total patients in the study,85% (n=110) were on amphotericin, out of which 87% (n=26) patients required ICU admission.
The preoperative laboratory investigations are shown in Table 2. Fasting blood sugar, blood urea, and serum creatinine were deranged in 43% (n=56), 68% (n=89) and 50% (n=65) of the patients, respectively. TLC was significantly deranged in 35% (n=46) of patients. However, hemoglobin, sodium, and potassium levels were within the normal range in most of the patients. Patients with deranged values of blood sugar, serum creatinine, and TLC had significantly higher chances of requiring ICU admission in the postoperative period.
Airway assessment revealed that 11% (n=14) of patients had difficult mask ventilation. Also, it was noted that 26% of patients had difficult laryngoscopy (Cormack-Lehane grading >2b) and 35% (n=46) had difficult intubation with MPG >2. In Table 3, in context to the use of different airway devices, over 35% (n=46) of patients required either ambuscope (24%) or video laryngoscope (11%); whereas, in 65% (n=84) conventional direct laryngoscopy was used to secure airway.
Intraoperative parameters like hemodynamic perturbations and blood loss were also noted. Only 8% (n=10) of patients showed hemodynamic perturbations. Table 4 shows a significant correlation between intraoperative blood loss to postoperative ICU requirement as all the 20 patients who had massive blood loss got admitted to the ICU in the postoperative period. It was also noted that out of a total of 30 patients admitted to ICU, 26 (87%) expired and only four recovered and were shifted back to the ward and later discharged. Out of 30 patients admitted to ICU, 87% (n=26) received invasive ventilation, and the rest were admitted for observation only.
Table 5 shows the various causes of death amongst subjects. Sepsis (65%,n=17) was the most common cause of mortality in these patients followed by acute respiratory distress syndrome (ARDS) (23%,n=6). Further, acute kidney injury and heart failure were the causes in 8% and 4% of patients, respectively.
Multivariate forward logistic regression of independent risk factors is shown in Table 6. It was observed that old age, history of steroid intake, uncontrolled sugar, serum creatinine, serum potassium levels, and TLC are independent risk factors predicting the risk of ICU admission in patients scheduled for elective surgery.
Multivariate forward logistic regression to find out the risk factors of mortality following the removal of multicollinearity is shown in Table 7. It reveals that deranged TLC and significant blood loss were significantly associated with mortality in these patients.
This retrospective cohort study, therefore, showed middle age, a history of steroid intake, elevated serum creatinine, blood sugar, and TLC levels to be independent factors predicting the risk of postoperative ICU admission among patients scheduled for surgery for the management of CAM. This fungal infection is angioinvasive in nature, and the organism responsible is common in the environment. Increasing reports of this disease have created alarm and drawn attention to the need for an effective treatment since it is associated with an extremely high mortality rate [11]. The COVID-19 pandemic has been associated with a surge in mucormycosis cases in India, especially after the second wave of COVID-19 [12,13]. Patients with rhino-orbital-cerebral mucormycosis commonly receive sinonasal debridement as well as orbital exoneration and decompression. During these surgical procedures, the anesthetic management of the patients has become challenging because theyhave associated co-morbidities and difficult airways and may also be receiving nephrotoxic drugs such as amphotericin. Therefore, it is necessary to mandate the evaluation of the various predictors of postoperative morbidity and mortality for COVID-19 patients associated with mucormycosis, an issue that no previous study has explored.
Regarding the patients demographic profiles, our study is consistent with previous research showing that CAM is more prevalent in male patients than female [9,14-17]. Our findings are also consistent with those of a collaborative study of 2,826 CAM patients showing that their mean age was 51.9 years (with a range of 12-88 years) and that most were male (71%; n=1,993) [11]. Likewise, a multicentric study observed that the patients with CAM tended to be middle-aged (mean age 56.9 years) and male (80.2%) than non-CAM patients [12].
The literature is replete with studies that identify diabetes mellitus and steroid intake as common and pertinent risk factors for the development of CAM. Singhet al., in a systemic review of 101 cases of CAM patients, identified diabetes mellitus (83.3%) and corticosteroid therapy (76.3%) as the most common risk factors for the disease and reported mortality in 30.7% of the cases [9]. Likewise, Sen et al. found, in a study of 2,826 CAM patients, 87% of patients had a history of steroid use and 78% had diabetes mellitus [11]. Similarly, Johnet al. reported that 94% of the CAM patients in their study had diabetes mellitus [14]. Other studies have also observed that the majority of CAM patients had diabetes mellitus and were receiving corticosteroid therapy [9,12,13]. Similarly, Ravaniet al. conducted a retrospective study and identified uncontrolled diabetes mellitus (97.7%), COVID-19 infection (61.2%), and corticosteroid use (61.2%) as significant risk factors with a mortality rate of 9.78% [15]. Sharma et al. studied 23 CAM patients with a history of steroid use during their COVID-19 treatment, of whom 21 were diabetic; of these patients, 12 had uncontrolled blood sugar levels [16]. The non-diabetic patients in another retrospective comparative study showed a better survival rate than the diabetic patients (70% and 51%, respectively), and the mortality rate was 7.4 times higher in the mucormycosis patients with diabetes mellitus [18]. Consistent with the information available in the existing literature, we found diabetes mellitus and steroid use to be strong independent risk factors predicting ICU admission following sinonasal debridement for the treatment of CAM.
The use of steroids to manage COVID-19 appeared to be an important risk factor predisposing patients to mucormycosis. The literature pertaining to the use pattern of these medications, such as dose and duration, is scant. Our results indicate that patients with a history of extensive steroid intake tend to have a relatively higher risk of ICU admission after surgery as compared to those without such a history. In a collaborative study, Sen et al. observed that cumulative doses of greater than 600 mg of prednisone and 2-7 g of methylprednisolone have been found to predispose immunocompromised patients to mucormycosis [11]. Hoang et al. reported observing this effect with short courses of corticosteroids based on the case of a 66-year-old man with well-controlled type 2 diabetes mellitus (hemoglobin A1c of 6.4)who received a cumulative dose of over 600 mg of prednisolone over two weeks after being diagnosed with influenza A and contracted life-threatening pulmonary mucormycosis [19]. For the present retrospective study, we were unable to retrieve the type, dose, or duration of steroid use for the management of COVID-19 because we lacked access to the case files of those who were hospitalized for the management of COVID-19. Since many of the patients were undergoing isolation and treatment at home, the details of their steroid use were not uniformly available.
Because of the involvement of the eyes and sinuses in the infection, these patients may endure difficult mask ventilation and intubation. In the only study of this issue of which we are aware, Karaaslan et al. observed that three of 12 patients experienced difficult intubation because of fungal debris [10]. Similarly, more than 35% of the patients in our study required either a flexible fiberoptic bronchoscope or a video laryngoscope to secure their airways, potentially because of epiglottitis and fungal debris.
Moreover, most of the patients in our study had deranged blood urea, serum creatinine, and potassium levels, probably as a result of amphotericin B therapy, and these patients had a higher risk of postoperative ICU admission and mortality as compared to those without these characteristics. Various studies have shown that amphotericin B has significant renal toxicity at high doses [20-22].
The main cause of mortality among the patients in our study was sepsis followed by ARDS. Hong et al. also found that disseminated infection leading to sepsis correlated with an increased risk of death in mucormycosis patients [23]. Other studies have shown that other underlying conditions predispose individuals to the infection, including trauma, burns, intravenous drug use, use of broad-spectrum antibiotics, increases in iron or ferritin in the system, malnutrition, and use of voriconazole [24-26]. Additional studies are needed to explore and identify other various risk factors.
The present study has some limitations. To begin with, a few of the laboratory tests, such as those for serum iron and serum ferritin, that have been found to predict infections were not conducted in all cases and hence, were not considered risk parameters. Also, we followed the patients only during the in-hospital course of treatment and had no access to the follow-up details of the survivors. Lastly, the generalizability of our findings may be limited by the sample size. Of note, more studies are needed to evaluate these factors for management.
Upon our literature search, we could not retrieve any study exploring various factors predicting postoperative ICU requirement in patients scheduled for sinonasal debridement for CAM. Our study highlighted that middle age, uncontrolled diabetes, history of corticosteroid usage, increased serum creatinine, low serum potassium, and deranged TLC are independent risk factors predicting the postoperative ICU admission amongst patients of CAM scheduled for sinonasal debridement. There were certain limitations of this study such as a few laboratory tests like serum iron and serum ferritinwere not conducted in all patients and hence were not included as risk parameters.Also, the study followed the patients during the in-hospital course only and, therefore, the follow-up details of the survivors could not be commented on. Lastly, the interpretation of our findings might be limited by the sample size. Hence, more studies are needed to evaluate these factors for management.
The novel coronavirus SARS-CoV-2 (COVID-19) has progressed rapidly to reach pandemic levels, killing an estimated nearly one million Americans as of May 8, 2022 [1]. Its presentation varies from asymptomatic to acute respiratory distress syndrome (ARDS) and death. A striking feature of COVID-19 is that it affects every organ system, having various symptoms and complications unrelated to the respiratory system. Notably, patients with COVID-19 have an increased tendency to a prothrombotic state, most commonly presenting as stroke or pulmonary embolism. However, atypical sites of thrombosis have been reported, including basilic vein thrombosis, digital ischemia, and thoracic aorta [2-4]. We present a patient with COVID-19 ARDS who developed pulmonary vein thrombosis (PVT), a rare but life-threatening condition. To our knowledge, only two other cases have been reported of PVT in the setting of COVID-19 pneumonia [4,5].
A 67-year-old African American female with a history of hypertension, hyperlipidemia, and osteoarthritis presented to the emergency department with complaints of shortness of breath and a positive COVID-19 RT-PCR (reverse transcription-polymerase chain reaction) test on admission. Three days prior to admission, she experienced general fatigue, anorexia, productive cough, and dyspnea on exertion. On the day of admission, she experienced shortness of breath, which worsened throughout the day, prompting her to seek medical attention. She arrived at the emergency department via EMS (emergency medical service), and on arrival, she was hypoxic with oxygen saturation at 78% on a 100% oxygen non-rebreather mask. She transitioned to high-flow nasal cannula and eventually reached maximum settings with oxygen saturation ranging between 85% and 95%. She was placed on non-invasive positive pressure ventilation. However, she remained hypoxic, and was eventually intubated five hours after admission. The patient was admitted to the intensive care unit with the diagnosis of ARDS secondary to COVID-19 pneumonia and was placed on dexamethasone and remdesivir for treatment. She was also given subcutaneous heparin for prevention of deep venous thrombosis (DVT). She failed spontaneous awakening trials on the fourth, fifth, and sixth days post-admission. On the seventh day, she developed a fever and began treatment with vancomycin for Staphylococcus pneumonia. The patient was extubated on day 14 and placed on high-flow nasal cannula. Due to recurrent desaturations, she was reintubated the following day. A computed tomography (CT) angiography of the chest on day 15 showed a PVT, which was not seen on prior chest CT angiography from day 1 (Figure 1). She began treatment with therapeutic dosing of apixaban. As the patient failed extubation, she required tracheostomy and percutaneous endoscopic gastrostomy (PEG). She was discharged to a rehabilitation facility 20 days after admission and continued her anticoagulation therapy.
The pathophysiology of COVID-19 coagulopathy is poorly understood. Nevertheless, we know that COVID-19 affects all divisions of Virchow's triad: endothelial injury, hypercoagulability, and stasis. Direct cell injury occurs when COVID-19 enters endothelial cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. As COVID-19 invades endothelial cells, it induces inflammation, which activates the complement system, enhancing cellular dysfunction. Furthermore, the systemic inflammatory response and neutrophil extracellular traps (NETs) promote endothelial dysfunction, furthering the prothrombotic state [6,7]. Reportedly, alterations in prothrombotic factor levels occur in severely ill COVID-19 patients. One study found that 15 critically ill patients with COVID-19 pneumonia had plasma viscosity exceeding 90% of normal [8]. Finally, immobilization due to sedation or severe disease causes blood stasis.
PVT is a rare type of DVT that is potentially fatal. It is commonly associated with lung cancer, lung transplants, left atrial thrombus, and pulmonary lobectomy. In addition, polycythemia vera and blunt chest trauma are rare, documented causes of PVT. Previous to the COVID-19 pandemic, infection was not a known etiology for PVT [6,9-11].
The mechanisms that promote PVT development include mechanical, vascular torsion, hypercoagulation, and direct injury. Of these mechanisms, COVID-19 may influence the latter two. PVT may be underdiagnosed as it can be asymptomatic or have nonspecific symptoms such as cough, dyspnea, pleuritic chest pain, and hemoptysis. Furthermore, PVT and COVID-19 pneumonia share the same nonspecific symptoms, and infection with COVID-19 may mask the presence of a PVT [12]. The significance of PVT in the setting of COVID-19 infection can be related to shared complications of pulmonary infarction, pulmonary edema, right ventricular failure, and potential risk of thromboembolic disease [10]. Diagnosis of PVT is through imaging and pathology. The imaging modalities used include transesophageal echocardiography, CT scanning, MRI (magnetic resonance imaging), and pulmonary angiography [4]. There is no specific treatment for PVT. However, anticoagulation is used for preventing thrombus expansion and embolization, and for promoting vein recanalization. It is also important to initiate early DVT prophylaxis. Trending D-dimers and early hypercoagulable workup may also be recommended in patients with a high risk of clot formation.
COVID-19 infection causes an increased risk of thrombosis due to endothelial dysfunction or hypercoagulability. The rarity and nonspecific presentation of PVT may cause clinicians to overlook it. The concurrence of the PVT in the setting of COVID-19 can potentially increase symptom severity, morbidity, and mortality, but further investigations should be made, and high clinical suspicion is required to establish early diagnosis and treatment.
1. EXECUTIVE SUMMARY
The COVID-19 pandemic requires a complete public health response that spans non-pharmaceutical interventions and medical countermeasures to mitigate the impact of the virus on lives and livelihoods. Despite this need, equitable roll-out of COVID-19 diagnostics and therapeutics continues to be inadequate and threatens to undo public health gains achieved throughout the pandemic. With limited attention on procurement, delivery models and in-country planning, low-income and lower middleincome countries, are disproportionally affected, placing equitable access at risk.
Testing rates, already low in low-income and lowermiddle-income countries, have fallen everywhere since the beginning of 2022. As a result, the world lacks a complete understanding of the full evolution of the pandemic and emerging variants. The delay and shortfall in community-based diagnostics and self-testing with antigen rapid diagnostic tests is particularly concerning. This risks compromising the rollout of new lifesaving outpatient oral antivirals, which are most effective at reducing hospitalisation and death when given within 5 days of symptom onset, and thus reliant on targeted and effective testing to identify early those at risk of severe disease progression. Alongside the challenges of getting treatments to the right people in the right timeframe, realizing the full potential of these new medicines also continues to be hampered by limited access to these products for LMICs, unaffordable prices, delays in adopting test-to-treat strategies, lack of guidance, and a limited ability to deploy these medicines to the primary care and community level. Furthermore, most LMICs are making challenging resource allocation decisions within scarce resource environments and the priority given to COVID-19 diagnostics and therapeutics will therefore depend on broader health demands. The case for supporting greater efficiencies through integration of COVID-19 interventions with existing primary health care systems is strong.
Affordability is an important aspect that will impact availability and equitable distribution of therapeutics and diagnostics. It is critical that affordable diagnostics and therapeutics are not treated as siloed interventions, and to recognise the importance of the broader ecosystem in enabling their development, such as a strong R&D and clinical trials infrastructure. Strengthening primary health care systems is necessary for the rollout of medical countermeasures and general pandemic response. As such, we need to consider medical countermeasures within the wider context of primary health care systems and universal health coverage. National and local ownership and co-investment, alongside strong regional level support, are essential if integrated diagnostics and treatment approaches are to have sustained impact.
This reports central premise is that diagnostics and therapeutics, and associated test to treat strategies, are fundamental components of the pandemic response, both for COVID-19 and for future health threats. Addressing this is as much a structural problem as a technical one: diagnostics and therapeutics are often considered different markets with independent stakeholders. But integration of diagnostics and therapeutics including test to treat strategies in primary health care systems, along with vaccines and public health measures, is a core part of pandemic response. Two and a half years into the COVID-19 pandemic, this report reflects on the main challenges and key solutions on the road to equitable access to diagnostics and therapeutics.
Our Approach
This report draws from experience gained through the Access to COVID-19 Tools (ACT) Accelerator Diagnostics and Therapeutics pillars, and also includes the perspectives of collaborating stakeholders (countries, civil society representatives and the private sector). To ensure a consistent analysis, each pillar evaluated - as of July/August 2022 - the state of play across three areas:
a. regulation, manufacturing and supply;
b. sustainable markets and demand; and
c. in-country delivery and health system approaches.
Equitable access and effective uptake of tests and treatments are complex issues. For both diagnos-tics and therapeutics, recurring challenges have been identified:
Regulation: slow or incomplete at global level, regional level and in countries.
Manufacturing: highly concentrated in a few countries and manufacturers, with variable diagnostic product quality.
Allocation: lack of volumes reserved for low- and middle-income countries, including upper-middle income countries (UMICs).
Funding: delays in mobilizing funds in a timely manner, and scarce and uncertain funding for development of medical countermeasures, with vaccines receiving most attention and funding.
Access & Deployment: global, regional and national efforts to promote equitable access to medical countermeasures have had variable implementation and accountability. This has not resulted in equitable or affordable access.
Forecasting: dynamic and unpredictable nature of the pandemic has led to challenges in demand forecasting. Determinants of local demand and fragmented international response have hindered efficient planning.
Demand: evidence suggests diagnostics and therapeutics continue to be crucial for those at highest risk of progression to severe disease, but awareness and demand remain low.
Building on these findings, this report proposes sixteen recommended actions to address what have been identified as key structural challenges and specifies a potential owner for each action. The report offers a potential high-level roadmap of where efforts should be concentrated to support country-level decisionmaking.
The recommended actions follow two different time frames:
Six recommended actions are in the context of the six-month ACT-A plan (October 2022 to March 2023). These actions are relevant during the next period of the ACT-Accelerators work and thus focus on the downstream part of the value chain. It is recommended that the ACT-Accelerator Tracking and Accelerating Progress Working Group - or the mechanism that will continue to track and monitor ACT-A's work - together with the G20 & G7 health track, review the implementation of the recommended actions.
Ten recommended actions are made in the context of long-term COVID-19 control and the broader Pandemic Prevention Preparedness and Response (PPR) agenda. Therefore, these actions span across the value chain (upstream and downstream).1 This reports long-term recommendations consider ongoing proposals to strengthen the Global Health Architecture, as identified in the WHO White Paper and the G20 health track, as well as the new Financial Intermediary Fund (FIF) for pandemic prevention preparedness and response and the Pact for Pandemic Readiness launched by the German G7 Presidency, which will help ensure the world is better prepared for future pandemics.
In this study we investigated potential correlations between detected antibody levels indicating exposure to Borrelia and the risk of increased severity of COVID-19. Previous exposure to Borrelia was identified by multi-antigenic serological testing, and it revealed that increased levels of Borrelia-specific IgGs strongly correlated with COVID-19 severity and with the risk of hospitalization (Fig.1 and 3, Supplementary Tables S1 and S2). For Borrelia-specific IgMs, correlations were weaker and mostly insignificant (Fig.2 and Supplementary Fig. S3, Supplementary Tables S3 and S4).
Typically, pathogen-specific IgM increases at the early stage of infection, while IgG development takes more time. In borreliosis, at the early stage of infection (24weeks) the immunological system detects only a few antigens of Borrelia, e.g. p41 (flagellin) and Osp proteins (outer surface proteins), targeted by IgM antibodies. Borrelia-specific IgGs, in turn, can be observed several weeks after the tick bite, and their increased serum concentration can remain for a long time, even after the resolution of clinical symptoms. OspC, OspA, and p41 are considered the most immunogenic proteins of B. burgdorferi19,20,21; consistently, in this study IgGs targeting these antigens were also the most frequent and they reached the highest levels (Fig.1). Other important targets for IgG diagnostics include VisE, p83, p58, and p17 19,20,21, also detected in this study. Interestingly, in many patients we observed antibodies targeting different species (e.g. B. burgdorferi sensu stricto, and at the same time B. afzelii, and/or B. garinii). This may reflect some cross-reactivity of antibodies, but likely it may result from co-infections with more than one species, which according to the literature may also occur 22. Also, severe COVID-19 patients demonstrated significantly higher levels of IgG specific to Anaplasma (Fig.1), which is often co-transmitted with Borrelia by ticks. This further supports the suggestion that increased risks in COVID-19 are linked to a history of tick bites and related infections (Fig.4).
Risks in COVID-19 are linked to a history of tick bites and related infections.
Important limitations should be considered for a full understanding of this studys results. First, diagnostics of Lyme disease (active borreliosis) is still difficult and often unclear. Laboratory testing should be considered in conjunction with potential exposure and compatible clinical symptoms10; data on patients history of tick bites and on potential borreliosis-related symptoms were not available here. Particularly severe COVID-19 patients under intensive care were not able to give them. Thus, in the investigated group at least some individuals may demonstrate immunological memory of previous Borrelia infection/s but not an active disease. On the other hand, difficulties with rapid and unambiguous diagnosis may lead to some Borrelia-infected patients going untreated, with the pathogen affecting their health condition even for a long time.
Second, although this study demonstrated a significant correlation between serum levels of anti-Borrelia antibodies and COVID-19 severity observed in the same individuals, a correlation cannot be assumed to indicate causation. One cannot exclude that there was an unidentified primary factor that in these patients caused both higher vulnerability to Borrelia infection and to severe COVID-19. This could possibly be immunodeficiency, other physiological disorders or comorbidities. Of note, patients in the severe COVID cohort were likely to have more comorbidities than those in the other two groups. For instance, obesity has been indicated as associated with the risk of COVID-19-related hospitalizations and death23. In Lyme disease, obesity was associated with attenuated and delayed IgG responses to B. burgdorferi, thus suggesting less efficient protection from adaptive immunity in obese individuals24. Since these patients demonstrated an efficient antibody response to SARS-CoV-2 (Fig.1), this issue calls for further research. Demographic parameters, in turn, have been agreed between groups (Supplementary Fig. S2), so for instance elderly age was not a contributing factor here.
Alternatively, prolonged Lyme disease might affect the immune system, decreasing its efficacy in antiviral responses in the viral infection. This has never been demonstrated yet, though important effects that Borrelia may have on the immune system have been described25,26. Furthermore, one of the possible explanations for studied relationship may be a more detailed insight into the mechanisms of the immune system, more specifically the Toll-like receptor pathway (TLR), whose innate immunity receptors recognize ligands derived from bacteria, fungi, and viruses27. Studies indicate that the TLR pathway mediates, at least in part, the release of inflammatory mediators in human monocytes stimulated with live B. burgdorferi spirochetes28. Similarly, the role of TLR receptors has been described in SARS-CoV-2 infection, which contributes to the elimination of viruses, but it can also harm the host due to persistent inflammation and tissue destruction29. Particularly, B. burgdorferi has been demonstrated to interact with TLR1/TLR2 heterodimers with resulting stimulation of inflammatory response, including increased inflammatory cytokine markers, like IL-6 and TNF-28. The same molecular pathway is targeted by SARS-CoV-2, where stimulation via TLR1 and TLR2 has been indicated as the key factor of excessively upregulated cytokine response and its harmful effects within severe COVID-1930,31. This suggests that co-stimulation from both B. burgdorferi and SARS-CoV-2 may result in even more pronounced excessive inflammatory response and a higher risk of severe COVID-19. This hypothesis needs to be further verified in future studies.
In spite of above mentioned important reservations and considerations, a strong link between detected anti-Borrelia antibodies and COVID-19 severity was observed in this study (Fig.1, 2, and 3). This was further supported by post-hoc analysis of IgG targeting selected antigens of Borrelia. These antigens included Osp proteins, p41, and VlsE, being highly immunogenic19,20,21 and important in the life cycle of spirochetes; they are engaged in bacterial colonization of ticks and mammals, virulence, and immune evasion by Borrelia32,33,34. The analysis with multivariant logistic regression revealed that increased levels of IgG targeting Osp proteins (only) can be significant predictors of hospitalization due to COVID-19; in this study OspB, OspC B. burgdorferi sensu stricto, and OspC B. spielmanii demonstrated significance in this model (Supplementary Fig. S4, Supplementary Table S5).
To the best of our knowledge, this is the first observation that suggests links between Lyme disease and COVID-19 prognostics. Screening for antibodies targeting Borrelia may contribute to accurately assessing the odds of hospitalization for SARS-CoV-2 infected patients. Though mechanisms of this association are not clear yet, it may help in establishing optimal treatment schedules and in efficient predictions of individual patients prognostics, supporting efforts for efficient control of COVID-19.
